Lets See

Summary of comments on 3662
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Type: Highlight Author: mehreen916 Subject: Highlight Date: 1/16/2017, 11:50:12 PM
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Type: Highlight Author: mehreen916 Subject: Highlight Date: 1/17/2017, 12:20:42 AM
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Type: Text Author: mehreen916 Subject: Sticky Note Date: 5/6/2017, 1:19:14 AM
nbme>>>>3,2,1 gel shows that the DNA form H inlfuenza was cleaved into numerous fragments while that from E.coli
was not.>>>>>>>this is explained by methylation of E.coli DNA not by presence of intron or
transoposon................... explaination Adenine or cytosine methylation is part of the restriction modification
system of many bacteria, in which specific DNA sequences are methylated periodically throughout the genome. A
methylase is the enzyme that recognizes a specific sequence and methylates one of the bases in or near that
sequence. Foreign DNAs (which are not methylated in this manner) that are introduced into the cell are degraded by
sequence-specific restriction enzymes and cleaved. Bacterial genomic DNA is not recognized by these
restriction enzymes. The methylation of native DNA acts as a sort of primitive immune system, allowing the
bacteria to protect themselves from infection by bacteriophage.
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Type: Highlight Author: LENOVO Subject: Highlight Date: 7/13/2017, 7:11:14 PM
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this mosatic pattern of X-chromosome expression generally prevents X-linked recessive conditions from
manifesting in female carriers. However, in rare cases, skewed lyonization (uneven inactivation of
maternal/paternal X chromosome due to chance alone) may result in females developing an X-linked
recessive condition (eg, classic hemophilia). a small proportion of genes remain transcriptionally
active on the inactivated X chromosome. For this reason, inheritance of an abnormal number of X
chromosomes can cause clinical manifesttaions due to a gene-dosage effect, as seen with Turner (45,
XO) and Klinefelter (47, XXY) syndromes.
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Type: Highlight Author: mehreen916 Subject: Comment on Text Date: 1/17/2017, 3:15:23 AM
this enzyme is inhibited by UMP
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reversibly inhibit a critical step in de novopurine nucleotide synthesis (IMP dehydrogenase), which is required for
proliferation of activated lymphocytes. it selectively targets lymphocytes, reducing B cell and T cell proliferation
and antibody production while promoting T cell apoptosis
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Type: StrikeOut Author: LENOVO Subject: Cross-Out Date: 6/9/2017, 9:34:08 PM
Deamination of adenine makes hypoxanthine. Deamination of guanine makes xanthine. Deamination of
5methylcytosine makes thymine.
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negatively regulated by increase level of deoxyribose nucleotide.
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uworld mention phenytoin also
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nbme>>6,3,33
sugar are attached to nitrogen containing basses by>>>>N-glycosidic bonds not by hydrogen or
phosphodiester bond.
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and its derivative oxipurinol, are predominantly non-competitive inhibitors (u world say competitevely)of xanthine
oxidase
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Excess dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase •
prevents DNA synthesis and thus • lymphocyte count.
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due to increased activity of PRPP amidotransferae
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Type: Text Author: mehreen916 Subject: Sticky Note Date: 7/5/2017, 8:43:09 PM
X-linked activated mutation in PRPP synthetase which causes increased production and degradation of purine.
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urate kidney stones,and involuntary movement(choreoathetoid)
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xanthine oxidase deficiency results in low level of uric acid in serum but lead to renal calculi due to relative
insolubility of xanthine at urine Ph.
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this substrate accumulate when HGPRT is not working.
and its accumulation results in increase activity of PRPP amidotransferase.
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first origin of replication is identified and bound by several monomers of the DnaA protein which serves to locally
dissociate double strand DNA (ds DNA) into ssDNA at the origin of replication.there after SSB proteins bind to ssDNA
to stabilize it.
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topoisomerase 1 makes single-stranded nicks to relieve negative supercoiling,
while topoisomerase 2 induces transient breaks in both DNA strands simultaneously to relieve
both positive and negative supercoiling.
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DNA dependent RNA polymerase.which gives first 3^hydroxyl group to start replication.
the 3'-hydroxyl group is placed on the strand to be duplicated by primase.
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viral RNase H (removes the RNA primer, allowing for completion of newly synthesized DNA.
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the 5' to 3' exonuclease activity of DNA polymerase I also performs exonuclease excision and repair of damage to
parent DNA.
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separated by RNA primers
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syndromes of premature aging such as BLOOM syndrome are associated with shortened
telomeres.
1438
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Type: Text Author: aishazulfiquar Subject: Sticky Note Date: 5/24/2017, 8:55:52 PM
primase in prokakyotes and DNA polymerase alpha in eukaryotes have same function
1437
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is a reverse transcriptase enzyme and add TTAGGG.
is composed of two main subunits: the revertanscriptase TERT and the RNA component TERC.
TERC is a "built in: part of the telomerase enzyme.
the TERC RNA template is repeatedly read by the reverse transcriptase to add TTAGGG DNA
sequence.
1438
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phopsphate group of 5^end and OH group of 3^ end
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also do proofreading in this direction.(excision repair enzyme)>>>remove damaged DNA
segments.
The gaps created by this are also filled by this enzyme(DNA polymerase I in 5^ to 3^ direction)
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all DNA polymerase has this function but only DNA polymerase 1 has 5'>>3' exonuclease activity
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nbme>>5,2,32
topoisomerase cut one strand(phosphodiester) of DNA, which result in>>>
free rotation of the two sections of the DNA helix on either side of the nick
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Helicase binds DNA at the origins of replication with the assistance of DnaA protein and acts at
the replication fork to separate DNA
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only DNA ploymerase III fuction all the major replication in eukaryotes.
DNA polymerase I, II, and III all involve in replication in prokaryotes
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single base substitution.
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it is constitutively expressed.
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Type: Highlight Author: mehreen916 Subject: Comment on Text Date: 5/8/2017, 8:52:24 PM
aflatoxin induced p53 mutations are a classic G:C to T:A transversion in codon 249>>>>causes
hepatocellular carcinoma
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mutation at operator receptor causes constitutive expression of structural genes.
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splice site mutation>>>larger, non-functional but preserved immune reactivity.
missense>>same size,may be dysfuntional.
nonsense and frameshift>>shorter and nonfunctional.
trinucleotide repeat exapnsion>>>larger, often unstable
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these dimers in prokaryotes are directly corrected by photolyase.
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covalently bound.
the presence of pyrimidine dimers interferes with base recognition during transcription and
replication.and DNA mutations can result if the damage is not repaired.
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for repairing various non-bulky DNA base alterations, including depurination, alkylation, oxidation
and deamination.
1475
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nitrites in food causes this.
eg cytosine,adenine,guanine deamination to uracil,hypoxanthin, and xanthine.(cytosine to uracil,
adenine to hypoxanthine, and guanine to xanthine)
these bases are not present normally in DNA
1475
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ie ATP synthesis.
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causes hypersensitivity to ionizing radiation (gamma and X-rays)
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other disease associated with impaired DNA repair include Bloom syndrome (hypersensitivity to
UV damage and chemotherapeutic agents) among others.
bloom syndrome >> autosomal recessive, mutation in the BLM gene, genes encode helicase,
helicase dysfunction causes chromosomal instability and breakage.
presents as growth retardation, facial anomatles eg micrcephaly, photosensitive rash and
immunodeficiency
1436
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Non-homologous end joining, the main mechanism in primates, is more prone to cause mutations
than homologous recombination.
2028
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caused by hypersensitivity to DNAcross-linking agent
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mismatched nucleotides are repaired through the proofreading activity of DNA polymerases delta
and epsilon.the mismatch repair system involves several genes, including MSH2 and MLH1, which code for
components of the human MutS and MutL homologs. mutation in these 2 genes account for around 90% of
cases of lynch ........ mismatch repair begins with MutS homolog detecting a mismatch on the newly
created daughter strands, which is distinguished from the parents strands by occasional nicks in
the phosphodiester bonds. MutL homolog is then recruited, and the resulting complex slides along
the DNA molecule until 1 of the daughter strands nicks is encountered. at this point, exonuclease
1 is loaded onto and activated by the repair complex. the daughter strands is then backward past
the initial mismatch points, leaving a variable gap of single-stranded DNA that is stabilized by
ssDNA-binding protein. The complex then dissociates while DNA polumerase delta loads at the 3’
end of the discountinuity and begins synthesizing a new daughter strand segment. Finally, DNA
ligase I seals the remaining nick to complete the repair process. 2028
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without disruption of phophodiester backbone
1475
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also called phosphodiesterase.
1475
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autosomal recessive. there are atleast 8 different form of this disease. causes
photosensitivity,hyperpigmentation,Poikiloderma (is a skin condition that consists of areas of
hypopigmentation, hyperpigmentation, telangiectasias and atrophy.). and increase risk ok skin
cancer:malignant melanoma , SCC, and BCC
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excised by 5^>>>>3^ exonuclease and after that sythesis of the gap also
??????????????????????
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as we have hypermethylation (of adenine) of parent strand in some prokaryotes>>>which act as a
template.
because daughter strand remain unmethylated for some time after replication
1477,1474
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hogness box, 25 bases upstream
2025
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though they dont translated into protein
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45s pre-rRNA that subsequently processed into mature 5.8s,28s,18s ribosomal subunit.
only these are coded by ribosomal DNA in nucleolus.
5s ribosomal unit is not transcribed in the nucleolus
2039
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RNA polymerase II also transcribe micro RNA>>>>>cause gene silencing via translation arrest or mRNA
degredation. RNA polymerase II also transcribe snRNA>>>>besides splicing also involve in transcription regulaiton
RNA polymerase 2 is the highly regulated out of 3 rna polymerases.with its function determined by multiple
transcription factors and regulatory processes2039
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ricin (from the castor oil plant ricinus communis) is a potent toxin that inhibits protein synthesis by
cleaving rRNA component of the eukaryotic 60S subunit.
8482
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prokaryotic promotor sequence ( eg the pribnow box, -35 sequence)
2031
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Always monocistronic and have only one shine dalgarno sequence
Genes have exons and intrans
Large spacer (noncoding) D NA between
genes
Initiation of
transcription:
Promoter (-25) TATA and (-70) CAAT
Transcription factors (TFl lD) bind promoter.
Termination of
transcription:
Not well characterized
but in mRNA Poly-A addition/cleavage signal AATAAA
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Poly-A tails are not transcribed from the DNA template. instead a consensus sequence (usually “AAUAAA”)
found within the 3’ end of the gene being transcribed direst the addition of the poly-A tail onto the mRNA.
....................... the role of this is cleavage and polyadenylation
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polyadenylate polymerase complex, which recognizes a specific sequence (AAUAAA), cleaves the
pre-mRNA molecule a few residues downstream from this sequence, and then adds a stretch of
20-250 alanine residues called the poly A tail.the addition of the poly A tail occurs before the
mRNA exits the nucleus. In the cytosol, the poly A tail is gradually shortened, eventually
leading to mRNA degradation. 2035
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unique 5’ to 5’ linkage. the first step is the addition of guanine triphosphate to the 5'end of mRNA
in a reaction catalized by guanylyltransferase. 2nd step is the methylation of guanosine cap
catalized by guanine-7-methyltransferase this methylated cap protects mRNA from
degradation by cellular exonucleases, and allow it to exit the nucleus. 2035
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small interfering RNA and micro RNA>>>play role in RNA INTERFERENCE>>>induce post-trascriptional gene
silencing via translation arrest or mRNA degredation 11595
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May be polycistronic and have multiple shine dalagarno sequence
Genes are continuous coding regions
Very little spacer (noncoding) DNA between genes
Initiation of
transcription:
Promoter (-10) TATAAT and
(-35) sequence
Sigma initiation subunit required to
recognize promoter
Termination of
transcription:
Stem and loop + UUUU
Stem and loop + rho factor
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alpha 2 beta,beta^
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transported to the liver via portal circulation after absorption where active transport by organic
anion transporting polypeptide (OATP) and sodium taurocholate co-transpoter (NTCP)
concentrates the toxin with in hepatocytes.>>>>bind DNA- dependent RNA polymerase 2 and halt
mRNA synthesis,resulting in apoptosis also effect rapidly dividing cells>>>GI track and proximal
convulated renal tubular cell. symptoms with in 6-24 hours>>>cholera like diarrhea that may be
bloody>>>severe toxicity can cause liver and kidney failure urine testing for alpha amanitin
confirm the diagnosis. 8482
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nucleolus is a round, dense basophilic (dark staing) bod that can be identified with in hte nucleus
on standard light microscopy.
it is the primary site of rRNA transcription.
although there are several hundred copies of the 45S pre-rRNA gene divided among multiple
chromosomes, these are arranged into clusters called nucleolar organizing regions that psoitions
themsleves so that all copies are located within the nucleolus.
RNA polymerase 1 funcitons exclusively to transcribe the 45S pre-rRNA gene into a single
template that is subsequently processes into mature 18S, 5.8S,and 28S rRNA.
regulaiton of ribosomal synthesis occurs in part by controlling the number of active rRNA
genes.generally as cell become more differentiated their growth slows and theu require fewer
numbers of riosomes for protein production. in contrast malignant cells with high metablic activity
usually have a large number of active rRNA genes and prominent nucleoli.
2039
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NBME>>>>2,4,8>>> a protien contains a 30 amino acid strutural motif with four cysteine residues
coordinated to a zinc atom. these structtual motif more likely related to transcription factor
nbme>>>3,1,1>>>
expression of specific cellular RNAs in the fast growing liver cells of an infant>>>>>result by
nuclear transcription factor.
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70-80 bases upstream
2025
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alternative splicing also play a prominent role in the lifecycle of many retroviruses. for instance
HIV produces a single primary RNA transcript that is alternatively spliced to produce over 40
different mRNAs
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nbme>>5,2,24
splicing of prmary transcript is eukaryotic cells is most likely>>>>increased repertoire of gene
products
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spinal muscular atrophy in infants is due to mutation in survival motor neuron (SMN1) gene which
encodes a protein involve in assembly of snRNP in lower motor neuron, causes degenration of
anterior horn cells in spinal cord
2036
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always has adenine residue at this end.
recognition sequence.
The CCA tail hangs off the 3’end. with the amino acid bound to the 3’ terminal hydroxyl group.
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tRNA is the only RNA species that contains the nucleoside thymidine.
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The 5’ nucleotide of the anticodon may be inosine, a nucleotide not found in mRNA. one tRNA
molecule recognizes 3 codons (GGU, GGC, and GGG) because only two base pairs
(corresponding to the GG of the codon) form “traditional” bond.
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nbme>>>4,4,1
amino acid covalently attached to t-RNA.
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A CCA tail is added to the 3’ end of tRNA as a posttranscriptional modification is eukaryotes and
in most prokaryotes. In some prokaryotic tRNAs, the tail region is directly transcribed from the
genome. Several enzymes utilize this tail to help recognize tRNA molecules, and its presence in
necessary for protein translation
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these two arms help to determine tertiary structure also
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composed of terminal guanosine
5’ terminal phosphate.
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the peptidyltransferase function of the 23S rRNA found in 50S/60S ribosomal subunit facilitates
peptide bond formation in protein translation...
a defect in rRNA coding for ribosomes would be require to interfere with this function.
2086
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whereby an aminoacyl-tRNA is shifted from the ribosomal A site (after initial binding) to the P site
(after AA incorporation into the peptide chain during elongation) to the E site (after AA cleaving
from its tRNA). The initial N-formylmethionine-tRNA notable binds at the P site
1488
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the folding of a formed polypeptide into its secondary and tertiarry strutures is entirely
spontaneous and is dtermined completely by the amino acid sequence in the proteins primary
structure.
heat shock proteins assist in the spontaneous refolding of proteins.
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play an important role in antigen processing, muscle wasting, cell cycle regulation, DNA repair, and disposal of
misfolded protein and regulatory enzymes.
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nbme>>4,3,2
The release factor eRF1 terminates protein biosynthesis by recognizing stop codons at the A site
of the ribosome and stimulating peptidyl-tRNA bond hydrolysis at the peptidyl transferase center.

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Each cycle uses 4 high-energy bonds (2 from
the ATP used in amino acid activation to charge the tRNA, and 2 from GTP)
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16s RNA is the only piece of rRNA found in prokaryotic 30s ribosomal subunit.
this rRNA is essential for the initiation of protein synthesis in the prokaryotes.
16s RNA within 30S ribosomal subunit expresses a sequence complementary to the shine-
dalgarno sequence in all prokaryotic mRNA (the shine dalgarno sequence is located
approximately 10 bases upstream (in the 5' untranslated region (UTR)) from the AUG start codon
on prokaryotic mRNA).
Transcription and translation can occur simultaneously in prokaryotes
Because there is no processing of prokaryotic mRNA (no intrans), ribosomes
can begin translating the message even before transcription is complete.
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along with integral membrane proteins of the nucleus and the cell membrane, and protien within the ER, golgi
network and lysosomes.
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ribosomes attach to rough endoplasmic reticulum via the translocon, a protein complex containing ridophorins that
bind to large 60S subunits
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nucleosol, peroxisome matrix, and nuclear-encoded mitochondrial proteins
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also play role in lipid synthesis, carbohydrate metabolism.
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all ribosomes begin protein translation is the cytoplasm, but some translocate to RER
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mucus release is increased in inflammatory states, stool will have visible mucus in conditions such as inflammatory
diarrhea, giardiasis, vibrio cholera and crohns disease.
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p27 also
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special form of beta-oxidation.
defective in zellweger disease (cereberohepatorenal syndrome),
this disease is due to defective myelin synthesis.
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proteasome (MHC 1) mainly degrade intracellular protein. while lysosome (MHC 2) degrade extracellular protein.
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ATP dependent attachment of ubiquitin.
attachment of 4 or more ubiquitin protein are required before proteasome degredation
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Peroxisome Deficiency:
Several genetic diseases are associated
with the impairment or absence of
peroxisomes. These patients fail to
oxidize very long chain fatty acids and
accumulate bile acid precursors. The
4 most common disorders are:
• Zellweger (cerebrohepatorenal)
syndrome
• Neonatal adrenoleukodystrophy
• Infantile Refsum disease
• Hyperpipecolatemia
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FUNCTIONS:
1 Synthesis and degradation of hydrogen peroxide
2 Phospholipid exchange-peroxisomes contain enzymes that convert
phosphatidylserine and phosphatidylethanolamine.
3 Bile acid synthesis
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are cytoplasmic organelles containing oxidative enzymes such as catalase, D aminoacid oxidase,
and uric acid oxidase.
these organelles are ubiquitous among eukaryotes and are most abundant in liver and kidneys
where detoxification of ingested and environmental material occur.
in the liver also play a role in breakdown of fatty acid.
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defect in park,PINK-1 and DJ-1 gene are responsible for autosomal recessive parkinsons disease
that have an early age of onset <50.........
in alzheimer disease this defect also play a role
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ATP required to pass through the tubular proteasome.
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branch point at odd number carbon such as phytanic acid by alpha-oxidation.
defective in refsum disease>>>>result win accumulaiton of phytanic acid in the body, treatment is
strict avoidance of cholophyll in the diet.
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nbme,6,3,29
which of following best explanins why protein synthesized in the RER and secreted from
eukaryotic cells have a shorter length than would be predicted by their respective mRNAs, is due
to>>>>cleavage of 5' segment of nascent polyeptides being synthesized on polyribosomes in the
endoplasmic reticulum.and not by nonspecific protease activity during passage of these proteins
through the endoplasmic reticulum membrane.
explanation.
1-protein syntheis starts on the free ribosomes in the cytoplasm and continues in the ER
2-Almost all proteins that are transported to the endoplasmic reticulum have a sequence
consisting of 5-10 hydrophobic amino acids on the N-terminus
3-The protein is guided to the ER by a signal-recognition particle (SRP), which moves between the
ER and the cytoplasm
4- The N-terminus (one end) of a polypeptide chain (i.e., a protein) contains a few amino acids that
work as an address tag, which are removed when the polypeptide reaches its destination
the N terminus corresponds to the 5' end.....as the carboxy terminus is for the 3' end
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microvilli are cylindrical extension of apical plasma membrane that contain actin thin filament.
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smooth muscle actin and caldesmon are also used.
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immunohistochemistery stains that employ keratin markers are used by pathologists in the
identification of poorly differentiated tumors or tumors with an unclear site of origin.
tumors stain positive for keratin include carcinomas, mesotheliomas, thymomas, various
sarcomas, trophoblastic tumors and desmoplastic small round cell tumors.
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like nuclear lamins>>>are skeletal framework of nucleus.
need to be breakdown before initiation of mitosis.
there mutation result in muscular dystrophies and porgyria(aging)
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nbme>>>>4,1,7
At high magnification, the squamous cell carcinoma demonstrates enough differentiation to tell
that the cells are of squamous origin. The cells have pink granular cytoplasm,polygonal in shape
with intercellular bridges (seen as desmosomes or "tight junctions" by electron microscope) and
pleomorphic round nucleoli.
In a moderately differentiated squamous cell carcinoma in which some, but not all, of the
neoplastic cells in nests have pink cytoplasmic keratin.
antibody recognizes cytokeratin (CK) 13, 14, 15, and 161
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chromogranin A and neuron specific enolase are markers used for neuroendocrine tumors
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made up of glycine and alanine because of their small structure are tightly coil and form large number of hydrogen
bond. additionally has significant number of sulphur containing amino acid cysteine and formation of disulfide bone
b/w cysteine residues that give additional rigidity and toughness to the protein.
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endothelium can be identified with special stains for CD34 and von willebrand's factor, among others
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microtubule>>23nm in diameter
intermediate filament>>>8-10 nm in diameter
microfilaments>>6nm in diameter
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nbme>>>2,2,16>>>migration of conceptus is defected not completion of meiosis by ovulated cells.
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nbme>>>>3,4,30
The most common infectious organisms affecting children with primary ciliary dyskinesia (PCD)
are Haemophilus influenza and Staphylococcus aureus. All primary ciliary dyskinesia patients
should receive comprehensive immunizations, including the influenza A and pneumococcal
vaccines
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15% if their are more cholesterol.cholesterol are rigid structure than plasma membrane
membrane become rigid, decrease fluidity and increase melting temperature
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abnormal nasociliary motility is a nonspecific finding that is seen most commonly in patients with
primary ciliary dyskinesia and in some patients with CF (due to abnormally thick mucus).
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due to flagellar defect
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also in spleen and lymphnode
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primary structure>>>peptide bond b/w amin acids.
2ndry structure>>>hydrogen bond>>>alpha helix has hydrogen bond after every fourth AA. b-
sheet has hydrogen bond b/w every residue of antiparallel strand.
tertiarry structure>>>overall shape that a single polypeptide chain assume after compact folding of
2ndry structure. tertiarry structure maintain by many forces including ionic bond, hydrophobic
interaction,hydrogen bond and disulfide bond
disulfide bond is a very strong covalent bond b/w two cystein residues within the same polypeptide
chain that enhance a protein ability to withstand denaturation.
2026
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many of the amino acids designated X-Y are proline residues
essential for alpha-helix formation,its ring structure introduces the bend into the polypeptide chain.
Give rigidity to collagen
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helps to attain maximum tensile strength
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intrachain disulphide bonds form at the N and C terminal globular region, helping to stabilize them.
special interchain disulphide bond also formed at C terminus b/w 3 pro-alpha chains, aligning the
helical domain into to conformation favorable for triple helix formation.
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oxidatively deaminate lysine and hydroxylysine residues, forming reactive aldehydes that create
covalent cross linking.................
catalyzes the conversion of the amino terminus of lysine residues to an aldehyde in collagen
fibers.extracellular collagen fibers are strengthened by this mechanism.
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before this we have pre-pro alpha chain which has amino acid signal sequence at N-terminus,
fecilitates in ribosomal binding to RER
1245
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tropocollagen self assemble into collagen fibrils which subsequently cross-linked by lysyl oxidase
into mature collagen fiber
1245
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in EDS cross-linking defect is due to defective propeptide protease (procollagen peptidase) that causes
formation of more soluble collagen that does not crosslink properly with other collagen molecule.
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N and C terminal propeptide(globular region = nonhelical region) removal by procollagen peptidase
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other X and Y amino acids form clusters of hydrophobic and charged regions on the surface of molecule that
enables crosslinking to other collagen molecules, lysine is commonly used in collagen for this purpose
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most abundant and smallest AA in collagen..
it fits into restricted space that exist when 3 alpha chain come together to form triple helix
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nbme>>>2,2,33>>>type 1 collagen secretion in the first stage of matrix formation is mediated by osteoblast.
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Type: Highlight Author: mehreen916 Subject: Highlight Date: 5/7/2017
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either due to defective procollagen peptidase or lysyl oxidase or gene defect
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when this is due to defective lysyl oxidase enzyme>>>characterized by kyphoscoliosis and ocular fragility.
biochemical analysis will show decrease hydrolyxine within collagenous tissue
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Cu-dependent enzymes include lysyl oxidase, ceruloplasmin, tyrosinase, cytochrome c oxidase
(ETC), and superoxide dismutase.
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nbme,11,4,17
defect in the synthesis of the fibrillar collagen
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hemarthrosis,wound healing problem
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Bone matrix comprised of inorganic (hydroxyapatite crystals ) and organic (type 1 collagen)
components. Type 1 collagen serves to give flexibility to bone, and thus osteogenesis imperfecta
causes bone to be brittle and prone to fracture.
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aging cause decrease collagen fibril production.
proline hyproxylation indirectly decrease during aging.
although collagen decrease but their quality remains intact(eg normal collagen cross-linking).
Aging=decrease synthesis and net loss of dermal collagen and elastin.
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lysyl oxidase oxidatively deaminates some of lysine residues of tropoelastin , facilitating formation
of desmosine cross-links between neighbouring polypeptides, this cross linking give rubber-like
properties to elastin
1249
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triple helix formation is the basis of the collagen molecule,elastin does not form triple helix.
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fibrillin-1(major constituent of microfibrils of the extracelullar matrix).microfibrils form a sheath
around elastin fibers..
fibrillin in the extracellular space acts as a scaffold for deposiiton of elastin extruded form the
connective tissue cells.........
fibrillin is an extracellular glycoprotein
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most common cause of death is aortic dissection.
2nd most common cause of death is heart failure due to mitral valve prolaspe or aortic
regurgitation.
........
Dilatation of the ascending
aorta is seen in 90% of patients and frequently leads to aortic rupture or congestive
heart failure.
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patient also has high arched palate, crowded teeth and a narrow face.
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myxomatous changes (patholgic weakening of connective tissue) in the media of large arteries are
found in cystic medial degenration.
medial degeneration is charaterized by the fragmentation of elastic tissue ("basket weave" pattern)
and seperation of the elastic and fibrimuscular componenet of the tunica media by small cleft-like
spaces that besome filled with amotphous extracellular matrix(pooling of proteoglycan in the
media)
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through desmosine cross-linking
1249
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lysyl oxidase is inihibted by beta-aminopropionitrile (a chamical found in certain kinds of sweeet
peas. can mimic marfan syndrome ingestion of this compound can cause a change in elassticity
of the aorta that mimics the myxomatous degeberation seen in pateints with marfan syndrimel 462
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also nucleases and histones.
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c-jun and c-Fos are nuclear transcription factors that directly bind DNA via a leucine zipper motif. the genes that
code for c-jun and c-Fos are proto-oncogene, genes that can become oncogenes following a mutation or with
constitutive expression.
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western blotting is similar to the enzyme-linked immunosorbent assay (ELISA) techinque, however
is ELISA the patients serum is tested directly, whereas in Western blotting the proteins are first
separated by electrophoresis.
2041
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the probe in this case is double-stranded DNA,
unlike southern and northern in which probe in single stranded DNA in both cases.
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horseradish peroxidase is useful in immunoblotting (eg western blot)..
normally peroxidase we use to differentiate different types of acute leukemia
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use radiolabeled DNA probe just like southern blot. 2040
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side scatter, detect complexity of cell and shape of cells
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the genomic DNA or cDNA being analyzed is labeled with flourscent tag,which hybridize with
complememntry sequence on a gene chip for a large number of genes, the degree of flourscese
corresponds to the mRNA expressed in a particular sample
2041
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this is similar to southern and northern blot but involves hybridization of large number of probes at
once
2041
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forward scatter detect size of cells
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in a bacterial host ."
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expression cloning is a type of DNA cloning where the signals necessary for transcription are
included in the cloned DNA. this process allows bacteria to be used to produce large amounts of a
protein of interest.
First mRNA,of eukaryote is used as a template by reverse transcriptase to produce a cDNA strand
which is modified by prokayotic promoter sequences (such as the Pribnow box, or-35 sequence on
prokaryotes) and translation stimulatory sequences (Shine-Dalgarno). The gene is then
incorporated into a plasmid ans subsequently transcribed and translated into protein. In order to
then be radiolabeled by a DNA probe, the protein must be able to bind DNA. examples of proteins
that are able to bind DNA include transcription factors, steroid, thyroid proteins, vitamin D
receptorss retinoic acid receptor, DNA transcription and replication proteins and others. Of the
choices listed N-myc is the only protein that an bind DNA. The MYC proteins are mammalian
transcription factors, C-myc is the protein that is overexpressed in Burkitt lymphoma.
2031
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An advantage of FISH is that chromosomes do not have to be in the metaphase stage for
accurate diagnosis: Even though interphase and prophase chromosomes cannot be clearly
visualized themselves, the number of hybridization signals can still be counted accurately.
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TheELISA is a test commonly employed to measure the amount of a protein in body fluid. It can
be quantitative for example to measure plasma insulin levels
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new mutattion:
common finding in those diseases in which the mortality rate is high or fertility is adversely
affected.
For example, osteogenesis imperfecta type 2, which results from a
defect in collagen synthesis, occurs as a result of new mutations in
100% of cases.
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two allele loci are said to be linkage disequilibrium when a pair of alleles from two loci are inherited
together in the same gamete (haplotype) more or less often than would be expected by random
change alone given their corresponding allele frequencies.
to estimate expected probablity of 2 allels form seperate loci appearing together, multiply thier
occurance rates.
Note that the Hardy-Weinberg principle (2pq) is not applicable since we are comparing allelic
frequency at two distinct loci,
8283
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nbme>>5,2,43
linkage disequilibrium is the occurrence of some combinations of alleles or genetic markers in a
population more often or less often than would be expected from a random formation of
haplotypes from alleles based on their frequencies.
Random assortment or Mendel's law of independent assortment, states that allele pairs separate
independently during the formation of gametes. This means that traits are transmitted to offspring
independently of one another.
Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg)
and therefore are not passed on to children.
Variable expressivity occurs when a phenotype is expressed to a different degree among

individuals with the same genotype
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It is important to understand that this can occur even if the genes are on different chromosomes.
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Although the Hardy-Weinberg
equation applies equally well to autosomal dominant and recessive alleles, genotypes,
and diseases, the equation is most frequently used with autosomal recessive
conditions. In these instances, a large percentage of the disease-producing allele

is "hidden" in heterozygous carriers who cannot be distinguished phenotypically
(clinically) from homozygous normal individuals.
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either by exogenous small interfering RNA (siRNA) and microRNA
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mosaic somatic mutation during embryogenesis in the GNAS gene encoding the stimulatory alpha subunit of G-
protein.
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multiple osteolytic-appearing lesions of the hip and pelvis>>>>increased proliferation of fibroblast
like cells, increased secretion of IL-6 and activation of osteoclast (fibrous dysplasia).
polyostotic means lesion in multiple bones but the are typically unilateral
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heterozygote advantages for several other recessive besides malaria
diseases that are relatively common in some populations. Examples include:
• Cystic fibrosis (heterozygote resistance to typhoid fever)
• Hemochromatosis (heterozygote advantage in iron-poor environments)
• Glucose-6-phosphate dehydrogenase deficiency, hemolytic anemia (heterozygote
resistance to malaria)
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In osteogenesis imperfecta type
2, for example, the defective phenotype can result from mutations in
any one of the three protein chains that make up the triple helix of
type 1 collagen. Two of the chains are encoded on chromosome 17 and
one on chromosome 7, and mutations in any of these loci can produce
phenotypes which are clinically indistinguishable.
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Allelic heterogeneity usually results in phenotypic variation between families, not
within a single family.
It is relatively uncommon to see a genetic disease in which there is no allelic
heterogeneity.
there is no allelic hetergeneity within a family but it exists between families.
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to determine the probability of a particular outcome, identify the probability of all individual variable
and then multiply them together,
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in autosomal recesssive disease most of the q are hidden in 2pq, as in this case there are far
more heterozygous carrier than homozygous recessive.(in this we cannot assume
P=1).................in autosomal recessive disease most of the abnormal allele are in heterygous
genotype(2pq)
in autosomal dominant disease q is not hidden in 2pq,the largest number of

affected individuals will be heterozygotes, or 2pq. Using the shortcut
that the normal alleles in a population far outnumber the disease
alleles, we can approximate the value of p as being close to 1, and
then the formula becomes 2q.(only in autosomal dominant we use 2q)
in X-linked recessive the majority of
the recessive alleles are hidden in the female heterozygotes, but a
significant number are expressed in affected males.
in this case we also use 2q instead of 2pq just like autosomal dominant.
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heteroplasmy describes the condition of having different organellar genomes (eg, mutated and
wild-type) within a single cell.
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dit
marfan syndormee, MEN2b, homocystinuria all cause similar marfanoid body habitus.
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mosaicism of a disease-causing allele may lead to
variable severity, t issue-specific effects, or even variable inheritance
if gametes are mosaic.
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nbme>>2,3,3>>>> Genetic heterogeneity (GH)
pedigree given is of "Li Fraumeni syndrome" , an Autosomal Dominant pattern.
Multiple mutations "WITHIN a GENE" (Tp53) i.e G.heterogeneity----->giving rise to Multiple

Phenotypes (Multiple cancers) i.e Phenotypic Heterogeneity.
G.heterogeneity: can be either
*Multiple mutations(within a single locus or multiple loci-------->"SAME" Phenotype

*Multiple mutations(within A single locus)---->"MULTIPLE" Phenotype (Phenotypic Heterogeneity)
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usually the first manifestation,
large and irregular with an irregular 'coast of maine' border
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because during mitoses mitichondria r randomly distributed between daughter cell.
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behavioral problem: (autistic spectrum and OCD) is also common
1808
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Angelman syndrome,
is produced if there is a deletion of 1 5q l l - 1 3 from the maternal chromosome.
In this case the locus imprinted in the maternal chromosome includes a gene
involved in the ubiquitin pathway known as UBE3A, for which the maternal gene
is normally expressed while the paternal gene is silenced.
Prader-Willi syndrome is caused by loss from the paternal chromosome of an
imprinted locus mapping to l 5q 1 1 - 1 3 that includes the gene SNRPN. This gene,
normally active from the paternal copy of chromosome 15, encodes a component
of mRNA splicing.
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this occurs via an epigenetic process that alters the phenotype of an organism independent of the
genetic code. Specifically this epigenetic process involves DNA methylation which can silence
gene expression without altering the genetic sequence.
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1,Skipped generations are not typically seen exception occurs when there is reduced penetrance,
2,Autosomal dominant alleles are relatively rare in populations,
3,If both parents are heterozygous,
the recurrence risk is 75%.
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Affected male-homozygous normal female:If the fetal sex is known, the
recurrence rate for a daughter is 1 00%, and that for a son is 0%. If the sex
of the fetus is not known, then the recurrence rate is multiplied by 1/2,
the probability that the fetus is a male versus a female. Therefore if the
sex is unknown, the recurrence risk is 50%.
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mutation involving mtDNA or nuclear DNA that code for mitochondrial proteins can cause a variety
of mitochondrial disorders,including leigh syndrome and MELAS.
most of the gene code for mitochondrial proteins have migrated to the to nuclear DNA.
mt DN still codes for 14 proteins (some involved in oxidative metabolic pathways) and the
ribosomal and transfer RNA needed for mitochondrial protein synthesis.
1473
mitochondria has circular DNA.DNA encodes 1 3 proteins that are subunits
of complexes in the electron transport and oxidative phosphorylation processes. In addition,
mitochondrial DNA encodes 22
transfer RNAs and 2 ribosomal RNAs.
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androgenic alopecia:
hair loss is driven by both hormonal (eg circulating androgens) and genetic factor.. The hair loss
occur primarily at the temporal areas and vertex and progresses.
demonstrates polygenic inheritance with varibale expressivity.
genetic influence have been identified on the short arm of chromosome 20, and also on the X and
possibly Y chromosomes. Therefore some of the genetic factors may be transmitted with X-linked
recessive inheritance (eg, gene variations in the androgen receptor)
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nbme,11,4,36
mitochondria encode their own tRNA cause of>>>>mitochondria use a non-standard genetic code.
Leigh's disease, also known as Subacute Necrotizing Encephalomyelopathy (SNEM), is a rare
neurometabolic disorder that affects the central nervous system.
There is another form of this disease called the X-linked Leigh's syndrome (OMIM 308930), which
is a mutation in the oxidative phosphorylation enzymes (which are on both the mtDNA and the
nuclear DNA). The X-linked Leigh's disease is a mutation of a gene encoding PDHA1, part of the
pyruvate dehydrogenase complex, located on the X chromosome
It is an inherited disorder that usually affects infants between the age of three months and two
years, but, in rare cases, teenagers and adults as well. In the case of the disease, mutations in
mitochondrial DNA (mtDNA) or in nuclear DNA (gene SURF1[2] and some COX assembly factors)
cause degradation of motor skills and eventually death.
Mitochondria are an essential organelle in eukaryotic cells. Their function is to convert the
potential energy of glucose, amino acids, and fatty acids into adenosine triphosphate (ATP).
Mitochondria carry their own DNA, called mitochondrial DNA [mtDNA]. The information stored in
the mtDNA is used to produce several of the enzymes essential to the production of ATP.
Mutations in the mtDNA that cause the mitochondria to fail, to function improperly, a person is at
risk for a number of disorders, including Leigh's disease. In the case of Leigh's disease, crucial
cells in the brain stem have mutated mtDNA, creating poorly functioning mitochondria. This
causes a chronic lack of energy in the cells, which, in turn, affects the central nervous system and
inhibits motor functions
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mitochondrial myopathy, encephalopathy ,
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There are three potential mechanisms by which
dominant diseases cause pathology. Those
which act as gain-of-function mutations cause the
production of a protein with adverse function (e.g.,
Huntington disease). In cases where there is a dominant
negative, the mutated gene product blocks the function
of the normal gene product (e.g ., osteogenesis
imperfecta). In some cases haploinsufficiency is the
cause, since the one normal allele product is not
sufficient to maintain normal function (e.g., familial
hypercholesterolemia).
Most recessive diseases
are due to loss-of-function
mutations in genes
encoding enzymes.
Typically, these pathways
can function normally
even if half of the normal
amount of enzyme
is being produced.
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Blotchy red muscle fibers on Gomori trichrome stain are characteristic of the mitochondrial
myopathies. In these conditions, abnormal mitochondria accumulate under the sarcolemma of
muscle fibers.
electron microscopy of the affected muscle reveals a increased number of enlarged, abnormally
shaped mitochondria.
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kearns-sayre syndrom is an example of mitchondrial inhritance .
3
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In this condition, females are
differently affected than males, and whereas penetrance in males is 100%, that
in females is approximately 60%.
females are more affected than males.
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Normal male-carrier female>>>>If the fetal sex is known, the recurrence rate for a daughter is 0,
and
that for a son is 50%. If the sex of the fetus is not known, then the
recurrence rate is multiplied by 1/2, the probability that the fetus is
a male versus a female. Therefore if the sex is unknown, the recurrence
risk is 25%.
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acute intermittent porphyria
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CFTR mutation can lower the rate of bicarbonate secretion in the pancreatic ducts, promotig
mucin precipitation which causes exocrine pancreatic insufficicnecy.
804
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it try to suck water out of the cell and make mucus thin
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focal biliary and multilobular cirrhosis due to plugging of bile canaliculi by dehydrated mucinous material
develops in approximately 5% of patients.
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rectal prolapse in CF children is also common.
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clara cell
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1, Pyruvate
dehydrogenase
complex deficiency.
2, SCID most common (IL-2 receptor gamma chain)
3 sideroblastic anemia (ALA synthase gene defect)
4, Adrenoleukodystrophy
5, IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome—
6, Chronic granulomatous disease.
7, hyper IgM syndrome.
8, Red-green color blindness
9, Menke's d isease
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Type: Text Author: mehreen916 Subject: Sticky Note Date: 5/8/2017
X chromosome inactivation:
occurs at the blastocyst stage of female embryo development,
and results in a highly condensed structure known as a Barr body.
Inactivation occurs in each cell of the blastocyst in a pattern that is:
• Random: In the blastocyst stage, cells have no preference and
may inactivate either the paternal or materna I X chromosome.
• Fixed: After the initial inactivation of an X chromosome in a cell
at the blastocyst stage, all future cells derived from that cell will
maintain the same pattern of X chromosome inactivation.
• Incomplete: Although the inactivated X chromosome is condensed
into a Barr body, some sections are still transcribed.
• All X chromosomes are inactivated except one. In cases where a

female has three X chromosomes, there will be two Barr bodies in
each cell.
• The XIST gene has been identified as the primary cause of X
inactivation. This gene produces an RNA product that coats the
chromosome, encourages its condensation into heterochromatin
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regardless of lung and pancreas function, virtually all adult men with CF have azoozpermia and
infertility. Although spermatogenesis is usually normal, almost all males with CF are unable to
secrete semen due to congential bilateral absence of the vas deferen (CBAVD). CFTR mutations
are likely responsible fo abnormal development of Wolffian structures, resulting in vasal agenesis
and defective sperm transport.
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quite specific for cystic fibrosis
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they have bilateral sinusitis
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persistent treatment resistant infectious pneumonia. bronchiecatsis, bronchitic obstructive
pulmonary disease and associated cor-pulmonale account for 80% of eventual death due to CF
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the channel protein open after binding of 2 ATP molecules,allowing transport of chloride ion along
its concentration gradient.
1514
CFTR mutattion also impair the passive transport of chloride along its concentration gradient
804
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most common mutation is 3-base pair deletion (inframe)of Phe508 this causes impaired posttranslational
processing (eg imrpper folding and glycosylation) of CFTR, which is detected by endoplamic reticulum.as a result
abnormal protein is targeted for proteasomal degredation, preventing it from reaching the cell surface. lumacaftor
and ivacaftor partially correct this folding defect>>>>restoring protein to the membrane and also by enhancing
protein fucntion eg chloride transport less common mutation are: 1, premature termination of transmembrane
protein) eg non-sense, frameshift) also leed to complete absence pf CFTR protein (usually seen in ashknazi
jewish population). 2, mutation that cause defective ATP binfding by CFTR can result in a membrane-bound,
nonfunctional protein. due to inability of channel to open 3, mutation imparining chloride ion conduction through
CFTR 4, decreased production of functionaly normal CFTR (eg reduced mRNA or protein stability), often causes a
milder form of the disese with normal sweat chloride levels that may not be diagnosed untill adulthood 802
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causes low sperm volume and acidic pH of ejaculate
1207....
these patients are infertile but not sterile and can have children via assisted reproductive
technology.
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channelopathies make up a group of disease caused by mutation of muscle ion-channel proteins.
hyper or hypokalemic periodic paralysis is an example of ion channel myopathy.
..............
ion channel myopathies manifest with myotonia and episodes of hypotonic paralysis (often
associated with exercise). no muscle atrophy is seen on light microscopy.
PAS-positive intracytoplasmic vacuoles are found in these conditions.
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nbme>>>2,1,29>>>mother of 1 year old son says even though her son is weak but his muscle
appear larger than before.
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initially there is true hypertrophy to compensate proximal muscle weakness.
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nbme>>5,2,18>>>>germ line mosaicism.
When there is no history of DMD in the family, the mother or the patient may have a de novo (or
sporadic) mutation. In 2/3 of DMD cases, the boy inherited the gene from a carrier mother. 1/3 of
cases where there are no other affected family members are due to a new mutation. When a new
mutation is suspected, the patient may have a new mutation, or the mother may be germline
mosaic for the disorderTypically, a person with only germline mosaicism will not be affected with
the disorder caused by the mutation because the mutation is not in the other cells of the body.
Genetic testing using blood or tissue samples (other than germline tissue) from individuals who
only have a germline mutation will be negative for the mutation.Germline mosaicism can be
observed with any inheritance pattern, but it is most commonly seen with autosomal dominant and
X-linked disorders.Most individuals are unaware they possess a germline mutation until they have
children that are affected. Because the mosaic germline mutation is present in the egg or sperm
cell, it will also be present in all cells of the child developing from that germ cell. If it is an
autosomal dominant mutation, the child will be affected with the disorder, and will not be a mosaic
like his or her parent. The recurrence risk for a parent with germline mosaicism for an AD disorder
is hard to predict since it depends on the proportion of germline cells with the mutation, which can
not be determined through testing. Based on family studies, the risk for another affected child may
be low (around 1%), moderate (as in 6%), or high (30%), depending on both the proportion of
mutated germ cells and the disorder in question.In most instances where unaffected parents have
a child with an autosomal dominant (AD) disorder, it is because of a new mutation that occurred by
chance in only one egg or sperm cell, not in a proportion of them. This is called a sporadic
mutation. However, in rare situations, unaffected parents can have more than one child with an AD
disorder. This can be caused by germline mosaicism.Germline mosaicism has been observed in a
number of conditions, including osteogenesis imperfecta and Duchenne muscular dystrophy.
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in-frame
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defects in cardiac function(conduction) are the most common causes of death.
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present almost always
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ch 19; within the noncoding 3′ untranslated region .................... 2nd most common inherited muscle
disorder. present in early childhood or late adulthood........ type 1 fibers most affected
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Satellite cells are stem cells
situated outside the plasma membrane of skeletal cell
that form new myoblasts.
Muscular dystrophies deplete the pool
of satellite cells.
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histologic presentation of DMD is widespread muscle necrosis. on light microscopy, variations is muscle fiber size
and angulated fibers are seen. some fibers have centrally located (interalized) nuclei
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have kyphoscoliosis>>>due to asymmetric weakness of paraspinal muscle.
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X chromosome p 21
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female generally have milder and variable presentation due to 2 X chromosmes...
1808
Attention deficit disorder (in females)
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also have hyperlaxity of joints in hand
1808
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nbme,11,2,50
most likely effect expanded nucleotide repeats on transcription of FMR1 mRNA
is>>>>>>decreased transcription not incorporation of CGG repeats into mRNA.
EXPLANATION.
Fragile X syndrome is a genetic disorder caused by mutation of the FMR1 gene on the X-
chromosome.
Expansion of the CGG repeating codon to such a degree results in a methylation of that portion of
the DNA, effectively silencing the expression of the FMR1 protein.
Mutation of the FMR1 gene leads to the transcriptional silencing of the fragile X-mental retardation
protein, FMRP. In normal individuals, FMRP is believed to regulate a substantial population of
mRNA: FMRP plays important roles in learning and memory
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Amplification that occurs in noncoding areas of the gene (intron) produce
a loss-of-function type of mutation manifested as a decrease in protein
synthesis.
a. Examples of diseases that fit under this category include FXS, myotonic dystrophy,
and Friedrich ataxia
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repeats: CAG,5' coding CTG, 3'UTR CGG, 5'UTR GAA,lntron 1
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Amplifications that occur in the coding region of the gene (exon) all have CAG triplet
repeats that code for glutamine residues.
a. In this group, the expansion of CAG repeats that encode for glutamine residues
produces neurodegenerative types of disorders (polyglutamine disorders); examples
include:
• HD and various subtypes of spinocerebellar ataxia
b. Proteins that are produced with an excess of glutamine residues are misfolded and
produce aggregates that:
(1) Suppress transcription of other genes
(2) Interfere with mitochondrial (mt) function
(3) Trigger apoptosis of neurons
c. Aggregates also produce intranuclear inclusions, which are a key feature of the
previously mentioned neurodegenerative diseases.
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However all examinations findings tend to be subtle during infancy and become most noticeable
after puberty.
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normal 5-55, have potential to expand during oocyte meiosis, abnormal >200
1421
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1, developmental delay (motor and speech) (earliest manifestation) in infancy 2,
neuropsychiatric feature (anxiety, ADHAD,autism) in childhood. 3, physical
symptoms, post-puberty 1808
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due to increase CGG repeats, so there is hypermethylation of cytosine
residues>>>>>causes decrease transcription and production of fragile X mental
retardation protein, 7791............. loss of funtion mutation, long arm of X chrosome...
1808 folate deficient medium for cytogenetic studies , the area of increase repeats
does not stain and appears “broken” hence the name fragile X. Cytogenetic studies
(chromosomal anaylsis) typically shows a small gap near the tip of the long arm of the X
chromosome. 344....... we use southern bloot to detect methylation and repeat
1421
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punched out lesion with ovelrying thin skin on scalp
1822
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increase risk of hypothyroidism, type 1 DM, and obesity.
increased risk of atlantoaxial instability.
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is a form of familial down syndrome.
unbalanced robertsonian translocation individual have 46 chromosomes, but an extra arm of ch 21
is attached to another ch (translocation).
approximately one-third of these cases are due to a balanced translocation in one parents..
these balanced translocation are associated with high recurrence risk.
genetic councling for the parents is indicated if a translocation is isdentified in the infant.
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in maternal meiosis 1
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Robertsonian translocation accounts for 3-4% of Down syndrome cases and is inherited from one
of the parents, most commonly the mother, during conception. Common translocations are
t(14:21) and t (21:22).
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low maternal serum a-fetoprotein (AFP) and unconjugated estriol levels are associated with DS
and correlate with decreased fetal levels (possible due to suboptimal fetal tissue function),in
addition increased B-hCG and inhibin A are secreted from the placenta, possibly due to
compensatory placental hyperfunction.
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Although the recurrence risk for trisomy 2 1 due to nondisjunction during meiosis is very low, the recurrence risk for
offspring of the Robertsonian translocation carrier parent is significantly higher.
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increased risk meckel diverticulum and malrotation
1822
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defect in fusion of prechordal mesoderm>>>midline defects
1822
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supravalvular aortic stenosis
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usually with monosomy
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Type: Highlight Author: LENOVO Subject: Comment on Text Date: 6/18/2017, 4:56:16 AM
TSC1>>>tuberous sclerosis
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TSC 2>>>>tuberous sclerosis
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Cri du chat is most commonly due to a de novo partial deletion of the short arm of chromosome 5
(5p-)
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ilium
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Biotin (vitamin B7) and pantothenic acid (vitamin B5) are absorbed in the small and large intestine via the
sodium-dependent multivitamin transporter. 7584
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abnormal squamous cell proliferation and keratinization of the conjunctiva
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after single high dose ingestion
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unlike vitamin A isotretinoin is not stored in liver.
1568.
more than 90% of the body’s vitaminA reserves are stored in the liver,mainly in the perisinusoidal
stellate (lto) cells. These stores are often sufficient enough to last around 6 months.
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myalgias also
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include horizontal nystagmus, bilateral abducens palsy, and complete ophthalmoplegia (ocular
irregurities are the first to respond to thiamine infusion).
..........
damage involving CN 3, CN 6 and vestibular nuclei
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characteristic of wernick encephalopathy>>>>foci of hemorrhage and necrosis
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demyelination of peripheral nerves.unlike guillain-barre no perineural inflammation.
symptoms include muscle weekness and areflexia,associated with pain and
paresthesia,.involvement of distal lower limb is characteristic
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manifestations o infantile beriberi appear between the ages of two and three months and include a
fulminant cardiac syndrome with cardiomegaly, tachycardia, cynaosis, dyspnea and vomiting.
adult beriberi is categorized as dry or wet. dry beriberi describes a symmetrical peripheral
neuropathy accompanied by sensory and motor impairments, especially of the distal extremities.
wet beriberi includes this neuropathy as well as cardiac involvement (e.g, cardiomegaly,
cardiomyopathy, congestive heart failure, peripheral edema, tachycardia).
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anterior thalamic nuclei also involve
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due to damage to cerebella cortex (degenration of all layers of cortex) and vestibular nuclei.
unlike oculomotor functions, ataxia takes longer to resolve, and some patients may have permanet
symptoms.
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mental status changes (disorientation, apathy, and decreased attention span) respond well to
treatment.
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also causes sponateous abortion in first trimester
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also hyperlipidemia
1568
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isotretinoin is a synthetic 13-cis-isomer of naturally occuring all-trans-retinoic acid (tretinoin)
it is used systmeically when topical tretinoin, benzoyl peroxide, and antibiotic fails.
it inhibit follicular epidermal keratinization, thus loosening the kertin plugs of comedones and
facilitating their expulsion.it also reduce the size of sebaceous glands and inhibit sebum
production.some of its actions mediated by its interaction with nuclear retinoic acid receptor
(RARs) that affect cell proliferation and diferentiation.this interection may account for its severe
teratogenic effects.
RAR interaction causes
1, increase cell turnover
2, normalize epidermal differentiation
3, decrease sebum production
1568
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vulnerability to infection( especially measles)
humoral and cell mediated immune system inhibition via damage done to phagocytes and T-
lymphocytes.
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can be caused by toxic retinopathy due to phenothiazine or choloquine.
congenital rubella,syphilis and other infection.
diabetic retinopathy.
MCC of night blindness is hereditary retinitis pigmentosa
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dietary intake come from combination of beta-carotene, a provitamin found in plants and
preformed vitamin A from animal source.
liver content of vit A is very low in newborn but increases rapidly with intake of colostrum, breast
milk and fortified formula.
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component of complex II and also in TCA cycle.
1807
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cheliosis>>inflammation of lips.
stomatitis>inflammation of mouth
glossitis>>inflammation of tongue.
...
deficiency also causes seborrheic dermatitis, anemia, keratits
1807
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diagnosis of deficiency can be established with the performance of erythrocyte gluthatione reductaseassay or
urinary riboflavin excretion
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in HMP shunt of glucose metabolism and for biosynthesis of cholesterol and fatty acids
1064
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usually bilateral and symmetrical roughened, thickened and scaly skin.
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neuronal degeneration in brain and spinal cord with lesion similar in appearance to those with
pernicious anemia
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burning feet syndrome:
TCA will be interrupted due to deficiency of CoA>>>leading to weakness and burning feet.
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importnt in synthesis of vitamin A, D,cholesterol,steroids, heme A,fatty acids,amino
acids and proteins.
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chemically similar to pyridoxine>>>
increases urinary excretion of pyridoxine, also compete for binding site of pyridoxine result in
defective synthesis of neurotransmitters like GABA.
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alanine, serine,threonine, valine, leucine,isoleucine, phenylalanine, tyrosine, trytophan, and histidine
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precursor for nicotinic acid, serotonin and melatonin.
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most children with hartnup disease are asymptomatic, but some children experience
photosensitivty , and pellagra like skin rashes.
neurologic involvememnt can occur most commonly leading to ataxia.
neurologic and skin symptoms typically wax and wase during the course of this disease.
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except proline,hydroxyproline and arginine that differentiate it from fanconi syndrome
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pyridoxine (vitamins B6) absorption occurs in the jejunum and the ileum by passive diffusion
7584
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deficiency also causes seborrhiec dermatitis,glossitis
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first step conversion of oxaloacetate to citrate in TCA cyce is affected due to
deficicy
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pantothenic acid is actively transprted in to the cell and then undergoes ATP
dependent phosphorylation , which transforms it into coenzyme A,
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arises due to columnar epithelium atrophy and occasionally ulceration
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niacin obtain either from diet or synthsize endogenously form tryptophasn
people who eat just corn are prone to pellagra cause niacin is in bound and unabsorbable.
in developed countries it is due to chronic alcoholic, and debilitating diseases eg HIV
1064
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used in dehydrogenases involved in metabolism of fats. carbohydrate and amino acid. 1064
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erythrocyte glutathione reductase activity may be decreased in pateins with Vit B2 deficiency
because glutathione reductase uses FAD (derived form vit B2) and NADPH as a cofactor to
reduce disulfide bonds.
64.........
gluthatione reductase catalyzes reduction of gluthatione disulfide to glutathione using NADPH
1035
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component of complex 1 in ETC.
1807
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Biotins acts as a CO2 carrier. all of these enzymes play roles in carbohydrate and lipid and amino acid
metabolism. 1063
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normal individual due to folate recycling manifests anemia months after decrease intake,
but alcoholics manifests within weeks
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one of most common causes of folate deficiny due to poor dietry intake and impaired folate absorption, utilization
and enterohepatic recycling.
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deficiency also causes metabolic acidosis as a result of increased conversion of pyruvate to lactic
acid (due to pyruvate carboxylase deficiency)
1063
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propionic acidemia an autosomal recessive organic acidemia caused by congenital deficiency of
propionyl-coA carboxylase
patient have severe metabolic acidosis and hypoglycemia and ketosis develop secondary to the
acidosis.
affected pt present 1-2 weeks after birth with lethargy, poor feeding, vomiting and hypotonia.
treatment>> low protein diet containing minimal amounts of valine, isoleucine, methionine and
threonine
1340
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Type: Text Author: LENOVO Subject: Sticky Note Date: 6/7/2017, 11:51:48 AM
secondary folate deficiency>>>>due to B12 deficiency, which make folate to traped in methy-THF form...
primary folate deficiency >>>>due to THF def as thymedylate synthase enzyme inhibition due to folate def,
which normally convert dump>dtmp, ...... dump incorporation into DNA cuases apoptosis
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deficiency present with nonspecific symtoms includiing, mental status changesm ,myalgias,
anorexia amd chronic dermatoligic changes, such as macular dermatitis, also have metabolic
acidosis due to build up of lactate
1063....
deficiency of pyruvate carboxylase causes lactic acidosis and fasting hypoglycemia
1010
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such as macular dermatitis
1063
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deficiency also causes erythroid precursor cell apoptosis. supplementation with thyimdine can moderately increase
dTMP (by using enzyme thymidine kinase,5-10%, salvage pathway) level, it can reduce erythroid precursor cell
aopotosis 1847>>>best folate picture
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used in amino acid, thymidine and purine syntheseis. used in thymedylate synthase ....................... THF converison is
by enzyme dihydrofolate reductase, whihc is rate limintg emzume in folate synthseis
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also in methylcrotonyl Co-A carboxylase>>>defect in degredation of amino acid
leucine
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also called isomerase
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in older mentally slow woman of northern european descent who is lemon colored(anemic and icteric) has
smooth shiny tongue indicative of atrophic glossitis and demostrates a shuffling broadbased gate
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product of fatty acid oxidation.
its elevation results in myelin synthesis abnormalities
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+impotantly neurologic abnormalitites can occur in B12 defeiciency in the absence of frank
anemia..........
+ in late disease neurological dysfuntion may be irreversible.
In fact, the usage of folate alone can worse demyelination and cause abnormal myelin synthesis
by depleting the concentration of unmethylated cobalamin available for methylmalonyl-CoA
processing.
High doese of folate may antagonize phenytoin thereby precipitating seizures in a select group of
patients.
1792
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once B12 replacement therapy begin, effective erythropoieses increases immediately , and immature erythrocytes
are released from bone marrow., the perpheral count of these reticulocytes begins rising with in 3-4 days and peaks
around 1 week.reticulocytes produced early are left-shifted and take longer to mature than reticulocyte
produced later. the anemia typically takes as long as 8 weeks to correct. Hemoglobin and erythrocyte count level
increases gradually. 1848
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also myelin synthesis
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caun cause microcytic anemia
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in children subperiosteal hemorrahge and hemarthrosis are chactarestic along with bony deformation
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vitamin C is absorbed in the distal small bowel through an active transport process. Pyridoxine
(vitamins B6) absorption occurs in the jejunum and the ileum by passive
7584
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can give false negative stool guaiac test and are associated with diarrhea and abdominal bloating.
1048
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collagen cross linking is compromised so greatly reduced tensile strength.
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reducing agent,
deficiency causes atheroma formation acceleration
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spinal cord shows symmetric myelin layer vacuolization and axonal degeneration involving the
posterior columns and the lateral corticospinal tracts
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serum haptoglobin level are usually low with B12 deficiency anemia, as there is increased red
blood cell breakdown due to ineffective erythropoiesis and enhanced peripheral destruction.
with B12 replacement, haptoglobin, methylmalonic acid and homocysteine level normalizes
1848
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besides 3 other tracks, axonal degeneration of perpheral nerves which can cause numbness or paresthesia. also
occur
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+ bone marrow is hypercellular in megaloblastic anemia., but these megaloblastic erythroid
precrusor cells are rapidly destroyed in the bone marrow and few differentiated large RBCs are
released into the circulaiton...
+ associated with pancytopenia cause B12 involve in DNA synthesis
+ megaloblastic anemia and pancytopenia is due to impaired DNA synthesis
peripheral neuropathy is due to impaired myelin synthesis.
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schilling test is used to diagnose b12 deficieny due to
insufficient intake, pernicious anemia, or malabsorption.
normal absorption>>>>is due to insufficienct intake.
absorption with intrinsic factor>>pernicious anemia
no absortion at all>>>>malabsorption (eg pancreatic insufficency, bacterial overgrowth or short gut
syndrome)
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even a single neutrophil with more than 6 lobes should raise suspicion of megaloblastic anemia
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nbme>>>1,2,38>>>person whose vegetarian diet does not permit intake of milk or eggs>>>>>result in vit 12
deficiency
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also known as homocysteine methyltransferase
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in excessive state, kidney has 24-hydroxylase enzyme which converts 25-hydroxy to inactive form 24,25 hydroxy Vit
D3
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muscle atrophy may occur in Vit D deficiency but serum CK level are often normal.
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melanin prevents conversion of 7-dehydrocholesterol to previtamin D3
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causes mental status changes, muscle weakness, constipation, polyuria/polydispisa and dehydration.
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also causes ectopic calcium deposition paradoxically..
it might also cause osteoporosis secondary to excessive mobilization of bones
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breast milk in well nutrieted mother is sufficient for most of vitamins except Vit D and K.. Vit D deficiency can occcur
around 6 months of age if no supplementation given.
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also have indentations in the lower ribs (harrisons sulci), softening of the skull (craniotabes)
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deficiency could cause infertility and decreases in some serum phospholipid.
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both are plant source (green vegetables)
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The small qunatity of vitamin K normally stored in the liver is only sufficient enough to meet the
body’s biochemical requirements for 1-3 weeks. However, severe vitamin K deficiency generally
does not develop from dietary deprivation alone, since bacteria in the larger intestine normally
produce functional forms of vitamin K.
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Type: Highlight Author: mehreen916 Subject: Comment on Text Date: 5/9/2017
it allows for the creation of calcium-binding sites. the calcium binding sites attract the clotting
factors to negatively charged phospholipids on platelets and endothelial cells. encouraging
coagulation and thrombin formation....
+ post-translational conversion of glutamate to gama-carboxyglutamic acid.
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menaquinone(vitamin K2)>>>derived from gut bacterial flora.
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The cells that are most susceptible include neurons with long axons (due to large membrane
surface areas) and erythrocytes (due to high oxygen exposure).
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EXCESS:
higher mortality rate due to hemorrhagic stroke in adults and higher rate of necrotizing enterocolitis
in infants
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histologically, deficiecny is characterized by an increase in unmineralized osteoid and widening
between osteoid seams.
the latter can be measured by bone histomorphometry and by double tetracyclone labeling
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causes growth retardation in infants
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1-alpha hyproxylase.
eg in sarcoidosis, TB, and in some hodgkin and non-hodgkin lymphoma.
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in northern area even sun exposure in winter seasons do not produce vit D cause of too much oblique and low
wave length sun rays.
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+ 7-dehydrocholesterol (provitamin D3) converted to previtamin D3 by exposing skin to ultravoilet B-rays form the
sun at wave length of 290-350 nm which open up B-ring of provitamin D3, which then undergo to thermal
isomerization to form Vit D3... provitamin D3>>>>previtamin D3>>>Vit D3. + excessive sunlight exposure shunts
previtamin D3 to a pathway that form inactive products such as tachysterol and lumisterol, as a protective
mechanism against excessive Vit D3.
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not tightly regulated therefor circulating 25-OH D3 accurately reflects the status of dietery and skin production of
vit D
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also have nightblindness
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around body orifices, predominantly vesicular and pustular with a central clearing
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the alteration of NAD/NADH ratio in alcoholics induces fatty liver through inhibition of
gluconeogeneis and ad fatty acid oxidation.
.....
+ contirbuting pathogenic factor in liver injury due to alcohol are impaired lipoprotein assembly and
secretion and an increase in peripheral fat catabolism.
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convert into acetyl CoA which cant go into TCA cycle but can go to fatty acid
synthesis or ketone body synthesis.
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pyruvate carboxylase catalyzes initial step in gluconeogenesis.>>>>this enzyme function with in the mitochondria.
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nbme,6,3,15
3 year old girl brought unconscious after ungesting unknown quantity of ethanol.her serum blood
glucose concentration is 30mg/dl.the mechanism of hypoglycemia is>>>>>increasing reduction of
pyruvate to lactatae(deue to increase NADH from alcohol metabolism) not by inhibiting pyruvate
dehydrogenase (which occur due to B1 def in prolonged user of alcohol)
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fact accumulate most prominently in the centrilobular zone.
macrovascular steatosis is often noted.
frequently the hepatocyte nucleus is displaced eccentrically by one or more large fat droplets.
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in frozen section, lipids can be demontrated by staining with oil red O or sudan black.
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this is increased by the presence of insulin, which increases phopshofructo kinase 2 (PFK-2) and
result in formation of fructose 2,6-bisphospahte.
insulin by increasing levels of fructose 2,6 bisphosphate stimulates FA synthesis, glycogenesis,
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elvated insulin kevels also increase fructose2,6 bisphosphate formation,the rise of fructose 2,6
bisphoshate levels in hepatocytes is typically concurrent with increased glycogen synthesis.
as fructose 2,6 bisphosphate decreases gluconeogenesis.
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also activated by Ca,particularly in excercising muscle
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HMG CoA lyase is a mitochondrial enzyme that is responsible for ketogenesis from HMG CoA.. HMG CoA results
from the degredation of leucine, a strictly ketogenic amino acid, and also from synthesis by HMG CoA synthase.
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only in liver not in skeleltal muscle free glucose inhibit glycogenolysis
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normally insulin suppresses gluconeogenesis
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" Combines 2 molecules into 1 (condensation reaction) either using energy from ATP or other highenergy phosphates
(synthetase, eg, PRPP synthetase) or energy from other sources (synthase, eg, citrate synthase, glycogen synthase).
"
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uworld say , rate limiting enzymes are pyruvate carboxylase and phosphoenlopyruvate
carboxykinase
and these enzymes are stimulated by glucagon
849
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synchronization between muscle contracton and glycogenolysis occur due to Ca increase not due
to cAMP.
though glucagon and epinephrin(via beta-1 receptot) increase glycogenolysis via incrase in cAMP.
epinephrine can also act on alpha-1 receptor found in muscle and liver to increase intracellular
calcium and promote glycogenolysys
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cytosolic HMG-CoA synthase is the starting point of cholesterol synthesis. where as mitochondrial version of the
enzyme is the rate-limiting step in ketone body synthesis
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which increase when acetyl-coA is abundant, as with active glycolysis).
therefore, fatty acid synthesis is likely to be upregulated in metabolic states in which fructose 2,6-
bisphosphate concentration is increased.
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have role only in muscle,not in liver
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nbme>>>1,4,31>>increase in intracellular concentration of AMP in muscle after 15 minutes of strenous
exercise>>>results in increase breakdown of glycogen
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bidirectional>>phosphoglucoisomerase/glucose 6-phosphate isomerase
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fructose in metabolized by the liver faster than the other monosacchrides (gaalctose, mannose, glucose) cause it
bypasses phosphofructokinase, key regulator enzyme of glycolysis.
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glyceraldehyde-3-P dehydrogenase, this enzyme uses NAD-dependent oxidation, and in this reaction NAD is
converted into NADH
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by phosphoglycerate kinase and produce ATP
1029
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aldolase B play a non-essential role in glycolysis due to reduntant funciton of aldolase A......
aldolase B can use both fructose 1-6 bisphosphate and fructose-1-phosphate as substrates
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when acetyl CoA is high it allosterically activate pyruvate carboxylase and shunt acetyl CoA toward gluconeogenesis
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congenital deficiency of propionyl CoA carboxylase>>>propionic acidemia>>>clinically
characterized by poor feeding, vomiting, hypotonia, lethargy, dehydration and an anion gap
acidosis.
1340
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pyrimidines (thymidine, uracil) and
cholesterol also give propionyl CoA
1340
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glyceraldehide convert into glycerol by usingNADH and produce NAD
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Fructose bypasses rate-limiting step
of glycolysis (PFK) via this pathway
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propionic acidemia an autosomal recessive organic acidemia caused by
congenital deficiency of propionyl-coA carboxylase patient have severe
metabolic acidosis and hypoglycemia and ketosis develop secondary to the
acidosis. affected pt present 1-2 weeks after birth with lethargy, poor feeding,
vomiting and hypotonia. treatment>> low protein diet containing minimal amounts
of valine, isoleucine, methionine and threonine 1340
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nbme>>5,2,12
the adipocyte TGs are mobilized, the nonfatty acid domain of this molecule can be used by the
liver for gluconeogenesis, the enzyme initiates this process>>>>is glycerol kinase
explanation.
TG metablizes to Glycerol and Fatty Acid . Adipocytes lack glycerol kinase so they cannot
metabolize the glycerol produced during triacyl glycerol degradation. This glycerol is instead
shuttled to the liver via the blood where it is:
phosphorylated by glycerol kinase to glycerol phosphate which is

converted to DHAP (dihydroxyacetone phosphate) which can participate in glycolysis or
gluconeogenesis.
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citrate is an indicator of high energy cellular stores and abundant biosynthetic intermediates.
citrate is therefor impotant positive regulator of acetyl-CoA carboxylase and fructose 1,6
biphophotase, key enzymes involved in fatty acid synthesis and gluconeogenesis, respectively
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thiolase condenses two equivalents of acetyl CoA to form acetoacetyl CoA
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enolase
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1,3 is converted into 2,3 form by the enzyme bisphosphoglycerate mutase (producing noATP). this enzyme present
in RBCs and placenta 2,3 bis catabolized to 3-phosphoglycerate by bisphosphoglycerate phosphotase ( also
producing no ATP) 1029
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triokinase
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fructose also converted into fructose-6-phosphate by hexokinase
1070
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bidirectional>>>phosphoglucomutase
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and kidney
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is a GLUT-2 receptor
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Gene mutation associated with
maturity-onset diabetes of the
young (MODY) is of glucokinase.
characterized by mild nonprogressive hyperglycemia that often worsens with pregnancy-induced
insulin resistance.
homozygous mutations lead to fetal growth retardation and severe hyperglycemia at birth.
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and brain
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allosteric stimulator of pyruvate kinase which produces ATP and is essential for RBCs as they dont have
mitochondria, so this is the main source energy>>>>>>its deficiency causes hemolytic anemia.>>>>splenic
hypertrophy
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regulated by PDH kinase and PDH phosphatase. inacitive, phosphorylated form active, dephosphorylated form.
kaplan
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lipoic acid and lipoate, is an essential cofactor in numerous facets of aerobic metabolism ( eg
transfer of acyl and methylamine groups in 2-oxoacid dehydrogenase and glycine cleavage
complexes, respectively).
it is also an antioxidant capable of scavenging reactive oxygen species and reducing metabolites.
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alanine allosterically inhibit pyruvate kinase, preventing phosphoenolpyruvate form being consumed by the
glycolysis during the gluconeogenic state.
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abdominal pain.impaired level of conscoiusness,hypotension,tachycardia.
also have QT-prolongation>>>>progress to life threatening torsades.
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odorless, tasteless and easily absorbed.
present in insecticides/pesticides, contaminated water, pressure-teated wood, metullargy, minning
or glass-making,
arsenic binds to sulfhydral groups, impaining cellular respiration via inhibition of pyruvate
dehydrogenase and disrution of glucuneogenesis and glutathione metabolism.
arsenic poisoning treated with dimercaprol which displaces arsenic ion from sulfhydral groups of
enzyme.
dimercaprol also itself toxic compound
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nbme,6,3,42
PF kinase is regulated by AMP not cAMP
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LDH convert pyruvate to lactate in anaerobic condition most classically in the skeletal muscle.
LDH play a key role in the liver where lactate, usually generated by working skeletal muscles, is
taken up from the blood and converted to pyruvate for gluconeogenesis.
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nbme, 7,1,7. 9 month old girl has tonic-clonic seizure, she has failure to thrive and developmental delay since
birth.she is 3rd percentile for length and weight. physical examination shows microcephalym tachypnea and
hypotonea. laboratory stydy show hypoglycemia, hypoalaninemia and lactic acidosis........after intravenous
glucose is administered, her serum glucose concentration returns to within the referenace range, deficicny of
enzyme>>> Pyruvate carboxylase is a mitochondria enzime requiring biotin. It is activated by acetylCoA( from beta-
oxidation. The product oxaloacetate(OAA), a citric acid cycle intermediate, cannot leave the mitochondria but is
reduced to malate that can leave via a Malate shuffle. In the cytoplasm malate is reduced to (OAA). Pyruvate
carboxylase deficiency is an inherited disorder that causes lactic acid and other potentially toxic compounds to
accumulate in the blood. High levels of these substances can damage the body's organs and tissues, particularly in
the nervous system. Pyruvate carboxylase deficiency is a rare condition. A deficiency of pyruvate carboxylase can
cause lactic acidosis as a result of lactate build up. Normally, excess pyruvate is shunted into gluconeogenesis via
conversion of pyruvate into oxaloacetate, but because of the enzyme deficiency, excess pyruvate is converted into
lactate instead. As a key role of gluconeogenesis is in the maintenance of blood sugar, deficiency of pyruvate
carboxylase can also lead to hypoglycemia
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these ketogenic amino acid are contraindicated in propionyl CoA carboxylase
deficiency pte.
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stimulated by Ca , ADP, and NAD
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by the enzyme aconitase
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ketogenic diet is high in fat, low in carbohydrate and moderate in protein.this diet forcees the
production of ketone bodies from fat and amino acid catabolism to fuel the body in the place of
glucose
998.
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this will use to transphosphorylate ADP to ATP or used by specific GTP-hydroysing enzyme such
as phosphoenolpyruvate carboxykinase
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lactate dehydrogenase require zinc
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under anaerobic glycoslysis NADH give electron to pyruvate to form lactate and regenerate NAD, NAD is required to
convert glyceraldehyde 3 phosphate to 1,3 biphosphoglycerate in glycolysis
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Glycerol can aggravate lactic acidosis in patients with pyruvate dehydrogenase deficiency
because it can be converted to dihyroxyacetone phosphate, which in turn can form pyruvate and
subsequently lactate.
+ PDH deficiency has a wide spectrum of presentations. Because carbohydrates may aggravate
lactic acidosis, a ketogenic diet is recommended is these patients. Amino acid catabolism
following removal of the amino group results in formation of intermediates that are either
glucogenic (producing intermediates of the critic acid cycle or pyruvate) or ketogenic (producing
acetoacetate or its precursors).
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mainly from conversion of succinate to fumarate by succinate dehydrogenase in TCA cycle, which
transfer electron to conenzyme Q (ubiquinone) via FAD.
complex 2 also accepts electrons from other sources of FADH2 such as, fatty acid oxidation
1807
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cytochome C oxidase is a multisubunit complex act as a terminal enzyme of the mitochondrial respiratory chain.
deficiency is most commonly due to autosomal recessive mutation that results in variable myopathic and
encephalopathic findings 571 ................
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another fish poison
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is called uncoupling protein that return the proton back to matrix which were pumped out by ETC.
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white fat is huge vacuole of fat (not membrane-bound) (uniocular) which pushes and flattens the
cell
nucleus to one side.
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oxaloacetate to malate (in mitochondria)and malate to oxaloacetate(in cytoplasm) again both are
done by malate dehydrogenase
997
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deficiency of pyruvate carboxylase result in lactic acidosis and fasting hypoglycemia.
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in neonates 5% of body fat.
neonates have immature nervous system,high body surface area to volume ratio and decreased
ability to shiver.
composed of adipocytes with multiple small
vacuoles of fat(multilocular) and with a round central nucleus.have abundant mitochondria which
give it,its characteristic color.
has higher oxygen requirement and more capillaries.
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statins decrease levels of CoQ by decreasing farnesylPP
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also by sodium azide and hydrogen sulfide,
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cu requiring complex. a-a3 .......... cytochome oxidase(a+a3) is a component of electron transport chain that reacts
with molecular oxygen to produce water) 1767
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acetyl-CoA is allosteric activator.
citrate is positive activator.
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MPP (metabolite of MPTP) also a complex 1 inhibitor>>>>causes parkinsonian
syndrome
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because PPP is the main source of NADPH, the pathway is particularly active in:
1, cells experiencing high oxidative stress (eg eythrocytes) where NADPH is used to regenrate
reduced glutathione.
2, organs (eg liver, adrenal) involved in reducing biosynthesis (eg fatty acid, cholesterol, steroids)
and cytochrome -450 metabolism.
3, phagocytic cells generating a respiratory burst (NADPH oxidase)
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2nd NADPH is produced by using enzyme 6-phosphogluconate dehydrogenase 1035
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activity of non-oxidative patheay is governend by cellular demand for ribose-5-phophate.
all cell can synthesize ribose-5-phophate from glycolysis intermediate fructose-6-phosphate and
glyceraldehide-3-phosphate witt the help of transketolase and transaldolase even if the oxidative
reactions of HMP pathway are not active in those cells.
transketolase transfers 2 carbon groups between substrates of HMP and require thiamine
pyophosphate.
tranaldolase transfer 3 carbon groups between substrates of HMP.
1035
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and WBC
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xylulose is an end product of glucuronic acid metabolism and an intermediate in the pentose
phosphate pathway
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taken up by liver and kidney.
rapidly absorbed in proximal intestine by hexose GLUT-5 transporter.
initial metabolism of frustose involve 3 enzymes, fructokinase, alsolase B, and triokinase.
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in its deficiency hexokinase takes over control of fructose metabolism.
1070
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clinitest tablets.
fructose similar to glucose and galactose is a reducing sugar and can be detected by a copper
reduction test, which nonspecifically detects the presence of reducing sugar.
1067
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taken by liver,brain,lens
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can cause hyperuricemia(not sure)>>>by not converting AMP to ATP..
so adenosine increases(purine)
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beta-galactosidase is one of the lysosomal enzyme involved in breakdown of glycosaminoglycans. its deficiency
results in accumulation of keratin sulfate within lysosome and manifests as short stature, normal inteslligence,
atlanto-axial instability and valvular heaart disease. this enzyme is also responsible for the breakdown of lactose
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excess galactose also convert into glactonic acid by the enzyme galactose oxidase >>>>>
glactonic acid can be metabolized by HMP shunt>>>so do not accumulate.
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type 1 galactosemia
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liver dysfunciton causes:
1,transaminitis,
2,hyperbilirubinemia
3,hypoglycemia
renal dysfunciton causes:
1,aminoaciduria
2,hyperchloremic metabolic acidosis
1071
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rarely causes pseudotumor cerebri
1071
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type 2 galactosemia
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UDP galactose 4-epimerase.
type 3 galactosemia (rare form)
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in breast tissue alpha-1,4 glycosidic linkage between glucose and gaalctose(UDP-galactose) is formed resulting in
galactosyl-1,4 glucose (lactose or milk sugar)
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can be converted to lactose (galactosyl beta 1,4-glucose) by lactose synthase.
this lactose can further be converted to galactose by beta-galactosidase
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feed with soy based infant formula which result in regression of cataracts and improvement in
renal and liver function.
soy milk consist of sucrose, whihc is metabolized to glucose and fructose.
1071
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about 20-30 minutes after ingestion.
hypoglycemia results from intracellular accumulation of fructose-1-phosphate and depletion of
inorganic phosphate, which inhibit glycogenolysis and gluconeogenesis.
undignosed individual eventually develop liver and renal failure.
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which uses glucose oxidase for detection of glucose
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breast milk contains disaccharide lactose and maltose (2 glucose molecule)
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polyol pathway is specially active in the seminal vesicles, as sperm use frustose as thier primary
energy source.
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u wrold say
human lens dones contain significant levels of sorbitol dehydrogenase, which allows for the
produciton of fructose.
however this enzyme has significantly lower Vmax in the sorbitol-to-fructose direction than in the
reverse direction.
when glucose levels are low, the limited forward activity of this enzyme is sufficient to convert
enough sorbitol into fructose to prevent sorbitol accumulation.
in contrast state of long standing hyperglycemia lead to the prodeucition of excessive amount of
sorbitol that is trapped in cell.
in addition to osmotic damage, oxidative stress rresulting from the depletion of NADPH contributes
to cataract formation and other diabetic complications such as neuropathy and retinopathy.
846
U WORLD says
schwann cell, retina and renal papilla have much less sorbitol dehydrogenase activity.
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renal mesangial
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called milk sugar(galactosyl beta 1,4-glucose)
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bacteria degrade lastose in short chain fatty acid and H ion.
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is a precursor or intermediate in the synthesis of cysteine, carnitine, taurine, and lecithin
2088
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histidine is an essential amino acid in children. histidine is deaminated to urocanic acid, which is
then converted to N-forminino glutamate..
the forminino group of FIGIu is donated to tetrahydrofolate.
oxidative decarboxylation of histidine forms histamine, which is released by mast cells in TYPE 1
HS reactions.
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lysine is an essential amino acid that is stricktly ketogenic.
the metabolism of lysine is unique compared with other amino acids, as it is not transaminated as
an initial step.
proline is a non-essential amino acid that is oxidixed to glutamate, which in turn is transaminated
to alpha-ketoglutarate
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Type: Text Author: aishazulfiquar Subject: Sticky Note Date: 5/28/2017, 3:08:30 AM
nbme>>>>2,2,39,
modifications of an endogenous pharmacologically active peptide would be most likely to slow
metabolism of the peptide, thus decreasing its clearance & increasing half-life.>>>Substituting a D
for an L amino group>>>"Proteolytic enzymes"(endogenous protease) prefer L-
configuration(natural) rather than D-configuration(unnatural).
so in a peptide chain to break the bond between two amino acids(L-configurated) peptidases
quickly recognize it and will lead to peptide degradation hence short half life(e.g. endogenous
Opiod peptide) But if we replace either or both of the susceptible amino acids(aa1=aa2) in the
peptide chain with D-configurated aa the endogenous peptidases/proteases will be unable to
cleave the bond b/w the amino acids that will lead to decrease or prevent peptide degradation
hence the LONGER half life
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MATT VIL PHLY
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serine in a non-essential amino acid that can be converted to pyruvate by deamination reaction
catalyzed by serine dehydratase. alanin also non-eesential converted to pyruvate by
transamination reaction catalyzed by alaine tranaminase 998
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non-polar hydrophobic amino acids such as alanine, isolucine,leucine, methionine, phenylalanine,
tryptophan, proline and glycine are generally located interiorly on globular proteins, where the
shielded from direct contact with water>>>>they from the transmembrane domain with 7-alpha
helical segments each containing approximately 20 amino acids with hydrophobic, non-polar R-
group. these amino acid anchor the transmemebrane region of protein to the hydrophic core
of the phospholipic bilayer 1383
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glutamine trasports ammonia from peripheral tissue to kidney.
in the nephron the amides nitrogen is hydrolysed by the enzyme glutaminase, there by producing
glutamate and free ammonium ion. the ammonium ion can then be excreted in urine
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asparagine is a non-essectial amino acid with a nitrogen containing side chain that is produced
from oxaloacetate in a tranamination reaction.oxaloacetate is first converted to aspartate using
glutamate to provide amino group, then the enzyme asparagine synthase trasfers the additional
nitrogen molecule from glutamine to asparatete to produce asparaine.
asparagine becomes essential for rapidly dividing tumor cell
asparagine is a non-essential amino acid that is catabolized initially to aspartate by th enzyme
asparaginase. in rapidly dividing leukemic cells, the synthesis of asparagine is impaired, so these
cells survive by collecting asparagine from circulating plasma. L-asparaginase work as an
antineoplastic agent by lowering circulating asparagine levels.
Asparagine is a non-essential glucogenic amino acid that is catabolized initially to aspartate by the
enzyme asparaginase. Aspartate is transaminated with alpha ketoglutarate to produce glutamate
and oxaloacetate, a glucineogenic intermediate and an intermediate in the TCA cycle.
998
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caused by gene defect near(but seperated from) lactase gene
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also called beta-galactosidase (lactase-phlorizin hydrolase)
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also endothelial cells
846
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sorbitol accumuation causes both
1, osmotic damage
2, oxidative damage (due to depletion of NADPH)
934
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also called polyol dehydrogenase.
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autosomal recessive
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arginase deficiency present as progressive development of spastic diplegia, abnormal
movements, and growth delay in the setting of elevated arginine levels.
Arginase deficiency is likely underdiagnosed because the spasticity seen commonly in this
disorder may simply be attributed to cerebral palsy. Treatment of arginase deficiency consists of a
low-protein diet that is devoid of arginine. Administration of a synthetic protein made of essential
amino acids usually results in a dramatic decrease in plasma arginine concentration and an
improvement in neurologic abnormalities.
unlike other urea disorder, pte with arginase def have mild or no hyperammonemia
1480
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allosteric activator.
formed by the enzyme N-acetylglutamate synthetase by using glutamate and acetyl-CoA in a
reaction activated by arginine
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Alanine and glutamine play an important role in transporting nitrogen throughout the body.
Glutamine is produced by most body tissues and is catabolized primarily by the gut and kidney
for maintenance of cellular metabolism and acid-base regulation,respectively. A significant
portion of the glutamine used by these tissues(intestine and liver) is converted to alanine and
released into the circulation. Alanine is also release by skeletal muscle tissue during protein
catabolism as part of the glucose-alanine cycle that helps remove excess nitrogen. Alanine is
then transported to the liver, where it serves as a vehicle for nitrogen disposal and as a
source of carbon skeletons for gluconeogenesis. 1369 + alanine is a non-polar amino acid, most
commonly produced by the transfer of an amino group to pyruvate. it has single methyl group as its side chain
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muscle are using amino acid as enegy molecule instead of glucose.
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is also used for travelers diarrhea>>>it inhibits bacterial RNA synthesis by binding with DNA-dependent RNA
polymerase
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when ammonia levels rise acutely, astrocytes and neuron function are affected. within the brain, astrocytes and
neurons interact to regulate the metabolism of glutamate, glutamine and ammonia in a process known as the
gluamate-glutamine cycle.. glutamate released by neurons during neurotrasnmission is taken uo by astrocytes
and converted to glutamine, a non-neuroactive compound, glutamine is then released by astrocytes and taken up
by neurons, where it is either converted back to glutamate for use as a neurotransmittor or transaminated into a
alpha-ketoglutarate for use in krebs cycle. ammonia toxicity results in part from depletion of glutamate and
alpha-ketoglutarate in the brain during the process of ammonia detoxification.hyperammonemia increases the
conversion of glutamate into glutamine by glutamine synthase with in astrocytes.. the resulting increase in
glutamine leads to hyperosmolarity and mitochondrian dysfunction, causing astrocyte swelling and impairment.
increased glutamine formation also decreases total brain glutamate stores, impairing excotatory neurotranmission
(mediated by NMDA, AMPA and kainate receptors) and neuronal energy production.in addition, ammonia can be
detoxified to glutamate via glutamate dehydrogenase, depleteing alpha-ketoglutarate(use in kreb cycle) and
further impaining energy metabolism in the brain. 8578 ......... glutaimine is the major amino acid in the blood.
glutamine trasports excess ammonia from peripheral tissue to kidney. in the nephron the amides nitrogen is
hydrolysed by the enzyme glutaminase, there by producing glutamate and free ammonium ion. the ammonium ion can
then be excreted in urine 1480 ...... free ammonia is also excreted into the urine by the kidney
for regulaiotn of acid-base status 1369 ........................... when urea synthesis
decreases>>>>glutamine synthesis increases as a compensatory resposne kaplan .............. urea cycle is an
ATP dependent process, kaplan ..... ammonia normally produced in enterocytes by catabolyzing glutamine and
by colonic bacterial catabolism of dietry protein.
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this amine nitrogen predominantly come from glutamate by oxidatively
deaminating it, using enzyme glutamate dehydrogenase, this reaction also
produce alpha-ketoglutarate for use in TCA cycle 1066, 1340
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Type: Text Author: LENOVO Subject: Sticky Note Date: 6/5/2017, 12:15:48 PM
tachypnia due to cerebral edema(ammonia accumulation) causes central hyperventilation and respiratory
alkalosis 1370
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hyperammonemia decreases the amount of glutamine (becuase there is more glutamine synthase
activity which uses glutamate and ammonia to form glutamine) available for conversion to
glutamate in neurons by glutaminase enzyme, thus low glutamate in neurons and disruption of
excitatory neurotranmission.
in the setting of hyperammonemia, ammonia is detoxified to glutamate via glutamate
dehydrogenase, depleting alpha-ketoglutarate and imaprining energy metabolism in brain.
8578
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oxindole is a tryptophan derivative formedy by bacteria in the gut and normally cleared by the liver.
it causes sedation, muscle weakness, hypotension and coma.
elevated levels of oxindole have been found in patients with hepatc encephalopathy.
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glutamine deposition in astrocyte which is hyperosmotic and also impair mitochondria(cause its swelling)
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can be pyruvate or oxaloacetate depending on which amino acid are used (alanine
or aspartate respectively). pyruvate and oxaloacetate are deaminated products
+ almost all aminotransferase enzymes use alpha-ketoglutarate as the amino group acceptor . 1369
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transmination reaction occur between amino acid and an alpha-keto acid.
the amino group is transfered to the alpha-ketoacid from the amino acid and convert alpha-
ketoacid to AA.
eg glutamate (AA) reacts with oxaloacetate (alpha-ketoacid) to form asparate (resulting AA) and
alpha-ketoglutarate (resulting alpha-ketoacid)
1482
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this is an example of hydrolysis reaction.
protein hydrolysis
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urea cycle is a cyclic process their is no net loss or gain of citrulline,ornithine,argininosuccinate
and arginine.
2 enzymes in mito and 3 in cytosol
ammonia is generated by the metabolism of alpha AA
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Excessive amounts of orotic acid are usually found in OTC (ornithine transcarbamylase)
deficiency, citrullinemia, and often in argininosuccinic aciduria. but not in arginase deficiency
1480
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inhibitory NT in the CNS, with particular influence in the spinal cord, causes inhibitory post-synaptic
hyperpolarizing potential by binding to glycine receptors and cause chloride to enter the neuron via inotropic
receptor
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through transamination reaction of alpha-ketoacid, glutamate is able to be the principle Amino
donor in the synthesis of many AA.
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is a tripeptide>>>formed by glutamate, cysteine and glycine
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synthesis of NO depends on presence of asymmetrical dimethylarginine (an endogenous
analogue of arginine that work as a competitive inhibitor of eNOS)
8563
NO found in cortex, hippocampus, hypothalamus, cerebellum and olfactory system, and is thought
to participate in formation of new memories.. it is unique NT in that it freely diffuses across cell
membranes and does not need to interact with other neuron via a synapse
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deficiency of this enzyme causes a rare form of dysautonomia characterized by ptosis, orthostatic hypotension,
hypoglycemia and hypethermia.
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Type: Highlight Author: LENOVO Subject: Highlight Date: 7/13/2017, 3:30:37 AM
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nbme,7,3,27
1- Phenylalanine --A= phenylalanine hydroxylase----> 2. tyrosine--B= tyrosine hydroxylase--
-> 3. DOPA-- C= dopa decarboxylase----> 4. Dopamine-- D= dopamine hydroxylase--> 5=NE
Tyrosine hydroxylase is the rate-limiting enzyme(but this is not the reason of this answer)
explanation
In Enzymology, it's the concept of the "COMMITTED STEP" which occur at the Branch point
during biosynthesis of some molecules.
*just read about "Committed Step" on net and u can figure out the answer.
Compound 5 -----> regulate Enzyme B

Compound 7 -----> regulate Enzyme E
committed step>
committed step (also known as the first committed step) is an effectively irreversible enzymatic
reaction that occurs at a branch point during the biosynthesis of some molecules.[1][2] As the
name implies, after this step, the molecules are "committed" to the pathway and will ultimately end
up in the pathway's final product. The first committed step should not be confused with the rate-
determining step, which is the slowest step in a reaction or pathway. However, it is sometimes the
case that the first committed step is in fact the rate-determining step as well.
.............................
"Most of the pathways of amino acid biosynthesis are regulated by feedback inhibition, in which
the committed step is allosterically inhibited by the final product".
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this does not produce neurological symptoms.
tyrosinase convert DOPA to dopaquinone in melanocytes
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besides these 3 it is also a precursor of ornithine and agmatine.
1064
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NAG produced from glutamate and acetyl-CoA in a reaction activated by arginine
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synthesis through decarboxylation by glutamate decarboxylase. catabolism of GABA occurs by means of
transamination performed by the enzyme GABA tranaminase. both enzyme use vit B6 as a cofactor + inhibitor of
presynaptic tranmission in the CNS and retina
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formed by hydroxylation (tryptophan hydroxylase) and decarboxylation of AA trytophan (amino
acid decarboxylase)
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N-acetylglutamate synthase deficiency: Required cofactor for carbamoyl phosphate synthetase
I. Absence of N-acetylglutamate causes hyperammonemia: Presents in neonates as poorly
regulated respiration and body temperature, poor feeding, developmental delay, intellectual
disability (identical to presentation of carbamoyl phosphate synthetase I deficiency).
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rate limiting step in catecholamine synthesis
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regenerated by the enzyme dihydropteridine(dihydrobiopterin) reductase.
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inhibitory effect of excess phenylalanine on melanin synthesis by tyrosinase
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classic PKU (the most common form) occurs most frequently in persons of scandinavian descent.
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inability to degrade their deaminated alpha-keto acid state.
leucine normally converted to acetyl-CoA by this enzyme.
valine and isoleucine converted to popionyl-CoA by this enzyme.
leucine=neurological symptoms(due to deposition)
isoleucine=burnt sugar smell
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alpha-ketoacids are neurotoxic>>>>>>>feedig difficulties, seizures and cerebral edema.
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degenerative joint disease.
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cystathionase enzyme also required Vit B6. ..... this enzyme also called cystathinine Beta synthase (kaplan)
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premature acute coronary syndrome
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intermediates are homogentisate>>>>maleylacetoacetate>>>fumarylacetoacetate>>>fumarate>>TCA
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homogentisic acid oxidizes
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can result from mutation in any of the 4 gene coding for the 3 catalytic subunits of this complex
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catalyzes decarboxylation of alpha-ketoacid derivatives of all 3 branched chain amino acids.
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new born screening>>>tandem mass spectrometry
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abnormal pallor of catecohlaminergic brain nuclei (which produce a dark pigment known as neuromelanin) on
autopsy (substanctia negra,locus ceruleus and vagal nucleus dorsalis)
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classic type dont have dopamine problem after correction with diet modification(supplemental tyrosine)
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or atypical. These patient still have dopamine deficiency(high prolactin) after diet modification by adding tyrosine
and restricting phenylalanine.
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according to Uworld liver and muscle both have alpha receptor to increase intracellular Ca and stimulate
glycogenolysis
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epi increases glycogenolysis and gluconeogenesis in the liver and decrease glucose uptake by the skeletal
muscle. epi also increases alanine release release from the skeletal muscle, which serve as a source of
gluconeogenesis in the liver. in adipose tissue epi increases the breakdown of TG, thereby increasing the
circulating free fatty acids and glycerol that can be utilized as gluconeogenic substrate
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phosphorylation dependent activation of glycogen phosphorylase is through epinephrine and
glucagon nduced increase in cyclic AMP.
non-phosphorylation dependent activation of glycogen phosphorylase is through increase in
intracellular Ca concentration (during muscle contraction) and by AMP under extreme conditions
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insulin inhibit glucagon secretion, but glucagon increases insulin secretion
849
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glycogen phophorylase a (active form)
glycogen phosphorylase b (inactive form)
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also called phosphoprotein phosphatese
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epi is more effective than glucagon in stimulating renal gluconeogenesis.
normally glucagon is more effective
849
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Ca is reponsible for synchronization of skeletal muscle contraction and glycogen breakdown.
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phosphorylated glycogen phosphorylase (active form) is allosterically inhibited by ATP and
glucose-6-phosphate in both liver and muscle cell..
in liver cell only free glucose is also an allosteric inhibitor of glycogen phosphorylase.
AMP In muscle only stimulate glycogen phosphorylase.
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muscle do not have glucagon receptor,
EN produces cAMP to stimulate PK in muscle, but Ca has major role in muscle for activating PK.
???????????????
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beta-1 receptor
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starch: similar to glycogen in mammals.is the major storage form of
carbohydrates in plants. starch consist of unbracnhed portion composed of
amylose and branched portion called amylopectin
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glycogen appears as clear cytoplasm vacuoles and stains pinkish purple with the periodic acid-
schiff reaction.
glycogen is abundant in the liver shortly after a meal.
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only free one
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Type: Highlight Author: LENOVO Subject: Comment on Text Date: 6/10/2017, 9:03:13 PM
defect in cori>>>>>glyceogen with single glucose residues left on outer branches.
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alpha 1,4-1,6 transferase>>>>>> defected in anderson disease>>>>fatal by 2>>>>many long chains with very
few branches.
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this enzyme is also called glucosyltransferase. or alpha 1,4-1,4 transferase ..... defect in cori>>>>glycogen with
short outer branhces at the periphery periphery
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phosphoglucomutase>>bidirectional
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glycogen storage disease that affect liver typically present with hypoglycemia and lactic
acidosis.symptoms usually do not strat untill age 3-4 months.when glycogenolysis is needed to
sustain blood glucose during longer feeding intervals.
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short stature doll-like facies,
protruding abdomen emaciated
extremities
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some amount of glycogen is engulfed by lysosomes in cells containging high quantity of
glycogen>>>hypatocytes and myocytes.
cardiac and skeletal muscle are more susceptible.
balloning lysosomes interfere with contractile function
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usually present in infancy or childhood with both liver and muscle involvemnet. muscle weakness and hypotonia
help to differentiate the condition from other glycogen storage diseases with hepatic involvement ( eg von-gierke)
hepatic fibrosis in common but fatty infiltration is not usually seen. short outer chain is distinguising feature
(limit dextrin)
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IV: Andersen(amylopectinosis)>>>>Branching enzyme>>>> Infantile hypotonia, cirrhosis,death by
2 years>>>> Very few branches, especially toward periphery ............ VI: Hers>>>> Hepatic
glycogen phosphorylase>>>>>Mild fasting hypoglycemia, hepatomegaly, cirrhosis>>>Normal no
lactic acidosis?????? not sure
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alpha-1,4 glucanotransferase is normal.
so they can break down 1,4 linkage but cant breakdown 1,6 linkage.
so glycoegn can be breakdown but just not perfectly
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nbme>>>4,1,2 cant understand<<<following exerccise of an ischemic left forearm, his serum lactic acid
concentration does not increease in blood pntainging form the vein proximal to the exercised extremity>>>
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have normal life expectancy
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this is given at night to prevent sleep time hypoglycemia,corn starch digest more
slowly
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no rise in blood lactate levels after exercise.
muscle biopsy shows an excess of normally structured glycogen
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serum glucose level is normal.
also have hepatomegaly and increased risk of cirrhosis. generalized hypotonia,
macroglossia
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inc G6P>inhibits lactate to pyruvate conversion>>so more lactic acid
inc G6P, more substrate for HMP, more bases formed>>hyperuricemia
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affects mainly the liver and kidneys, enzyme is not expressed in significant quantities in muscle
tissue.hepatic steatosis is a cardinal manifestation of the disorder
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neuraminidase(sialidase) deficiency is the cause of human sialidosis.
neuraminidase is also a surface enzyme found on the influenza virus.
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are punctuate, dark red, non-blanching macules and papules that classically occur between umbilicus and the
knees.
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spastic paresis can also occur in this disease.
also occur with cerebral palsy and fucosidosis
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cleaving sphingomyelin into phosphorylcholine and ceramide
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normal development occur in the first couple of months, but between 2-6 months of age infants
develop progressive weakness, hypotonia, loss of motor skills, an abnormal startle relex with
accoustic stimuli, and a characteristic cherry-red macula. infants also develop macrocephaly due
to accumuation of glycolipid material in the brain.
histology typically shows neurons with cytoplasmic distension and lysosomes with "onion skin"
lamellar lipid rings on electron microscopy.
pateitns eventually develop seizyres, blindness and spasticity. life expectancy is 2-5 years.
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manifests b/w 2-5 months of age with irritability,developmental delay or regression and muscle tone abnormality
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along with galactocerebroside also accumulate galactosyl sphingosine
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also called globotriosylcermide (Gb3)
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small nerve fiber
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in r=early and mid adulthood, ceerebrovascular (eg TIA nad stroke) and cardiac (left
ventriculr hypertrophy)>>>>are the most common causes of death
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also accumulate in smooth muscles of vessels and causes cerebrovascular disease (eg TIA and
stroke)....
causes ventriulcar hypertrophy
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accumulate in glomerulus and distal tubule causes proteinuria and polyuria respectivelly
with out enzyme replacement result in progressive renal impairment that lead to renal failure and
death
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glactolipid that is found in abundance in myelin and start accumuating
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globoid cell leukodystrophy
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sphyingomyelin accumulation in the retina causes blindness as well.
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loss of previously acquired motor abilities,after a period of normal development.
the neurologic deterioration typically progresses to hypotonia and blindness by age 1..
death usually occur before age 3
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also a plant enzyme used for the breakdown of starch
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acroparesthesia>>episodic often debilitating, burning neuropathic pain in the extremities.
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ceramidase deficicny causes Farber disease, an autosomal recessive condition chracterized by
ceramide accumulation within neurons and within granulomas in the skin
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TRIGLYCERIDE>FA and GLYCEROL 1, fatty acid by beta-oxidation used for
ketone production or TCA cycle(which generate energy` for gluconeogenesis) but
does not go to gluconeogenesis. 2, glycerol (glycerol kinase)goes to either
gluconeogenesis or glycolysis. TGA stored in adipose tissue are metabolized to free
fatty acids and glycerol by hormone-sensitive lipase in response to low insulin
and high catecholamine levels. adipocytes are unable to metabolize glycerol, so
it is secreted into circulation and transported to liver, where it is phosphorylated to
glycerol--3-phosphate by glycerol kinase. glycerol-3-phosphate is subsequently
converted to DHAP by glycerol-3-phosphate dehydrogenase, which can be used
to produce glucose through gluconeogenesis. 1889............. in diabetic ketoacidosis
their is both beta oxidation and glycerol metabolism, but only glycerol goes to
gluconeogenesis
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TG stored in adipose tissue is metabolized to the free fatty acid and glycerol by hormone sensitive
lipase.
glycerol is then transported to the liver where it is phosphorylated to glycerol-3 phosphate by the
liver specific enzyme glycerol kinase.
subsequently glycerol-3-phophate is converted to DHAP by glycerol-3-phosphate dehydrogenase.
DHAP can be used to produce ATP through glycolysis or glucose through gluconeogenesis.
glycerol in the liver can also be utlized for TG synthesis.
only the liver can utilize glycerol produced by the degredation of TG by HSL.
in the liver , glycerol is used for TG synthesis , gluconeogenesis and as an intermediate in
glycolysis.
(adipose tissue synthesizes the glycerol phosphate needed for triacylglycerol synthesis from
DHAP)
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acetyl CoA generated in mitochondria by glycolysis is transferred to the cytosol as citrate. in the cytoplasm, ATP-
citrate lyase converts citrate back to oxaloacetate and acetyl CoA
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also has increased creatine kinase due to myopathy and increased serum lactate level due to inability of liver to
synthesize ketone bodies from FA and use of these ketone bodies as energy source by skeletal muscle and cardiac
myocytes in the case of catabolic stress (hypoglycemia)....so energy is obtained from anaerobic glycolysis not by
FA oxdation.
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accumulation of lipids within muscle fibers>>seen in lipid myopathies>>>due to carnitine palmitoyl transferase def
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there are several different forms of acyl-coa dehydrogenase but all causes similar clinical findings
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urea cycle is an ATP dependent process, in fasting when we cannot break fatty acid we break protein to
have glucose and ATP.the break down product of protein is ammonia which is converted into urea, when we
have low atp , urea cycle stops and we have accumulation of ammonia kaplan
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catalizes the 1st step in the b-oxidation and is the most commonly deficeint enzyme.
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the most common enzymatic deect leading to impaired b-oxidation is acyl-CoA dehydrogenase
deficicny.normal b-oxidation of FA yields FADH2 and NADH for atp production and generates
acetyl-CoA for the citric acid cycle and ketone bodies............
during periods od fasting.patients with this enzyme deficicncy cannot oxidize FA for energy or
produce ketone bodies.causing hypoketotic hypogycemia.
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carnitine is synthesized from lysine and methionine.
Vit C is essential for the synthesis of carnitine
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also go for cholesterol,bicarbonate synthesis
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Acetyl-CoA carboxylase (ACC)
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lead to FA oxidation defects in cardiac and skeletal muscles.
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liver cannot use ketones for energy cause it lacks enzyme succinyl-CoA acetoacetate CoA transferae
(thiophorase), which is required to convert acetoacetate to acetoacetyl-CoA ................................ the first step in
the synthesis of cholesterol or ketogenesis is condensatin of 2 molecules of acetyl-coa by acetyl-coa acetyl
transferase (thiolase) to form acetoacetyl-coa. condensation with 3rd molecules of acetyl-coa yields HMG-
coa. cholesterol syynthesis continues in cytoplasma but ketone synthesis occur in mitochondrias and start when
mitochondrial HMG coa lyase break down HMG coa into acetoacetate
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NADH convert into NAD when we convert acetoacette into hydroxybutyrate.reverse happen in target tissue
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amino acids
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12-18 hours of fasting
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*Glycerol KinASE* ( burn ATP) convert glycerol to Glycerol 3P then it convert in to
Dihydroxyacetone P by using NAD -> NADH(enzyme is glycerol 3 phosphate dehydrogenase)
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FA is used by skeletal muscle and heart, it cannot cross BBB, so brain use only ketone bodies
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during prolonged starvation glycerol kinase is responsible in providing substrate for gluconeogeneis
................ also hormone sensitive lipase is reponsible during starvation for increase in both gluconeogenesis
and fatty acid oxidation, by degrading TGs into FA and glycerol
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along with glycerol by the action of hormone sentivie lipase
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HDL deliver cholesterol to liver and steroidogenic tissues via scavenger receptor B1
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increases in blood when we eat diet high in glucose not high in fat. kaplan
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nbme,11,1,2>>
When blood sugar is low, glucagon signals the adipocytes to activate hormone-sensitive lipase,
and to convert triglycerides into free fatty acids
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abetalipoproteinemia.
lipoprotien synthesis occur in SER
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Type: Highlight Author: aishazulfiquar Subject: Highlight Date: 5/31/2017, 1:50:06 AM
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xanthomas are associated with hyperlipidemia or lymphoproliferative malignancies.
can be divided clinially into 5 categories,
1, eruptive xanthomas>>yellow palques that abruptly appear when plasma TGs and lipid
increases
2, tuberous and tendibous>>>tendinous often found on achilles tendon and the extensor tendons
of the fingers
3, plane xanthomas>>>linear lesions in skin folds that are strongly associated with primary biliary
cirhhosis
4, xanthelasma >>>>soft eyelid or periorbital plaques with no associated lipid abnormalities in
50% of affected individuals
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lipoprotein lipase deficicny can cause familial hypertriglyceridmea (heterozygous deficicny ) and chylomiconemia
(homozygous deficicny ) syndromes.
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tyep III hyperlipoprteinemia (familial dysbetalipoprteinemia) >>>due to deficiency of APO-E3 and E4>>>>results in
xanthomas and premature coronary and peripheral vacular disease.
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normally small amount of pancreatic lipase is screted in pancreatic capillaries, which releases free FA
which has toxic and inflammatory effect on the pancreas. the risk of pancreatitis increases when when TGs
level increases .......... TGs looesly reflect caloric balance, resitricted caloric diet, increased exericise and
reduced alcohol>>drop in TGs levels
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due in part to insulin resistance promoting increased VLDL production, diabetics may develop a
secondary Type IV and V hyperlipidemia (increased VLDL, chylomicrons) and/or secondary
diabetic dyslipidemia with elevated LDL cholesterol and low HDL cholesterol.
191
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70% receptor are present on the liver.
remaining are present on the smooth muscle cell, adrenocortical cell, fibroblasts and lymphocytes
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histologically xanthomas are composed of benign macrophages packed with finely vacuolated
"foamy" cytoplasm. this cytoplasm contains high levels of cholesterol, phospholipids and TGs.
the lipid laden macrophages are frequently also enclosed by inflammatory cells and fibrotic
stroma.
with xanthelasmas, the small aggregates of dermal foam cells are present without any surrounding
inflammation or fibrosis
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containing proliferating B-cells and follicular dendritic cells
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and dendritic cells.
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subcapsular sinus are in direct communication with afferent lymphatic vessels and the cortical
sinuses that line the trabecula.
the cortical sinuses are continuous with the medullary sinuses and single efferent lymphatic
channel exiting the hilum
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in agammaoglobulinemia, germinal centers and primary lymphoid follicles do not form due to an absence of B-
cells.
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infraclavicular lymph node>>>found beside the cephalic vein b/w pectoralis major and deltoid muscles,
immediatley below the clavicle>>>drain lymph from portions of upper limb and breast.
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lymphatic drainage of the colon generally follows the arterial supply.
lymph node are located on the bowel wall (epicolic nodes), inner bowel margins along the arterial
arcades (paracoloc nodes), around the corresponding mesenteric vessels (intermediate nodes)
and at the origin of the superior and inferior mesenteric arteris (principal nodes). the sentinal
lymph nodes (first 1-4 lymph nodes draining a specific colonic segement) are usually the first site
for colon cancer metastasis.
lymphatic channels proxiaml to anal dentate line drain into the inferior mesenteric and internal iliac
lymph nodes.
the upper rectum and superior part of the middle rectum follow the superior rectal nodes along the
superior rectal artery into the inferior mesenteric lymph nodes.
the middle to lower third of the rectum can drian upward into the inferior mesenteric nodes or folloe
the middle rectal nodes along the middle rectal artery to the internal iliac lymph nodes.
areas distal to the anal dentate line drian primarily into the inguinal nodes, although some lymph
can also reach the inferior mesenteric and internal iliac nodes.
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the lymphatic system of the extremities is divided into the superficial lymphatic vessels which
follow the venous system, and the deep lymphatic vessels, which follow the arterial system.
superficial vessel receive lymph from the skin and subctaneous tissues, whereas the deep vessels
drain both the deep muscles and the superficial vessels.
in lower extremities, the superficial lymphatic system is divided into medial and lateral tracks. the
medial tracks run along the long saphenous vein up to the superficial ingional lymph nodes,
bypassing the popliteal nodes.therefor lesion on the medial foot cause inguinal lymphadenopathy,
whereas lateral lesions, whihc drain via the lateral track and communicate with the popliteal and
inguinal nodes, are more likely to cause lymphadenopathy in both the popliteal and the inguinal
areas.
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located on anterior thigh inferior to the inguinal ligament and between sartorius muscle and
adductor longus muscle.
Overlie femoral artery,vein and nerve
......
also drain parts of genitalia ( eg penis(skin) , scrotum, perineum and vulva)
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primarily in internal but also to external iliac and sacral nodes (minor pathway)
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Type: Highlight Author: aishazulfiquar Subject: Highlight Date: 5/25/2017, 10:06:36 PM
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vermiform process, and parts of ascending and transverse colon
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superior portion>>>external iliac
inferior portion>>>>internal iliac
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are mesenteric, iliocolic and mesocolic.
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deep inguinal lymphnode>>>drain glans penis(via the deep lymphatic system) and cutaneous
portion of posterior calf along with draining superficial inguinal lymph node
............
deep inguinal lymph node drain into external iliac nodes
............
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left colic lymph nodes and their branches are located along the left colic artery and drain the left
colic flexure and upper descending colon.
right colic lymph node drain upper ascending colon
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nbme,11,3,8
The paraaortic lymph node group is divided into three subgroups: preaortic, retroaortic, and right
and left lateral aortic.
The preaortic group drains the abdominal part of the gastrointestinal tract above the mid-rectum.
The retroaortic group drains from the lateral and preaortic glands.
The lateral group drains the iliac lymph nodes, the ovaries, and other pelvic organs. The lateral
group nodes are located adjacent to the aorta, anterior to the spine, extending laterally to the edge
of the psoas major muscles, and superiorly to the crura of the diaphragm.
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spleen is site for nearly half of body immunoglobulin production including opsonizing Igs.
also and emergency source of blood cells and platelets.
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in the thymus the processes of TCR gene rearrangement, positive selection, negative selection
and expression of extracellular membrane markers and co-stimulatory molecules occur.
..........
costimulatory molecules are CD28 andCD45
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subcapsular zone >>>>double negative, begins thier diffeerentiation in the
subcapsular zone. then the procerss of TCR beta gene rearrangement with
simultaneous expression of cd4 and cd8. once in thymic cortexalpha gene
rearragment produces funcitonal alpha-beta TCR.then process of positive(cortex)
and negative(medulla) selection occur
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TCR DNA rearrangement is an exceeedingly complex process that results in excess of 10'5
different possible antigen binding sites.
the process is similar to that of immunoglobulin gene rearrangement in that it involves joininh of V,
D, J and C regions of the TCR gene and the process of junctional flexibility, N and P-region
nucleotide addition, alternative joining of genes, and multiple peptides combining to form the intact
receptor.
the mature TCR is formed from joining of an a and a b protein segement, and these proteins are
membrane-bound in close association with either CD4 or CD8 as well as the costimulatory CD28
and CD 45
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fetal thymus has immature T cell at 9th week of gestation which are derived from bone marrow.
mature naive T-cell are not released into circulation untill the 16th week at its earliest.
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pro-T cells arrive at the thymus as "double negative" cells, cells that lack both CD4 and CD8
antigens. Next the process of TCR gene rearrangement begins first with rearrangement of the b
chain genes which leads to stimulation of production of both CD4 and CD8 antigens wihc
simultaneously expression of both CD4 and CD8.these cells are referred to as 'double positive' T
cells or immature T-lymphocytes.subsequently, the process of rearrangement of the a chain of the
TCR occurs followed by positive selection in the thymic cortex and negative selection in the thymic
medulla..
once these processes are complete, the final step in maturation of -lymphocytes is loss of either
the CD4 or the CD8 antigen so that the mature thymocytes only express one or the other of these
antigens
......
positive selection is responsiblre for the development of a T cell repertoire that can recognize self;
................
thymic epithelial cells play a role in positive selection of immature thymocytes in the thymic cortex.
these cells express MHC antigens on their cell surface that interacts with the TCR on the
immature thymocytes. thymocytes able to bind MHC receive a protective signal and do not
undergo apoptosis, while thymocytes unable to bind MHC will be killed.
this is how self MHC restriction is generated in the T-lymphocyte population.
..........
in the thymus the processes of TCR gene rearrangement, positive selection, negative selection
and expression of extracellular membrane markers and co-stimulatory molecules occur.
..........
costimulatory molecules are CD28 andCD45
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red pulp cord have spaces as small as 1 micron in diameter.
bacteria and defromed RBCs lodged there.
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nbme>>>2,1,1 LPS bacteria. LPS bind to TOL ( a single transmembrane receptor)>>>>>activation of inhibitory
kappa B kinase (IKB kinase)>>>>>>>phosphorylation of the IKB of the complex (NF-IKB) and now this
phosphorylated IKB get degraded and NF-KB is released>>>>>NF-KB move to nucleus where it upregulate gene
expression of TNF>>>>sepsis. ............ note that NF-KB is a transcribption factor that exist in cytoplasm bound to
inhibitory kappa B(IKB) protein in inactive form (NF-KB-IKB)
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characterized by the production of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1b), IL-6 and IL-8.
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nbme,1,2,12
HLA region of Chromosome 6.The human leukocyte antigen system (HLA) is the name of the
major histocompatibility complex (MHC) in humans. The super locus contains a large number of
genes related to immune system function in humans. This group of genes reside on chromosome
6, and encode cell-surface antigen-presenting proteins and many other genes. The HLA genes are
the human versions of the MHC genes that are found in most vertebrates (and thus are the most
studied of the MHC genes). The proteins encoded by certain genes are also known as antigens,
as a result of their historic discovery as factors in organ transplantations. The major HLA antigens
are essential elements for immune function. Different classes have different functions:
HLA antigens corresponding to MHC class I (A, B & C) present peptides from inside the cell
(including viral peptides if present). These peptides are produced from digested proteins that are
broken down in the proteasomes. The peptides are generally small polymers, about 9 amino acids
in length. Foreign antigens attract killer T-cells (also called CD8 positive- or cytotoxic T-cells) that
destroy cells.
HLA antigens corresponding to MHC class II (DP,DM, DOA,DOB,DQ, & DR) present antigens
from outside of the cell to T-lymphocytes. These particular antigens stimulate T-helper cells to
multiply, and these T-helper cells then stimulate antibody-producing B-cells to produce Antibodies
to that specific antigen. Self-antigens are suppressed by suppressor T-cells.
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ubiquitin proteasome pathway (UPP) has role>>>>>ths is perfromed by ubiquitin ligase.
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virus particle, or freely circulating antigenic material. in case of virus>>>expression of nucleocapsid protein on MHC
class 2 stimulates CD 4 TH 1 type T-cell response (which stimulates CD 8 + cell production through cytokines) and
CD4 + Th 2 response that generate antinucleocapid antibodies that do not appear to play a role in protective
immunity
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lysosomal acidification has role.
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obligate or facultative intracellular bacteria. in case of virus MHC class 1 associated peptides derived from
nucleocapsid protein can kill infected cell and limit disease severity but are not thought to prevent infection
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Major histocompatibility alleles (the
most polymorphic gene system in the human species)
are also expressed codominantly.
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do not directly lyse cell.
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recruit neutrophil in addition to stimulating production of antimicrobial peptide. IL-17 improves the host defense
against fungi and bacteria at epithelial and mucosal surface. dysregulation has been implicated in many
autoimmune condition
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initially produced in the bone marrow, but they migrate from that location to mature during the first trimester of
gestation in the thymus.
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do not require the thymus for maturation and are present in athymic patients .
have no antigents-specific activities, do not require exposure to antigen for activation, and do not
possess antigen memory ability.
are activated by interferon-y and IL-12.
.........
Natural killer cells are derived from lymphoid stems cells and comprise approximately 10% of all
circulating lymphocytes.
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helper T cells (naive ThO) possess the TCR as well as CD3 and CD4 proteins on their celll
surface.
when an antigen MHC-II complex is presented to a naive Th cell by an APC, both the TCR and
CD4 proteins interact with the anigenic MHC II complex, while CD3 transmits the signa to the cells
interior.
if the antigen is presented by a macrophage, the macrophage will produce IL-12 that stimulates
differentiation into Th1 subset. IL-4 released by the other types of APC facilitataes differentiation
into the Th2 ausbsets,
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adminitration of INF-gamma is beneficifal for intracllular pathogens. adminitration of IL-4 is beneficial for some
extracellular viruses and bacterias
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IL-2 and lymphotoxin B
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opsonizing antibody (IgG) protects complement (C3b) degradation>>>>phagocytosis.
........
capsule bind serum "Factor H" a complement regulator that degrades C3b.
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nbme>>>2,4,18 The immature B cells whose B cell Receptors (BCRs) bind too strongly to self antigens will not be
allowed to mature. If B cells are found to be highly reactive to self, three mechanisms can occur. 1.Clonal deletion:
the removal, usually by apoptosis, of B cells of a particular self antigen specificity. 2.Receptor editing: the BCRs of
self reactive B cells are given an opportunity to rearrange their conformation. This process occurs via the
continued expression of the Recombination activating gene (RAG). Through the help of RAG, receptor editing
involves light chain gene rearrangement of the B cell receptor. If receptor editing fails to produce a BCR that is less
autoreactive, apoptosis will occur. Note that defects in the RAG-1 and RAG-2 genes are implicated in Severe
Combined Immunodeficiency (SCID). The inability to recombine and generate new receptors lead to failure of
maturity for both B cells and T cells. 3.Anergy: B cells enter a state of permanent unresponsiveness when they
bind with weakly cross-linking self antigens that are small and soluble.
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Type: Highlight Author: aishazulfiquar Subject: Comment on Text Date: 5/26/2017, 3:54:15 AM
occurs in naive B lymphocytes upon initial exposure to antigens.
........
isotype switching refers to the process by which B-lymphocyets modify the gene coding for the
constant region of the immunoglobulin molecule that they actively synthesize.
the gene lie in the following order, IgM, IgD, IgG, IgE, IgA.
modifiction of the Ig genome during class switching is executed by the aciton of a DNA
recombinase enzyme as well as other enzymes that excise loop of DNA containing the code for Ig
constant region.
if genome is coded for IgE then first three are never be produced by this genome(cause it were
excised) but it can produce IgA later time.
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this recombination occur during B-cell maturation within the bone marrow, not in the lymph node,
later on during primary immune response affinity maturation occurs in the germinal centers (lymph
node) through the process of somatic hypermutation
1614
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only in B-cell. this occur after initial binding of antigen to membrane-bound immunoglobulin on a naive B lymphocyte
and sbsequent migration to that B lymphocyte to a lymph node. within the germinal center of the lymph node,
affinity maturation is accomplished by somatic hypermutation. where the DNA coding for the immunoglobulin
variable region is mutated randomly at a very high rate.this process results in new immunoglobulin with similar,
better or worse affinity for the antigen, only B cells expressing antibody with enhanced affinity for antigen will be
selected for.
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TCR DNA rearrangement is an exceeedingly complex process that results in excess of 10'5 different possible antigen
binding sites. the process is similar to that of immunoglobulin gene rearrangement in that it involves joininh of V, D,
J and C regions of the TCR gene and the process of junctional flexibility, N and P-region nucleotide addition,
alternative joining of genes, and multiple peptides combining to form the intact receptor. the mature TCR is formed
from joining of an a and a b protein segement, and these proteins are membrane-bound in close association with
either CD4 or CD8 as well as the costimulatory CD28 and CD 45 .............. this TCR gene rearrangement occur in
thymic cortex
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disulfide bond hold the two heavy chain just before the hing region.
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IgG is the most effective immunoglobulin opsonin, and it is the key immunoglobulin
in providing immunity against bacterial toxins.
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IgA class switching is induced by stimulaiotn of the B-lymphocytes with TGF-beta
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while most other out of 9 protein produced by plasma cell
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concurrently expressed with IgM on the membranes of B-lymphocytes and is
believed to act as a cell surface antigen receptor for those cells.
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nbme>>>1,4,25>>>>if immunoglobulin isotype switching is diffecitve>>>>antibodies do not opsonize for
phagocytosis but antibodies make normal passive hemagglutination and complement mediated lysis of antigen
coated erythrocytes..
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which facilitates movement across mucosal surface and prevent its degradation in secretions.
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upon intestinal exposure to a novel antigen , B cells found in payers patches and mesenteric
lymph nodes become activated and preferentially migrate to lamina propia underlying the intestinal
mucosa, there they become fully differentiated plasma cell and begin to synthsize IgA dimers.
these IgA dimer then bind to polymeric immunoglobulin receptor (PIgR) found on basolateral
surface of intestinal epithelial cell and undergo trancytosis. as linked IgA dimer is released onto
intestinal lumen, a portion of PIgR remain attached to the antibody (secretory component)
forming the complete secretory IgA molecule
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association of ten distinct protein molecule.
4 IG light chain
4 IG heavy chain
1 J chain (protein)
1 secretory compoanent (protein)
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nbme 7,2,37
movement of dimeric IgA molecules through polarized epithelial cells to reach the ductal lumen
is>>>transcytosis not endocytosis not pinocytosis.
explanation.
Transcytosis is the process by which various macromolecules are transported across the interior
of a cell. Vesicles are employed to intake the macromolecules on one side of the cell, draw them
across the cell, and eject them on the other side. While transcytosis is most commonly observed in
cells of an epithelium, the process is also present elsewhere. Blood capillaries are a well-known
site for transcytosis, though it occurs in other cells, including neurons, osteoclasts and intestinal
cells.
Eg : Insulin and Antibodies
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amyloid protein has a pale rose color after congo red staining.
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hypoxia and erythropoiesis decrease the release of hepcidin from liver.
inflammation and high iron level increase the release of hepcidin.
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intracellularly stored..
which are present in enterocytes and macrophages.
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Decreased serum C4 level is seen hereditary angioedema. Here,the classical pathway is activated
secondary to a lack of C1 esterase inhibitor, which permits unopposed breakdown of C4 by C1
esterase.
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C3 deficiency also causes increased risk of encapsulated organism infection (due to opsoinization
defect)
732
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by binding of the C1 complement component to two molecule of IgM or IgG after these immunoglobulin have bound
circulating antigen such as bacterium
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recruits and activates neurophil,monocytes,basophil and eosinophil.
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mannose binding lectin and C-reactive protein can also opsonize cells.
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IgM is most efficient in activating C1 (classic pathway) cause it circulate in pentamer form and C1
needs to bind to the complement binding domains of two immunoglobulin before it can activate.
IgG on the other hand circulate as monomer so not very efficient in activating C1
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C1, C3 and C4 deficiencies are associated with lupus like syndrome.
...........
deficiency of C1 complement component (not C1 esterase inhibitor) is associated with SLE
development.
also have increase susceptibility of encapsulated organism (SHiN)
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Autosomal dominant.
Active kallikrien and bradykinin level are increased.
Bradykinin , C3a and C5a mediate angioedema by increasing vasodilation and vascular
permeability.
usually present in childhood and early adolescence.
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C1 esterase inhibitor normally inhibit classic complement pathway stimulation, it also inactivates kallikrein. activates
plasminogen to plasmin.
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type 2 HS reaction
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C5a enhance phagocytosis by macrphages, but it does so by binding to receptors on the phagocytes and
stimulating them directly , not by coating the foreign cells.
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form a pore in bacterial cell membrane, leading to electrolyte disturbances, inflow of free water and eventual lysis.
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recruits and activates basophil and eosinophil but not neutrophil
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C1INH prevents C1-mediated cleavage of C2 and C4, thereby limiting activation of the
complement cascade. It also blocks kallikrein-induced conversion of kininogen to bradykinin, a
potent vasodilator that also causes increased vascular permeability.
Acquired or hereditary C1INH deficiency (due to the complete absence of C1INH or the presence
of a dysfunctional variant or an anti-C1INH antibody) leads to elevated levels of bradykinin, and
patients can develop bradykinin-associated angioedema. Symptoms include facial swelling
(without urticaria), life threatening laryngeal edema, and gastrointestinal manifestation (e.g,
nausea/vomiting, colicky pain, diarrhea).
Management of acute attack involves supportive care and the administration of C1INH
concentration or a kallikrein inhibitor.
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Interleukins-2 (IL-2) receptor is transmembrane protein complex that acts via a multipathway
system, including a JAK-STAT signaling component, a MAP kinase pathway, and
phosphoinositide 3-kinase
........
function in an autocrine manner whereby activated T-lymphocytes (Th1 )provide costimulus to
themselves by secreting IL-2 and producing IL-2 receptors
........
IL-2 stimulates the autocrine proliferation of Th1
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5 families:
immunoglobulin
hematopoetin
chemokine receptor
TNF receptor
interferon
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nbme>>>1,2,15>>>impaired snthesis of IL-1>>>impaired function of T lymphocytes
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B cell activating factor (BAFF) is a cytokine belonging to the tumor necrosis factor
ligand family. inadequate levels of BAFF will lead to immunodeficicny, whereas
excess levels can cause autoimmune diseases (eg systemic lupus erythematous)
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proinflammatory cytokine induces nuclear factor kappa B,impotant in production of many
inflammatory cytokine.
...........
causes hepatic release of acute phase reactant>>C-reactive protein, and fibrinogen
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influence on hypothalamus that lead to appetite suppression, inhibiting lipoprotein lipase and and increases insulin
resistance in peripheral tissue
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first IL produce by T cell after antigen contact. mainly by T-Helper cell
..........
also promote the growth of B-cells, and activation of NK cells and monocytes
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jak-STAT pathway.
is a type II interferon produced mainly by T-cells and NK cell..
promotes Th 1 differentiation, increases expression of MHC class II molecules on antigen
presenting cell, and improves intracellular killing ability of macrophages.
..............
IFN-y production is responsible for phagolysosome formation, inducible nitric oxide synthase
release, and the development of granulomas and caseous necrosis.
..........
also induces death of epithelial cell
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uworld says MHC 2 expression on antigen presenting cells
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and differentation
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parasitic infection,
also in chronic eosinophilic bronchitis in asthma
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important for antigen presentation and T-helper cell response.
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when antigenic peptide (on MHC 2 of macrophages) binds the T-cell receptor on CD4 helper T
cells, the macrophages secretes IL-1.
IL-1 stimulates the helper T-cells to proliferate and/or secrete lymphokines
526
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secreted by helper t cells and funtions to activate macriphages, thereby promoting
adaptive immunity against intracellular pathogens
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also induces phagocytoses in neutrophil once has arrived.
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besides Th2 also produced by macrophages.
limits the production of proinflammatory cytokines (eg gamma interferon, IL-2,IL-3 and TNF-alpha),
also has immunomodulatory roles
...........
effects of IL-10 results in the attenuation of cellular-mediated immunity with some enhancement of
the humoral response, leading to a protective effect in crohns disease.
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almost all cell express TGF-beta receptor.
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play role in type 1 HS.
class switching to IgE also occur with IL-13
...........
IL -13 is a TH2 type helper cell product which may also promote IgE production by B cells.
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which inhances viral and paratsitic resistance
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jak-STAT pathway.
is a type II interferon produced mainly by T-cells and NK cell..
promotes Th 1 differentiation, increases expression of MHC class II molecules on antigen
presenting cell, and improves intracellular killing ability of macrophages.
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increased activity of T cells and NK cells is responsible for IL-2 antitumors ability (aldesleukin)
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TNF-alpha also causes insulin resistance by phosphorylating serine and threonine residues of insulin receptor and
insulin receptor substrate.
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nbme>>>3,1,6>>Tumor necrosis factors (or the TNF-family) refers to a group of cytokines family
that can cause cell death (apoptosis).
1.Tumor necrosis factor-alpha (TNF-α) is the most well-known member of this class, and
sometimes referred to when the term "tumor necrosis factor" is used.
2.Tumor necrosis factor-beta (TNF-β), also known as lymphotoxin is a cytokine that is inhibited by
interleukin 10
It can cause cytolysis of certain tumor cell lines;

it is involved in the induction of cachexia;
it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion;
finally,
it can stimulate cell proliferation and induce cell differentiation under certain conditions.
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induces and maintian granulomaformation,............... beside macrophages also produce by mast cells,NK cells and
T-cells. funciotns to siganl for the apoptosis of tumor cells and activation of imflammatory cells such as CD4 T
lymphocytes, neutrophil, fibroblasts, endothelial cells and hematopeotic stem cells.
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IL-3 produced by activated T cells.
stimulates growth and differentiation of stem cells (eg immature T-cell) in bone marrow.
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besides macrophages secreted by epithelial cells.
......
also activate metalloprotienase
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IL-1, 4, 5, 12 regulate local immune reactions and are proinflammatory,
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nbme>>>4,2,15
activation of cytotoxic T cells to eliminate virus infected cell require>>>>MHC class 1 and IL-2,
NOT interferon-gamma.
explanation
Once activated, the TC cell undergoes clonal expansion with the help of a cytokine called
Interleukin-2 (IL-2) that is a growth and differentiation factor for T cells.
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neutrophil myeloperoxidase is responsible for the green color of the pus and sputum in bacterial infection.
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alpha and beta interferons work either by autocrine or paracrine manner results in tranmscription
of antiviral enzymes capable of halting protein synthesis, scuh as RNase L(ENDONUCLEASE
THAT DEGRADES ALL rna in the cell) and protein kinase R (inactivates elF-2, inhibiting
translation initiaion).
however these enzymes become active only in the presence of double stranded rna,which forms
in infected cells as a result of viral replication
1468
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riboflavin
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myeloperoxidase deficiency>>>>majorly r asymtomatic but can predispose to candidal infection
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interferon alpha and beta produce by viral infected cell>>>impair intracellular viral assembly and viral genome
replication in neighbouring cells.
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both are type 1 interferon,these interferon causes macrophages and cytotoxic T cell activation
>>>leading to destruction of infected cell.
......
defect in type 1 interferon release result in increased susceptibility to viral infection
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contained with in azurophilic granules of neutrophils.
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nbme>>2,2,38
The OKT3 monoclonal antibody(is an immmunosuppressant) reacts with an epitope on the
epsilon-subunit within the human CD3 complex.
clinical use: immunosuppression after kidney transplant. S/E: cytokine release syndrome,
hypersensitivity reaction
OKT3 is a murine monoclonal antibody of the immunoglobulin IgG2a isotype. The target of OKT3,
CD3, is a 17-20 kilodalton (kD) molecule that is part of a multimolecular complex found only on
mature T cells and medullary thymocytes. This complex is uniquely situated next to the T-cell
receptor for antigen. An interaction between T cells, OKT3, and monocytes causes T-cell
activation (mitogenesis) in vitro. Because of the unique association between the antigen receptor
and CD3, antibodies that react with CD3 block T-cell receptor function and vice versa. Thus, OKT3
blocks both the generation and function of cytotoxic T cells. After an initial dose of OKT3, T cells
virtually disappear from the circulation within minutes to hours. During treatment with OKT3, T
cells bearing the usual array of surface molecules (CD2, CD4, CD8) reappear in the peripheral
blood circulation but these cells are devoid of the OKT3 target molecule, CD3. Within 48 hours of
discontinuing OKT3, the normal array of surface molecules including CD3 is found again on all T
cells. The selective removal of CD3 by internalization is thought to be the key mechanism of action
of OKT3. Comodulation of the antigen receptor with CD3 explains the immunoblocking action of
OKT3 in vivo. Experience with a second or third treatment with OKT3 indicates that OKT3 is
ineffective clinically if the CD3 target molecule is not modulated. OKT3 has been found to be
effective for induction of immunosuppression and for treating initial and steroid-resistant rejections.
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CD 19, 20 present on pre B cells.
CD 19, 20, and 21 present onto mature circulating B lymphocytes.
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cd16 is a low affinity Fc receptor found on the surface of NK cells, neutrophils and macrophages.
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CXCR4/CCR5
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surface marker of monocytes and macrophages. serve as a receptor for LPS. binding of LPS to
this receptor results in activaiton of the macrophages.
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CD7 is a multi chain complex T-cell marker.
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Central tolerance is acquired within the fetal thymus during negative selection. Peripheral
tolerance develops by mean of T-cell anergy, which is the functionalinactivation of T-cels that
are reactive to self antigens
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adult routine vaccine
Tdap or Td
PPSV23
+/- pcv13(if already not taken PPSV23, not give at the same time with PPSV23)
influenza
HPV(male and female)
MMR and varicella(both are catch up vaccine)
zoster (all over the 60,we give this even they already has shingles)
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approved carrier protein: mutant nontoxic diphtheria toxin, nesseria meningitis outer membrane protein complex ,
and tetanus toxoid.>>>they attached with covalent bonding
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influenza vaccine given annually and in all patients greater than 6 months of age
.........
INFLUENZA” is MC vac preventable illness seen in travelers (studies show UP 2% ALL travelers
got gift in their trip) Vaccination rec FOR all travelers Age 6 mon & older.
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cannot effect host cell so cannot enter into the cell. produce neutralizing Abs against hemagglutinin
antigen>>>>these Abs inhibit binding of hemagglutinin to sialyated receptors on host cells membrane upon
subsequent having a natural influenza infection. this prevent live virus from entering cells via endocytosis
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BCG vaccine contain live attenuated M bovis which is used for M tuberculosis.
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BCG,salmonella typhi(oral form), francisella
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genetically attenuated sporozoites are being investigated as malaria vaccine.
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unlike inactivated, live attenuated enter into the cell and stimulate MHC 1 mechanism to produce CD8+ cell
mediated immunity >>>these cytotoxic CD8 +lymphocytes than kill infectd cells
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vibrio cholera nad yersiia pestis also are killed
1853
.......
pertussis also
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nbme>>>5,1,31
blood group O receive blood group A. Ab-RBC complex trigger "classic complement pathway",
mechanism of hemolysis is >>>action of C5-9 complex of complememnt(which make hole in
RBCs).
mechanism of shock in this patient is>>>release of histamine by the action of C5a
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containing hyalurounidase, phospholipase and other proteins which initiate an IgE mediated response.
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antibody-dependet cellular cytoxicity (type II hypersensitivity) is part of the
bodys defense against viral and parasitic infections. antibodies bound to antigens
on the surface of infected cells are recognized by the Fc receptors on effector cells
(eg natural killer cells, neutrophils, esinophils) hat then destrpy the infected cells
by releasing cytolytic granules
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Type: Highlight Author: aishazulfiquar Subject: Comment on Text Date: 5/26/2017, 7:02:41 PM
wide spread mast cell and basophils degranulation and resultant release of preformed histamine
and tryptase.
typtase is an enzyme that is relatively specific to mast cell, and elevated serum level of tryptase
are often used to support a clinical diagnosis of anaphyalxis
.......
serum tryptase would be elevated for several hours after an anaphylactic episode.
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autoantibodies are formed against the noncollagenous domain of the alpha-3 chain of collagen IV
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IgE antibodies become crosslinked and receptor aggregation occur after interaction of IgE with multivalent
antigen>>>>>this clumping of receptors leads to non-receptor tyrosine kinases>>>triggering an intracellular
cascade that ultimately result in mast cell and basophil degranulation and reelease of preformed mediators...........
the strength of IgE-FcRe1 is the result of sum of many weak noncovalent forces.;it is not associated with the
formation of covalent bonds (eg disulfide or peptide) ; most of total IgE in the body is bound to the surface of mast
cells and basophils and not circulating freely. ........... medications such as beta-lactam and sulfonamides
antibiotics>>>>these 2 drugs also has serum sickness type 3 reactions
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Pseudoallergic drug reactions mimic immunologic reactions but occue via a non-immunologic mechanism
(eg, direct immune cell activation, inhibited prostaglandin synthesis) Examples include rhinitis with
NSAIDs,anaphylaxis to radiocontrast media, and pruritus with opiates. .......... also caused by chemical,
heat and certain drugs (eg opiates and vancomycin) ........... IgEA independent mast cell
degranulaiyon>>>by activationof prteinkinase A and PI3K (IgE dependent is by non-receptor tyrosine
kinase)
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serum sickness can occur following administration of antigenic heterologous proteins such as
chimeric monoclonal antibodies (eg rituximab and infliximab) or non-human immunoglobulins (eg
venom antitoxin). a serum sickness like reaction is also associated with the use of certain non-
protein drugs (eg penicillin, cefaclor, and TMP-SMX)....
the most common manifestation include fever, pruritic skin rash, and arthralgias that begin 7-14
days after exposure to an antigen..lymphadenopathy and proteinurua may also occur in some
patients..
histologic examination of affected tissue typically show small vessel vasculitis with fibrinoid
necrosis and intense neutrophil infiltration.
deposition of IgG/IgM complement fixing antibodies results in localized complement consumption
and hypocomplementemia (decreased serum C3 levels)
serum sickness causes release of the C5a complement fragment (a neutrophil chemoatractant) at
sites of immune complex deposition.. this leads to neutropenia and due to extensive neutrophil
margination and and tissue infiltration..in addition infliximab and other TNF-alpha inhibitors can
also cause neutropenia.
mild thrombocytopenia due to platelet consumption at the site of the active vascular inflammation.
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oak and sumac all produce urushiol>>>a small allergenic substance that causes an immune
response when attached to protein (ie hapten)..
mediated by CD8 T cell cytotoxicity>>>directly destroy keratinocytes expressing heptenated
protein.
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the pathogenesis of contact dermatitis predominantly involves repeated binding of small foreign molecules
(haptens) applied tot he skin surface to proteins on the surfaces of cutaneous cells, including antigen presenting
langerhans cells. LCs with bound hapten migrate to local draining lymph nodes where they generate circulating
Th1 type memory cells. upon cutaneous reexposure to the hapten these, Th1 cells release inflammatory cytokines at
the site of exposure. the result ia a type IV, cell mediated hypersensitivity immune response in the dermis and
epidermis.
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in scabies has type 4 against mite, its egg and feces
.....
sarcoidosis is a type IV hypersensitivity.
.......
dress syndrome also has type 4
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depending on etiologic agent can be mediated primarily by the cytotoxic CD8 T cell or CD4 Th 1
cell (that cause indirect damage by activating macrophages....
..............
in urushiol-induced contact dermatitis, CD8 T cells are the primary effector cells and directly
destroy keratinocytes expressing haptenated proteins
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most pateitns with hypresensotivity pneumonitis have specific serum IgG antibodies whihc precipitate
actinomyces species antigens, consisting with a type III hypersensitivity mechanism producing intersticial alveolitis
and broncholitis via immune complex and complememnt depostition in vessel walls.
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blood transfusion containing bacterial infection can cause septic shock (TNF alpha) but would not
cause hemoglobinuria in otherwise matched product
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" Two known mechanisms: 1) Type II hypersensitivity reaction with host antibodies against donor HLA antigens and
WBCs; 2) induced by cytokines which are created and accumulate during the storage of blood products ."
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also chest and back pain.
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pre existing antibodies especially IgM.
causes complement activation>>C3a, C5a, anaphylatoxins,
also production of C5b-C9>>>comlement mediates lysis of RBCs
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1 and 3
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also called anti-histidyl-tRNA synthetase
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due to antigen mimcry with geeneration of self recongnizing CD-4 T lymphocytes that damage
hepatocytes
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Cardiac defects associated with this syndrome are Tetralogy of Fallot and interrupted aortic arch. ..........
aberrant formation of mandible and palalate (frequently associated with cleft palate) and low set ear
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Xq21.3
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pyogenic (encapsulated) due to absence of opsonizing antibodies
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absence of germinal center and primary lymphoid follicle in the lymph node. outer cortex which contain primary
and sencondary lymphoid fillicle also contain prominent number of CD4 T-cells within interfollicular regions
(allowing for T-B cell interaction). in patients with agammaglobulinemia ,the outer cortex is present but
diminshed. 1134
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otitis media, sinusitus, bronchitis, pneumonia by encapsulated bacteria due to absence of secretory IgA.
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often form IgG antibodies directed against IgA ( eg anti-IgA antibodies)>>>when transfused with
blood which contain small IgA they develop anaphylactic reaction.
gamma-globulin preperation should not be used for treatment of these patients as it may increase
the synthesis of anti-IgA antibodies.
..........
ABOVE EXPLANATION IS WRONG>>now uworld say its IgE antiboides against IgA which
causes analphylaxis
1130
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protozoan and intracellular bacterial pathogen
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these patietns are treated with adminitration of INF-gamma.
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immunodeficiency wanes as patient ages due to maturation of T cell other than thymus
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acute or chronic diarrhea by viral bacterial and giardia lamblia infections deu to absence of secretory IgA
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because serum IgG an IgM can also be secreted by the mucosa although to a lesser extent than secretory IgA
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enterovirus along with giardia lamblia due to absence of neutralizing antibodies
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failure of bone marrow pre-B cell into mature B lymphocytes.
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bare lymphocyte syndome>>>immunodeficiency result from defect in expression of HLA class II antigens on the
surface of antigen presenting cell. MHC class II is needed to present foreign antigen to T-cells to elicit a cell mediated
and humoral mediated response
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nbme,11,3,50
Common variable hypogammaglobulinemia, unknown molecular defect, onsets in late teens, early
tewnties, B cells presents in peripheral blood, immunoglobulin levels decreased with time,;
increased autoimmunity, the albumin can be normal or low, but the gamma globulin always is low,
this curve is the same for Lymphoproliferative disorders, inflammatory bowel disease, congenital
immunodeficiencies
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2nd most common cause.
this enzyme deaminate adenosine to inosine as an initial step in the elimination of excess
adenosine from the cell.
adenosine accumulation is toxic to lymphocytes and leads to widespreas death of both T and B
lymphocytes.
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treatment with retro viral gene therapy>>>transfer geentic code for adenosine deaminase. .......... retroviral vesctor
are used becasie of the ability of retroviridae to incorporate their genome directly into the genome of infected human
cells by the action of the enzyme integrase.
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complete DGS (less than 1% of cases) is a form of SCID.
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presents in 1st year.
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autosomal recessive. DNA is hypersensitive to ionizing radiation (X-RAYS) which causes multiple chormosomal
breaks
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due to impaired gene rearrangement. ................. can
also be due to deffective enzyme such as
DNA recombinase. ............... this occurs by splicing out DNA coding for different
types of the heavy chain constant region, untill the seired isotypeis reached, the
variable region and there forer the antigenic specificty of the antibody, stays the
same
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onset of disease early in life>>>thrombocytopenia present at birth, with eczema and repeated
infection (encapsulated org particularly) at 6-12 months of age.
........
recurrent infections that worsen with age.
.........
treatment>>>HLA-matched bone marrow transplant
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CD 18 antigen is necessary for the synthesis of integrin.
which play a role in migration
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peripheral and cranial neuropathies.
nystagmus is also present..
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in myeloperoxidase deficiency both CATALASE positive and negative organism survive within
phagocytes........
........
Increased risk for Candida infections; however, most patients are
asymptomatic.
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detect flourescent green compound that is produced by conversion of dihydrorhodamine to rhodamine
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both test detect presence of superoxide free radicals
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(due to abnormal dense granules in platelets
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or CD40 deficiency on B cell(rare, autosomal recessive)
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normally reactive oxygen species reduces the yellow NBT to dark blue formazan that precipitates within the cell
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and macrophage phagolysosome.>>>>increased risk of fungal and bacterial infection.
normal response to virus and parasites.
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these oxidants has direct microbicidal activity and also function to activate granule proteases (eg elastase and
cathepsin G) that destroy engulfed pathogen.
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pus is thin protein rich fluid and dead leukocytes especially neutrophil.
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pyogenic infection>>>>due to deficient humoral immunity>>>susceptible to encapsulated org (
SHiN).
opportunistic infection>>T-cell defect
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commonly result in lymphoid hyperplasia and recurrent sinopulmonary infections.
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defect in DNA repair enzyme>>>increase risk of hematological malignancies and causes an
immune deficiency consisting of both humoral and cell-mediated dysfunction.these immune
deficiency primary manifests as an IgA deficiency.
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oculocutaneous telangiectasia presents later in disease course.
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sinopulmonary infection.
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unlike CVID symptoms appear in infancy (as maternal immunity wanes). SCID present with recurrent infection in
adults and children.............. in SCID laboratory studeis shows>>very low or absent CD3-T cells and
hypogammaglobulinemia.thymic hypoplasia and aplasia in another common finding. in CVID laboratory studeis
show hypogammagolbulinemia, cell mediated immunity is not as affected as in SCID and thymic aplasia is
unlikely.
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also defect in MHC class II
.......
Null mutations in rag1 or rag2 genes
No rag enzyme activity.
AUTOSOMAL RECESIVE
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promoter of intracellular survival is accomplished by inhibition of phagosome-lysosome fusion or resistance
to lysosomal enzymes. These properties are expressed by Mycobacterium tuberculosis, M leprae,
Legionella, and Ehrlichia.
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chronic rejection is a major cause of morbidity and mortality and occurs in almost half of all
patients within 5 yearss of transplantation. these patients commonly present with dyspnea and a
dry cough.spirometry shows an airflow limitation with a drop in both the forced expiratry volume in
1 seconds (FEV1)and the FEV1 to forces vital capacity (FVC) ratio. chronic rejection affects the
small bronchioli producing the obstructive lung disease knowns as bronchiolitis
obliterans.initially histopathilogy shows lymphocytic inflammation and destruciton of the
epithelium of the small airways.subsequently fibrinopurulent exudate and granulation tissue are
found in the lumen of the bronchioli. which ultimtely results in fibrosis, scarring and the progressive
obliteration of small airways. Ischemia-reperfusion injury (or reperfusion edema) is a form of
noncardiogenic pulmonary edema that can occur in the allograft due to surgical trauma, organ
ischemia, denervation, or interruption of lymphatic outflow. Reperfusion edema is seen during the
first few days following transplantation.CMV is the most significant opportunistic infection in
lung transplant recipients
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patchy necrosis with granulaiton tissues is indicative of ischemic damage to donor heart.
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Complement
activation,
endothelial
damage,
inflammation
and thrombosis
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most common form.
type 2 and type 4 HS
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acute rejection ocurs in approx 2 of every 5 heart transplanted and in large majority of cases occurs by the cell
mediated pathway. in rare cases cardiac rejection is due to anti-donor host antibodies, and cases of humoral
rejection are diagnosed by direrect immunofluorescence.
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Parenchymal
cell damage,
interstitial
inflammation
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primarily of the T lymphocytes.
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acute rejection causes vascular damage. light microscopy shows perivascular and peribronchial lymphocytic
ingiltrates. in acute lung transplantation rejection clinically present with dyspnea, dry cough and low grade
fever(contrast to chronic have wheezing). chest Xray shows perihilar and lower lobe opacities.............. it is
importsant to note that bronchial circulation is not routinely revascualrized
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irreversible.
chronic rejection is mediated by host T lymphocyes and B lymphocytes as wll as antibodies.
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this type of rejection can be prevented bu calcineurin inhibitor and chronic corticosteroid therapy
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which do not have competent T-cell to attack graft
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any organ may be affected but skin, liver and GI track are commonly involved
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prevented by exact HLA matching in bone marrow transplant and histoidentical siblings are
preferred donor.
additional prevention can also done by washing the donor cells with antithymocyte immune
globulin in an effort to remove T-lymphocytes from donor tissue.
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or transfusion of non-irradiated blood
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graft T-cell sensitization against host MHC antigens.
......
both donor CD4 and CD8 cells participate in destroying host cells.
symptoms develop within one week of the transplantation procedure.
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Chronic DTH
reaction in
vessel wall,
intimal smooth
muscle cell
proliferation,
vessel occlusion
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morphology:
humoral>>>>C4d deposition, neutrophilic infiltrate, nectrotizing vasculitis.
cellular>>>lymphocytic intersticial infiltrate and endothelitis
..........
Presence of complement component C4d (degradation product of C4 activation)
in the inflammatory tissue indicates that the complement system has been
activated and is an important marker that there is a humoral component in the
rejection.
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such as calcineurin inhibitor (eg cyclosporine and tacrolimus) and mycophenolate
treatment of active acute rejection is with systemic corticosteroids and continuation of calcineurin
inhibitor.
calcineurin inhibitors itself reduce renal blood flow and are directly toxic to renal endothelial and
tubular cells>>>histologic finding is early arteriole hyalinization and tubular vacuolization. despite
their nephrotoxicity, these agents are beneficial for prevention of acute rejection
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major role in acute rejection
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acute rehjeciton is usually diagnosed before symptoms set in beacuse of close surveillance of these patietns
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typically are asymptomatic, but some develop fever, chills, malaise and arthralgias. other manifestation of acute
rejection include increased serum creatinine, hypertension and reduced urine output. cell mediated acute rejection is
associated with lymphocytic infiltrate of the vessels (endothelitis), tubules and renal interstitium (diffusely increased
cellularity)
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neutrophilic
infiltrate with fibrinoid necrosis
......
graft blood vessel spasm and diffuse intravascular coagulation, with resultant ischemia..
for this reason hyperacute rejection is sometimes called "white graft" reaction.
it is rare and ofte irreversible
........
morphology>>>gross mottling and cyanosis
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rejection of lung transplant differs form rejection of an intraabdominal organ (eg renal tranpant).
in chronic rejection (major cause of mortality in lung transplantation). causes inflammation of the
small bronchioles(ie bronchiolitis obliterans), inflammation and fibrosis of the bronchiolar walls
lead to narrowing and obstruciton of the affected bronchioli.
clinically bronchiolitis obliterans present with dyspnea, non-productive cough and wheezing.
this mechanism contrast to the chronic rejection often seen in renal transplantation (primarily
vascular obliteration)
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nbme.11,1,29
kidney transplantation in combination with bone marrow tranplantation from the same
donor.monitoring of the allograft post-translation show good function despite the lack of treatment
with immunosuppressive drugs.the transplanted bone marrow is most likely inducing which of the
following immune phenomenon>>>
tolerane , not costimulaiton, hypersenssitivity senescenece and survillance.
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increase osteoclast differentiation and activity, decreasing osteoblast activity and synthesis of
bone matrix, inhibiting the intestinal action of Vit D in promoting calcium absorption , and
increasing parathyroid hormone level.
glucocorticoid>>>>decrease intestinal Ca absorption, decreases osteoblast collagen depostion,
decrease GnRH (hypogoadism) and increase urinary excretion of Ca.
1773
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thereby inhibiting activation and proliferation of TH-subset of T-lymphocytes.
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nbme>>>2,4,30
Adverse effects include nephrotoxicity with 3 stages:
(1) immediate, secondary to renal ischemia;
(2) 2-3 weeks after transplantation, secondary to renal vasoconstriction; and
(3) chronic, secondary to interstitial nephritis.
Other adverse effects include hyperkalemia, hypomagnesemia, nausea, vomiting, diarrhea,

hypertrichosis, hirsutism, gingival hyperplasia, hyperlipidemia, glucose intolerance, infection,
malignancy, and hyperuricemia. Hypertrichosis and hirsutism can be alleviated by switching from
cyclosporine to tacrolimus, provided the patient is carefully monitored. Multiple drug interactions
are possible, primarily with agents affecting the cytochrome P-450 system
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preventing G1 to S phase progression and lymphocyte proliferation.
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immunophilin FK-506 binding protein (FKBP). forming a complex that inhibits mTOR.
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histologically>>>early arteriolar hyalinization and tubular vacuolization.
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calcineurin inhibitors such as cyclosporine cause dose-dependent renal vasoconstriction and
tubular cell damage, which can precipitate acute renal failure.cyclosporin is extensively
metabolized by the liver and GI tract via the cytopchome P450 system, specifically the CYP3A
isoenzyme.
inhibition of intestinal P450 cyp3a enzymes by the furocoumarins presents in grapefruit juice
,.........
toxicity is due to intestnal CYP3A inhibitor not due to hepatic CYP3A
11761
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nbme,6,4,46
the question is about thrombopoietin receptor -CD110 (TPO-R) is a member of the hematopoietin
receptor family and is expressed on hematopoietic stem cells, a subfraction of hematopoietic
precursor and on cells of the megakaryocytic lineage and platelets. CD110 is the receptor for
thrombopoietin. Upon binding of thrombopoietin to CD110 megakaryocyte proliferation and
differentiation is induced and stem cells are protected from apoptosis..
And as thrombopoietin is a glycoprotein hormone ... the receptor should be at the cell membrane
....
answer...on the cell membrane of the megakaryocytes
q 46 ...thrombopoietin is i a glycoprotein hormone produced mainly by the liver and the kidney that
regulates the production of platelets by the bone marrow...
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is a protein phosphatase that once activated dephosphorylates NFAT, which allows it to enter the nucleus and bind
to an IL-2 promoter
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increased activity of T cells and NK cells is responsible for it antitumor property
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glycoprotein that inhibits various stages of viral RNA and DNA synthesis
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in BM IL-11 made by fibroblasts & stromal cells
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with "Daclizumab, basiliximab ,
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activates macrophages, increasign antigen presentation in all cells and promotes Th1 cell differentiation
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nbme>>>2,3,4>>>
side effects of erythropoetin:
Erythropoietin can cause an increase in blood pressure, . Blood pressure should be monitored
while on this medicine
A common side effect due to erythropoietin administration is pain or burning at the site of the
injection. This can be decreased by making sure that the erythropoietin is at room temperature
before giving the infection. Ice can be placed in the area of injection to numb it before receiving the
shot, and the site of injection should be changed with each shot.
Common side effects of patients who receive erythropoietin include diarrhea and swelling.
Less common side effects in cancer patients include fever, nausea and vomiting, fatigue,
shortness of breath, and weakness.
Seizures have been reported in patients with kidney failure

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nuclear factor of activated T cell
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inhibits the NFAT from entering the nucleus and modulating transcription activity, impairing the production and
release of IL-2, inhibiting IL-2 induced activation of resting T-lymphocytes.
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nbme>>>6,1,6,
significant myelosuppression after HAART therapy, begins treatment with hematopoetic growth
factor, thirty minutes later, he develops dyspnea, severe muscle pain, vomiting and sinus
tachycardia, his blood pressure is 80/40mmhg, most likely hematopoetic growth factor used is
>>>>sargramostim
explanation
Among the two drugs filgastrim and Sargramostim, sargramostim is well known to have the so
called First Dose effect... the side effect happened on the first dose and 30 minutes later ....• A
“first dose effect” may occur, which is characterized by an increased heart rate, feeling faint, low
blood pressure and reddening of the face. This tends to only happen on the first dose of
sargramostim• Diarrhea or stomach upset• Swelling, pain, redness, tenderness at the site of
injection• Flu-like symptoms that may include fever, headache, achiness or pain, weakness and
fatigue• Bone pain• Swelling of feet or handsAnswer Sargramostim
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is a tyrosine kinase receptor.
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can cause hypomagnesemia...
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is a tyrosine kinsae receptor
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administered during angioplasty in patients with acute coronary syndrome
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o>>>mouse
u>>>human
xi>>>chimeric (human contant region foreign variable region)
zu>>>>humanized(human constant and varibale region except complementary determining
region)
xizu>>>chimeric/humanized hybrid
8523
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use to reduce skeletal related events if metastasis to bone occur.
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(Ramicade) is a chimeric (human/murine) IgG1 monoclonal antibody to TNF-alpha.
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active form
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also used in menetrier disease (in which there is TGFa overexpression)
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by binding it >>>produces direct cytotoxic effect through complement fixation and antibody-dependent, cell
mediated toxicity
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its precusor molecules consists of disaccharides composed of N-acetylglucosamine and N-acetylemuramic acid
that combine with an amino acid to form peptidoglycan.
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used to classify gram negative bacteria.
it is the most extracellular component of LPS.
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flagellar (H) antigen is a heat labile protein, which is one component of serologic classification of the
enterobacteriaceae.
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outer membrane protein and inner membrane protein principally act in cellular homeostasis for the
bacterium.
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teichoic acid servee as antigenic determinent for org detection and antigenic target for the human
immune system
1215
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endotoxin found in gram - bacterial cell wall is strongly associated with sepsis. but gram + cellular wall component
(including peptidoglycans and lipoteichoic acid) along with various bacterial products and exotoxin, can also cause
sepsis.
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used by neisseria meningitis, uropathogenic and diarrheogenic E.coli, bordetella pertussis and vibrio cholerae.
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release occur during division or by bacteriolysis, but not actively secreted by the bacteria.
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cellulose is a linear polysachharide of glucose that is mainly present in the cell wall of plant.
cellulose is an insolube, indigetible dietery fiber that is responsible for the bulk of fecal matter.
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nbme>>3,1,14
filter size
,mycoplasma,viruses ricketssiae all are very small in size less than 0.45micron,here only staph
aureus can be removed,becoz it is greater than given size,if it were only 0.22micron filter only
viruses would pass,if the diameter of a cell described in a clinical case is greater than 2 micron it
would be a eukaryotic cell
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the cell membrane and cell wall of mycobacteria are most similar to those in gram-positive
orgnaism, causing mycobacteria to appear weakly positive on gram stain.
but mycobacteria cell wall also encapsulated by mycolic acid, a waxy, long chain fatty acid that is
covalently bound to the sugars within the cell wall.
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is an aniline dye gives red color after binding with mycolic acid.
the slide is then treated with hydrochloric acid and alcochol, mycobacteria prevents
decolarization,and counter stain eg methyline blue is applied and taken up by decolarized
bacteria.
therefor acid fast bacteria gives red color and non-acid fast gives blue color.
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periodic acid oxidizes carbon-carbon bonds, forming aldehydes that produce a brilliant magenta
color upon reacting with the fuchsin-sulfurous acid.
PAS is effective for highlighting polysaccharide of the fungal cell wall, mucosubstances secreted
by epithelia, and basement membranes.
diastase can be used in conjunction with PAS to demonstrate glycogen, which is found in skin,
liver, parathyroid and skeletal/cardiac muscle.
the diastase works by digesting glycogen to form maltose and glucose, two sugars that are easily
washed from sections during processing (therefore giving a negative reactions)
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uniqueLPSchqians on outer membrane inhibot gram staining 960
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nbme, 6,3,10
streaking technique.
"STREAKING": is is a technique used to inoculate organism on agar plate.For this we use cotton
swab or "Inoculant WIRE Loop" which is a wire that have very small loop at it's tip.
At first we sterilize and then dip this loop into sample that we have collected.Now we roll it on 1/4th
of the agar plate(Just like u see in stem pic the region marked with "A").
Second Next we sterilize the loop again and this time we don't dip it in the collected sample rather
we drag it over the FIRST 1/4th inoculated region which will pick up the organisms and spread it to
the next 1/4th space on the agar plate.
Third Next we sterilize the loop again and this time we drag it over the SECOND 1/4th inoculated
region which will pick up organisms and spread it to the next 1/4th space on the agar plate.
Fourth Next we reapeat the same previous step to spread on the last 1/4th space on the agar.
** Every time we repeat the streaking it picks up fewer and fewer organisms and in the end we
end-up separating the "PURE COLONY OF SINGLE ORGANISM" as u see the colony that is
marked with "D".Now in our second step of streaking we got Gray and White colonies but not the
black one and again in the third step we just got Gray colonies which means the black one was not
present at all in 2nd and 3rd 1/4th region of agar but showed up on the fourth step that tell us that
it was contaminated as is also present in the first 1/4th streaked space..
.....
the colonies will grow from the" SAMPLE "..."ONLY on the Streaking Lines" , so any colony is off
the streaking line can not be from the sample hence it must be the contaminant
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neutral lipid stain with nile red or sudan black
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Macconkey and EMB agar is both differential and selective
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part of anaerobic oral flora>>>potentially cause aspiration pneumonia or pharyngitis (lemierre disease)
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for anaeobic infection
1, extended spectrum antibiotics with beta-lactamase inhibitor (eg piperacilin and tazobactum).
2,metronidazol,
3, clindamycin
4, carbapenems
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propionibacterium
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⊖ bacteria
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chocolate agar based(heated blood)
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gram negative rod that produces beta-lactamase.
have unique surface polysaccharides that have been shown to favor abscess formation.
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bile salt and crystal voilet containing agar that inhibit growth of many gram + org
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leishmania is facultative intracellular protozoa
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1, blocking the fusion of phagosome lysosome>>>salmonella and mycobacterium tub. 2,
inhibiting phagolysosome acidification>>>M tuber. 3, escaping from phagosome into
cytosol>>>listeria and shigella
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innate phagocytosis
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urease convert urea into CO2 and ammonia which increase the pH and resultant color change of
the phenol red pH indicator.
an alkaline (pink) color persisting more than five minutes is considered a positive test for H.pylori.
although pink color typically deveelops within 30 minutes when H pylori is present, the sample
should be observed for 24 hours before considereing negative.
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11 or 12 years old with booster at 16 years.
can be given to young infant as young as 2 months if risk factor are present
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PCV is given early on and then we use PPSV as a booster.
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PPSV23 is given to all adults over the age of 65 and for those age 2-64 with certain medical
conditions (eg diabetes, chronic pulmonary or cardiovascular disease). this is not immunogenic in
children age <2 due to their relatively immaure humornal antibody response
pateints younger than 65(after age 2). therefore PCY13 is strongly immunogenic in infancy and
part of routine childhood vaccinations.similar to PPSV23, PCV13 is recommended for
immunocompromised patients and adults age >65
11872
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(NH2)2CO + H2O → CO2 + 2NH3
its a urease reaction.
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bacillus anthracis
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cryptococcus, histoplasma, coccidioidis.
plasmodiuma and toxoplasma
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obligate intracellular protozoa is toxoplasma
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at its hinge region (yielding Fab and compromised Fc fragments)
IgA bind to pilli/fimbria and outer membrane protein that mediate adhesion and penetration to
prevent these two.
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interferes with opsonization by the alternaltive complement pathway
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it also binds to fibrinogen resulting in inflammatory mediator release and vascular leakage. M-
protein is the major virulence factor which inhibit phagocytosis and complement activation,it is also cytotoxic for
neutrophil in the serum,and a mediator of bacterial attachment, also antigenic and produe type specific immunity.
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present in cell wall.
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Transformation alters the genetic composition of the host cell but typically causes no genomic
change in progeny virions.
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extended-spectrum beta-lactamses can be produced by gram-negative bacteria
(E.coli)>>>thes genes of these enzymes are located on plasmid and are therefore
cen be transfered betwee organisms and between different species through
conjugation.some have been incorporated into bacterial chomosomes.
carbapanems (eg imipenem) are treatment of chice for ECBL-producing
organism 11626
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not all C diphth produces the disease causig exotoxin.
C difpht acquire virulence via bacteriophage mediated infection. with the TOX gene, which code
for the diphtheria AB exotoxin. the bacteriophage responsible is called corneyphage beta.
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E coli acquire the ability to form pilli via bacterial conjugaiton.
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nbme,1,3,42
INSERTION OF A TRANSPOSON by SITE SPECIFIC RECOMBINATION (transposition is the
name of site -specific integration of transposons) ...brings an increase in the SIZE ...becuase SITE
SPECIFIC RECOMBINATION integrates rather than EXCHANGES pieces of DNA ,the end result
is a molecule THE SUM OF THE TWO ORIGINAL MOLECULES...in this case the
INDEPENDENT MUTANT + TTHE TRANSPOSON....
--IN Homolgous recombination there is only ONE TO ONE EXCHANGE OF DNA =No increase
from the original SIZE and it also mostly involves CHROMOSOMES than PLASMIDS...
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chromosomal mutation can theoratically lead to endotoxin production.but more commonly mtation
lead to bacterial antibiotic resistance.
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nbme>>>2,1,11>>>>transposon are >>>>genetic element found to contain genes and to catalyze
its own movememnt within and between chromosomes.
inverted 35 nucleotide repeates are present at the ends of this genetic element.
this genetic element in hepatocytes is incapable of replicating independenlty
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5,2,8
Transposons are sequences of DNA that can move or transpose themselves to new positions
within the genome of a single cell. The mechanism of transposition can be either "copy and paste"
or "cut and paste". Transposition can create phenotypically significant mutations and alter the
cell's genome size
Genetic recombination is a process by which a molecule of nucleic acid (usually DNA, but can also
be RNA) is broken and then joined to a different one. Recombination can occur between similar
molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-
homologous end joining.
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have 5 binding B subunit, causes receptor mediated endocytosis tof toxin 1098
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bacteriophage encoded and production enhanced by iron deficiency.
also called vero cytotoxin.which kill vero cells in cell cultre
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in stool miscroscopy we have many erythrocytes without leukocytes
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other one like this is yersinia enterocolitica.
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the B component has 5 subunit in vibrio and campylobacter jejuni.
A component has 1 subunit
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also have post tussive emesis..
chest X-ray is unrevealing.
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nbme,11,1,24
neutrophil chemotaxis and oxidative metabolism are deffective due to increased activity of the
>>>>>>adenylate cyclase..
Pertussis toxin - increases cAMP Tracheal toxin - blocks mucociliary movement Capsule
Hemagglutinin Pili.
Pertusis Toxin interferes with the early chemokine production and the inhibition of the neutrophil
chemotaxis. Chemokines are signaling molecules produced by infected cells and attract
neutrophils and macrophages.
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also causes neutrophil and macrophage dysfucntion
1101
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both bacillus and bordetella has calmodulin depednet adenkytae cyclase toxin
1101
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Lymphocytosis promotion.
Islet-activation causes hypoglycemia.
Blocks immune effector cells,phagocyte dysfunction.
Increased histamine sensitivity.
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3 phases. fastidious org produces virulence factor that include adhesins and toxins.. pertactin which from the basis
of acellular pertussis vaccine promotes pertussis adhesion to the UR epithelium. local tissue distruction due to
tracheal cytotoxin is responsible for the cough. adenylate cyclase toxin and pertussis toxin appear to prevent
phagocytosis and persistance of organism in alveolar macrophages and cilated epithelial cell, likely explain the
prolonged disease course.lymphocytosis is due to pertussis toxin
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stool microscopy with mucus and some epithelial cells like ETEC
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other 2 adenylate cyclase activator are campylobacter jejuni,
bacillus cereus
besides 4 these.
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inhibits protein synthesis in colonic mucosal cells and renal endothelial cells.
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transfer ribose residue from NAD to histidine on EF-2
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receptor mediatd endocytosis
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increase serotonin release from enterochromaphin cell 966 toxin also induces mucin
ejection by goblet cells.
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released in small amount by normally dividing becteria but in large amount during wide spread bacteriolysis.
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variable region of helper T lymphocyte receptor.
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its concentration correlated with its lethal and necrotic effects,
it hydrolyzes lecithin-containing lipoprotein complexes in cell membranes, causing cell lysis
(including erythrocyte hemolysis), tissue necrosis and edema.
C perfringens has at least 12 toxins of which phospholipase C is the most injurious.
C perfrigens uses carbohydrates for energy. Its rapid metabolism of muscle tissue carbohydrates
produces significant amount of gas, which can be demonstrated radiographically by plain film x-ray
or CT scan.
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Lechithinase (a toxin) is an enzyme with phospholipase C activity and the major virulence factor
produced by Clostridium perfringens. The toxins increases platelet aggregation and adherence
molecule expression on leukocytes and endothelial cells, resulting in vasoocclusion and ischemic
necrosis of affected tissue.
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on APC
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activation of T cell is responsible for the release of IL-2 from T-cells and IL-1 and TNF from
macrophages.
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autolysin produced by sterp pneumo is activated by bile, resulting in cell lysis, therefor addition of bile salt in test tube
containing strep pneumo convert turbidity to the clearing of turbidity (cell lysis)..
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prevents mucopeptide transfer into the growing cell wall,thereby inhibiting bacterial cell wall
synthesis.
bacitracin is not appropiate AB for stable bacterial population
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and micrococcus
11812
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but can also form pairs and rarely short chains.
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desquamation of palms and soles which occur 1-2 weeks after the onset of illness.
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form part of the outer peptidoglycan layer of S aureus....
hemolysin and superantigen are not part of the outer peptidoglycan layers but rather are secreted
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nbme>>1,4,11>>>after abdominal operaiton, if blood culture show staph aureus>>>>likely site of
infection is wound, not anterior nares
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also produce hemolysin which causes beta-hemlysis
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superantigen that acts locally in GI track causing vomiting.????????
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one of the most common causes of infection associated with foreign bodies....
foreign bodies quickly become coated with a layer of host proteins, including fibronectin and
fibrinogen. these proteins than serve as binding sites for S epidermidis.
after attachement occurs, the bacteria multiply and communitae with one another to induce
synthesisi of an extracellular polysachharide matrix that encases the bacteria.
the resulting biofilm functions as a barrier to antibiotic penetration and interfers with host defenses,
including opsonization, neutrophil migration and even T lymphocyte activation.
once matue these biofilms can disperse individual pathogen "seeds" (planktonic cells) into the
blood stream and surrounding areas, further disseminating the infection.
definitive treatment of infection caused by biofilm producing organism often requires removal of
the foreign body.
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coagulase lead to fibrin-coating of the organism and resistance to phagocytosis.
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+ ciprofloxacin resistance appears to accompany methicillin resistance in staphylococci due to the
simultaneous presence of multiple antibiotics resistance genes.
..............
+ methicilin resistance S epidermidis will likley have cephalosporin resistance, as the mechanism
of methicilin resistance (mecA chromosomal gene) involves alteration s in the PBP2a, which is
used for both.
645
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listeria also has very narrow zone beta-hemolysis 1391
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These organisms produce a polysaccharide slime facilitating prosthetic device adherence. most
(>80%) CoNS strains are methicilin-resistant. Therefore, particularly with nosocomial infection
(as is likely in this patient), CoNS should be assumed to be methicillin-resistant until proven
otherwise. Vancomycin should be a component of initial therapy. additionally antimicrobial
agents (e.g, gentamicin and/or rifampin, which kills bacteria on foreign material) are
administered in some cases of deep-seated methicillin-resistance CoNS infection or
staphylococcal PVE. If susceptibility results later demonstrate a methicillin-susceptible isolate,
vancomycin can be switched to a semi-synthetic lactamas-resistant penicillin such as
nafcillin or oxacillin 645
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org resistant to multiple AB(eg methicilin,cipro,clindamycin) so initial aggressive AB is must
(pending AB sensitivity analysis);
VAN and rifampin/gentamicin are used
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but recovery of org from multiple culture is diagnosticx
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nikolskeys sign positive, epidermal necrolysis, fever and pain associated with skin rash.
more common in infants and young children, frequently nonfetal unless secondarily effected.
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pathologic specificity in blistering only the superficial epidermis (epidermolytic).
they act as protease and cleave desmoglein in desmosomes.
bullous impetigo is the more localized form of SSSS with tha bulla formation being another effect
of exfoliative toxin
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complement binding site.preventing the conformational change in Fc region that exposes the C1
binding domain and keeping it away from the bacterial surface.
ultimately decreases C3b levels>>>alternative complement pathway
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most strain of Ecoli also demostrates B-hemolysis
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also for bacterial conjunctivitis
1103
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Hyaluronidase produced by staphylococcus, group A sterp and clostridium difficile most notably
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Under the microscope, the capsule swells and appears as a halo around the blue-stained bacterial
cells when specific anti-capsular antibodies and methylene blue bye are added ( “quellung
reaction” ).
Other virulence factor of S pneumoniae include IgA protease (inactivates secretory IaG), adhesins
(necessary for adhesion to epithelial cells), and pneumolysin (cytotoxi that causes pores in cell
membrane and cell lysis).
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using sucrose as substrate produce insoluble extracellular polysaccharides (dextran).
due to dextran also adhere to tooth enamel.
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superficial skin lesion characterized by painful erythematous plaque with raised well demarcated
border.
erysipelothrix rhusiopathiae>>>gram postive rod>>rare cause of erysipela
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pharynx is swollen,erythematous and covered with gray-white exudate.. scarlet fever can occur
with pharyngitis can lead to acute rheumatic fever if untreated.
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PS glomerulonephritis:
dec C3 but not to dec C4.
elevated anti DNAse and anti HAase only in prior skin infection
elevated ASO, anti DNase, anti HA ase and anti NAD only in prior pharyngitis
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although early antibiotics are effective in preventing ARF, they have not been shown to reduce the
risk of PSGN.
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classically occur as superinfection of preexisting skin condition.
golden crust color...............
have two type bullous or non bullous.
non-bullous most commonly caused by staph aureus
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also causes deep wound infection, abdominal abscesses and septicemia
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four histological stages of inflammation:
1, exudation
2, red hepatization (histologic liver appearance)
3, gray hepatization
4, resolution.
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staph aureus is not a usuall cause of UTI>>>but if it is found in culture>>>its a metastatic infection either from
abscess or endocarditis
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and N-acetyl-beta-D-glucosamine also against lysoganglioside 724
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most commonly cause this
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cystoscopy is most common.
colonoscopy and pbstetric procedure can also cause.
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enterococci have both intrinsic (beta-lactams, macrolides, aminoglycosides, TMP-SMX) and
acquired (vancomycin) resistance to antibiotics, making them important nosocomial pathogens.
11812
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cutaneous anthrax most common,
5% have pulmonary and GI anthrax is very rare.....
no person to person transmission,not a nosocomial.
but person have occupational history(animal contact)..
bacilluas spread via lympjatics to the bloodstream, and the organism multiplies in the blood and
tissue.
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treatment is with ciprofloxacin
1678
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PYR positive
unable to converte nitrates to nitrite
11812
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anthraxtoxin is a trimeric toxin, composed of protective antigen, edema and lethal factor.
protective antigeen functions to translocate both edema and lethal factor to cytosisol
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biological weapon.100% mortality
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spores inoculated into the subcutaneous tissue germinate into vegetative cells and release toxins(lethal factor and
edema factor)
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also linezolid resistant enterococci has emerged.
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chistie, atkins, and munch-peterson
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infant type preceded by constipation and can be mild or severe.
Adult type is almost always very severe.
culture,isolation of org and bioassay are time consuming.
rapid in vitro test for detection of types of org and their toxin (A,B,E and F) are used based on
ELISA and PCR
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combination of nicotinic blockage (eg diplopia and dysphagia) and muscarinic blockage (eg dry
mouth) is strongly suggestive of food poisoning with clostridium bolulinum toxin.
loss of muscle contraction can be partially overcome by high rate repetitive nerve stimulation,
which explains the compound muscle action potential
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which germinate in intestine, produce intracellular toxin>>bacteriolysis>>toxin release>>mild systemic absorption of
toxin
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soluble NSF attachment receptor
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tetanus vaccine to infant is not given at birth cause of immature immune system.
first dose is given at 2 months.
in endemic areas can be given as early as 4-6 weeks but nor earlier
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clinical presentation>>>fever, abdominal pain, watery diarrhea(due to enterotixin A, typiclaly
during or within 5-10 days of antibiotic use)and leukocytosis.
ranges from mild watery diarrhea to fulminant colitis (toxic megacolon)
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broad spectrum ceph, pen, fluoroquinolones
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inactivate rho regulatroty protein, involved in signal transduction (disrupt intracellular siganlling) and actin
cytoskeletal structure maintenance.as a result toxin cause disruption of intercellular tight junctions leading to cell
rounding/retraction as well as increased (paracellular) intestinal fluid secretion.
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Uworld says heat stable exotoxin
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perfringes used carbohydrate for energy, rapid metabolism of muscle tissue carbohydrtae
produces gas
1395
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metro is used for primary infection which are mild to moderate.
vanco is used for primary and recurrent infection which are severe.vanco has minimal systemic
absorption.
although it is typically bacteriocidal but it is bacteriostatic in the concentration it is used for C.dif
fidaxomicin is used for recurrent infection, it has minimal systemic absorption, bacteriocidal and
macrocyclic (related to macrolide)
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large intestine
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clinical manifestation may begin during AB therapy or upto 4 weeks later.
both toxin seem to be act synergistically in the pathogenesis of C-dif colitis.
toxin bind specific receptor and are internalized,allowing them to exert their effect.
both toxin inactivate rho regulatory protein also both have inflammatory effecs (including neutrophil
recruitment) and can induce apoptosis.
although these toxin have overlapping activity , toxin A appears to be more enterotoxic and toxin B
more cytotoxic
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nbme>>>2,1,23>>>evades destruction by neutrophil>>>by damaging neutriphil membrane by
means of membrane damaging toxin.
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potent metalloprtotease that is deadly in nanogram quantities.
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tetanus toxin inhibit inhibitory neuron that normally regulate the motor neuron
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generally readily destroyed by heat.
if food containing the toxin is not cooked properly, the classic diplopia, dysphagia and dysphonia
can develop within 12-36 hours of consumption.
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characteristically present with descending paralysis that first manifests with cranial nerve
abnormalitites (diplopia, dysphagia dysphonia)
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C perfringes can also cause late-onset food poisoning that is characterized by transient watery
diarrhea. This gastroenteritis is caused by a toxin formed when large quantities of clostridila
spores are ingested. The spored germinate in the digestive trast and then begin to elaborate toxin,
which explains the disease’s delayed onset. This is in contrasts to early-onset food poisoning
caused by the preformed toxins of Staphylococcus aureus and Bacillus cereus.
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exotoxin which is released by bacteriolysis,(infants) generally this is the feature of endotoxin
1400
the toxinis not secreted actively, they secrte through autolysisi
1399
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ring enhancing lesion in CNS in nocardia
granulomatous inflammation in actinomyces
11638
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suflur granules are yeloow aggregates of organisms bound together by proteins
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parenteral,
and also surgical debridement.
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immunocompromised patient has fever, a headache with a ring-enchancing lesion ‘(likely abscess
on brain MRI, respiratory symptoms with pulmonary nodules, and sputum studies revealing
branching gram-positive organisms.
catalase-positive, healthy gingiva
form partially acid-fast, beading branching filaments (resembling fungal hyphae but not as wide
Nocardiosis typically affect the lung, brain or skin and is mostly seen is immunocompromised
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pregnant and neonates are susceptible to infection cause of suppressed cell mediated immune response.
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characteristic tumbling motility at room temperature 22'c not at body temperature 37'c.
it grows easily in anaerobic and microaerophilic
11650
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fibrinous exudate>>>>systemic circulation>>>cortical neurons and cardiac tissue.
The toxin acts locally to cause pharyngitis and laryngotracheitis with extensive, coalescing
exudates (ie, forming a pseudomembrane). This pseudomembranous exudate is compose of C
diphtheriae bacteria, leukocytes, fibrin, and necrotic mucosal epithelial cells.
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culture take too many days and disease need to be treated acutely(otherwise fatal) developed
immunochromatoghraphic strip assay which detect more rapidly
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tto administration (in order of importance)
1, diphtheria antitoxin(prognosis depend on this)
2, penicillin or erythro(prognosis not depend on this but is essential to kill bacteria)
3, DPT vaccine
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nonmotile, unencapsulated,Catalase+, aerobic or facultative anaerobe.
chinese latter shape.
transmitted by respiratory droplet
diphtheroids once thought to be clinically insignificant but now recognized as pathogens that
cause septicemia,UTI,erythrasma and endocarditis in immunocompromised patient
B-subunit of toxin bind specifically to heparin-binding epidermal growth factor receptor found on
cardiac and neural cell.
cardiomyopathy is the most common cause of death
1093
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and in healthy gingiva
11638
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grossly appear yellow, but H&E stain make it purple/blue
10993
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causes granulomatous inflammation
11638
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IgA directed against C diphtheriae adhesion proteins can develop as part of the natural immune
response.
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Vaccine-induced immunity wanes over time unless periodic booster is given or exposure to
toxigenic Corynebacterium diphtheriae occurs
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the DPT vaccine contains diphtheria toxoid,which stmulates production of neutralizing antibodies
against the binding component (B subunit) of the diphtheria exotoxin.
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on Löffler medium.
visualizable after staining with aniline dye like methylene blue
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dilated type.
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Tox gene.
through a process of lysogenization by a temperate phage
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causes significant disease in patients with cell-medicated immunodeficicny, including neonates
upto 3 month of age.HIV, organ transpkant and certain malignanecies.
clinical syndrome include:
febrile gastoenteritis, septicemia and meningoencephallitis.
examination of CSF will show purulent meningitis with intracellular gram-positive bacilli
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listeria produce listeriolysin O, which is able to lyse vacuolar membrane,
listeriolysin O is a pore-forming toxin that is activates only within acidified phagosome
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pulmonary nocardiosis can present as cavitary pneumonia (often misdiagnosed as tuberculosis).
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systemic infection anywhere in the body when mucosa is disrupted.
alcoholic patients are at increased risk,
also form abdominal abscesses but not as fast as bacteroides
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cord factor is a mycoside. means two mycolic acid combine with disaccharide trehalose.
responsible for inactivating neutrophils , damaging mitochindria and release of TNF-alpha
1216
without this mycobacteria cant be able to cause disease
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mycobacterium sacrofulaceum is commonly found in and around environmental water sources...it is the etiologic
agent of scrofula, a disease characterized by lymphadenitis (usually cervical lymphadenitis) that occurs with
greatest frequency in children.
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classic location of extrapulmonary tuberculosis include the basal meninges (tuberculous meningitis), the lumbar
spine (pott disease), the psoas muscle (psoas abscess) and serous membrane such as pericardium and pleura.
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caseous and liquefactive necrosis and extensive cavitary disease>>>>this cavity can be secondary infected with
aspergillus flavus.
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nbme>>>3,2,31
31.C
Disseminated disease can occur within weeks of the primary infection, or may lie inactive for years
before causing illness. Infants, the elderly, those infected with HIV. and those who take immune-
suppressing medications are at higher risk for disseminated TB, because of their weaker immune
systems.
Symptoms
The primary infection usually has no symptoms.
Symptoms of disseminated tuberculosis include:

•Cough
•Fatigue
•Fever
•General discomfort, uneasiness, or ill feeling (malaise)
•Shortness of breath
•Sweating
•Weight loss
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hemoptysis is due to pulmonary vessel erosions.
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both test does not distinguish acute versus latent infection
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also have wax D virulence factor
1309
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trehalose dimycolate is a cell wall componenet>>>>major virulence factor
962
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live attenuated>>>obtain from strain of mycobacterium bovis
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does not cross-react with bacille calmette-Guerin.
advantage of not being follow up for the test result
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Most droplets of infectious size carry approximately five organisms. Pulmonary tuberculosis
infection is first established after the gravity-assisted entry of small, organism-laden droplets into
the lower lung fields.
The mycobacteria are then phagocytosed by alveolar macrophages, and the sulfatide virulence
factor expressed by M. tuberculosis allows for intracellular bacterial proliferation. Continued
proliferation eventually kills the macrophage and causes cellular lysis allowing, M. tuberculosis to
be phagocytized by and infect additional macrophages. Virulence factor expressed by the
mycobacterium promote the recruitment of additional native, inactivated macrophages and also
undermine the immunologic intracellular signaling between antigens presenting cells and helper T-
cells. Eventually, antigens carrying macrophages or dendritic cells migrates to the lymph nodes
and induce a helper T-cell response. However, this occur approximately 2-4 weeks following the
initial infection.
When Th1 activated macrophages consume a relatively indigestible agent (such as M.
tuberculosis) they lose their motility, accumulate at the site of injury and transform into epithelioid
cells. Eventually, multi nucleated Langhans giant cells are formed by the fusion of multiple
epithelioid cells.
small foci of bacteria are destroyed by thus process, while the larger necrotic areas are simply
“walled off” and calcified. These “walled off” areas (Ghon foci) are a potential source of
reactivation should the patient later become immunosuppressed
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most droplet of infectious size carry aproximately 5 organisms.
inhaling the organism in the aerosilized respiratory secretions
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due to decreased lymphatic flow or increased oxygen tension.
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the lesion which heals form a benign, calcified ranke complex that is not associated with reactivation, unlike ghon
complex.. if the necrotic area is small enough activated macrophages has an opportunity to kill the remaining
mycobacteria and eliminates infection.
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allow mycobacteria to persist as facultative intracellular organism. allows intracellular bacterial proliferation
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kansasii may yield pulmonary tuberculosis like symptoms.
mycobacterium kansasii (acid-fast rod) similar to legionella is also water borne>>>however it is
particular contaminate of municipal drinking water system and is not frequently found in nature.
960
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transmission is promoted in unhygienic conditions and likely occurs throgh respiraotry route, with
some orgaism bieng transmitted through prolonged direct skin-to-skin contact.
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in southwestern US
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thisulfate-citrate-bile salts-sucrose agar
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means cytochrome oxidase present or not.
11812
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enterobacter cloacae>>>gram negative>>characterized by extensive drug resistance>>.causes nosocomial
infections, including UTi, pneumonia and surgical wound infection
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indole positivity (ability to convert tryptophan to indole) of E coli distinguishes it
from enterobacter cloacae, another lactose fermenting gram-negativerod that is a
common cause of UTI in women
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micraerophilic, thermophilic require different growth medium than V.cholerae
unable to survive alkaline media unlike vibrio
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eg schwann cell.
also effect eyes and testes
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also have testicular destruction and blindness.
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often self limited.
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penetrate mucosa one type in genital region and other type in nasopharynx region.
IgA bind to pilli/fimbria and outer membrane protein that mediate adhesion and penetration to
prevent these two.
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asymmetric polyarthritis (knee, elbow, wrists)...
but meningococcal arthritis is very rare and is monoartricular.
has leukocyte count greater than 100,000/mm3
gout has leukocyte count in between 200-100,00/mm3
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gonococci are resistant to penicillin and fluoroquinolones.
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the lipooligosaccharide in gono is similar in structure to human cell membrane
glycosphingolipids>>>>>antigenic mimicry
meningococcal LOS differ from enteric LPS in that it lacks the repeating O-antigen of LPS.
meningococcal growth and lysis lead to the release of outer membrane vesicles with membrane-
atached LOS.
disease severity correlate with the increasing concentrations of OMV-bound LOS in the
bloodstream.
high levels are associated with increrased rates of septic shock and death.
LOS causes sepsis by release of IL-1beta, IL-6 and IL-8 (mostly due to LOS interaction with Toll-
like receptor 4)
LOS has been implicated in the petechia and bilateral adrenal hemorrhage
1006
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N.meningitis bacteremia/sepsis frequently occur without meningeal involvement
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increases risk of dissemination if young adults produce too much IgA.
cause this block attachment of IgM and IgG that induce complement madiated cell lysis.
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is the one of the most common serogroups responsible for infection.
uworld says>>vaccine against subtype B (causes 1/3 of meningogoccus casses in US) have
recently been introduced
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post exposure prophylaxis with vaccine is not recommended for the following reasons.
1, group b meningo with is most common serogroup is considered to be poorly immunogenic
2, children younger than 2 years of age respond poorly to capsular polysaccharide alone with out
protein conjugation.
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250mg for adults IM single dose
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six serotypes(a-f)
serotyping is based on antigen in the polysaccharide capsule.>>>>>they are called typed.
H.influenza that do not produce a capsule are referred to as nontypable.
nontypable are part of the upper respiratory tracts normal flora, but they can also cause otitis
media, sinusitis and bronchitis.
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''satellite phenomenon''
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only serotype that contain pentose monosacharide rather than hexose sugars,
capsular type has 6 serotypes (a-f) and type b is one of them
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such as outer membrane protein complex of N-meningitis as a carrier protein.
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1st month maternal IgG protection.
2 4 6 months of age with a booster at 15 or 18 months of age
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vaccine causes immune activation with antibody production and memory B-lymphocyte induction
against PRP provide lasting immunity.
antibodies to PRP facilitate complement-dependent phagocytosis and killing through opsonization
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disseminated gonorrheal infection>>>(traid of polyartharligi, skin lesion, and tenosynovitis in a
sexually active woman) or purulent artheritis without skin involvememnt
1007
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hypervaribale pilli is a characteristic of both meningitis and gonorrhea
1401
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due to inadequate CSF humoral immunity (eg complement and immunoglobulin)
11862
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nbme>>>>>5,4,33
Neisseria gonorrhoeae complication if not treated :In men, inflammation of the epididymis
(epididymitis); prostate gland (prostatitis) and urethral structure (urethritis) can result from
untreated gonorrhea./>>>not orchitis, cystitils,pyelonephritisIn women, the most common result of
untreated gonorrhea is pelvic inflammatory disease. Other complications include: perihepatitis,a
rare complication associated with Fitz-Hugh-Curtis syndrome
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immunity to nontypable strains, as well as capsular strains other than type b, is not conferred by vaccination with H
influenza type b vaccine.
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or tetanus toxoid.
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induction of active B-lymphocyte mediated humoral immunity and reduce oropharyngeal carriage of H.influenza type
B.
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more than 90% of H influnenza strains isolated from middle ear aspirates of children are nontypable, the remaining
10% are H influenza type b (Hib)
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5mg for less than 30 days born
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prophylaxis is prescribed to all close contacts of any patients who have active disease within two weeks of
diagnosis in order to be effective.
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petechial skin rash and on palms and soles is due to neisseria induced small vessel vasculitis
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two types of vaccine
1, polysaccharide quadrivalent (ie against subtypes A, C, Y and W-135) vaccine is made from the
outer polysaccharide capsule.
2, conjugate vaccine are made from capsular outer polysaccharide antigens individually
conjugated to diphtheria toxoid protein.
....children younger than 2 years of age respond poorly to polysaccharide vaccine without protein
conjugation.
...in US vaccine is given to all adolscent age 11-18,
specific indication are also present
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pilli mediated adheence ro mucosal epithelium.they subsequent invade the epithelium and gain
access to the vasculature where they can spread hematogenously.
pilli may also play a role in the ability of meningococci to cross the blood-brain-baarrier and
interact with meningeal tissues......
meningococcal survivial in the circulaiton is dependent on the antiphagocytic properties of the
polysachharide capsule.
most existing meningococal vaccines target the capsule, facilitating bacterial opsinization,
phagocytosis and lcearence of the organism from the blood.
1005
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virulence factor for neisseria meningitidis are
1, polysaccharide capsue(inhibit phagocytosis)
2, lipooligosaccharide(induces cytokine production,leading to ciculatory collapse)
3, pilli( bacterial attachment to respiratory mucosa)
4, IgA protease.(cleaves secrwtory IgA that would otherwise inactivate the pilli)
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polysaccharide capsule of group A and C elicit an immune response but group B not and thus is
not covered by vaccine...............
polysacchride capsule helps it to evade phagocytosis and also survive within phagocytes in the
event that the organism is phagocytized.
expression of capsule can also be downregulated to facilitate cellular invasion.
........................
capsular polysaccharide level do not correlate with morbidity or mortality associated with disease
but it does assist in resiting phagocytosis.
individual who become colonized produce protective antibodies directed against the capsular
polysaccharide.
LOS plasma level correlate with diseasemanifestation and outcomes
1006
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ophthalmia neonatorum( can cause blindness)
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repeated infection is either due to:
IgA or IgG antibody production are of low titer. also they are either highly strain specific or are
poorly protective
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lactase
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elevated transaminases is also common.
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sputum gram stain shows many neutrophils but few or no organism cause it is facultatively
intracellular.
also unique lipopolysaccharide on outer membrane inhibit gram staining.
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may be due to inappropriate ADH secretion and/or tubulointerstitial disease impairing sodium reabsorption
(possible due to either direct effect of legionella, cytokine, or natriuretic peptides)
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recent travel (especially cruise/hotel visit)
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self-limited
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aeromonas hydrophilia is an oxidase postive, non lactose fermenting, gram negative rod. it causes gastroenteritis,
wound infection and bacteremia. following exposure to contaminated water.
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extracellular products production>>>elastase,fibrinolysin,collagenase, phopholypase C,and DNAse. but Exotoxin
A is a major virulence factor.
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in neutropenic and burn patient
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and in diabetics(malignant type)
granulation tissue seen with in the ear canal is an important characteristic finding of
MOE.tympanic membrane is usually intact.
can lead to osteomyelitis of skull base and cranial nerve damage
tto: cipro
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also in febrile neutropenic patient seen in chemotherapy patient and septic patient..absolute neutrophil count
less than 500
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diagnose in adults with acute tracheobronchitis who has not had vaccination boosters.
generally a disease of children
11680
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pertussis has normal X-ray, besides person have acute tracheobronchitis.
different from croup which have bilateral xray findings
11630
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which is polymyxin E
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in cystic fibrosis and ventilated patient
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pseudo is an encapsulated, gram negative that can appear mucoid in culture
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cysteine culture>>>legionella>>>facultative intracellular org which inhibits phagosome lysosome
fusion inside macrophages and survives
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typically patchy infiltrate that may progresses to consolidation.
Lobar consolidation is classic for "streptococcus pneumonia"
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mycobacterium kansasii (acid-fast rod) similar to legionella is also water borne>>>however it is
particular contaminate of municipal drinking water system and is not frequently found in nature.
960
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intracellular motile rod
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have bradycardia relative to high fever.
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pertactin (mediates adhesion to ciliated upper respiratory track) form the basis of acellular
pertussis vaccine
11630
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perivascular bacterial invasion of arteries and veins in the dermis and subcutaneous tissue with
subsequent destructive exotoxin release,all this causes decrease blood flow to the affected
portion. exotoxin> exotoxin A, elastase, phospholipase C, and pyocanin. 973
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enteroaggregative E coli (EAEC)>>adhere to human jejunal, ileal, and colonic mucosa in an
aggregative or stacked-brick pattern and do not invade.
this strain causes persistent diarrhea in infants in developoing contriws.
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type 1 fimbriae, P fimbriae and S fimbriae.
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fimbriae(pilli) are responsible for bacterial attachment to small intestinal mucosa.
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also does not produce glucuronidase which also distinguish it form other.
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upper lobe(one sided)>>>>cause it is aerobic
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cause it is a normal oropharyngeal flora
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klebsiella can be grown on standard agar but often macconkey agar is preferred because it contains bile which will
inhibit the growth of contaminant organism.
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granuloma inguinale (donovanosis) caused by klebsiella granulomatis.
previously called calymmatobacterium inguinale.
lymphadenopathy is less common with ganuloma inguinale.
if left untreated scarring and stricture can ultimately lead to severe lymphatic obstruction and
lymphedema (elephantiasis)
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treat with fluoroquinolones,
but due to world wide resistance can be replaced with erythromycin
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campylobacter fetus (or intestinales) is an opportunistic pathogen that infects immunocompromised persons.
infection can cause speticemia in newborns, women in the third trimester of pregnancy and debilitated elderly
patients.
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Gram stain showed rods with halos surrounding them:
gram(-),encapsulated,urease (+), lactose fermenting
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klebsiella can cause monomicrobial lung abscess in alcoholics but most of the time lung abscess
in alcoholics are due to anaerobes and aerobes (ie polymicrobial).
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thick capsule is seen as a clear zone on gram stain
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more commonly in children under 10 years of age and in association with treatment of EHEC
gastroenteritis with antibiotics
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in most cases are selflimiting,
loperamide(opiate antimotility drug) may be prescribed in some cases where there is no fever or
blood in the stool.
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other invasive are campylo.shigella.salmonella,entamoeba
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invade the blood stream of infants from nasopharynx or GI track>>.travel hematogenously to meninges. capsule
prevent antigen recognition, complement fixation and subsequent phagocytosis. capsule is immunogenic and anti
capsule antibodies are protective against repeat infection.
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characteristic "corkscrew" motility
1422
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in general vibrio, clostridium perfringes, E coli has large ID 50 (10*4-10*8)
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shigella exhibit specificity for the M (mcrofold) cells that lie in the base of mucosal villi within a
payers patch region of the ileal mucosa.
M cells are specifically designed to sample the contects of the gut lumen and trnaser antigens to
their basal lamina within endosomes. at the base of the cell, within a special pocket (microflod),
await macrophages and lymphocytes, ready to mount an imune reponse.
shigella first penetrates the mucous membrane of the gut by passing through M cells.
following hsr epithelial cell invasion and penetration of the mucosa. shigella infection is
charaterized by degenration of the epithelium due to inflammation of the lamina propia and
bacterial spread laterally from M cells to other mucosal cells.
this resutls in denudation and ulceration of the mucosa.....
..........................................
mucosal invasion is the pathogenic mechanism for the shigella infection.shigella invades the GI
mucosa, particularly via the M cells the overlie payers patches, after cell entery, shigella is able to
lyse its containment vacoules and enter the cytosolic compartment . it then can induce apoptosis
of the host cell adn spread to adjacent cells via protrusions created through the host cell actin
polymerization..
shigella also escape the phagosome and spread laterally to other epithelial cells via actin
polymerization.
shigella invasion triggers a robust inflammatory response that is largely mediated by neutrophil.
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shigella never be a normal gut flora
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shigella infection rarely causes bacteremia,as the bacterium is readily phagocytosed and
destroyed after entering the bloodstream.
enteric bacteremia is more likely to be caused by E.coli, S typhi, klebsiella and proteus
1135
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most common in developing nations
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escalating type
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salmonella is able to penetrate the gut mucosa via phagocytosis by M cells and bacteria mediated
endocytosis by enterocytes, the bacteria are then able to survive and proliferate within
macrophages found in the submucosal regions (peyers patches), causing severe inflammaiton
and ensuing bactermeia.
patients classically develop fever with with relative bradycardia followed by watery diarrhea OR
constipation, abdominal pain, and salmon colored rose spots on the chest/abdomen.
widespread dissemination across the reticuloendothelial system (eg liver, spleen, bone marrow)
can also cause hepatosplenomegalya , where as ulceraitons of peyers patches can result in GI
bleeding. in severe cases transmural necrosis can also causes intesttinal perforation., with
subsequent polymicrobial peritonitis and death.......
.....................
multiplies in mesenteric lymph node and engulfed by macrophages.
...............
recolonization of gut occur which causes payers patches inflammation,hemmorhagic diarrhea,and
perforation(causes polymicrobial peritonitis and sepsis,which are causes of death)
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such as TCBS (thiosulfate-citrate-bile salt-sucrose media)
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patients with chronic liver disease are at increased risk for severe disease with vibrio vulnificus,
which can cause gastroenteritis.
however V vulnificus typically occurs in the setting of wound infeciton (although some cases are
due to oyster consumption) and rarely causes outbreaks.
there is no evidence of person to person transmission.
.......................
consumption of raw oysters is associated with vibrio parahaemolyticus ( voluminous watery
diarrhea, like cholera) vibrio vulnificus ( sepsis with upto 50% mortality) as well as other vibrio
infection.
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week1>>>>risiing fever, bacteremia,relative bradycardia
week2> rose spots and abdominal pain
week 3>>>hepatospleenomegaly and intestinal perforation
1138
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vibrio has fimbriae(pilli)
1140
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mostly in childrens of 5-14 years
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vaccine exist but are not used in US cause disease is not endemic here.
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highly sensitive to acid.
achlorhydria or proton pump inhibitor predispose to infection.
with water 10"10 org,with food 10"6 org due to buffer effect required to cause infection
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salmonella enteritidis causes invasive diarrhea most frequently with out hemorrhage
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common in those with cholelithiasis or other biliary tract abnormalities that allow S typhi to persist in the bile.
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most common in US
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shigella species produces acid (not gas) during glucose fermentation (in contrast to E coli)
1135
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proliferation in lymph node is not a charcteristic of shigella.
in contrast both salmonella and yersinia enterocolitica(grows at low temperature like listeria) can
gain access to the lyymphatics and priliferate in the mesenteric lymph node.
yersinia enterocolitica can cause inflammation and enlargement of lymphoiud tissue around the
appendix and terminal ilium (pseudoappendicitis)
1135
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fecal oral route by dirty hands,fomites in day care center,and food contaminated by unhygienic
handlers..
..................
shigellosis is primarily a pediatric disease but also show predilection for men who have sex with
men and adults in skilled nursing facilities.
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ID 50 for dysenteri is 10, flexneri is 100 and sonnei is 500.
shigella is highly adapted to acidity and bacteriostatic effect of bile.
incubation is 24-72 hours
other which has small ID 50 are campylobacter jejuni 500, entamoeba histlytica (as few as 1-10)
and giardia (as few as 1-10)
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biopsy of gastric mucosa is definitive confirmatory test.
culture is not done to time consuming.
urease test in which urea containing solution turn pink with in 30 min but have to monitor for 24
hours before definitive diagnosis
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nbme,11,3,5
Biphasic disease.
• Leptospiremic phase—severe headache, fever, myalgia.
• Immune phase—high fever, meningismus, central and peripheral nervous system manifestations.
• Ocular manifestations occur in the majority of patients.
• Conjunctivitis, uveitis, subconjunctival hemorrhages.
ASSOCIATED FEATURE
• Weil’s disease—severe disease with hemorrhages, renal failure, and jaundice.
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occurs at the site of borrelia inoculaiton.
the lesion usually begins as an erythematous macule 7-14 days following the tick bite and
enlarges with an advancing erythematous border as the bacteria migrate slowly through the skin
outward form the inoculation site.
the classic lesion is erythematous and ring shaped(annular) due to development of a central
clearing and is typically describes as a bulls-eye rash.
however central clearing is not always total, particularly during the first few days when the lesion
may appear unifromly erythematous.
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decreased memory, somnolence, and mood changes.
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lyme vaccine (withdrawn due to low demand) contains recombinant bacterial outer surface protein.
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infected ixodes tick are commonly encountered in forested regions, including backyards and
outdoor recreational areas.
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in case of neurological and cariac invilement we give IV ceftriazone
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asymmetric chronic of single large joint eg knee
1897
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In this test the patient’s serum is mixed with a solution of cardiolipin, cholesterol and lecithin.
Aggregation, or “flocculation,” of the sample demonstrates the presence of cardiolipin antibodies in
the patient’s serum.this test is considered a nontreponemal serologic test because it does not
detect treponemal orgnanisms or antibpodies directed against treponemal organisms. instead, is
detects antibodies to human cellular lipids released into the bloodstream after cell destruction by
T. pallidum. These serologic testes will be positive in cases of syphilis, yaws, pinta or bejel as all
of these illnesses are caused by subspecies of T. pallidum
1316
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maculopapular or pustular type unlike vesicular type in reactive arthritis (keratoderma
blennorrhagicum).
in 2ndy syphilis there is generally polyarthitis unlike reactive arthiritis where there is mono or oligo
type
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manifests as a progressive dementia,and generalized paralysis.
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nbme,11,4,4
treatment in with intramuscular penicilin G.
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Latent syphilis: is an asymptomatic period divided into early latent (infection within past year) and late
latent (infections >1 year ago)..
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VDRL-\RPR>>>used for disease prrogression and therapeutic respose
FTA-abs>>>are not affectedby antitreponemal therapy and remain positive for life
1315
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Gummas are characteristic and often begin as painless, indurated granulomatos lesions that
progress to white-gray rubbery lesions that may ulcerate. They are most commonly cutaneous but
also appear in the subcutaneous tissue, bones, liver, and other organs.
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neurosyphlis which may be asymptomatic or cause subacute meningoencephalitis, tabes dorsalis, or other sequela,
is a common manifestation of late syphilis but can occur at any stage.
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cardio said>>
3ry -> specific treponemal serologic test (FTA-ABS/or microhemagglutination test need it)
remember VDRL => revert to NEG in phase here.
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plaque shows
a dense chronic inflammatory infiltrate rich in plasma cells and swelling of endothelial cells
obliterating lumina of small vessels)
"ENDarteritis Obliterans>>>>>>resulting in inflammation, ischemia and weakening of
adventicia.>>>>>aeurysmal dilation>>>>that can extend to dilate the aortic valve ring>>>causes
mediastinal widening and aortic regurgitation murmur
.................
cardiovascular syphilis (asymptomatic murmur with loud second heart sound [S2], ascending
aortic arch calcification
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carried out through indirect immunofluorescence of patient serum mixed with whole killed T.
pallidum.
A positive FTA-ABS confirms infection with T-pallidum
1316
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besides these two also causes culture negative endocarditis.
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these vascular proliferation can also be found in visceras.
life threatening if left untreated
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fever, malaise, lymphadenopathy and hepatosplenomegaly characterize the srultant brucellosis,
which is extremeley rare in US
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or direct contact with infected sheep and goats.
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a mild form of pneumonia.
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cutaneous sinus track, lymphadenopathy,septic joint,
its an acute infection not chronic.
typically develop with in 24 hours.
management include wound care and antibiotics ( amoxicilin-clavulanate)
11547
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other org associated with dog bite>>>streptococcus, staphylococcus, capnocytophaga canimorsus.
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nbme, 6,3,14
recurrens of infection is due variable surface antigens.
this recurrence is not due to babessia.
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cause of release of amine
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Brown recluse spider bites can cause fever and malaise and less commonly anemia.
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has a characteristic mouse like odor (indole-postive species)
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severe febrile pulmonary infection, ulcerative disease at inoculation site.
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Diagnosis
• Culture is hazardous.
• Serum agglutination test, fourfold increase in titer
- Antibodies against Brucella > 1 : 1 60 considered positive
Treatment
• Adults: rifampin and doxycycline minimum of 6 weeks
• Children: rifampin and cotrimoxazole
Prevention
• Vaccinate cattle.
• Pasteurize milk, especially goat milk.
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•Brucellosis (undulant fever)
.>>>>>>Acute septicemias
Fever 1 00-104°F (often in evening)
- Influenza-like symptoms, including arthralgias, anorexia, myalgia, back
pain
- Sweating (profuse)
Hepatomegaly
•>>>>Undulant form
- Milder, often a result of incomplete treatment
•>>>>> Chronic form (disease for more than one year)
Usually B. melitensis
- Usually in older people (veterinarians)
Cyclic bouts of depression and sweating
Fever rare
Ocular complications (uveitis) in 5-10%
- Chronic fatigue
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potential biowarfare.
pathogenesis:
1 Endotoxin
2 Facultative intracellular parasite (localizes in cells of the RES, can cause septicemia
3 Granulomatous response with central necrosis
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stellate shape non-caseating ganuloma.
characterized by low grade fever, lymphadenopathy and self limiting course.
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risk factor for tick borne illness include frequent contact with dogs and exposure to wooded areas or grassy
fields.
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characterized by blanching erythemtous rash or petechial eruption
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intersticial type
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acute form>>>fever >10 days, debilatating headache, retroorbital pain,
photopohobia,, myalgias,, normal leukocytes, decrease pletelets, increased liver
enzyme, always present consolidation in lungss chronic>>infective endocarditis,
and death.... acute form is like dengue 11859
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negative weil-felix test
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in reactive arthritis there is vesicular type of lesions on palms and sole (kertaderma blennorrhagicum)
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palmoplantar erythemaotus macules that migrate centripetally toward the trunk
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other important one is ureapalsma urealyticum.
less important one mycoplasma and trichomonas
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or vesicles
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if not treated causes fibrosis, lymphatic obstruction, stricture and anogenital fistulas develop.
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histologically lesions contain areas of mixed granulomatous and neutrophilic inflammation with chlamydial inclusions
bodies seen in epithelial and inflammatory cells
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bilateral
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most often cause tracheobronchitis than pneumonia
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inclusion conjunctivits 1154
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also called trachoma 1154
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extra-pulmonary manifestation of M-pneumonia beside anemia is stevens johnson syndrome, joint pains,
encephalitis, cardiac rhythm disturbances, and bullous myringitis.
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this is rare in US but endemic in africa, asia,south america and carribian
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proctitis with tenesmus and bloody discharge can be seen in this disease.
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followed by this.
painful inguinal lymph node is cardinal finding
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infection can create inflammatory state that favors thrombosis. but IgG antibodies against chlamydia pneumonea
were not correlated with the prothrombotic inflammatory mediators as IL-6 and IL-8.
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chlamydia produce PBPs and also contain genes for peptidoglycan synthesis.>>however
peptiglycan has not been found within the cell wall of this organism.>>>>this is known as
chlamydia anamoly..............
beta-lactam antibiotics delay the development cycle of the organism but do not eliminate the
organism>>>not clear whether this delay is due to PBPs or if another mechanism.
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skin lesion, fever, hepatosplenomegaly and pancytopenia in HIV pte 275
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sporangium is a structure that produce and contain spores. it is present in mold fungi.
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TB caseating granuloma is AFB +
Fungus caseating granumola is GMS +
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can be asymptomatic, mimic community acquired pneumonia (self resolve) or chronic pneumonia
(indistinguishable with TB and cancer)
In half of immunocompetent host>>>in the form of flue like illness or pneumonia
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(ie southern and central californa, arizona, mew mexico, and western texas)............
also present in northern mexico and some regions of central and south america.
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can present in 5 ways:
1, acute pneumonia (most common)
2, chronic progressive pneumonia
3, pulmonary nodule and cavities
4, extrapulmonary nonmeningeal disease
5, meningitis
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seen on examination with 10%KOH or silver stain of body fluids, sputum and tissue samples.
culture on sabourauds agar and serology is also important in making diagnosis
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bone pain by lytic lesion
120
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causes pulmonary disease in immunocompetent
extrapulmonary disease (skin, bone and GI) in immunocompromised
121
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immune compeptent>>>asymtptomatic or self limitng pulmonary disease
immunocompromised>>hepatosplenpmegaly and tongue ulcers
267
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serologic test (complement fixation, immunodiffusion) can be used to measure the
level of anti-histoplasma-antiboodies
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dissmeminated histoplasmosis in immunocompromised may show diffuse pulmonay infiltrates with
hilar adenopathy
267
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and great lakes regin
103
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have double refractive wall
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spores are formed by fregmentation of hypahe.once inside the lungs , the spores turn into
spherules that contai endospores.
the spherules subsequently rupture and release endospores that disseminate to other organs and
tissues. each endospore is capable of forming a new spherules
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skin lesion>>>papules, pustules, ulcers and verrucous lesion
bone pain>>>due to lytic none lesions
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because fungus targets reticuloendothelial system ans histiocytes it may present as lymphadenopathy and
hepatsplenomegaly
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hyphae.
so on tissue biopsy of these fungi hyphae are not found
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antigen detected by immunoassay
267
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chronic mucocutaneous or cutaneous ulcers
103
culture 25c>>>multiple blastoconnidia,
biopsy>>>cells vcovered in budding blastoconnidia
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hyphae(cigar butt appearence)
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spores
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melanocytes in basal layer but infection limited to stratum corneum.
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also in emhysema and sarcoidosis
108.
causes massive hemoptysis (invades blood vessels).
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pregnancy.OCP
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almost always susceptible for candida albicans
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unlike systemic mycosis which are yeast at 37
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candidia exist in yeast(single cell) form characterized by small oval yeast with narrow-based
budding forming pseudohyphae.
true hyphae also occur, usually only when candida becomes invasive (in early stages, these
hyphae can be identified as germ tubes)
103
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host defenses os provided by 2 immune system.
1, T-lymphocytes (in particular Th cells) are important for prevention of superficial candida
infection (eg oral/esophageal candidiasis, cutaneous candidiasis, candida vulvovaginitis).
conditions such as HIV (low T-cell count) increase the risk of superficial candidiasis.
2, neutrophils prevent the hematogenous spread of candida. disseminates candidiasis ( eg
candidemia, endocaarditis) is more likely in patients who are neutropenic or otherwise
immunocompromised ( eg cancer with chemotherapy) and in those with inherited impairments of
phagocytesis.
the interplay of these 2 components can be seen in patients with HIV. these patients have
superficial infections due to low T-cells but they do not typically suffer from disseminated
candidiasis as a result of HIV itself. if they have neutropenia, there is a risk for both localized and
disseminated candidiaisi
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in immunocompetent people with decreased local defenses,potential manifestation includes.
1, oral thrush
2, vulvovaginitis candidiasis
3, cutaneous candidiasis>>>areas exposed to heat or high humidity ( eg dish washers hands,
infants groin etc). sign include erythema, a vesiculopapular rash, maceration and fissuring.
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aspergillus is a low virulence fungus generally except in immunocompromised or debilitated patients.. aspergillus is
more common in neutropenic patients due to leukemia or lymphoma. immunosuppressed transplanted patients
than HIV patient,not an opportunistic infection in AIDS...... has predilection for blood vesselsand spreads
hematogenously. invasive aspergillosis can cause interruption of blood supply and and tissue necrosis....
epidemic fungal meningitis due to aspergillus fumigatus has been associated with
contaminatedglucucorticoid preparations
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occurs in 5-10% of steriod-dependent asthmatics.........
patients with ABPA has high serum IgE levels, eosniphilia, and IgE plus IgG antibodies to
aspergillus.
there is intense airway inflammation and mucus plugging with exacerbations and remissions.
repeated exacerbations may produce transient pulmonary infiltrates and eventual proximal
bronchiectasis.
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is only pathogenic fungus that has polysaccharide capsule.
usually affects immunocompromised, with HIV being the most common cause followed by
glucocorticoid use, solid organ transplant, and cancers (particularly hematological).....
in immunocompetent host they are cleared by macrophages and T cells.
in individual with an impaired cellular immune response it causes most commonly
meningoencephalitis
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is a neurotropic fungus. subacute or chronic meningoencephalitis is the most common
presentation of cryptococcosis.............
It infects humans via the respiratory tract and enters the lungs. Lung infection by Crytococcus is
usually asymptomatic; from the lungs the infection may disseminate to other organs.
c. neoformans has a predilection for the CNS. Cerebrospinal fluid does not contain the
complement components of the alternative pathway.
the presence of HIV infection or another immune-suppressing illness is central to the diagnosis.
113
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CSF findings include low glucose, increased protein, and low leukocyte count (particulalrly in HIV
patietns), lymphocytes predominate, although some neutrophils may also be seen.
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for life long prophylaxis.
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absidia also.
all 3 are saprophytic fungi present in environment.
transmitted by spore inhalation.
exist in mold form only......
mucosal biopsy is diagnostic
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rhizopus and aspergegillus exist only in mold (ie multicellular hyphae) form (forming true hyphae)
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also solid organ transplant,glucucorticoid therapy
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causes vascular thrombosis and necrosis.
tissue invasion is also seen.
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candida intertrigo>>satellite papules or pustules, axilla, genital areas and web spaces of fingers
and toes and skin flods
10168
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candida grows on potassium hydroxide medium
117
also for coccidioides
268
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on palate and nasal turbinates are characteristic
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infection is acquired through spore inhalation.
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increase incidence in diabetics due to ketone reductase activity of mucor (allowing it to survive in acidotic and
hyperglycemic environment) and possibly to the release of iron from binding proteins during ketoacidosis
(facilitating rhizopus growth)
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most common genus causing mucormycosis.
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unstained capsule.
india ink is a negative stain technique>>>stains the background and capsule surround the yeast is
clear.
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also methenamine silver (GMS) is used.
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although it is transmitted by respiratory route but not acquired via person-to-person route although usually
asymptomatic but can cause pneumonia like symptoms, complain of cough with scant sputum and pleuritic chest
pain. dyspnea and hemoptysis may also occur. chest X-ray are non-specific and may show infiltrates or nodules.
diagnosis is made by identifying crypto in sputum, bronchioalveolar lavage, or tissue sample.
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does not invade the lung cavity, but grows inside the cavity forming fungus ball.
on chest X-ray aspergilloma appear as radiopaque structure that shift when the patient changes
position
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type I and type III hypersensitivity.
wheezing, fever and migratory pulmonary infiltrate are characteristic
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Vessel invader with hemorrhagic infarctions and a necrotizing bronchopneumonia.
widely distributed in environment and grow on decaying vegetable.
monomorphic and exist only in mold form(ie multicellular hyphae)
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candida albicans can be isolated from an infection resulting from perforation of the proximal bowel
such as a perforated peptic ulcer.
....
can cause candidemia>>>>in patient with central venous catheter or patient taking parenteral
nutrition>>>.colonize catheter and lipid emulsion in parenteral nutrition.......
Disseminated candidiasis occurs in neutropenic patients and most often affects the esophagus,
heart, liver and kidney.
candida does not usually cause lung disease.
the Candida in his sputum only that his oral cavity is colonized, it does not contribute to the
diagnosis.....
...
Candida albicans is a normal inhabitant of the GI tract (including the oral cavity) in up to 40% of
the population
presence of Candida in sputum does not indicate disease.
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blastoconidia are spores that grow as buds on the fungal hyphae
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incoluation of candidia albiacans into serum at 37 v for 3 hours lead to formaiton of true hyphae
from yeast cell.
this test is used to distinguis albicans from other species (tropicalis, glabrata)
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elongated yeast cell but not true hyphae
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range from low grade fever to multiorgan failure..occasionaly with characteristic chriorhetinitis and
clustered pustular skin lesion...
decreased visual acuity diagnosed by ophthalmoscopy
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3 types.
1, oral thrush
2, cutaneous candidiasis(diaper rash)
3, vulvovaginitis
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we do serologic test to diagnose this,
increased titers of IgE and antibodies to aspergilles is diagnostic.
also we can do skin hypersentitivity testing
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also has eosinophilia and aspergiluus specific IgG
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primarily effect lung with necrotizing pneumonia and granuloma formation
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involve paranasal sinuses and show close clinical resembalence with mucor unless differentiate
with light microscopy.
invasive aspergillosis characterized by prmiary lung involvement with symptoms of cough,
hemoptisis and pleuretic hest pain and fever, necrotizing pneumonia and granuloma formation
also occur.
in chest imaging invasive aspergillosis can show consolidation, nodules or cavitary lesions.
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which have granuloma formation>>>containing histiocytes, giant cell, neutrophil and surrounded by plasma cell.
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numerous P. jiroveci cysts with central dots representing spores. Some cysts look like crushed
ping-pong balls.
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eosinophilic foamy alveolar material and cystic and trophic forms that can be stained with giemsa
or silver (producing cup in saucer appearance with these stains)
1576
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in patients without HIV/AIDS, PCP can present with fulminant respiratory failure, and chest radiograph reveal
diffuse, bilateral interstitial infiltrates.
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also used to treat leishmania and african sleeping sickness
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diagnoses is made by culturing the affected site and isolating organism
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most common enteric parasite in US and CANADA......
giardia can colonize the duodenal and jejunal mucosal lining......
stool smear with iodine staining>>>>>reveals ellipsoidal cysts with smooth, well defined walls and
2 + nuclei,
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also fecal oral transmission in day care centers
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infective stage.. oval shaped and have upto 4 nuclei.
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biopsy show basophilic clusters on surface of intestinal mucosal cells.
colonoscopy show nonulcerative inflammation..
.....
CD-8 T cell provide immunity against intracellular parasite such as cryptosporidium and
toxoplasma gondi
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amebic liver abscesses caused by entamoeba infection may also produce liquefactive necrosis,
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upper small bowel biopsy is often done in nondiagnostic cases which show villous atrophy and crypt hyperplasia
in varing degree depending on the severity of the disease
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pear shaped bilaterally symmetrical with four pairs of falgella and two nuclei... pathogenic stage..
attach to brush border of duodenum and jejunum.
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children with X-linked agammaglobulinemia and coomon variable immunodeficiency has documented chronic
giardial inection
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formation of cysts and trophozoites
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obligate intracellular
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occasionaly microcephaly occurs when hydrocephalus is not severe
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seizures are common complication of such brain lesions
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if mother is infected during the first 6 months of pregnancy..
as most healthy individual are esposed to toxo early in childhood, most adults are immune and
primary infection in pregnancy is rare.
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also form pseudocysts containing bradyzoites
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IgM nonreactive & IgG reactive/low titer will show in studies..........
REACTIVATION of LATENT tissue CYST/or preexisting toxo
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multiple ring enhanching>>toxo
single ring enhancing>>>invasive aspergillus
2082
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pentamidine is also used to treat.
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this is first line treatment (which can be given empirically,particularly if test result are unrevealing)
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pyrimethaime + sulfo
effective on trophozoites but not cyst form..
drug effective against both>>atovaquone
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to destroy >>56C/133F for 15minsOR freeze it -20C/-4F. also form pseudocyst
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brain infection are exceedingly rare in immunocompetent host, unlike neurocysticercosis caused by taenia solium,
which is common in immunocompetent host living in central and south america
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cotton-like white/yellow scars on the retina visible on fundoscopy
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instead this we use clindamycin in case of sulfa allergy..... we use these drugs
along with leucovorin(folinic acid) 2082
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chronic form
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thin blood smear (wright/giemsa stain)
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can cause ARDS most commonly in aseplenic pte,
11540
CHF, DIC, splenic rupture
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cause medication induced muscle atrophy.
chronic corticosteroid therapy can also cause.
chloroquine/hydroxychloroquine>>>>long term use can cause irreversible retinal
damage>>>>used for mild RA and SLE
1965
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Visceral leishmaniasis (kala-azar)manifests as progressive splenic enlargement and
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american trypanisomiasis............
destroy the myenteeric plexus and causes intramural, parasympathetic denervation of smooth
muscle.
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primarily effects macrophages.
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only exist in this form
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Triatomine bugs, a type of reduviid bug (" kiss ing bug").
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organism infect squamous epithelium and causes inflammation in the urogenital tract
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pentamidine is also used to treat.
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also megaureter due to changes in ureter.
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charcol-leyden crystal (from eosinophil breakdown) in the stool are sometime seen in intestinal
parasitic infections.
diarrhea with peripheral eosinophilia can be seen with strongyloides, ancylostoma, ascaris,
toxocara and trichinella (but not with giardia or entamoeba)
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oval asymmetrically flattened eggs with a bean shaped appearance
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Most common
helminth worldwide
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Supportive therapy
during pneumonitis;
surgery for ectopic
m igrations; mebendazole
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pruritic, erythematous linear streaks (known as larva currens) may occur on the
thighs and buttocks as the larva migrate subcuabeolsy away from the perianal
region.
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diagnose by detection of rhabdiform larvae(non-infectious) in stool as the eggs and adult parasites are usually seen
only in inestinal biopsies
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Ancylostoma braziliense
Ancylostoma caninum
(dog and cat hookworms causes
Cutaneous Larva Migrans
Thiabendazole
Topical corticosteraids
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(NM agonist >>>> spastic paralysis)
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splinter
hemorrhages, eosinophilia
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killing of the microfilaria/in onchocerciasis can result in a dangerous Hypersensitivity/ “Mazzotti"
Rxn -fever-headache-dizziness-somnolence-HypOtns.
We give them antihistamines or steroids to help.
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causes immobilization of microfilaria, and change surface structure>>so it destroyed by host immmune
system ............
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surgical removel of worm can also be done in these three
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hyperpolarization due to Chloride influx.
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+Steroids for severe
symptoms.
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iron deficiency anemia
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Autoinfection cause of some rhabtiform larvae can molt directly into filarofirm larva within the intestine and re-infect the hos by
penetrating the intestinal wall or perianal skin.leads to indefinite infections(hyperinfection) unless treated>>>>>>multi organ failure
and septic shock. hyperinfection occurs most often in patients taking immunosuppressants (eg corticosteroid) or with HTLV-1
infection. these patiens have impaired Th2 DIRECTED CELLULAR IMMUNITY (mediated by the antiherlmintic action of
eosinophils and basophils). ........ autoinfection cycle occur entirely within the affected individual.
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strongylodiasis can cause pulmonary symtomps including cough, asthma-like bronchospasm, and
hemoptysis.it can also produce a transient pneumonia as larvae migrate through the lungs on theri
way to larynngopharynx.
in rare cases, chronic lung involvemnet may cause features of obstrucitve and/or restrictive
pulmonary disease.
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filariform(infectious).
reach the intestine after passing thorugh lung, in instestine they develop into adults that lay eggs
within the intestinal mucosa. these hatch into rhabditiform (non-infectious) larvae that migrate into
the intestinal lumen to e excreted in the stool.
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Bile stained,
knobby eggs
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albendazol 1st line.
pyrantal pamoate is an alternative preferred in pregnant women
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most common helminthic infection in the united states
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also causes swimmers itch and katayama fever 1898
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Cysticercosis is a disease caused by the larval stage of the organism following ingestion of eggs
found in the excrement of T solium tapeworm carries.
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once released into the enviornement, the larvae can penetrate intact human skin and
subsequently travel to the liver where they mature into adults over a period of several weeks, After
maturation, the adults worms migrate to specific destinations: the mesenteric venules of the
intestine (S japonicum and S mansoni) or the urinary bladder venous plexus (S haematobium).
The adult worms remain in these blood vessels for life (5-30 years), adhering to the vessel wall
with suckers and releasing eggs into circulation. Eggs released by S japonicum and S mansoni
have tendency to penetrate the bowel wall and be excreted in the feces.they also frequently
traverse the portal venous systme and lodge in the liver.S haemaobium eggs tend to pierce the
vesical and ureteral walls and be expelled in the urine.on exposure to freshwater,these egges
release larvae that can infect snails and perpetuate the life cycle.
The clinical manifestations of schistosomiasis result from a TH2-mediated granulomatous
response directed against the eggs that is composed of infiltration TH2 cells, eosinophils, and M2
macrophages. This ultimate leads to the development of marked fibrosis and ulceration and
scarring of the bowel or bladder/ureters (depending on the species). Eggs that settle into the
presinusodial radicals of the portal veins can cause periportal “pipestem” fibrosis (pathognomonic
for hepatic schistosomiasis).
8541
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proglotids formation occur in cestodes.
shedding of distal proglotid(distal end of worm), can be detected in the stool of infected individual
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consumptio of undercooked pork>>cysticercosis could manifest as seizures, subcutaneous nodules or intramuscular
calcification.
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multiple brian lesion, but may be single lesion.
patients are immunocompetent and are living in central and south america where this disease in
endemic.
patient has a seizure and cystic brain lesion on MRI...
neurocysticersosis has eosinophilia and increased ESR.
MRI has cyst and scolex
11670
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systemic effect. mebendazol remain in gut
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when infection first occur, the echinococcal larvae implant within the capillaries, triggering an
inflammatory reaction composed of monocytes and eosinophils.
some larvae are destroyed by the host, but others encyst.
microscopic examination of hydatic cyst tossue demonstrates a characteriastic encapsulated and
calcified cyst ("eggshell calcification") that contain fluid and budding cells that will eventually
become daughter cysts.
the outer cyst wall is composed pf many layers of delicate, gelatinous sheets surrounded ba a
thick fibrous capsule
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both imaging (US, CT, MRI) and serology testing can be used for diagnoses.
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diagnose by detection of eggs in stools
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intestinal ulceration causes iron def anemia caused by mansoini
8541
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most cases occur either in individuals from endemic regions (eg mediterranean countries, middle
east, southern south america , iceland, australia, new zealnad and southern africa) or in those
people residing in the southwest region of the US with sheep and dog exposure( two animals that
participate in the tapeworm life cycle)
the initial infection is asymtopmatic with subsequent signs and symptoms dependent upon the site
of the cyst and their size.
the liver is affected in most cases though other organs can be involved, such as lung, muscle or
bone.
unilocular lesion are typical of E.granulosus and multilocular lesions are typical of E,multilocularis
infection.
ultimately patient experience hepatomegaly, right upper quadrant pain, nausea and vomiting.
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we do not use praziquantel for ocular cysticercosis>>>>destroy org in the eye>>>which causes irreversible damage
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Praziquantel(increase Ca2+ influx, increase vacuolization)>>>paralysis of worm.
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embryos attach wall of small intestine and migrate hematogenously to tissues, including the brain where the form
cysticerci, fluid filled cysts surrounding the invaginated scolex (head of tapeworm with hooklets)
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nbme>>>1,3,17>>>>patient emigrated from costa rica>>present with new onset seizure>>CT shows numerous
cortical lesions with calcification, some have surrounding edema.
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infection is not possible in the united states due to absence of the specific freshwater snails that incubate the
infectious larvae.
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Th2 medicated granulomatous response mdirected against the eggs, eosinphils,
Th2 cells and M2 macrophages periportal pipestem fibrosis>>pathognomonic 8541
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type 4 HS reaction.
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interference occurs when one virus inhibits the replication and/or release of a second virus that
is infecting the same cell. 1461
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recombinant surface protein vaccine>>created by inserting relevant DNA into host org (eg bakers
yeast) which then produces the desired antigen in the large quantities.>>same drawbacks as of
killed vaccine.
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recombination is echange of genetic informaiton between two virus strains that have non-
segmented double-strand DNA genomes., which may be defined as the exchange of genes
between two chromosomes via crossing over within homologous regions.
1461
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1373
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(+) RNA.Viruses: Call Henry Pico and Flo To Come Rightaway
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means able to induce viral protein synthesis and genome replication in host cell
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nbme, 6,3,48
Generally, enveloped (lipophilic) viruses are susceptible to alcohol: Herpes simplex virus (HSV),
human immunodeficiency virus (HIV), influenza virus (Flu), respiratory syncytial virus (RSV),
vaccinia virus, Hepatitis B and C viruses are considered susceptible to alcohols.
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Acute cerebellitis (post-viral cerebellar ataxia) occurs most often in children 2-3 weeks following varicella,
measles, or Epstein-Barr virus infection. It presents with cerebellar symptoms (eg, ataxia, nystagmus,
dysarthria) that usually resolve completely within 3 weeks.
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has hexon and penton capsomeres on its surface. rodlike strutres (fibers) that project form the
penton bas capsomeres are responsible for mediating absorption to host cells.
the cell receptor for most adnovirus fibers is a tranmembrane protein member of the
immunoglobulin superfamily.
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serotypes 11 and 21 of adenovirus subgroup B have been particularly implicated in this illness.
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virus attack and destroy proerythroblasts.
recent infection can be confirmed via the detection of anti-B19 IgM antibodies in serum.
.............
PRCA pathogenesis often involve the inhibition of eythropoetic precursor and progenitor by IgG
autoantibodies or cytotoxic T lymphocytes,
it has been associated with immune system diseases such as thymoma and lymphocytic
leukemia.
thymoma removel can occasionaly cure PRCA.so all patient with PRCA should have chest CT
scan
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HPV 1 through 4 -> Plantar warts/ "soles of the feet"/skin warts"verruca vulgaris" HPV 6 & 11
Genital warts (condylomata acuminata)/ laryngeal papillomas HPV16,18,31,33,35,51 -> carcinoma
of the cervix/penis/anus/vulva
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also cause vaccinia and monkey pox
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most common clinical manifestation(characterized by vesiculoulcerative lesion) and cervical
lymphadenopathy, of primary infection in children aged 6 months to 5 years.
symtomps appear after 1 week of getting infected ftom person who is clinically asymptomatic
.....
dehydration is the most common cause of hospitalization in these patients
1499
.......
vesicular lesion>>>>accumulation of fluids between dermis and epidermis and cell lysis and tissue
distruction
1409
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vaccinate infants od 12-18 month old, women of childbirth age, high risk individual, household contact of
immunocompromised host, vaccine induced immunity dissipate overtime
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in HSV exposure in pregnants and neonates,, post exposure prophylaxis is IMMUNOGLOBULIN...
antiviral in primary infection is for reduce viral shedding, local pain and decrease time for lesion
healing.
1550
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Acute arthropathy(symmetric arthritis or arthralgias) found primarily in adults: This symmetric
polyarthritis involves the proximal interphalangeal, metacarpal, knee and ankle joints. The arthritis
is self-limited and nondestructive.
The initial nonspecific period of infection is associated withheavy viremia and viral shedding. By
contrast, erythema infectiosum and acute arthropathy signify an active immune response with
formation of immune complexes and minimal or undetectable viremia. These patients have much
reduced infectivity.
.........................
Rheumatoid arthritis may cause an acute polyarthropathy that is initially similar to parvovirus
arthritis. The symptoms may be temporarily relieved with nonsteroidal anti-inflammatory drugs but
would not resolve as promptly as they did in this patient.
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limited to affecting erythrocytes, shouold not be confused with aplastic anemia, whih has
pancytopenia
1496
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zoster reactivation seen in individual with suppressed cellular immunity.
........
in zoster the pateitn is contagious untill the lesions are dry
.............
most commonly involve thoracic and trigeminal sensory distribution (CN V) dermatome.
lesions end abruptly at the midline
.......................
in zoster>>>
skin biopsy will show acatholysis of keratinicytes and intraepidermal vesicles.dermal inflammatory
infiltration and leukocytoclastic vasculitis may be pesent
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PHN is typically descried as “stabbing: may be constant or intermittent, and often lasts for several
months.
...........
capsaicin is used for PHN>>>causes release of substance P>>>chronic use causes depletion of
substance P and reduction in pain.
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primary infection travel via olfactory track,
reactivation travel via trigeminal nerve to spread in cerebral vault.
latent in trigeminal ganglia.
reactivation cause lesion which is in single site and less severe than the primary infection
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hydrops fetalis (particularly when infection occurs before the 20th week of gestation).
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chronic CNS demyelination through infection of oligodendrocites
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acute/aubacute changes in mental status, seizures, headache and in some cases focal neurologic deficits. CSF
reveals a hemorrhagic lymphocytic pleocytosis with increased protein and normal glucose. abnormal MRI signal in
the bilateral temporal lobe.... ... reactivation of latent virus. most common initial symptoms is headache and fever......
.... aphasia due to (speech center), olfactory hallucination(olfactrory cortex) personality changes, eg hypersexuality,
aggression,(amygdala damage) these 3 are specific temporal siign. ..... macroscopically present as edema and
hemorrhagic necrosis. . microscopically present as eosinophilic intranuclear inclusions(cowdery type A) in glial cell
and neurons.multinucleated giant cell may also be present. EEG show focal temporal abnormalities,CT MRI shows
edema and hemorrhage in temporal lobe. CSF typical of viral pattern
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contain white crude like material. found on anogenital area and on trunk. ... poxvirus causes eosinophilic
cytoplasmic inclusions (molluscum bodies) in infected cell and dome shaped umbilicated papules on exam
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also cause hemorrhagic cystitis in immunocomromised
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papilloma on true vocal cords>>>hoarsness and possible stridor (airway obstruction)
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though to attach to human erythroid cells via the blood group P antigen (globoside), which is
expressed by mature erythrocytes, erythoid progenitors, megakaryocytes, placenta and the fetal
liver and heart.
immature cells of the erythroid family (eg, adult bone marrow, fetal liver) are most vulnerable to
parvovirus B19 infection.
...........
there is no polymerase in the virion.
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self limited out breaks occur.
nasal congestion,conjunctivitis and cervical lymhadenopathy present
...........
pharingoconjuctival fever,
upper respiratory more common.
penumonia is rare.
transmission by person-person, fecal oral, respiratory droplept,
1497
...............
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double stranded DNA virus that is neurotropic is herpes virus and JC papova virus
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intranuclear acidophilic inclusions are characteristic of herpes simplex virus infection, intranuclear
basophilic inclusions are typically seen with cytomegalovirus.
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EBV is typically transmitted from as asymptomatic virus shedder to a susceptible individual
through saliva transfer (e.g, kissing)
........
latent EBV(90% of individual normally have), if become chronic and transforming.could result in
EBV associated Bcell lymphoma
........
in immunocompromised host,
EBV causes CNS lymphoma in HIV + patient and post transplant lymphoproliferative disorder
(PTLD) in allograft recipients.
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nbme,11,1,17,
CMV has a unique method of escaping immune response it dec. the expression of MHC 1 and
also expresses a decoy molecule. The normal for the MHC 1 molecule is that its made in the RER
and then transported to the Cell membrane. If it get translocated to the cytosol, its likely to be
degraded(by proteases)
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90 percent caused by this. other causes are CMV, HIV, and toxoplasmosis and HHV-6
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EBV infected B-cell stimulate them to enter in cell cycle continuously a process termed as transformation or
immortalization>>>>they secrete immunoglobins and B-cell activated products(eg CD23) with very few of these
cells releasing virus particle at any one time. EBV encoded oncogenes activate proliferative and anti-apoptotic
siganlling pathway in infected B-cell. In immunocompetent host this proliferation is held in check by humoral or cell
mediated response
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EBV envelop glycoprotein gp350 binds to CD21 (also known as CR2), the cellular receptor for the
C3d complement component.
CD21 is nomally present on the surface mature B-cells and nasphayrangeal epithelial cells
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the proportion od CD4 helper lymphocytes to CD8 cytotoxic lymphocytes is decreased in acitve EBV infection 7643
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phryngitis and lymphadenopahty are seen less commonly than with EBV.
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intraneuclear and intracytoplasmic inclusions (viral particles) have clear halos
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typically with in first few months.
mostly with lung transplant>>universally give valgancyclovir
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most often 6-15 months, rash appear on trunk and spread peripherally
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reddish/violet flat maculopapular lesions or hemorrhagic nodules on colonoscopy spindle shaped tumor cell with
cytologic atypia, small-vessel proliferation and extravasated RBSs with hemosiderin deposits on biopsy. Presents
as diarrhea in HIV patient.
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monospot test has horse RBCs
paul-bunnell test has sheep RBCs
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for some of these lymphomas risk seems correlated with a decrease in cytotxic lymphocytes
specific to EBV
1724
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however most patient do not develop seizures.
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is one of the most common cause of febrile illness in neonates.
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in leukocyte-laden blood products,as CMV infect leukocytes of granulocyte-macrophage lineage.
irradiation help reduce this risk.
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common after organ transplant and it is intersticial type
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can be negative in early stages of disease but repeat later on to confirm the disease.
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activated cd8 cytotoxic are much larger than quiescent lymphocytes with abundant cytoplasm, an eccentrically-
placed nucleus, and a cell membrance that appears to conform to the borders of neighbouring cells. .......... b
lymphocytes also proliferate during acute phase but they represent only a small fraction (5%) of the atypical
lymphocytes seen on the peripheral blood smear. ..
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nbme>>>2,1,28>>>EBV first proliferate in the pharyngeal B cells than after that become latent in blood peripheral
B cells.
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most common sign and symptom. symptom-Sore throat 75% Sign-Lymphadenopathy 95 %
(Splenomegaly only 51%)
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like other herpes virus, CMV requires initial contact with glycosaminoglycan chains on host cells
surface proteoglycans for entry into the host cell.
.......
cellular receptor for CMV is cellular integrins
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Urine can harbor pathogens such as cytomegalovirus, adenovirus, Escherichia coli,
Staphylococcus saprophyticus, and Klebsiella pneumoniae,
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measles infection occasionally associated with intranuclear inclucions also.
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CD54
8324
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CR2
8324
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basophilic in CMV
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stain with wright-giemsa stain
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associated with flaccid paralysis
1906
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nbme,6,3,38.
2 day history of fever, headache, muscle weakness and confusion. temperature 38, physical
examination show generalized lymphadenopathy and weakness of right lower extremity.
laboratory studies show antibodies to a virus that is maintained in wild birds.carried to humans by
cullex species mosquitos. and has low fatality rate.>>>WNV
West Nile virus (WNV) is a virus of the family Flaviviridae. Part of the Japanese encephalitis (JE)
antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects
birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels,
domestic rabbits.
The virus is transmitted through mosquito vectors, which bite and infect birds.
in the US Culex pipiens (Eastern US), Culex tarsalis (Midwest and West), and Culex
quinquefasciatus (Southeast) are the main sources.
Approximately 90% of West Nile Virus infections in humans are without any symptoms.
WNV produces three different outcomes in humans. The first is an asymptomatic infection; the
second is a mild febrile syndrome termed West Nile Fever;[the third is a neuroinvasive disease
termed West Nile meningitis or encephalitis
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replicate in oropharynx and intestine
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the RNA has a protein on the 5' end that acts as a primer for transcription by RNA-dependent RNA-polymerase
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eastern and western and venezuelan equine encephalitis most common in summer and fall when arthropod are
most active.
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only this is + strand which is helical
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causes symptoms of UPPER respiratory infection with extreme tiredness, fever and cough. patient generally recover
fully after about 2 weeks.
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Viral bronchiolitis is a lower respiratory tract infection Bronchiolitis typically starts with upper rspiratory
track symtopoms,eg rhinorrhea and congestion followed by cough, low-grade fever and increased work of
breathing. Classic findings include hypoxemia, tachynea and retractions with diffuse wheezes and
crackles. Although illness severity peaks at 3-5 days, symptoms (eg, cough) may last several weeks. In
older infants and children, bronchiolitis is typically a mild self-limited illness, however in young infants
(age <2 months) or those born prematurely, symptoms may be severe and lead to apnea and/or respiratory
failure. pertussis starts with upper respiratory symptoms (eg, rhinorrhea, congestion) and progresses to a
“whooping” cough, also has post tussive emesis, Lungs are usually clear to auscultation.
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febrile aseptic meningoencephalitis or mild systemic flu like illness exposed to infected hamsters
and mice.
no person to person transmission
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nbme,11,3,11
polio vaccine produce>>>neutralizing antibodies in circulaiton not neutralizing secretory IgA
antibodies in gut.
Viral vacines that are living strains(sabin) elicit both-cell mediated and humoral immunity,whereas
killed viral vaccines(salk) elicit predominantly an antibody respond....
so common features of these two types... sabin and salk ...induce humoral immunity/antibody
respond..
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enveloped viruses with single-straded , negative sense RNA utilize different methods to initiate
genomic transcriptipn.
eg paramyxovirus transcribe by rna-depende rna polymerase with minimal dependence on host
cell mrna primers
other are orthomyxovirus which has virally endcoded endonuclease associated with rna-
dependent rna polymerase,this endonuclease is thoiught to cleave short 5' rna fragments that are
used to prime the viral rna transcription by the viral rna polynerase (cap snatching)
1411
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hemadsorption test are positive for some influenza and parainfluenza virus.
in this hemagglutinin or glycoprotein with a high affinity for erythrocytes expressed on the host cell
surface.
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viral encoded RNA dependent-RNA polymerase of this virus may be able to transcribe the viral genome with minimal
dependence on host cell mRNA primers
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in winter/spring (2nd),other are rhino summer/fall (NO 1) and adeno
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HIV is within the Lentivirus subgroup of retroviruses.
the genome is diploid, consisting of 2+ single stranded RNA molecules that are transcribed into
double-stranded DNA by a reverse transcriptase present in the capsid.
.........
HIV gp120 binds to CD4 transmembrane and the coreceptor (CCR5 and CXCR4) causes HIV
envelop to undergo conformational change that activates gb41 and initiates membrane fusion.
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has a febrile illnes wih a rash and neurological manifestations, including encephalitis (confusion
state) associated with flaccid paralysis syndrome.
it is tranmitted by female mosquitos (culex), most commonly in the summer.
diagnoses can be made when compatible clinical finding are associated with positive
cerebrospinal fluid anti-WNV antibodies. (PCR testing often not needed)
management is supportive.
1906
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MCC in winter months
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viral encoded protease is required for the replication of single-stranded, positive sense RNA
viruses that possess genomes which function as viral polycistronic mRNA and produce a
polyprotein product.
a mutation is such a protease would be expected to nonspecifically affect viral replication,
.................
many single stranded,positive sense, linear,non-segmented RNA>>>generated polyprotein
product>>that is cleaved by specific viral protease (often part of polyprotein)>>>>they are
independently infective as it often functions directly as its own mRNA.
.................
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nbme>>>3,2,27
Coxsackieviruses are divided into group A and group B viruses
group A coxsackieviruses tend to infect the skin and mucous membranes, causing herpangina,
acute hemorrhagic conjunctivitis (AHC), and hand, foot and mouth (HFM) disease.
Group B coxsackieviruses tend to infect the heart, pleura, pancreas, and liver, causing
pleurodynia, myocarditis, pericarditis, and hepatitis (inflammation of the liver not related to the
hepatotropic viruses). Coxsackie B infection of the heart can lead to pericardial effusion. Muffled
heart sounds and pulsus paradoxus are signs of this.
Coxsackieviruses are also the leading causes of aseptic meningitis

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most common cause of viral gastroenteritis in developed countries
, outbreaks occur>>fecal oral>>>>school, hospital, cruise,nursing homes,
resistant to acid, bile and pancreatic enzyme,,
clinically dagnose, or PCR
1498
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in some viral families, (eg paramyxovirus) the RNA polymerase may be able to transcribe the viral genome with
minimal dependenceon specific host cell mRNA primers.
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ss(-) RNA viruses: Pain Results From Our Bunions Always
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often causes URI followed by diarrhea
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do not typically cause gastroenteritis,but transmitted by fecal-oral
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enveloped viruses with single-stranded, negative sense RNA utilize different methods to initiate
genomic transcription.
some ( eg influenza virus) have a viral encoded endonuclease associated with the viral RNA-
dependent RNA polymerase.this endinuclease is thought to cleave short 5' RNA fragments that
are used to prime the viral RNA for transcription by the viral RNA polymerase ("cap snatching").
the host range of infecivity of an orthomyxovirus could conceibly be altered by an endonuclease
mutation.
however, other enveloped RNA viruses, including thosewoth negative sense RNA (eg
paramyxovirus) and those with positive send RNA ( eg hepatitis C virus)- can synthesize new viral
genomic and messenger RNA without endonuclease involvement.
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cellular receptor is ICAM-1 (CD-54)
8324
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but can also cause epidemics
12708
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surface glycoproteins that bind to sialic acid
(N-acetylneuraminic acid) receptors
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amantadine (limited use in influenza management due to viral resistance) impairs uncoating or
disassembly of the influenza A virion after host cell endocytosis.
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point mutation
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vaccinate children ar 12-15 months and again at 4-6 years. but also in nonpregnant women of childbearing age who
lack serum antibody against rubella. at time of vaccination women are strongly advised to not get pregnant in next
4 weeks
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fine, maculopapular rash..."
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compared to rubeola, the rash of rubella spreads faster and does not darken or coalesce..
...........
rubella pateint also have forchheimer spots on the soft palate
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painful.
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mutation in the hemagglutinin of an influenza A strain that was previously confined to domestic livestock conferred
a new binding affinity for a neuraminic acid-containing glycoprotein on the surface of human nasopharyngeal
epithelial cells.>>>>>so due to mutation both livestock and human are vulnerable to infrction.
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clips off sialic acids, thus aiding in release of virus.
neuraminidase (sialidase) deficiency is the cause of human sialidosis also.
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which code for NA and HA
12708
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causes due to point mutation in contrast to exchange of entire genome segment in shift...
drift occur in all viruses, not just in segmented
1469
.........
•Most noted in HIV and influenza>>>antigenic drift is common annually with the influenza virus
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complicationS include:
acute encephalitis(with in days)
acute disseminated encephalomyelitis(during recovery/with in weeks)
SSPE>>>>causes progressive dementia, spasticity and seizures..
microscopic examination shows myelin degeneration and viral inclusions.
primery meales pneumonia, and secondary bacerial infection(pneumonia and acute
otitis),occasionally measles causes radiographically evident pneumonia or
laryngotracheobronchitis (croup):
bronchiolitis is not typically seen
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Loss of PPD skin test accuracy: Cell-mediated immunity is temporarily depressed during
measles infection. IL-12 suppression is hypothesized to be mechanism behind this finding
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genrally orchitis in young adults are due to C,trachomatis and N.gonorrhea. and in elderly E coli is the most common
cause.
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characteristically present with fever,malaise,headache and myalgias followed by development of
parotitis within 48 hours
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respiratory transmission
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((((((((((((missing an antigen (M protein) in certain type of measles virus. microscopically>>>myelin degeneration and
viral inclusion)))))))))))) caused by a form of measles virus with a mutated or absent matrix protein that prevents
mature (enveloped) virion particle from forming. however virus continues to replicate intracellularly, leading to
persistant, non-productive infection that evades eradication by the immune system. accumulation of viral
nucleocapsids within neurons and oligodendrocytes results in formation of intranuclear inclusions and
eventually leads to inflammation, demyelination and gliosis in many cerebral areas.. patient with SSPE has high titer
of measles antibodies in serum and CSF(detectable as oligoclonalbands)
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measles genome code for several viral structural proteins, including hemagglutinin (mediates cell
surface adhesion) and matrix protein (important for viral assembly)
.....
occasionally measles also has intranuclear inclusions like HSV
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virus itself travel first goes to spinal cord,cerebellum, brain stem and hippocampus from there it travel with in nerve
axons to the tissue of salivary glands. At this point post exposure profilaxis no longer effective.
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generalized flaccid paralysis
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Postexposure rabies prophylaxis consists of immune globulin at presentation and vaccination on
days 0, 3, 7, and 14. Counseling patients and families about animal safety may help decrease
animal bites. In most states, physicians are required by law to report animal bites.
........
rabies vaccines consist of various rhabdovirus strains grown in tissue cell culture and inactivated
by beta-propionolactone
1465
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painful muscle spasm,
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Although bats are the main rabies source in the United States, many patients with bat rabies are aware that
they had been bitten. virus travels retrograde. .......... course of disease>>>prodrome(prodromal phase has
fever,pharyngitis and pain around the bite site.) >>spasm>>generalized flaccid paralysis and coma>>death with in 2
weeks of coma.
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hep C characterized with lymphoid aggregates within the portal tracts and focal areas of
macrovasicular steatosis.
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histologic findinds of acute viral hepatitis include hepatocyte necrosis and apoptosis with
mononuclear inflitration. Hepatocte necrosis is characterized by cellular swelling and cytoplasmic
emptying (eg, ballooning degenration) likely caused by ATP depletion and disruption of the
intermediate filament network. In severe cases, regions of adjacent lobules are interconnected by
swaths of dead hepatocytes called “bridging necrosis”. Hepatocyte apoptosis is characterized by
cellular shrinkage and nuclear fragmentation with intense eosinophilia (eg, Councilman bodies)
and is likely caused by mitochondrial oxidative damage. The presence of virally infected and dying
by mitochondrial oxidative damage. The presence of virally infected and dying hepatocytes
promotes mononuclear inflammation in the sinusoids and portal tracts.
.......
is acute hepatitis liver biopsy typically shows panlobular panlobular lymphocytic infiltrates,
hepatocytes necrosis (ballooning degenration) and hepatocytes apoptosis.
apoptotic hepatocytes form round acidophilic (pink-staining) bodies known as councilman bodies
or apoptotic bodies.
.....
in acute hepatitis, kupffer cells phagocytize hepatocellular debris and may appear hypertrophied
and laden with lopofuscin pigment in biopsy specimens.
hepatocyte hyperplasia occur in regenration which in histopathology show as formation of
pseudoascini of dividing hepatocytes and numerous mitotic figures.
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Hepatitis B virus infection can produce one of three syndromes; acute hepatitis with complete
resolution; chronic hepatitis (with or without cirrhosis nd the attendant increased risk of
hepatocellular carcinoma); or fulminant hepatitis with massive liver necrosis. By far the most
common outcome in HBV- infected adults (>95%) is acute hepatitis with mild or subclinical
symptoms that eventually completely resolve.
Only 4-5 %, of patients with hepatitis B virus infection will go on to develop chronic hepatitis. Of
those, 50-80% will remain stable with no evidence of cirrhosis.
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travel to endemic area, and insufficiently heated food (eg oysters), raw or steamed shell fish.
.....
high risk individual>>>travel to endemic area or living there, chronic liver disease or clotting factor
disorder, men who have sex with men>>should be given a hep A vaccine.
close contacts of hep A infected individuals should promptly be given immune globulins or vaccine
372
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vertical transmission take place during the passage of the fetus through the birth canal, but
transplacental infection can also occur.
this is especially common in women who developed acute hep B infection in 3rd trimester..
viral replicaation occur rapidly in infected infants dur to immune system immaturity in newborns.
the chance of progression to chronic hepatitis is 90% withpout treatment, which is higher than the
chance of progression in adults (<5%) and children (20-30%).
hewborns are rarerly symptomatic at birth adn the most common findings include persistent serum
antigens and mildly elevated liver enzymes.
due to high risk of chronicity all infants shiull be vaccinated. in addition all pregnant mother should
be screend for hepatits B , and if postive hepatitis B immunoglobulin should be administered
prophylactically to the newborn.this has been shown to lower the tranmission rates to 5-10%.
HBV is not inherently cytotoxic and the neonatal immune system is still immature (limiting
inflammatory damage), as a result laborotary markers of liver injury are usually only mildly
elevated in HBV-infected individuals.
.................
if mother is Hbe Ag is postive then ther is 90% chance of transmission to fetus.if no then there is
only 20%
..........
the new born of all mother is passively immunized with HBIG, followed by active immunization with
recombinant HBV-vaccine
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has 6 or more genotype and multiple subtypes that differ in genomic composition by as much as
30-35%.
this is largely due to virion encoded RNA-dependent RNA polymerase has no proofreading 3>>5
exonuclease activity
The continuous generation of novel envelop glycoprotein prevents infected individual from
mounting an effective immune response............
.................
multiple subgenotyes as demostrated by the genetic differences in the encoding of its two envelop
glycoproteis. the genetic variation has led to the development of a hypervaribale region of the
envelop glycoprotein that is especially prone to frequent mutation.
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35 nm double shelled particle that resemble dane particle of HBV
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unenveloped, single stranded RNA virus. occurs in young and middle-aged adults living in asia, sub,saharan africa,
and mexico. with an average incubaiton period of 6 weeks. virus is shed in stool during acute illness, the disease is
typically self limited and is not associated with either chronic liver disease or carrier state. HEV Ag or HEV RNA can
be detected in the stool or liver in the earliest stages of infection (when the patient is asymptomatic). later serum
transaminases and IgM anti-HEV titers rise in association with clinical illness 48
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in children <6 years most often ( >80%) are silent or subclinical (anicteric).
less frequently it present as acute, selflimited illness.
in clinical disease 70% of adults has jaundice, adults also develop aversion to smoking.
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chronic hepatitis B infection causes the hepatocellular cytoplasm to fill with hepatitis B surface
antigen. these inclusions are highly specific for hep B and have a finely granular, homogenous,
dull eosinophilic inclusion that give the gound glass appearance.
non-specific changes include heptocyte necrosis (eg balloning degenration) and apoptosis,
steatosis and portal inflammation with mononuclear inclusions (lymphocytes, macrophages)
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replication of the genome occurs with in a newly synthesized capsid containing the full-length viral
mRNA transcript. reverve transcriptase wcich has both RNA- and DNA-dependent DNA
polymerase activity acts on this RNA template to create a single strandewd DNA INTERMEDIATE
THAT IS THEN CONVERTED BACK INTO CIRCULAR, PARTIALLY DOUBLE STRANDED
DNA.the mature capsid is then enveloped by a portion of the endoplasmic reticulum containing
virall-coded proteins to form the completed virion.
.....
serves as a template for both translation of viral proteins (including a polymerae/reverse
transcriptase) and reverse transcription into a single stranded DNA intermediate, converted back
to partially double stranded DNA.
..........
the mature virion (called a dane particle) consists of hexagonal protein core (capsid) caovered with
a lipid bilayer envelope studded with proteins and carbohydrates.
..
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to be ineffective it must be coated externally by HbsAg(encapsulated with HbsAg)
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this is main route.
sexual is less common
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in korea, taiwan, mozambique and china has highest annual rates of HCC, this is due to the
vertical transmission of Hep B virus...
in these countries HCC present in 20-40 years of age as compare to after 60 in the US.
this is prevented by universal hep B vaccination at birth.
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sexual is main route
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mixed cryoglobulinemia is found in patients with hepatitis C. the renal disease is likley due to IgM
deposition in the glomerulus that leads to basement membrane thickening and cellular
proliferation.
.......
chronic hepatitis C infection has been associated with extraheaptic disease is as many as 38% of
infected patients. membranous glomerulopathy and mixed cryoglobulinemia are two examples of
common extrahepatic disease
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Hepatitis B virus infection progresses through two phases: the proliferative phase and the
integrative phase. Note that the virion itself does not have a cytopathic effect. In the integrative
phase, the HBV DNA is incorporated into the host genome of those hepatocytes that survived the
immune response. Infectivity ceases and liver damage tapers off when the antiviral antibodies
appear and viral replication stops. The risk of hepatocellular carcinoma, however, remains
elevated because of the HBV DNA that has been integrated into the host genome. ....... Host
antibody HBsAB neutralizes HBV infectivity by binding to the viral surface antigen HBsAg and
preventing the antigen from interacting with hepatocyte receptors. Note that this neutralization
occurs before the virus enters the hepatocyte, and therefore would not be associated with
hepatocellular damage. Antigens-antobody complexes cause some of the early symptoms of
hepatitic B virus infection (e.g, arthralgias, arthritis, and urticaria) as well as some of the chronic
complications (e.g, immune complex glomerulonephritis, cryohlobulinemia, vasculitis). These
complexes are not responsible for hepatocellular damage. ....... in HBV infection, the risk of
HCC remains elevated due to persistence of HBV DNA in the host genome. This allow continued
transcription of oncogenic viral proteins, such as HBx protein. This protein disrupts cell-cycle
control by activating multiple growth-promoting genes and inactivating the p53 tumor suppressor
protein. ......... the initial clinical presentation during prodomal period is typically describes as "serum sickness-
like" with patients experiencing malaise, fever, skin, rash, pruritis lymphadenopathy and joint pain. anorexia,
nausea , jaundice and right upper quadrant pain may ensue. once serum sickness-like synptoms start to abate
liver markers elevates ............ in acute viral hepatitis AST, ALT rise first followed by increase in bilirubin.
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found within the virus and on infected hepatocytes but does not circulate in the blood stream.
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is the most specific marker for diagnosis of acute infection
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first appear before the onset of symptoms
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nbme,6,3,18
an HIV virus has been isolated that is not inhibited by soluble CD4. mutation are most likely to
have occured in the viral progeny gene encoding>>>>glycoprotein not reverse transcriptase.
explanation
Structural glycoproteins are encoded for by HIV-1 env. gene,viral eversion of humoral immunity is
more likely to occur secoundary to a mutation of the env gene.
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nbme>>4,2,14
In Humans, the CCR5 gene location is on the short (p) arm at position 21 on chromosome 3.
Homozygous carriers of this mutation are resistant to M-tropic strains of HIV-1 infection.
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only the polyprotein product of the env gene is glycosylated to become gp160. the gp160 is then
proteolytically cleaved within the endoplasmic reticulum and Golgi apparatus to from gp120 and
gp41.
transmembrane gp41 anchors gp120 through noncovalent interactions.
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described as RNA-dependent DNA polymerase coupled with DNA-dependent DNA polymerase
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CCR5<>32 deletion>>>>CCR5 is a chemokine receptor.
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tropism; genetic drift,
causes absorption into host cell
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nbme>>>
5,1,21
HIV positive who have decreased CD4 T lympho, likely has decreased>>>IL-2 not antibody
dependent cytotoxicity
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HIV infection of CD4+ T cells i thought to primarily cause cell damage through a direct cytopathic
effect. Activation-induced apoptosis may occur in those uninfected CD4+ T cells that respond to
the MHC-associated HIV peptide displayed on the surface of infected cells.
..............
activation induced apoptosis can occur in uninfected CD4+ T cells as they respond to MHC- class
II associated HIV-peptides on the surface of infected cells..
abnormal intracellular signals transduced by HIV might also prime the infected CD4 + T cell for
apoptosis
............
hypothetically a reduction in CD4+ T cell apoptosis could result if mutation in HIV genome either
changed the MHC class II antigenic peptide on the infected cell or reduced host intracellular
capspase activation.
........
evasion of humoral immune response>>>mutation of HIV-1 env gene, which code for neutralizing
antibodies directed against the epitope of folded viral envelop glycoprotein.
evasion of cellular immune response>>>>due to mutation in HIV-1 epitope recongnized by CD8+
cytotoxic T-cells.
resistance to antiretroviral therapy>>>due to pol-gene mutation which result for emergence of
protease variants and reverse transcriptase that are resistant to protease inhibitor and reverse
transcriptase inhibitor
........
infected cell has direct cytopathic damage.
non-infected cell has HIV induced apoptosis
...........
replication rate is generally positive correlated with the mutation rate.
......
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naf gene> Decreases CD4 and MHC I
expression on host cells;
manipulates T-cell activation
pathways; required for
progression to AIDS.
tat gene> play role in replication.
.........
rev and tat are required for replication.
tat=virulence
nef=progression to AIDS
.........
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primary CNS lymphoma appear macroscopically as a solitary mass within the temporal lobe and
microscopically
as dense cellular aggregates of uniform, atypical lymphoid cells.the majority of primary CNS
lymphomas arise form B-cell.
diffuse large B-cell lymphoma is the most common subtype .the cells of CNS lymphomas are
commonly postive for the B-cell markers CD20 and
CD79a.
primary CNS lymphomas are unversally associated with the EBV.
most of CNS lymphomas are high grade and respond poorly to chemotherapy.
can be diagnosed with EBV PCR in the spinal fluid but definite diagnoses is by biopsy
..........
EBV genome is identified in approximately 50% of systemic B-cell lymphomas and almost all
primary CNS lymphomas occuring in the setitng of HIV infection.
........
ebv infection is present in up tp 90% of normal individuals. with reactivation commin in the
immunocompromised.
EBV is tropic for B lymphocytes mediating their transd=formation into long term proliferating cell
lines.
.....
for some of these lymphomas, the risk seems correlated with a decrease in cytotoxic lymphocytes
specific to EBV
........
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in both hemisphere
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causes progressive dementia,motor deficit and visual impairment.
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most common manifestation of CMV in HIV patients.
the inflammatory vascular sheathing and assicated hemorrahge are suggestive of CMV retinitis.
histologic examination of affected tissue woulg reveal full thickness retinal necrosis and edema,
with eventual replacememnt by atrophic scar tissue.
thought to develop secondary to the hematogenous spread when CD4 count is <50.
the most common complication is retinal detachement due to tearing of thin , atophic scar rissue
that forms in area of prior inflammation.
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disseminated CMV infection can cause diarrhea and hepatitis in immunocompromised
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CMV causes intracytoplasmic and intranuclear inclusions
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solitary is more suspicious of PCNSL but multiple lesion is also common.
on gross examination may be appearing as multiple brain lesions involving the deep gray matter,
white matter and cortex.
suspect in those patient who are unable to respond to toxo therapy for 1-3 weeks
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CD4 <50..
presents with nonspecific symptoms of fever, weight loss, and diarrhea in HIV patient.also have
negative X-ray finding
difficult to distinguish MAC with extrapulmonary tuberculosis.
but marked anemia, hepatosplenomegaly, elevated alkaline phosphatase and lactate
dehydrogenase are more common with MAC due to reticuloendothelial involvement.
In contrast to M tuberculosis MAC grows well at high temperature and will exhibit optimum growth
at 41 C..
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penicillium marneffei: opportunistic infection in AIDS patient in southeast asia.
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have increased risk of TB regardless of their CD4 count
1767
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microglial nodules are formed when microglia surround a neuron and phagocytize it.these structure along with
multinucleated giant cell,are characteristic of viral infection of CNS.especially in HIV associated encephalopathy
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Death in AIDS:
disseminated infection
(CMV, MAI)
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viral particles
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characteristically have polyneuropathy and transverse myelitis along with encephalitis.
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CMV pneumonitis often occur after organ transplantation.
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subacute
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can be ONLY single lesion (inflammation & central necrosis -> ring enchantment on contrast MRI
you see) if MRI not available contraindicated, on double shot contrast CT; Unenhanced: lesion
hypOdense/perifocal edema
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normal CD4 lymphocyte count for adults is 400-1400cells/microL
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nbme,11,1,32
The definitive diagnosis is arrived at from tissue, i.e. a biopsy, by a pathologist.
MRI or contrast enhanced CT classically shows multiple ring-enhancing lesions in the deep white
matter. The major differential diagnosis (based on imaging) is cerebral toxoplasmosis, which is
also prevalent in AIDS patients and also presents with a ring-enhanced lesion, although
toxoplasmosis generally presents with more lesions and the contrast enhancement is typically
more pronounced. imaging techniques cannot distinguish the two conditions with certainty, and
cannot exclude other diagnoses. Thus, patients undergo a brain biopsy
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along with myoclonic jerks
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detection of elevated amounts of 14-3-3 protein in CSF is helpful in diagnosing creutzfeldt-jakob disease.
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fatal familial insomnia is another form of prion disease.
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anterior nares.
both methicilin resistant and sensitive are present.
25-30% of general population is carrier.
risk of infection by this increases after surgery, peritoneal dialysis and hemodialysis.
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intraabdominal infection are polymicrobial with B,fragilis and E.coli being the most prominent organism isolated
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ingestion of undercooked shellfish is associated with vibrio, norwalk virus and hepatitis A infection.
.....................
travlers diarrhea, caused by bacteria (eg ETEC, camplylobacter, salmonella shigella) or less
commonly be parasites (eg giardia) is often due to contaminated water consumption.
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also person to person contact in families and day care centers (this route is important also)
drinking raw unpasteurized milk and after swimming or drinking sewage contaminated water.
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late onset diarhhea(toxin mediated) unlike B.cereus and staph aureus EARLY ONSET
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corynebacterium species,haemophilus,neisseria
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corynebacterium species,pseudomona
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these diseases have long incubation periods, however they are rapidly progressive after the onset of clinical
symptoms
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patients who have received contaminated corneal transplants, implantable electrodes or preparation of growth
hormone.
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in gray matter of brain vacuoles form in the cytoplasm of the neutrophil and neurons, as disease
progresses vacuolated areas transform into cysts. no inflammatory changes are present
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in altered conscious patient it is due to impaired cough reflux and glottic closure.
in patient with stroke and neurodegenrative disease it is due to dysphagia
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generally after influenza virus
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gram negative bacilli accounts for <5% of community acquired pneumonia. however they are
responsible for the majoroty of cases of nosocomial pneumonias and have high mortality rates.
the most common are E.coli, klebsiella, pseudomonas, enterobacter, serratia, proteus and
acinetobacter.
pneumnia caused by gram negative bacilli is rare in healthy individuals and usually occure in
pateitns with immunocompromised (especially neutropenia) and impaired host defenses ( eh
infants, the elderly and alcoholics)
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condiiton associated with osteonecrosis:
1, sickle cells disease>>due to thrombotic occlusion.
2, embolic occlusion> fat emboli, decompression sickness
2, vasculitis>>impaired blood flow eg SLE
3, high dise corticosteroid therapy and alcoholism of femoral head, mechanism is unknown.
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trauma>>leaking CSF>>>mininges>>>>staph aureus most common cause of meningitis.
common after neurosurgery.
staph aureus form the skin enter to CNS
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prevented by intrapartum penicillin or ampicillin
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lymphatic spread from pharynx and afterward hematogenously
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varicella, mumps and adenovirus are among the few viruses spread via respoiratory secretions and capable of
causing aseptic meningitis or encephalitis.
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involvement of metaphyses of long bone, in chikdren is common.as this region contains slow
flowing. sinosoidal vasculature that is conductive of microbial passage..
the epiphyses of long bone is usually sprared in osteomyeltitis unless the acute infection is not
treated.
adults are less likely to develop hematogenous osteomyelitis in the long bones due to changes
assicated with epiphysial colure.
hematogenous osteomyelitis begins with a seeding evnet that causes an acute cellulitis of the
bone marrow.
the resulting inflammaiton within the confined bosy space leads to increased intramedullary
pressure, which comproses blood flow and forces infectious exudate through vascular channels
into the cprtex and periosteal region.
disruption of periosteal blood supply further contributes to boe ischemia, leading to necrosis.
without tratment the infection can progress to chronin suppurative psteomyelotitis, a condition in
necrotic bone (ie sequestrum)serves as a reservoir for infection and becomes covered by a poorly
constructed shell of new bone called an involxurum.
one or more sinus tract develop to drain the purulent material in to the soft tissue or out of the skin
surface.
...............
osteomyelitis of flat bone(eg skull, sternum and bones of the pelvis) occur via contiguous spread
of infection
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antiobiotic coverage should cover both organism in SCD patients osteomyeltitis.
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followed by E Coli.
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this osteomyeltitis is common world wide typically has an indolent presentation.
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we can suspect diagnoses vertebral ostemyelitis in older if they have new neurologic symtptoms
and fever, with or without backpain.
11868
...........
unlike other back pain causing disease.vertebral osteomyelitis pain occur in both, during rest and
exacerbate with motion.
........
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polymicrobial are diabtees(bones of the feet), recumbent pte,(sacrumr and heels), recent trauma
or orthopedic surgery(variable)
646
........
enterocccus can cause osteomyeltits after UTI.
........
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pseudomonas blue green pyocyanin pigment(which can have toxic effect on nearby molecules) cause
ostemyelitis. 1137
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adhesion to collagen is the main virulence factor of staphylococcus aureus in osteomyelitis.
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salmonella with a special capsule called the "Vi antigen" (Vi stands for virulence) that protects it
from opsonization and phagocytosis........
scikling in the intestinal vasculature leads ti areas of necrosis, with the potential for transient
mucosal breakdown and bacterial seeding in pateitns with SCD who may have subclinical or
undiagnosed salmonella infection.
vascoocclusive crises cause focal areas of bone necrosis within which bacteria can easily
establish infections.
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group A strep is second MCC of hemotegnous spread osteomyelitis
646
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typically a disease of children. children>>metaphyses of long bone adults>>vertebra are the most common
location of hematogenous spread in adults after IV drug abuse or vascular catheters
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polio,echo,entero
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hematogenous spread form nasopharynx
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uworld says after 3 months
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physical examination reveals, restricted movement in the affected joints
with no swelling, erythema, or warmth in the surrounding area
microscopic analysis of the wedge-shaped zone of affected bone is notable for dead bony
trabeculae (empty lacunae) and fat necrosis.
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hematoma ove rthe mastoid process (battle sign), along with perorbital ecchymosis and clear
otorrhea, are signs of basilar skull fracture
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a wet mount with epithelial cells and rare leukocytes is consistent with normal vaginal discharge
(leukorrhea)
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antibiotic use is the most common cause of Candida vaginitis due to reduction of the lactobacilli
population, which facilitates Candida overgrowth.
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peritrichous flagella(uniformaly over the entire cell surface)
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This odor is caused by volatilization of amines produced by G vaginalis and other anaerobes.
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Duration of catheterization is the most significant risk factor for UTI. Preventive measures include
avoiding unnecessary catheterization, using sterile technique when inserting the catheter, and
removing the catheter promptly when no longer needed.
....
Bladder irrigation is reserved for patients with hematuria and blood clots and does not prevent UTI.
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most adult women with rubella develop polyarthritis and polyarthralgia as sequela
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with fever and mild hepatitis
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toxo>>>>transfer in first 6 months (2 trimester)
1038
rubella>>>fetal infection occur in first trimester
1575
cmv>>>transfer in first trimester
11551
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prevention is from vaccinating baby and non-pregnant females of child bearing age
1464
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chorioretinitis (most common eye related problem).
also have jaundice, hepatomegaly, splenomegaly and microcephaly
11551
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pulmonary artery hypoplasia or stenosis
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affected neonate also have hepatosplneomegaly, rash and multiple neurological abnormalities
such as seizures, altered muscle tone and ocular movement defects.
.......
also cause microcephaly and mental retardation
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6-15 months
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rash most prominent in skinfolds (eg groin, axillae, antecubital fossa)
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infect mature lymphocytes
1495
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transmitted by the respiratory route, via infected blood, and transplacentally.
incubation period is 7-14 days and infection presents with malaise, coryza, headache and fever
followed by slapped cheeks , usually spares the nasolabial folds.
as the facial rashes fades, an erythematous rash in a reticular (lacelike) pattern appears on the
truck and extremities.
symptoms generally resolve during the following week.
the disease is sometimes complicated by symmetric peripheral arthropathy of the fingers, wrists
and ankles, most commonly in adult females.
............
following a flulke illness.
also have reticular truncal rash besides slapped cheeks.
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infect immature erythrocytes>
rash of erythema infectiosum is result from local immune complex deposition once serum level of
virus-specific IgM and IgG have attained high enough levels.
1495
........
the blood group P antigen, globoside, is a parvovirus B19 receptor that is expressed in high
concentration on mature erythrocytes and erythroid progenitors. as a result, parvovirus B19 is
highly tropic for erythrocyte precursors, particularly pronormoblasts and normoblasts, and
replicates predominantly in the bone marrow. P antigen is also found to a lesser extent on
megakaryocytes, endothelial cells, placental trophoblasts, and fetal liver and heart cells.
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granuloma inguinale (donovanosis): caused by klebsiella grnulomatis>>painless progressive,serpiginous
ulcerative lesions without lymphadenopthy>>>>gram stain and culture are difficult, biopsy show donovan body
11927
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matted/supurative lymphadenitis
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require factor X(enrichment media) to grow
1315
...........
diagnose by gram stain (reveal gram negative rods in a 'school of fish' chain) and culture.
PCR also used
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men who engage in anal intercourse are also at risk for uretheritis caused by
coliform organisms like E-coli
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lesion histologically have mixed granulomatous and neutrophilic imflammation with
intracytoplasmic inclusion bodies
1154
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deep purulent
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tender lymphadenopathy with primary infection.
characteristic vesicles are often absent.
ulcers have characteristic erythematous base
11604
............
also has dysuria due to irritation from ulcers.
tender lymphadenopathy (common with primary genital HSV infection)
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first 3 months>>staph aureus, gram negative rods, anaerobes after 3 months>>staph epidermidus,
propionibacterium spp, enterococcus
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Nulliparity and IUD asso with INC risk of PID. Oral contraceptive/depot
medroxyprogesteroneacetate, dec risk of PID by virtue of the progestin thickening the cervical
mucus and thinning the endometrium.Candida vaginitis typically not involved in the development
of PID.
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this occur in small children, older children and adults has sore throat just
967
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decreased transpor protein expression at the cell surface would would interfere the effectiveness fo drug that require
protein mediated trasnport into the bacterial cell to reach the intended organ (eg fluorquinolones, macroliges and
aminoglycosides)
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cycloserine>>>inhibits incorporation of D-alanine into UDP-MUrNAc-oligopeptide during bacterial
cell wall synthesis.
this bacterial cell wall synthesis inhibitor has a high level of ototoxicity and is rarely used.
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when transpeptidase is inhibited cell wall degredation by bacterial autolysins proceed unchecked.
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irreversibly.
penicllin binding covalentaly to the active site of this enzyme.
(normally this enzyme join amino acid in the third position of one peptidoglycan molecule to the
terminal d-alanine d-alanine of another peptidoglycan molecule)
........
its a D-Alanine-D-Alanine analogue
..........
bacterial death occur due to osmotic lysis due to weakend cell wall integrity
..........
mnay bacterial speciesdsynthsizing multiple different penicillin-binding protein.

strep pneumonia can produce 5 different type of PBP.
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prevents mucopeptide transfer into the growing cell wall, thereby inhibiting the bacterial cell wall
sunthesis.
not an appropiate antibiotic for stable bacterial populations.
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nbme>>>4,4,12
Oral penicillins mainly excreted out Unchanged via kidney by:
.Glomerular Filtration
.Tubular secretion................*inhibited by Probenacid (which increases penicillin's t 1/2)
"Renal insufficiency" making the Drug to stay in the system for longer period of time. (Dose
adjustment is needed in these pts)
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methicilin
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nafcilin,oxacilin bile excreted rest renal
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if organism expressing beta-lactamase require the addition of a beta-lactamase
inhibitor or the use of carabapenem
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undergoes enterohepatic recirculaiton and is excreted primarily in unchanged form in the urine.
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if protein e;lectrophoresis and use od radioautography shows only one band>>>>than antibiotic
resistance is due to beta-lactamase.(this is due to the fact that ceftrizsone is soo much smaller
than the PBP, unbound ceftrizone would likely accumulate at one of the electrodes.
1211
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cefoperazone and ceftriaxone largely eliminated by bile
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bleeding
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renally excreted, ceftrazone>>>liver excreted
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cefamendol,cefoperazone and cefotetan causes hypoprothoombinemia>>bleeding and disulfiram like reaction
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enter CNS except cefoperazone
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only this enter CNS,others no,
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decreases thrush hold of seizure
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cell wall glycoprotein
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sterically hinder the transglycosylation reactions (and indirectly preventing transpeptidation)
involved in elongation of peptidoglycan chains
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alanyl alanine>>>>>> alanine lactate
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is an acquired resistance mediated by plasmid and transposone.
protein are synthesized by resistant enterococci that act as ligases
the most famous of these is vanA ligase.
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dose related
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is a glycopeptide antibiotic...
.............
Vancomycin is also associated with ototoxicity but it is a glycopeptide antibiotic that acts by
directly inhibiting peptidoglycan synthesis, not cell wall cross-linking.
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macrolide also used for this
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treatment of choice for ESBL-producing organisms (E.coli) genes encoding these enzymes are
often located on plasmids this enzyme producing org has resistance to extended-spectrum
penicicllins, cephalosporins and monobactams 11626
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only administered parenterally
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interfering with 30s ribosomal subunit,as a result it is unable to perform protein synthesis.
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with large dose and intrapleural administration.
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the resistant is not chromosomally mediated, it is an acquired resistance mediated by plasmid or tansposone
encoded enzyme ...... an important mechanism of resistance to amino is the methylation of the amino-binding
portion of the ribosome, which inhibits the ability of the amino to interfere with protein translation. ...........
pseudomonas has resistance mechanism to amino by decreased entry into bacterium(porin mutation)
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like clindamycin and macrolide inhibit translocation of peptidyl tRNA from acceptor to donor
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like linezolid
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one of oldest aminoglycoside so due to increase incidence of resistance, this drug only used for
TB, plague(yersinia pestis) and tularemia (francisella tularensis)
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also in oxacilin resistant staph
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pill-induced esophagitis.
........
renal damage when tetra is expired
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thrombocytopenia and leukopenia also.
All these are reversible with drug withdrawl
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unlike metronidazol, clindamycin is effective against anaerobic and aerboic bacteria>>>>so it is a drug of choice in
alchohilics which has lung abscess (which is polymicrbial, anaerobic+aerobic)
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idiosyncratic , irreversible>>>>is severe and fetal with out treatment (eg bone marrow transplant)
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also by production of protein that allow translation even in the presence of tetra
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like quinupristin, dalfopristin but bind to 50s
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optic neuritis
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torsade de point
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it is a weak monoamine oxidase inhibitor thus precipitate serotonin syndrome when use concomitantly with other
serotonergic agents (eg citalopram)
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MAI prophylaxis and treatment>>>>azithromycin
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23S of rRNA 50S subunit
8288
70S in bacterial case
8288
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bactrim(combination)
most important side effects are megaloblastic anemia, stevens jhonson syndrome and toxic
epidermal neccrolysis
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is a folic acid precursor in prokaryotes.
converted to folic acid by dihydropteroate synthase.
human lack the ability to convert PABA to folic acid so dietary folate is required
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PABA analogue
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sirum sickness type 3
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decrease uptake or increase efflux like tetracycline
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salvage pathway can restore metabolic funciton that would otherwise be inhibited by an antibiotic
such as TMP-SMX..
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cause agranulocytosis
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methotrexate also inhibit this enzyme competitively and irreverssibly.
S-phase specific
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nbme>>>2,1,5>>>methylparaba is a derivative of PABA.
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stenotrophomonas maltophilia.
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treatment of bacterial infection that causes exacerbation of COPD, sinusitis and community acquired pneumonia.
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nbme>>>1,4,22>>>ciprofloxacin antimicrovial most likely to be administered orally for the
treatment of potentially serious systemic infection because of its predictible bioavailability
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or topoisomerase gene
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increase CPK (possibly due to muscle fiber membrane disruption).
increase risk of muscle myopathy with concomitant use of statins.
CPK level should be monitered regularly after starting therapy
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bind to DNA within susceptible cell, unraveling the DNAs helical structure and breaking its strands. protein synthesis
is inhibited and cell dies soon thereafter.
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creating transmembrane channel that cause intracellular ion leakage>>>>depolarization of cellular membrane and
macromolecular (DNA, RNA and protein synthesis) inhibition which causes cell death.
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gatifloxacin associated with hypoglycemia...
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causing fracture of the DNA chain
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polymyxin also increases cytoplamiv membrane permeability
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cannot permeate the outer membrane of gram - bacteria>>so it is ineffective against these organism
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eliminate carrier state and prevent from active infection.
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due to spontaneous genetic mutation in DNA dependent RNA-polymerase.
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also causes blood dyscrasis
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or rifampin
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pyrazinamide must be converted to an active form by the mycobacterial enzyme pyrazinamidase.
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monotherapy increases the chance of resistance.
monotherapy may be used for PPD postive pateitn who have negative chest X-ray.
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arbinose into arabinan and then converted into arabinogalactan.
..........
arabinogalactan, one of the key constituents of the mycobacterial cell wall
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also result in decreased visual accuity, central scotoma,
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as the long branched chain fatty acids in the outer portion of the mycobacterial peptidoglycan cell
wall, mycolic acids are essential for proper cell wall structure and virulence factor synthesis (eg
sulfatides, wax D, cord factor).
mycolic acid in the cell wall cause mycobacteria to be acid-fast as they retain the carbolfuscin dye
and resist decoloration by an acid-alcohol decolorizing agent.
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also for atypical mycobacteria
........
ineffective against org other than mycobacterium TB
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resistence by increased activity of enzyme involved in cell wall polysachharide synthesis
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the second mechainism of resistance occur through modification of the protein target binding site for isoniazid
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cause INH induced hepatitis.
direct toxic effect.
occur usually 4-6 months after starting therapy.
in most cases LFTs return to base line with continued therapy.
rarely (<1%) progress to frank hepatitis similar to viral hepatitis and someotmes evolves into a
severe form with progressive liver dysfunction and death.
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by 2 mechanism:
1, compete with vit b6 in neurotrasnismitter synthesis eg GABA
2, increasaes vit b6 excretion
1308
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5th generation ceph
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we give gentamcicn and/or rifampic which kill bacteria on foriegn surface in some
cases of deep seated MR cogulase negative 645
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binds to, disrupts and interfere with the permeability of cell membrane
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TMP/SMX>>>treat skin and soft tissue infections caused by community acquired MRSA but not bacteremic
infection.
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polyene antifungal.
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DNA (replication) and RNA (protein synthesis)
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cell membrane component.
.........
inhibit the demethylation of lanosterol into ergosterol in fungal cells.
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belong to a class of antifungal called allylamines.
Page: 216
only for this
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multiple drug drug interections.
medication such as warfarin, cyclosporine, tacrolimus and oral hypoglycemics should be
avoided(or have their use carefully monitored) in patients who are receiving azole therapy.
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converted by relatively fungus specific enzyme>>>>causes RNA miscoding and inhibition of DNA synthesis.
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is a fluorinated analog of cytosine
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dose dependent nephrotoxicty: can result from a a drug-induced decrease in the glomerular filtration
rate.permanent loss of renal function is thought to be related to the cumulative total dose.
...................... its a main adverse effect all other are due to this. this is due to both decrease in glomerular
filtration rate and direct toxic effect. nephrotoxicity can lead to the anemia (decrease erythropoietin production) and
electrolyte disturbances. hypokalemia and less often hypomagnesemia are common and is due to increase
permeability of of distal tubule ........... the drug causes renal vasoconstriction and reduction in the
glomerular filtration rate. It may also act as a direct toxin on renal epithelial cells, leading to acute
tubular necrosis, renal tubular acidosis and electrolyte disturbances. severe hypokalemia and
hypomagnesemia (likely reflecting increased dital tubular membrane permeability) renal injury may also
lead to decreased erythropoietin production and produce a normochromic normocytic anemia patients
with mucormycosis who respond to initial amphotericin therapy may be switched to posaconazole. Liver
function test monitoring is recommended in patients taking azoles. ..... significant electrolytes
abnormalities : (hypomagnasemia and hypokalemia) can develop.these effects occur in the majority of
patients within the first week of therapy. Electrolytes should be monitored daily and replaced as
needed. Anemia: occurs due to suppression of renal erythropoietin synthesis. This effect may be
severe in patients with HIV who are taking zidovudine (which also suppresses bone marrow
function). Thrombophlebitis: can be seen at the site of injection., ......... Acute infusion-related
reactions , such as fever, chills, rigors, and hypotension, can occur. These are common and are
seen most frequently during initial infusions (often diminish with subsequent infusions).
Premedication with antipyretics and antihistamines can lessen the severity of these effects.
.................. profound hypokalemia can cause ventricular fibrillation or tachycardia, along with ECG finding, flat
T wave, ST depression and prominent U wave
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irreversible retinopathy>>>so baseline and regular eye checkups
718
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not active against cryptococcus neoformans,limited activity against mucor and rhizopus
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niclosamide>>>>inhibit mitcochondrial oxidative phosphorylaion ...............
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increase permeability of cell membrane to calcium>>>paraysis
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it is a main component of aspergillus and candida cell wall.
Page: 217
during metaphase
1195
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only effective against dermatophytes.
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can shorten the course and complication of influenza A and B infections if taken within 48 hours of
the onset of symptoms.
in addition, oseltamivir works to slow viral penetration of the mucous secretion that protest the
respiratory epithelium.
there fore can be used to treat or prevent influenza
..........
oseltamivir is a silaic acid analogue inhibitor
Page: 218
converted into acyclo-GTP in infected cells.
Page: 218
acyclovir treatment during a primary episode can reduce duration of viral sheding,
time to lesional healing, constitutional symptoms, and local pain.
Page: 218
especially when drug used IV.
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thymidine kinase resistant VZV almost exclusively found in AIDS patients.
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docosanol, a topical agent that prevents viral entery, is sometimes used for
herpes labialis, not genital HSV.
Page: 218
acyclovir triphosphate which competes with deoxyguanosine triphosphate for
viral DNA polymerase.
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neuraminidase inhibitor cause the newly synthsized virions to adhere to the host cells surface and
form viral aggreagates, thereby reducing the spread of virus to other host cells.
neuraminidase is required fpr release.
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EBV and CMV do not produce the same TK as HSV and VZV.... at very high intracellular
concentration of acyclovir,some of the drug appars to be activated by unidentified cellular
phosphorylating enzymes.
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gancyclovir triphosphate interfers with human host cell DNA synthesis to a greater extent than does acyclovir
triphosphate.
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foscarnet is a calcium chelator, also causes renal wasting of magnesium, with a reduction is release of PTH which
contributes to hypocalcemia. both hypocalcemia and hypomagnesemia can promote seizure
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neurtropenia is a significant adverse effect of ganciclovir theraoy, and its incidence is increased
with co-administration of zidovudine or TMP-SMX
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foscarnet must be administered intravenously
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or when we have refractory thrombocytopenia due to ganciclovir
1644
or when patient is on zidovudine. because these two causes bone marrow suppression and
resultant accumulated neutropenia.
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1463
side effect are neuropsychiatric symptoms and teratogenicity
Page: 220
prevents assembly and maturation of virions. non-functional and non-infectious virions are
produced instead.
inhibit HIV polyprotein cleavage.
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the full length mRNA also serves as the viral genome that is packaged into newly synthsized virions.
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due to nephrolithiasis.
adecuate hydration is required to prevent.
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side effect is hypersensitivty reaction
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lamivudine is a cytosine analog classified as a nucleoside reverse transcriptase inhibitor. it must
be phosphorylated to its active form, lamivudine triphosphate, by intracellular kinases. lamivudine
inhibits HIV reverse transcription through viral DNA chain termination.
side effects are unusual with lamivudine in contrast with other NRTIs.
occasionaly can cause peripheral neuropathy and lactic acidosis.
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after entery viral RNA is released from nucleocapsid and transcrinbed into double-stranded DNA by reverse
transcriptase.
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abacavir hypersensitivity reaction:
develops in 2-8% of patients and is strongly associated with HLA-B*57:01 allele of human
leukocyte antigen.
direct binding of abacavir to segment of HLA-B*57:01 molecule, which alter the presentation of
self-peptides to the immune system and results in delayed hypersensitivty reaction (type 4) and is
often characterized by malaise. fever, GI symptoms and a delayed rash.
negative test for allele has almost 100% negative predictive value for AHR.
discontinuation of drug results in rapid improvement.
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in side effects also have lipodystrophy
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allosteric inhibitor
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life threatening hepatic failure most likely to occur within first 6 weeks of therapy
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due to myopathy
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uworld says>> inhibit HIV entry by allosteric blocking of HIV gp120 interaction with CCR5 (tropism testing required)
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= protein processing not equal to late protein synthesisi
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inhibit HIV fusion with target cell membrane by binding to gp41. enfuvirtide binds to the heptad repeat 1 (HR1) of
gp41, thereby preventing gp41 from undergoing the conformational changes necessary for the viral membrane to
fuse with the target cellular membrane. as a result HIV genome is unable to gain entry into uninfected CD4 T cells.
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disrupt the ability of Double stranded HIV DNA to integrate into the host cells chromosome, there by preventing host
cell machinery from transcribing viral mRNA
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life threatening skin reactions (steven jhonson syndrome and toxic epidermal necrolysis
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NRTI>>competitive nucleoside/tide RT inhibitor
NNRTI>> allosteric RT inhibitor.
both inhibit HIV DNA synthesis from RNA template by terminating DNA chain elongation.
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triple therapy is given to pregnant mother who is HIV+ regardless of viral load and CD4 count till the end of breast
feeding period. infant is given ZDVprophylaxis for several weeks
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most common SE of ZDV present in 40% of patients.
ZDV produces bone marrow suppression (cause zidovudine inhibit some mammmalian DNA
polymerases)
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thimidine analogue
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side effect>>>asymptomatic macular rash on the palms and soles
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medication induced fat redistribution is a common adverse effect of HAART and can be
considered a product of 2 indiependent processes:wasting of fat from the face and extremities and
deposition of fat in the trunk and viscera.
1, lipoatrophy>>>loss of subcutaneous fat>>>primarily in pateitns take stavudine and zidovudine
and is also associated with protease inhibitor use.
2, central fat depostion>>>also occur in some patients and causes increased abdominal girth.
central fat deposition may be seen with any HIV treatment regimen and may be a result of treating
HIV rather than a specific medication adverse effect.
both syndromes have been associated with metabolic abnormalities including insulin resistance,
hypertriglycerdemia, and reduced HDL cholesterol levels.
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fat redistribution, hypertriglyceridemia.
lipodystrophy>>>>increased fat depositon on the back and abdomen and decreased adipose
tissue on the face, extremities and buttocks.
this give patient a buffalo hump appearence with central obesity and peripheral wasting
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nbme>>3,1,11>>>blockage the cleavage step in active virion production.
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docosanol
topical>>>inhibit entry of HSV virus>>>in herpes labialis, not genital
1551
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delayed type 4 HS reaction
11590
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decreases inflammatory cell movement across the BBB
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mechanism of action is multifactorial
1, incorporated into RNA>>causing hypermutation during RNA-dependent RNA replication, which
is lethal to RNA virus.
2, direct inhibition of HCV RNA polymerase by ribavirin triphosphate
3, rinavirin monophosphate inhibit IMDH
4, inhibit RNA guanyltransferase and methyltrasnferase, resulting in defective 5' cap
formation>>inefficient viral translation
5, enhances Th1 cell mediated immunity while inhibiting Th2 cytokine production.
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IL-28B are associated with better response to these two drugs
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formaldehyde and glutaraldehyde funciton by alkylating and cross-linking DNA and proteins.
they are most commonly used for sterilization of hospital instruments that cannot withstand
autoclave temperatures.
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it is excellent at disinfecting inanimate objects s but is less effective when used on organic
materials.
is often used for skin cleansing and wound debridement due to its effervescent quality
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in combination with 70% alcohol this is a antiseotic of chise for many surgical and percutaneous
procedures.
........
its use is contraindicated in neurologic, otologic and opthlamologic procedures due to neurotoxiciyt
........................
also causes coagulation of cytoplsam
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used for antisepsis in surgical and percutaneous procedures.
less effective than chlorhexidine-alcohol and cause more skin irritation
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require the presence of water for maximal activity and are msot effective at 60-90% concentration. they are
rapidly bactericidal and also tuberculocidal, fungicidal and virucidal, but do not destroy bacterial spores.
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inhibits nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase needed for hepatitis
C virus replication.
it requires intracellular activation.
1644
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this enzyme also inhibited by mycophenolate
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used against a number of DNA and RNA virus
.........
intracellularly phosphorylated(mono,di,tri) by adnosine kinase unlike Acyclovir which is done by
thymidine kinase
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alpha and beta interferons work either by autocrine or paracrine manner results in tranmscription
of antiviral enzymes capable of halting protein synthesis, scuh as RNase L(ENDONUCLEASE
THAT DEGRADES ALL rna in the cell) and protein kinase R (inactivates elF-2, inhibiting
translation initiaion).
however these enzymes become active only in the presence of double stranded rna,which forms
in infected cells as a result of viral replication
1468
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beside preganancy also avoid in before 8 year of age
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tetracycline localize in dentin(coloration) and enamel of decidious teeth(milk) (enamel hypoplasia)
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give nitrofurantoin instead
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caspases are a family of proteases (cysteine) that are essential for apoptosis. they also play a role in necrosis and
inflammation.
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although the cell membrane remain intact during apoptosis but cell becomes an appealing target for phagocytosis
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activated T cell express FAS ligand which bind on the same cell or nearby cell
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form trimeric structure
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first there is stimulation of initiator caspases (8 and 10) which ultimately activates executionar caspases (3 and 6)
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FAS receptor express on T lymphocytes
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and Bim
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which contain intracellular proinflammatory content that are not released into circulation so not followed by
inflammation
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the process of apoptosis involves the following steps. 1, initiation: cells damaged by ultraviolet light, heat,
hypoxia, toxins or radiation display intrinsic apoptotic signals (e.g, phosphatidylserine or
thrombospondin) on their plasma membranes. Extrinsic apoptosis, in contrast, is induced by the tumor
necrosis factor (TNF) when bound to tumor necrosis factor receptor 1 (TNFR1) or the Fas ligand when
bound to cell surface receptor Fas. 2, control: mediated by a group of bcl-2, some of the component of this system
are proapoptotic ( eg bak, bax, bimproteins), whike other are antiapoptotic ( eg bcl-x, bcl-2), imbalance are
responsible for the formation of the mitochondrial permeability transition (MPT) and the release of
cytochrome c and other pro-apoptotic proteins into the cytoplasm. In extrinsic apoptotic, the binding of the
death ligand and the death receptor allows for pro-caspase molecule to be brought into close proximity. 3,
destruction: both intrinsic and extrinsci pathway converge at this step, resulting in caspase
activation,caspase are proteolytic enzyme that destroy cell components.They contain cysteine and are
able to cleave aspartic acid residues. The eleven caspases that have been identified are classified as
either initiator or effector caspases. Initiator caspases activate the effector caspases, which then cleave the
cellular proteins.
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(due to fat content)>>>>>due to ischemic damage to brain ..... brain has predilection for liquefactive necrosis
due to large amount of lipids and lysosomal enzymes in the nervous tissues.
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and testes
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and diabetes mellitus
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it result from immune complexes and/or plasma protein (eg fibrin) leaking through damaged intima and being
deposited within vessel wall. ........ IC, complement and plasma proteins form fibrin like eosinophilic deposits
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or wide spread tissue destruction by bacterial infection.
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nbme,6,3,28 in Myocardial ischemia, degredation of membrane lipid bilayer and cytoskeletal proteins occurs following
activation of intracellular phospholipase A2 and proteases.an increase most directly responsible for activation of
those enzymes are >>>>calcium ion concentration explanation. 1.Lack of oxygen causes the neuron's normal
process for making ATP for energy to fail. 2.The cell switches to anaerobic metabolism, producing lactic acid. 3.ATP-
reliant ion transport pumps fail, causing the cell to become depolarized, allowing ions, including calcium (Ca++), to
flow into the cell. 4.The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels
get too high. 5.The presence of calcium triggers the release of the excitatory amino acid neurotransmitter
glutamate. 6.Glutamate stimulates AMPA receptors and Ca++-permeable NMDA receptors, which open to
allow more calcium into cells. 7.Excess calcium entry overexcites cells and causes the generation of harmful
chemicals like free radicals, reactive oxygen species and calcium-dependent enzymes such as calpain,
endonucleases, ATPases, and phospholipases in a process called excitotoxicity. ] Calcium can also cause the
release of more glutamate. 8.As the cell's membrane is broken down by phospholipases, it becomes more
permeable, and more ions and harmful chemicals flow into the cell. 9.Mitochondria break down, releasing toxins and
apoptotic factors into the cell. 10.The caspase-dependent apoptosis cascade is initiated, causing cells to "commit
suicide." 11.If the cell dies through necrosis, it releases glutamate and toxic chemicals into the environment around
it. Toxins poison nearby neurons, and glutamate can overexcite them. 12.If and when the brain is reperfused, a
number of factors lead to reperfusion injury. 13.An inflammatory response is mounted, and phagocytic cells engulf
damaged but still viable tissue. 14.Harmful chemicals damage the blood brain barrier. 15.Cerebral edema (swelling of
the brain) occurs due to leakage of large molecules like albumins from blood vessels through the damaged blood
brain barrier. These large molecules pull water into the brain tissue after them by osmosis. This "vasogenic edema"
causes compression of and damag. ........................... ....AMPA The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid receptor (also known as AMPA receptor) is a non-NMDA-type ionotropic transmembrane receptor for glutamate
that mediates fast synaptic transmission in the central nervous system (CNS). .....NMDA (N-methyl D-aspartate) The
NMDAR is a specific type of ionotropic glutamate receptor....................... Ca activate: 1-phospholipase
A2................Hydrolyses the membrane phospholipids 2-proteases (e.g Calpain).......degrade the cytoskeleton and
integral membrane proteins. 3-endonucleases....................breakdown neucleic acid 4-lipases and other enzymes it's
like a cell demolisher. -In the given stem, it's the Ischemic process in cardiac cells. -In case of Brain Ischemia ,
damage is called "Excitotoxin-mediated" cz it is the Glutamate and Aspartate (two Excitatory Neurotransmitters)
that + the Ca-Influx via NMDA-receptors and leading to cell destruction, therefore these Excitatory transmitters
are called here as toxins (Excitotxins) as they are mediating cell death by above process.
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is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or
apoptosis
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chromatin dissolution due to action of DNAses and RNAses
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possible due to decrease in intracellular Ph.
also have disaggregaiton of fibrillar and granular elements of nucleus.
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IMA nad hypogastric artery
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fatty change>>majorly in hepatocyes but also in skeletal muscle and renal cells.>>>>>due to
decrease synthesis of protein (apolipoprotein)
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nbme>>>2,2,49>>>>stressed myocardial cell that has no calcium gradient across its plasma
membrane most likely has undergone>>>>cell death not reversible cell injury
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destructive fragmentation of the pyknotic nucleus of a dying cell whereby its chromatin is
distributed irregularly throughout the cytoplasm.
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when blood flow cannot meet myocardial demand, anaerobinc metabolism results.
however anaerobic metabolism cannot maintian proper intracellular ATP levels, and ADP, AMP
and adenosine accumulate.
without ATP , NAk ATPase pump and and Ca-ATPase pump fail.
leadinng to increased intracellular Na and Ca and intramitochondrial Ca concentration..these
attract free water causing cellular and mitochondrial swelling.
failure of the sarcoplasmic reticulum to resequester Ca leads to cessation of contraction within
ischmic zones of myocardium..............
ischemia causes a net solute gain within cardiac myocytes.
.............
myofibril relaxation also occur within 30 minutes of ischemia and is due to ATP depletion and
lactate accumulation.
.................
decrease glycogen>>>early sign.
to provide energy by anaerobic glycolysis by degrading cell glycogen store.
in myocytes it occur within 30 minutes of ischemia
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nbme>>>5,1,7
NT release in excess following ischemia and can initiate a receptor mediated Ca influx that leads
to neuronal death>>>>Glutamate.
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testicles also but has single supply
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arteriolar dilation
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by macrophage presentation to CD4 helper T-cell to activate them.
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macrophage wall off(fibrosis) by fibrogenic growth factor and cytokines
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Continued acute inflammation—marked by persistent pus formation; IL-8 from
macrophages recruits additional neutrophils
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macrophages with abundant pale pink granular cytoplasm.CD 14+ .........
although granuloma may be surrounded by a collar of mononuclear leukocytes, mainly
lymphocytes (possibly including CD4+T cells) and some plasma cells, these are distinct from large
epitheloid cells that are almost always present in granulomas.
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by macrophage release of IL-10 and TGF-beta
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not depend on time but depend on response of cell.
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post capiilary venules
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occur in localized areas of prior necrosis, caseation, or scarring or with aging in the cartilaginous rings of
the bronchial tree
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due to fibroblast and endothelial death secondary to chronic hemodynamic stress (can be accentuated by valvular
abnormalities) or atherosclerotic inflammation.
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typically occur in more alkaline tissues involved in acid excretion, such as kidney, lungs, systemic
arteries and gastric mucosa.
...............
typically occur in the walls of airways, alveoli, and/or blood vessels.
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grossly appear as fine, gritty, white granules or clumps.
on H and E staining>>>appear as dark purple.
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or in cartilegenous ring of bronchial tree
........
with aging in these two locations
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in areas of necrosis that escape removal by macrophages.
dystrophic calcificaiton is a hallmark of cell injury and death.
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milder form>>no delay in separation of umbilical cord.
LFA 2>>>impaired fucosylation of sialylated carbohydrate ligands prevent selectin binding
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marker of hematopoetic stem cell
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silalyl lewis or PSGL-1
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absence CD 18 leads to inability to synthesize beta-2 integrin MAC-1 and LFA-1, affecting tight adhesion, crawling
and migration.
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platelet endothelial cellular adhesion molecule>>>is a member of the immunoglobulin family of
proteins>>>>present at the peripheral intercellular junction of endothelial cells............
CD31 is positive in liver angiosarcoma.
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inter cellular adhesion molecule
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LAD 3 is similar to type 1 and is also very severe disease. LAD 3>>>>impaired cytokine signaling prevents integrin
activation
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adhesion molecule>>besides having role in neutrophil margination also aids entry of lymphocytes from the blood
into lymphoid tissues
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release from Weibel Patade bodies is mediated by histamine
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also in liver angiosarcoma affected
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it is involved in tumorigenesis, inflammation and atherosclerosis due to free radical formation.
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P450 mediated
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macrophage dnt have effcient Oxygen dependent killing rather has oxygen independent killing. unlike neutrophil
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most dangerous free radical is hydroxyl free radical (OH)
........
Physiologic generation of free radicals occurs during oxidative phosphorylation.
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type 1 collagen
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thick, pink collagen bundles
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nbme>>>3,3,5
injury due to reperfusion is due to>>>superoxide radical not hydrogen peroxide.
explanation
High oxygen concentration produces superoxide anion which in turn produces hydroxyl and
peroxide free readicals
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excessive granulation tissue formation
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like many other toxic substances, CCL4 is oxidized by the P450 oxidase system in the liver.this
result in the formation of the free radical CCL3, which react with structurla lipid of cell membrane.
this result in lipid degredation and hydrogen peroxide (H2O2) formaiton.
this process is called lipid peroxidation.
the peroxides go on to form new radicals, continuing the vicious cicle of lipid degredation.
CCL4 cell injury develops rapidly and leads to swelling of the endoplasmic reticulum, dectruciton
of mitochondria ad increased permeability of cell membrane.
this process culminate in hepatocyte necrosis.
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also called retrolental fibroplasia
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Cu and Fe
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by oxidation and cause apoptosis
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both have problem in TFG-beta
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Zn containing enzyme . IL-1 Stimulates synthesis of metalloproteinases (i.e., enzymes containing
trace metals) .................. degrade basment membrane and ECM whihc are primarliy composed of
lamininn and collagen 4 and 7
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although the proinflammatory nature of IL-1 can induce the release of other proinflammatory cytokines that trigger
cellular VEGF expression.IL-1 does not appear to directly stimulate angiogenesis. Similarly although
interferon-y can indirectly promote neovascularization through activation of macrophages (can
release VEGF), it does not appear to directly stimulate angiogenesis.
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nbme,11,1,29.>>wrong question number before the blister resolves,epithelium forms at the base of the blister,this is
done by>>>basal layer keratinocytes not be firbosblasr not macrphalges not epithelial langhans cell... explanation.
The formation of granulation tissue in an open wound allows the reepithelialization phase to take place, as epithelial
cells migrate across the new tissue to form a barrier between the wound and the environment.[29] Basal
keratinocytes from the wound edges and dermal appendages such as hair follicles, sweat glands and
sebacious (oil) glands are the main cells responsible for the epithelialization phase of wound healing.[34] They
advance in a sheet across the wound site and proliferate at its edges, ceasing movement when they meet in the
middle. Keratinocytes migrate without first proliferating.[35] Migration can begin as early as a few hours after
wounding. However, epithelial cells require viable tissue to migrate across, so if the wound is deep it must first
be filled with granulation tissue.[36] Thus the time of onset of migration is variable and may occur about one day
after wounding.[37] Cells on the wound margins proliferate on the second and third day post-wounding in order
to provide more cells for migration
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Mediated by paracrine signaling via growth factors
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growth factor for endothelium, smooth muscle,
and fibroblasts
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MMP are enzymes capable of degrading various extracellular matrix proteins and
processing a number of bioactive molecules. they may be involved in cytokine
inactivation.
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Involve in wound repair,and also stimulates osteoblast(bone matrix formation) ..... regulate chondrogenesis and
osteogenesis ......................
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also inhibits inflammation>>>by suppressing TH-1 response along with IL-10
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granuloma often form after tissue macrophages encounter pathogens or substances that cannot
be easily digested or removed.
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hepatic granulomatosis is associated with treatment with methyldopa, hydralazine and quinidine
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after engulfing pathogen concomitent macrophge IL-12 secretion induces the T helper cells to differentiate into the
Th1 subtype.
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invasive aspergillosis also has granuloma
108.
actinomyces
11638
.........
brucella spp
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fibroblast are thin, spnidle shaped cells.................... maturation phase (scar formation)>>>starts the second week.
during this phase active fibroblast activity noted
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from activated macrophages>>>>which act to recruit additional monocytes and macrophages to the area.
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multinucleated giant cells appear to have low phagocytic activity, which may help the organism evade the immune
response.
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fibroblast proliferation and collagen production contribute to caseating granuloma formation.
fibroblast are thin, spnidle shaped cells
.........
central necrosis in granuloma is either due to hypoxia or free radical damage.
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by collagenase enzyme which require Zn.
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Amplification(mutattion)>>>> causes lung (erbb1) and breast (erbb2)
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MMP is important in wound healing, as it encourages both myofibroblast accumulation at the wound edges and scar
tissue remodeling. the amassed myofibroblasts initiates wound contraction during healing by second intention.
"contractures" may occur when unusually pronounced MMP activity results in excessive wound contraction.
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synthesized by most cells in the body>>arrest of the cell cycle ( leading to its action as a tumor suppressor
agent), promotion of angiogenesis ( leading to its action as an agent allowing tumor metastasis to survive after
they become resistant to TGF) and stimulation of fibroblast to lay down extracellular matrix ( leading to its
implication in atherosclerosis and fibrotic disease) ................. TGF-beta is critical for stimulating connective
tissue synthesis and remodeling of the extracellular matrix. its activity typiclaly decreases during maturation
phase of wound healing to limit the amount of collagenous scar tissue. hypertrophic or disfiguring scar caused by
persistently elevated TGF-beta, which leads to inclreases fibroblast proliferation and activity. hypertrophic scar often
have altered TGF signaling due to increased TGF-beta expression ...... TGF:-epithelial and fibroblast
growth factor
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fibroblast migration and proliferation are controlled by multiple growth factor including PDGF and TGF-beta
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PAF typically causes vasoconstriction, bronchoconstriciton and platelet stimulaiton. in very small amount causes
vasodilation and increased vascular permeability. PAF also enhance leukocyte adhesion to endothelium,
chemotaxis,phagocytosis and degranulaiton. ............... PAF is a secondary inflammaotry mediator released by
activated mast cells that may promote bronchospasm and bronchial mucoal cellular infiltration.
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Angiogenesis (blood vessel formation) is predominantly driven by the following 2 substances.: ・ Vasuclar
endothelial growth factor (VEGF): VEGF stimulates angiogenesis in a variety of tissues (normal,
chronically inflamed, healing or neoplastic). As VEGF increases endothelial cell motility and proliferation,
new capillaries being to sprout. ・ Fibroblast growth factor (FGF): FGF-2 is produced by a wide range of
cells and is involved in endothelial cell proliferation, migration and differentiation, FGF-2 also appears to
play an important role in embryogenesis by stimulating angioblast production. As a group, FGFs, not only
contribute to angiogenesis, but also to embryonic development, hematopoiesis and wound repair (by
recruiting macrophages, fibroblast, and endothelial cells to damaged tissues). the laminin is basement
membranes may pose a physical barrier to the sprouting of new blood vessels. ..........................
VEGF Stimulates angiogenesis (embryonic angiogenesis, particularly in the heart), repair of
tissue, cancer angiogenesis (stimulates from preexisting vessels) Stimulation factors: TNF
released by macrophages, hypoxia via hypoxia-inducible factor released by cells
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and in tumor invasion through the basement membrane(laminin) and connective tissue(fibronectin)>>>this i done by
tumor cell secretion of metalloproteinase and cathepsin-d protease
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nbme,11,2,10
Transudate Exudate
Main causes Increased hydrostatic
pressure,
Decreased colloid
osmotic pressure Inflammation
Appearance Clear Cloudy
Specific gravity < 1.012 > 1.020
Protein content < 2 g/dL > 2.9 g/dL
fluid protein
serum protein < 0.5 > 0.5
Difference of
albumin content
with blood albumin > 1.2 g/dL < 1.2 g/dL
fluid LDH
upper limit for serum < 0.6 or < ⅔ > 0.6 or > ⅔
Cholesterol content < 45 mg/dL > 45 mg/dL
*Types***
Purulent or suppurative exudate consists of plasma with both active and dead neutrophils,
fibrinogen, and necrotic parenchymal cells. This kind of exudate is consistent with more severe
infections, and is commonly referred to as pus.
Fibrinous exudate is composed mainly of fibrinogen and fibrin. It is characteristic of rheumatic

carditis, but is seen in all severe injuries such as strep throat and bacterial pneumonia. Fibrinous
inflammation is often difficult to resolve due to the fact that blood vessels grow into the exudate
and fill the space that was occupied by fibrin. Often, large amounts of antibiotics are necessary for
resolution.
Catarrhal exudate is seen in the nose and throat and is characterized by a high content of mucus.
Serous exudate (sometimes classified as serous transudate) is usually seen in mild inflammation,
with little protein content. Its consistency resembles that of serum, and can usually be seen in
certain disease states like tuberculosis. (See below for difference between transudate and
exudate)
Malignant (or cancerous) pleural effusion is effusion where cancer cells are present. It is usually
classified as exudate.
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derived from insulin
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lipofuscin (the result of indigestible byproducts of subcellular membrane lipid oxidation) ....... lipofuscin>>>lipid
polymer and protein complexed phospholipid.
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is a product of lipid peroxidation and free radical injury
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in pituitary gland>>>prolactin deposit
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FMF is due to a dysfunction of neutrophils (autosomal recessive) and occurs in persons of
Mediterranean origin. i. Presents with episodes of fever and acute serosal inflammation (can
mimic appendicitis, arthritis, or myocardial infarction) ii. High SAA during attacks deposits as AA
amyloid in tissues.
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especially in cachexia and malnourished individuals
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prussian blue stain differentiate b/w this and Iron deposits intacellularly
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irreversible and can only be treated by organ transplantation.
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mutation of the TTR gene results in misfolding and extracellular tissue deposition of transthyretin protein
(also known as prealbumin) which can cause familial amyloid polyneuropathy or familial amyloid
cardiomyopathy.
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production of keratin pearls by skin tumor cells is an example of dysplasia (ie disordered growth)
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in atrophy due to decrease workload first there is decrease in cell size, then decrease in number.
bone resorption also increases, resulting in condition describes as 'osteoporosis of disuse'
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anaplastic tumors demonstrate following features. 1, loss of cell polarity with complete disruption of normal tissue
architecture;cells coalesce into sheets or islands in a disorganized, infiltrative fashion. 2, significant variation in the
shape and size of cells (cellular pleomorphisim) and nuclei (nuclear pleomorphisim) 3, disproportinaly large nuclei that
are often deeep-staining (hyperchromic) with abundant, coarsely-clumped chromatin and large nucleoli. 4,
numerous, often abnormal, mitotic figures. 5, giant, multinucleated tumor cells.
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after squamous metaplasia it produces keratrin pearl.
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degrade collagen 4, 7 and also laminin
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cerebrovascular 3rd..
or respiratory 3rd????????????
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CD31 is positive in liver angiosarcoma.
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in children 1st accident
2nd cancer
3rd congenital defects
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most important prognostic factor.
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common location are axillae,posterior neck, and groin. other location are palm, soles, mucosal membrane and
vermilion border. lesion appear as hyperkeratotic, hyperpigemneted plaques with a classic valvety texture. skin tags
(achocordons) are pedunculated outgrowths of normal skin that are commonly present on regions affected by
aconthosis nigricans
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eg in diabtics, acromegaly and obesity. increased level of insulin and Insulin like growth factor stimulates epidermal
and dermal proliferation.
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HHM humoral hypercalcemia of maliganncy>>>hypercalcemia is very severe in it>>complication
include
1. polyuria (due to decreased concentrating ability of distal tubule)
2. nephrolithiasis
3. gastriintestinal
4. neuropsychaitric symptoms
.............
Low parathyroid hormone serum levels together with high calcium levels in a cancer patient may
suggest a CIH (cancer induced hypercalcemia)
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person with metatstic disease form cancer can cause these symptoms, but in addition aslo has
headache or decreased consiousness due to mass effect,
also autopsy will show metastatoc cells with surrounding inflammation instesad of purkinje cell
degeneration.
..............
cerebellar infarction has different finding on autospys>>>> liquafactive necrosis
(acute infarct) and glial scar (chronic infarct).
so these three condition have different autospy finding
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PRCA pathogenesis often involve the inhibition of eythropoetic precursor and progenitor by IgG
autoantibodies or cytotoxic T lymphocytes,
it has been associated with immune system diseases such as thymoma and lymphocytic
leukemia.
thymoma removel can occasionaly cure PRCA.so all patient with PRCA should have chest CT
scan
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closely related to PTH at the bioactive amino terminal region.
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GI and GU.
gastric adenocarcinoma is the most common cause.
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Paraneoplastic syndromes can occur due to the production of hormone-like substances from tumor cells.
They can also result from immune reactions against tumor cells that cross-react with normal cells,
causing dysfunction and/or damage to healthy organs and tissues.
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nbme>>>>4,4,7
some oncgogene are mutants of normal cell-surface receptors that have tyrosine protien kinase
motifs in their cytoplasmic domain. the type of mutation of such receptor is most likely to result
in>>>>constitutive activation of cellular transcription. not a deletion of cytoplasmic domain,or
failure to become phosphorylated upon receiving the signal, or failure to receive signal that
normally activates cellular transcription, or recognition of different signal than usual.
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mutations of the genes that codes for the epidermal growth factor receptors are associated with non-
small cell lung carcinoma (erbB1), breast cancer (erbB2 aka HER2/neu), and some ovarian and gastric
tumor. ........... ERB-B1 >>>>squamous cell carcinoma of lung
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BRCA1 and BRCA2 in particular are involved in repair of double-stranded DNA breaks inherited in an
autosomal dominant manner with variable penetrance. Affected women have a 70%-80% lifetime risk
for developing breast cancer.
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the sis protooncogene encodes platelet-derived growth factor. overexpression of sis is seen in astrocytomas
and osteosarcomas
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codes for 185KD transmembrane glycoprotein that has intracellular tyrosine kinase activity
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and endometrial cancers also
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small cell type
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amplified in this
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MAP-kinase associated pathway.over expression of this gene leads to increases sensitivity of cells
to mitogenic stimuli.
this mutation occur in large number of cancers.
...........
mitogen activated protein kinase associated signaling pathway.
mutated ras results in an increased cell response to GF stimulaiton.
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sporadic colon cancer and melanoma.
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it is a key suppressor of RAS,one of the more powerful activators of cell growth and proliferation.
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located on chromosoe 13q14
activated (dephosphorylated)
inactivated (hyperphosphorylated)
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most common ocular tumor of childhood. usually presents with a white pupillary reflex (leukocoria) in children <5 years
old. approximately 60% of retinoblastomas are sporadic (usually unilateral), while 40% are familial (often, but not
always bilateral) children with sporadic form are not at risk for other maligannacies, while patients with familial form
often develop other tumors usuallu sarcomas , later in life. familial form>>>>germ line mutation(mutation present in
all cells), second mutation sporadicaly in retina sporadic form>>>both mutation are acquired sporadically
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cyclin D is a protein that regulates cell cycle.its overexpression seen in breast,lung,esophagal cancer and mantle
cell lymphoma
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this gene is responsible for maintaining low level of beta-catenin(which is oncogenic) and for intercellular adhesion.
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nf1>>>17 nf2>>>22
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tsc1>>>ch 9 tsc2>>>>ch16
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which is Protien kinase B is a serine/threonine specific protein kinase, AKT in
activated form activates mTOR(mamalian target of rapamycin), whihc translocates
to the nucleus to induce gene inviolved in cell survival, anti apoptosis and
angiogenesis
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the p27 protein is a cell cycle inhibitor. it acts during the G1 phase by inhibiitng cyclin-dependent
kinases.normal tissues contain high levels of p27, while malignant tissue contain very low levels of
p27. upregulation of p27 would stop the cell cycle
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breast adenocarcinoma, small cell carcinoma of the lung and bladder carcinoma
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when the cell is stimulated by growth factor, activation of cyclin D, cyclin E, and the corresponding cyclin kinases
(CDK 4 and 6) occurs and the Rb protein is hyperphosphorylated( randering it inactive).hyperphosphorylated Rb
releases E2F transcription factor, which allows the cell to progress through the G1-S checkpoint.
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autosomal dominant>>>person inherit one mutant allele, other one get by sporadic mutation in ones life before age
45>>>>also have family history of breast, brain, adrenal cortex, sarcomas and leukemias in less than 45 years old
family members.
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prostate cancer also in men
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sporadic
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ras is a protooncogene that codes for a membrane-bound G protein. this G-protein acts as a secondary mediator
for several hormones and cytokines that act on cell membrane receptors. ras activation activates the MAP kinase
pathway and ultimately affects transcription. ras itself does not bind directly to DNA.
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located on chromosome 2
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in diminutive amounts also present in normal breast and ovarian cells
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in 20% of patients.
overexpression is often associated with aggressive tumor.
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in adult population.bad prognostic sign
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TGF-alpha>>>astrcytoma and hepatocellular carcinoma
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N-MYC also with small cell carcinoma of the lung
1627.
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A large number of malignancies are associated with aberrant signal transduction. For example,
overexpression of HER2 (a receptor tyrosine kinase involved in growth signal transduction) causes the
development of certain types of aggressive breast cancer. Unlike BRCA1 and BRCA2, HER2 mutations
are acquired, not inherited.
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phosphatase and tensin homolog>>>convert PIP3 to PIP2
8623
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also causes primary effusion lymphoma(arises from B-cells), most commonly in HIV infected.
histologically>>>large cells, big nuclei and prominent nucleoli.
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it is found in cigarette smoke,
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nbme,11,1,7
2-naphthaylamine>>>acivated in he liver but quickly deactivated by conugation to glururonic acid,
in the bladder glucuronidase re-activates it by deconjugation, whihc leads to development of
bladder cancer
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chinese adults or african childrens
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normally present in renal, intestinal and endothelial of capillaries forming BBB
1819
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ATP dependent efflux pump..,,,
has specificity for hydrophobic compounds
1819
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can do both decrease influx into cytosol and increase efflux out of cytosol.
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also called non-seminomatous testicular and ovarian carcinoma.
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is a glycoprotein involved in cell adhesion.
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by fetal liver and yolk cell.
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Multidrug resistance to chemotherapeutic drugs such as (vincristine, doxorubicin,
dactinomycin) occurs due to stepwise selection and amplification of gene that codes for a
transmembrane protein (P-glycoprotein)...this transmembrane P-protein is ATP-dependent
pump, which has six membrane-spanning loops forming a central channel for pumping of drugs
from the cell.... Note: P-glycoprotein is normally expressed at low levels in most cell types...
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also inhibit influx of drugs
1819
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verapamil, diltiazem and ketoconazol inhibits P-glycoprotein
1819
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osteoblastic>>>small cell lung carcinoma, and hodgkin lymphoma
osteolytic>>>>non-small cell lung carcinoma, non-hogdkin lymphoma, melanoma.
mixed>>>GI
11754
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common location is water shed area.. multiple location>>>lung and melanoma single location>>>breast,
colon, kidney
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autopsy will show metastatoc cells with surrounding inflammation
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In secondary active transport, this energy is generated by co-transport of a separate substance
down its concentration gradient. Transport of glucose against the concentration gradient occurs
via the Na/glucose symporter,which is found in the intestinal and renal tubular epithelium and is
used to transfer glucose intracellularly from the lumen.
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NBME,11,2,20
D-Noncompetitive Antagonist
This is the case on the concept of "Spare Receptors"
Assume ...100% receptor occupancy required by an Agonist to exert Maximum Effect (Emax) /
Optimal effect.
and now consider, if Emax is achieved with result
*Efficacy of Drug X decreases

*5 of the spare receptors are still Unoccupied
Now if we raise the drug "X" dosage.....it will bind to the remaining unoccupied spare receptors
and brings it Efficacy back to to the Emax.
there for "No Change in Efficacy" , only "Potency decreases"(as needed higher dose of Drug X)
---------------------------------Graph on the Right--------------------------
But at "High Dose" of of NCA (Drug Y), it will bind to e.g all the 10 spare receptors---->result
*Efficacy(Emax) of Drug X decreases

*there are non of the spare receptors left unoccupied
since there are no extra receptors left, even if we raise the Drug "X" dosage, it won't be able to
increase it's Efficacy back to Emax.
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covalent bonding
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the amount of decrease depend on dose of the inhibitor
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ionic bonding
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Pharmacodynamic potentiation is defined as a greater than additive effect that occurs when 2
different drugs are administered simultaneously due to functional interactions within the target
tissues.
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Transport across the cell membrane by carrier proteins (which undergo conformational changes
as the substrate is transported, unlikely channel proteins) is termed carrier-mediated transport.
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hypothetical volume of fluid into which the administered amount of the drug would need to be uniformly distributed to
produce the observed plasma concentration.
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avg total body water is 41 lit, of that extracellular fluid volume is 14 lit, or 1/3 of total. with in
extracellular plasma volume is 3 lit and intersticial fluid make up the rest.
low Vd>>>3-5 lit
medium Vd>>>14 lit
highest Vd>>>41 lit
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generally we use this equation in 1 compartment model with linear pharmacokinetics( cause
mutliple compartment will have different distribution and elimination phases)
...........
half-life of drug depends on physiochemical properties of drugs such as lipid solubility, protein
binding, volume of distribution, and metabolic conversion or elimination pathway
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also intracellularly
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nbme>>>3,4,9
so afeter 1 half life cocn in plsam will be 50%
2 half life = 75%
3half life=87.5%
4half life =93.75%
5half life =97%
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certain drugs are hydrolyzed by plasma esterases, which rapidly cleave ester linkages after drugs
enters the circulation. This rapid inactivation allows for the short duration of action of thse
medications. Many drugs used in anesthesia (eg, succinylcholine, tetracaine, remifentanil) are
metabolzed by plasma hydrolysis.
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enzymes are saturated
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other nonmicrosomal metabolism:
1 Monoamine oxidases:dopamine,
norepinephrine,serotonin and tyramine.
2 Alcohol metabolism:
Genetic polymorphisms exist(bimodality)
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Nonmicrosomal metabolism: includes esterases and amidases,, Genetic polymorphism exists with
pseudocholinesterases,,, Example: local anesthetics and succinylcholine,,,
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no bimodality(genetic polymorphism) eg morphine and chloramphenicol. reduced activity in neonates
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other conjugation type:
1 gluthathione
2 methylation: important in azathioprine and 6-mercaptopurine.
,,............
g;uthatione-s-transferase is involved in the detoxification of some chemical carcinogens, unlike
cytochrome p450 oxidase, this enzyme converts toxic substances into inactive metabolites
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most chemical carcinogen enter the body in an inactive form as procarcinogen.
these procarcinogen is converted into carcinogen by cyto P450 enzyme (microsomal
monooxygenase)
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bimodality exists such as in HIPD
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nbme>>>2,3,50
Drug metabolism is by 2 ways in liver
-
phase I = by CYP 450
it involves rduction ;oxidation and and during this process free radicals are produced which, if
excessive, can damage the liver cells.
Antioxidants reduce the damage caused by these free radicals. If antioxidants are lacking and
toxin exposure is high, toxic chemicals become far more dangerous.
Some may be converted from relatively harmless substances into potentially carcinogenic
substances.
Geriatric pts loose phase I 1st so we try and avoid to give drugs which are metabolised by phase I
phaseII
This is called the conjugation pathway, whereby the liver cells add another substance (eg.
cysteine, glycine or a sulphur molecule) to a toxic chemical or drug, to render it less harmful. This
makes the toxin or drug water-soluble, so it can then be excreted from the body via watery fluids
such as bile or urine. Individual xenobiotics and metabolites usually follow one or two distinct
pathways. There are essentially six phase II detoxification pathways:
· Glutathione conjugation
· Amino acid conjugation
· Methylation
· Sulfation
· Acetylation
· Glucuronidation
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microsomal metabolism: P-450 isozyme.Localized in the smooth endoplastic reticulum (microsomal fraction)<<<<present
in hepatic microsomes and the endoplasmic reticula of varied other tissues>>>>>> of cells (especially liver, but including GI
tract, lungs, and kidney) P450s have an absolute requirement for molecular oxygen and NADPH.Oxidations include
hydroxylations and dealkylations
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drug to be eliminated by hepatic route tend to be more lipophielic,have high volume of distribution and hight rate of
redistribution.
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independent of concentration
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nbme,6,3,30 hydrolysis has phenomenon of>>Multiple polymorphism:( aka Genetic Variation or Genetic
polymorphism) -SNPs (Single Nucleotide Polymorphism) is the most common
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the potency of the drug is primarily affected by the affinity of the drug for its
receptor and the amount of drug that is able to reach the target issues.
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refers to the intrinsic ability of a drug to elicit an effect.
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nbme>>>
4,4,10
The partial agonist X acts on the same receptor system that full agonist (NOREPINEPHRINE),but
has a LOWER MAXIMAL EFFICACY regardlees of the dose. A partial agonist may be more potent
,less potent or equally potrent.
potency is an independent factor
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these receptors are ion channels that are comprised of 5 subunits with two Ach binding site,
If and only If both binding sites are filled, the ion channel will open.
upon activation immediate Na and Ca influx into the cell and outflux of K occur.
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nbme>>3,3,33
Messages travel through SNS in bidirectional way.
Afferent messages carry sensations such as heat, cold, or pain.
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blockade of B2-adrenergic receptors inhibits hepatic gluconeogenesis and peripheral glycogenolysis
and lipolysis. Selective B1 blockers and B-blockers with intrinsic sympathomimetic activity (e.g, carvedilol)
are preferred for diabetics as these have minimal effect of glucose metabolism and adrenergic symptoms.
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nbme>>>>4,4,3
cAMP-dependent protein kinases are activated by>>>>.binding of cAMP to regulatory subunit,
which release the catalytic subunit.
explanation:
PKA is also known as cAMP-dependent protein kinase. Protein kinase A has several functions in
the cell, including regulation of glycogen, sugar, and lipid metabolism.
Each PKA is a holoenzyme that consists of two regulatory and two catalytic subunits. Under low
levels of cAMP, the holoenzyme remains intact and is catalytically inactive. When the
concentration of cAMP rises (e.g., activation of adenylate cyclases by G protein-coupled receptors
coupled to Gs, inhibition of phosphodiesterases that degrade cAMP), cAMP binds to the two
binding sites on the regulatory subunits, which leads to the release of the catalytic subunits.
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atria has more cholinergic innervation. ventricle has adrenergic innervation. contractility(decrease Ca). also
decrease conduction velocity by decreasing Ca current in SA and AV node.decreasing conduction may risk in
heart block.
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has major role in intracellular effects
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enhanced phospholipid metabolism would lead to an increase in the produciton of prostaglandin (via
diacylglycerol) and inositol triphosphate (leading to calcium release from the endoplasmic reticulum)
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stimulated by both DAG and increase intracellular Ca
also by RAS MAP through phospholipase C
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has minor role in intracellular effects
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by ciliary epithelium
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nbme,7,4,15
G proteins (guanine nucleotide-binding proteins) are a family of proteins involved in transmitting
chemical signals outside the cell, and causing changes inside the cell. They communicate signals
from many hormones, neurotransmitters, and other signaling factors.
G protein-coupled receptors are transmembrane receptors. Signal molecules bind to a domain
located outside the cell. An intracellular domain activates a G protein. The G protein activates a
cascade of further compounds, and finally causes a change downstream in the cell.
G proteins function as molecular switches. When they bind guanosine triphosphate (GTP), they
are 'on', and when they bind guanosine diphosphate (GDP), they are 'off'.
G proteins regulate metabolic enzymes, ion channels, transporters, and other parts of the cell
machinery, controlling transcription, motility, contractility, and secretion, which in turn regulate
systemic functions such as embryonic development, learning and memory, and homeostasis.[2]
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Insulin-secreting pancreatic B cells have a2 and B2 receptors; stimulation of a2 receptors inhibits
insulin secretions, where as stimulation of B2 receptors increases insulin secretion
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vesamicol>>non-competitevely blocks the vesicular acetylcholine transpoter
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causing a chemical sympathectomy.
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bretyleum and guanethidine>>>>>adrenergic neuron blocker>>>inhibit release
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metyrosine>>>inhibit tyrosine hydroxylase (rate limiting step in catecholamine synthesis) used
only in treatment of pheochromocytoma
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inhibited by bromoacetylcholine
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differentiate cholinergic crisis by myasthenic crisis
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highly lipid soluble
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tertiary amine.
other three are quaternary amines
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nbme>>>4,1,23
cholinesterase inhibitor>>>>increases in both amplitude and duration of EPP.
nicotinic acetylcholine receptror agonist only causes increase in amplitude but not duration.
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meclizine and dimenhydrinate (have both antimuscarinic and anticholinergic properties) other 1sr
generation are also effective but are not used because of sedation effects.
scopolamine have only antimuscarinic properties
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muscarinic and histaminic both pathway are involved.
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hallucination, delirium and psychosis.
CNS effects can progress to coma and respiratory failure.
......
atropine causes organic delirium and psychosis by blocking muscarinic receptor in CNS
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diazepam is used to treat seizure or agitation due to atropine toxicity.
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belladonna
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half life increase in elderly(>70) from 3 hours to 10-30 hours.
so risk of toxicity increases
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poisoning due to nicotinic receptor antagonist (eg pancuronium and tubocurarine) is uncommon,since these agents
have poor oral absorption.
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promethazine (antihistamine) also used for motion sickness
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anticholinergic medications (cycloplegics) reduce pain and prevent the formation of
adhesions in iridocyclitis (uveitis). atropine does not precipitate iridocyclitis
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in the vasculature, alpha1 agonist activity(vasoconstriction) balances the beta 2 agonist effects (vasodilation),
resulting in overall mild vasodilation. the net hemodynamic effects are a decrease in systemic vascular resistance
without a significant change in arterial blood pressure.
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weak cronotropic but can increase Heart rate.
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it is generally not a potent vasoconstrictor.
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can mediate vasodilation via beta2 receptor activation, particularly in straited muscle , renal and
mesenteric vascular beds., leading to decreased peripheral vascular resistance with increased
CO.
subcutaneous tissue blood vessels have a relatively low beta2 receptor density compared to
alpha1 receptros.
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treat bronchial asthma; as a stimulant,appetite suppressant
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also in cardiac arrest we use
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in the treatment of refractory cardiac failure and shock.
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in the management of refratory HF assoicated with severe LV systolic dysfunction and cardiogenic shock. .............
as dobutamine is more inotropic and also little bit chronotropic these both effect causes increase in myocardial
oxygen consumption.this can trigger or exagerate MI. however in patient with acute MI complicated by cardiogenic
shock, this drawback may be outweighted by improvement in CO and end-organ perfusion.
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Epinephrine limist glucose use by insulin-sensitive tissues and also stimulates hepatic glycogenolysis
and gluconeogensis.
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rebound hypertension is a concern with abrupt cessation after using central acting sympatholytic.
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<<<<<<<<<no reflex tachycardia cause alpha-2 is not blocked>>>>>>>> selective alpha blockers
usually do not cause much reflex tachycardia because presynaptic alpha-2 inhibition is not
blocked
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drop is systolic pressure >/20 and diastolic pressure >/10 from supine to standing position.
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adverse effect like bronchoconstriction (dose dependent) may be seen
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also has minor beta2 receptor agonist (sympathomimetic) activity.>>>>>used for severe hypertension and cocaine
abuse
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decreases cardiac work by slowing ventricular rate. it also reduces peripheral resistance (afterload) by decreasing
circulating levels of vasoconstricting hormones (eg norepinephrin, renin and endothelin)
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inhibits passive transport of Na
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and intestinal decontamination with gastric lavage and charcoal
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persistent..... batrachotoxin (south american frogs) have similar mechanism of action.
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death may occur due to respiratory failure and hypotension
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saxitoxin (dinoflagellates in "red tide") have also similar mechanism of action
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in severe cases.
in adults succimer and EDTA as first line.
works by forming non-ionizing salts to increase urinary lead excretion.
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3rd line agent
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cyanide binds to Fe+3 in cytochrome c oxidase,inibiting ETC.
cyanide is normally metabolized in the tissue by rhodanese, an enzyme that transfer a sulfur
molecule to cyanide to form thiocyanate,which is less toxic and excreted in the urine.
sodium thiosulfate works as an antidote by providing additional sulfur groups for rhodanese,
enhancing cyanide detoxication.
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vitmain B12 precursor, binds to the intracellular cyanide forming cyanocobalamin, which can be easily excreted in
urine.
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(eg british anti-lewistie).increases urinary excretion of heavy metals by forming stable, nontoxic
soluble chelates.
dimercaprol supply sulfhydryl groups
itself toxic and have narrow TI .most serious SE are nephrotoxicity and hypertension.
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reducing agent. non enzymatically reduce Fe+3 to Fe+2. methylene blue acts as an artificial electron transporter for
reduction of methemoglobin through the NADPH pathway.
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the sulfhydral group of dimercaprol combines with arsenic and displaces arsenic ions from the
sulhydryl groups of enzymes involved in cellular respiration.
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EDTA forming complexes with mono.di and trivalent ions
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it binds circulaitng iron and facilitates its urinary excretion.
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forms methmoglobin
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chloroquine and protease inhibitor
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in mild form>>>in children
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by binding to sulfhydryl group, it blocks 3 things 1, cellular repsiration (pyruvate
dehydrogenase. 2, gluconeogenesis 3, gluthatione metabolism
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centrilibular necrosis that can extend to include the entire lobule
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mechanism of action:
inactivates or alter bacterial robosomal proteins to inhibit protein and cell wall synthesis
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alpha-methyl dopa
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dapsone
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clozapine (antipsychotic at high doses)
ciprofloxacin(antibiotic)
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matabolized in liver by multiple hepatic microsomal mixed function oxidases, especially cyto P450
2C9.
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ranitidine and lansoprazole does not interect with diazepam
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2c9>>>warfarin 2d>>>>tamoxifen cyclophosphamide require bioactivation by cytochrome P450 2b
cyclosporine extensively metabolize by liver and GI p450 3A>>>>>grape fruit juice interection(intestinal).. ...
statin>>>3A4. halothane>>p450>>convert into toxic metabolite...except desfulrane
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ODC medicianl herb antinflammaotry and antidepressant>>>>>majorly interect eith warfarin
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inhibitors: acetaminophin, NSAIDs. metronidazol, TMP-SMX cranberry juice, Ginkgo biloba, vitamin E
omeprazol. thyroid hormones SSRIs (eg fluoxetine). verapamil amiodarone, ritonavir>>protease inhibitor
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inducers: Ginseng green vegetables (eg spinach) OCPs modafinil primidone
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MMSE measure attention and concentration, time/place orientation, calculation, language, visual-
spatial ability, and memory registration and recall.however it does not test executive function,
which must be measured by other means.(ie clock drawing)..
...
A mini-mental state examination is a 30-item assessment that provides a screening of cognitive
function. It would not assist in determining functional status .
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classical conditioning>>old response to a new stimulus.
operant conditioning>>new response to an old stimulus.
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Providing minimal information that the patient is “stable” would be appropriate. This response
protects the patient’s privacy by not revealing the diagnosis or other medical details, but also limits
emotional harm to the patient by informing those who are likely to be family about the patient’s
condition.
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sleep science has demonstrated “dose-dependent” effects of sleep deprivation on physician
cognitive performed and risk of medical errors. Impairment in cognitive performance and motor
skills typically manifest after 17 hours of wakefulness and are comparable to those seen in an
alcohol-intoxicated individual.
...........
Optimal patient handoffs should include a checklist of tasks and clinical status for each patient,.....
physician burnout refers to a state of emotional exhaustion , cynicism, depersonalization, and

decrease sense of personal accomplishment that can result in suboptimal patient care and
medical errors. Although sleep deprivation may contribute to burnout, there is no evidence that this
physician’s error was secondary to burnout, which often involves errors resulting from lack of
concern or carelessness toward patient;s rather than forgetfulness.
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Physician should remain alert to patients with a low level of literacy as this can often impair communication
and result in low-quality medical care and poor adherence. Alternate learning methods (eg, visual
resources) should be used to address this challenge.
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In a non-emergency situation, a person should contact the designated hospital committee,
commonly called a physician health program
if this is not possible or such a body does not exist then the state licensing board should be
contacted.
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New patients visits should always include a thorough review of current medications (including
over-the-counter medication) to determine if any are inappropriate and/or causing adverse effects
or problematic drug-drug interactions.
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A persistent vegetative state is a condition arising from severe brain damage that results in a state
of wakefulness without awareness. Patients may regain consciousness within 6 months in
approximately 50% of cases, but rarely without severe subsequent disability.
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optimal medical care of deaf individuals who use american sign language (ASL) requires provision
of trained interpresters to avoid potentially dangerous miscommunication.It face-to-face
interpreters are unavailable, video remote interpreting service should be offered.
If the situation is more urgent and there is no time to wait for interpretation services,
communication should be facilitated by any tools available, including friends/family, writing/drawing
instruments, and bilingual hospital staff.
....
Self-report questionnaires are sometimes used to monitor treatment progress, but they should not
substitute for a complete evaluation or for having a conversation with the patient.................
In nonemergent setting, trained language interpreters should be used to ensure optimal medical
care, this applies to deaf patients using American Sign Language.
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Relationships with former non-psychiatric patients may be acceptable on a case-by-case basis
provided the physician-patient relationship is terminated well beforehand.
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useful screening technique to assess language proficiency is to ask the patient, “How well do you
speak English: Not at all, not well, well or very well?”an interpreter is appropriate for patietns who
cannot respond or prespond "not well"
using the “teach back” method (in which patients are asked to “teach” the physician what was just
explained to them) can also serve to confirm understanding
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Although first trimester abortions are unrestricted, states have different restrictions on second-trimester
abortions, including mandatory waiting periods, parental consent for pregnant minors and mandatory
discussion of options. Request for an abortion is one example of situation in which a physician
may face a moral conflict. Physician are not required to provide medical services that are against
their personal beliefs. However, once a patient-physician relationship os established, the physician
is obligated to refer the patient to another provider who can perform the requested medical
service.........................
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in situations in which one physician disagrees with another’s practices (but that physician’s practices are
within the standard of care), it is inappropriate and unprofessional to undermine that physician’s
judgement discussions with the patient. The primary physician’s actions should be criticized in front of the
patient only if the physician has been grossly negligent or provided treatment well outside of the
acceptable standard or care.
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in the United States, the majority of overdose deaths are caused by prescription drugs, particularly
opioid analgesics.
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Student athletes typically sign an authorization form permitting the physician to share health-
related information with coaches under the Family Education Rights and privacy Act.
college health records on student athletes are not subject to the HIPAA privacy rule.
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It is always the patients, not the physician who must take the lead in lowering the level of formality.
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Effective discharge planning entails interdisciplinary collaboration among the social worker, nurse
and physician. Issues to consider include the patient’s cognitive status, activity and functional
status, availability of family support, transportation to follow-up visits, potential safety issues n the
home (eg, stairway) and ability to obtain and take medications. to be discharged home, a patient
(with help from a family member or caregiver if necessary) should be able to take medication
correctly, perform self-care, eat appropriately and attend follow-up appointments.
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the physician should neither confirm nor deny whether the person of interest is, in fact a patient.
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educational interventions to reduce the use of certain abbreviations (eg, QD, ug) and avoid zeros lead to a
significant decrease in prescription errors. computerized systems are helpful in eliminating illegible
orders, identifying patients at high risk for an adverse event, and alerting physicians to medication allergies,
drug interactions and dosage limits.
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Latency is very important issue to consider when studying disease epidemiology. In most
infectious diseases, the latent period (i.e, time elapsed from initial exposure to clinically apparent
disease) is relatively short. On the other hand, some disease processes (e.g, cancer or heart
disease) may demonstrate a very ling latent period before clinical manifestations develop. The
concept of a latency period can also be extended to risk factors and risk reducers. Exposure to
risk modifiers sometimes occurs a significant amount of time before the exposure’s effect on the
disease process is clinically evident. Additionally, sometimes exposure to risk modifiers must
occur continuously over extended periods of time before the disease outcome is affected. In this
case, at least 5 years of continuous exposure to antioxidants were required to reveal the protective
effect of the exposure on the outcome (stroke).....
Lead time is the time between the initial detection of a disease and a specific outcome or
measured endpoint. Lead-time bias can occur when a test diagnoses or detects the disease at an
earlier stage than another test does without impacting the natural history of the disease.
The concept of latent period can be applied to both disease pathogenesis and exposure to risk
modifiers. The initial steps in pathogenesis and/or exposure to a risk factor sometimes occur years
before clinical manifestations of disease are evident. Additionally, exposure to risk modifiers may
need to be continuous over a certain period of time before influencing the outcome.
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NBME>>>2,3,1
MME
Maximum total score = 30;
total score less than 25 --suggests cognitive problems;
total score less than 20 --suggests significant impairment
Attention and concentration --
1-repeat digit sequence backword
2-Subtract 7 from 100 and then continue to subtract
other tests
Orientation--- Tell me where you are and what day it is.
Language -----Name the object that I am holding.
Registration---- Repeat the names of these three objects.

Recall---------- After 5 min, recall the names of these three objects.
Construction ---Copy this design.
these are are mini mental scale and scoring is done-

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a case series is a descriptive study that tracks patients with a known condition
(eg a particular exposure, risk factor or disease) to document natural history or
response to treatment. unlike a case control study, a case series is a descriptive
study that cannot quantify statistical significance
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in this study subjects are not randomly selected but rather explicity recruited with (cases) and
without (control) disease.
...................
control are selected who do not have disease of interest, and regardless of exposure status to risk
factor.....
....
for rare disease we do case -control, we can not do cohort study.
....
a. Cannot assess incidence or prevalence of disease
b. Can help determine causal relationships
c. Very useful for studying conditions with very low incidence or prevalence.
d. this study is done rapidly.
.......
clinicians mostly done case-control study.
in case of outbreaks this study is generally done by CDC.
also done in rare disease study
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nbme,11,4,3
Cohort study by concept is prospective, the patient are follow forward in time, the population
should be follow long enough for incidence to appear,
cross sectional is used to determine prevalence or to establish etiology
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share 100% of their genes
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For a trait that is determined strictly by environment, we would expect:
• Equal concordance in monozygotic and dizygotic twins (assuming that
they were raised together)
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means having a control group,can be placebo or standard drug.
one of the inventive way to create control is cross-over study
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Randomized controlled clinical trial (RCT)>>>>> the group differe only in terms of the intervention
of interest
a. Subjects in the study are randomly allocated into "intervention''
and "control" groups to receive or not receive an experimental
preventive or therapeutic procedure or intervention.
RCTs often suffer from two major complications, i.e., noncompliance and missing outcomes. One
potential solution to this problem is a statistical concept called ITT(intention=to treat') analysis
ITT analysis is usually described as “once randomized, always analyzed
...........
intention to treat is an imporatant principle we use in randomized clinical trial,>>it preserves the
benefits of randomization and prevent bias of selective non-compliance.
investigators may alternatively use as treated rule, which is opposite of intention to treat
page number 72
...........
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cases reported bu physicians
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exposure status is determined at the begining of the study and then follwed over
time (eg vegetarian vs non-vegetarian) for development of colorectal cancers
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in clinical trial exposre is not determined at the baseline like cohort, instead
exposure is assigned to study group,
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Randomized controlled clinical trial (RCT)>>>>> the group differe only in terms of the intervention of interest .....
systemic reviews and meta analysis>>>take several studies (emphases on high quality randomized controlled
studies) and attempt to group the result to obtain pooled effect estimate, this increse statistical power of study. .....
qualitative studies group>>>use focused discussion groups, interview (structured, semi structured) and other
anthropometric techhniques to obtain narrative information that can be crucial in explaining quantitative information.
...... nested case-control design>>>start with cohort study>>>and participants who develop the disease of interest
become cases for the case-control study ...... ecological study>>>unit of analysis is population not individuals 10570
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concruent and non-concruent studies, same as proospective and retrospective,
longitudinal cohort study>>>>>>is done for many years
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in the question they generaly describe group of population, eg newyorkers, californinans. which is
under study...
.....
Chi-square is use to assess association.
........
the major limitaiton of a cross-sectional study is that a temporal relationship between exposure
and outcome is not always clear.
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Clinical trials (intervention studies):
1 RCT
2 community trial
3 cross-over study
4 clinical trial for drug
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first we randomly select than we randomly assigned.
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nbme,6,4,47>>>>not a cohort study but controlled trial
explanation.
Clinical research -A clinical study in which one group of participants receives an experimental drug
while the other receives either a placebo or an approved–'gold standard' therapy
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genetically same as siblings(share 50% of their genes)
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two individuals are concordant if they share the same trait.if they dont they are discordant
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a. Prospective; subjects tracked forward in time
b. Can determine incidence and causal relationships
c. Must follow population long enough for incidence to appear
.....
retrospective:
sometimes the exposure status is determined retrospectively and patients are tracked from the
point of exposure onward, typically using medical records.
.....
confirmational study.
Assess Single risk factor affecting
many diseases. eg smoking can cause HF, CVA, lung cancer etc.
can be randomized control trial if intervention(experiment) occur.
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assess many risk factors for single disease.
and risk factor with the highest OR is the No 1 risk factor for a disease.
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study just by seeing individuals taking statin drugs to prevent CHD is observational study.
by using drug alone not mean its an experimental study
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individuals are randomly selected to measure prevelance of disease and its associated risk factor
simultaneously.
both exposure and outcome is measured simultaneously (though subject can be measured over
several days to have an average measurement) at a particular point in time (snap shot).
in other study designs, a certain time period seperates the exposure from the outcome.
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FalsePos = (1 - Specificity) * (1 - Prevalence)
TrueNeg = Specificity * (1 - Prevalence)
FalsePosRate = 100 * FalsePos / (FalsePos + TrueNeg)
......................
TruePos = Sensitivity * Prevalence
FalseNeg = (1 - Sensitivity) * Prevalence
PreTestOdds = Prevalence / (1 - Prevalence)
FalseNegRate = 100 * FalseNeg / (TruePos + FalseNeg.....
.....
what is bayes theorem>>>>>. we use bayes theorum when we know the sensitivity, specificity
and prevalence of disease to find the PPV and NPV ...
uworld biostat review>>>49
.......
reciprocal of NPV>>>>>>1-NPV = 1-D/C+D = C/C+D
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one same test for different diseases has different specificity and sensitivity but are fixed for that disease. sensitivity
and specificity are pretest probabilities along with prevaslence
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accuracy>>>is samething saying few falses either be + or -
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Receiver Operating Characteristic (ROC) Curves:
sensitivity(truly positive rate)/1-specificity(false positive rate).
area under the curve ACCURACY.(accuracy of the test)
bigger area under the curve is better test and vice versa
uworld>>>page 42
..........
Accuracy = (TP + TN)/(TP +TN + FP + FN
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unlike predictive values (PPV or NPP) likelyhood ratio is independent of disease
prevalence
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the direction in which cutoff move value decreases and opposite value increases.
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Decreasing the lower limit of reference test value (i.e., the cutoff value) can be expected to both
decrease the number of false negatives and increase the number of false positives. Such
alterations will both increase sensitivity (T P/T P. + FN) and negative predictive value (T N/T N. +
FN) and decrease specificity (T N/T N. + FP) and positive predictive value (T P/T P. + FP) of the
test. A change in the reference interval would not affect the incidence or prevalence of prostate
cancer in the population. ????????????????
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PPV and NPV are post test probability along with accuracy of a 2*2 table
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if disease prevalence is high 1st vertical column increases. if disease prevalence is low 2nd vertical column increases
.......... trues are always on top ... by increasing prevalanece we are increasing both TP and FN. effect on PPV: cause
nominator increases(TP) PPV increases. effect on NPV"casue of denominator increases(FN) NPV decreases.... .....
screening test does not tell u nothing about the incidence ( ie when u got the disease) but tell u about the
prevalence (ie u have or not the disease) prevalence is the total number of the vertical diseased column not just TP
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RARE DISEASE ASSUMPTION:
refers to the practice of approximating odds ratio and relative risk when studying rare diseases
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odds of an event is defined as the probablility of that event divided by 1 minus probability of that event: Pr(event)/1-
Pr(event)
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both RR and AR require incident data which is provided by cohort study.
relative risk (RR) is our default choice in exam.
for AR we have to calculate (subtract)
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ARP=100*(risk in exposed-risk in unexposed) /risk in exposed.attributable risk percent in the
exposed: (ARP=100*(RR-1)/RR). 1186 ....... population atributable risk percent: impact of
exposure on the entire study population, first calculate the incidence of dsease
in the study population as a whole,next calculate the difference in risk of
developing respiratory disease between exposed and the study population as a
whole, and divide this value by the incidence of disease in exposed.
uworld>>>page 18 ....... AR=event rate in treatment group-event rate in control
group AR=incidence of disease(exposed group)-incidence of disease (unexposed
group) ............. for subtraction we have to have same denominator.
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ARR =Event rate(at risk) in control - Event rate(at risk) in treatment group.
ERtreatment = numbers of event in the treatment arm / numbers of subjects in the treatment
arm..........
ARR=control rate-treatment rate
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attributable risk also called absolute rishk increase.
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can say number needed to prevent
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survival analysis
uworld page 83
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RRR>>>percentage indicating relative reduction
ARR>>>percentage indicating actual difference
1174
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if data given in %, we can use the formula as:
100/ARR
100/AR
........................
IF data is not given in % and both groups have equal # of Subjects eg group has 1000 study
subject, we can use the formula as:
1000/ARR
1000/AR
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NNT is used to assess clinical effectiveness of drug.
important number to determine if a drug should be used or is cost effective.
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RRR=(AR control - AR treatment)/ AR control.
RRR=ARR/control group
......
RRR overstate the effectiveness of an intervention.
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nbme>>>3,1,16
Relative risk == incidence among exposed / incidence among nonexposed
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OR can be used for cohort study along with RR but only OR is used for case control study not RR
because such studies do not follow patients over time to calculate a risk
.....
in case control study total population cant be known,so true relative risk cannot be calculated, but
in OR does which is an approximation of RR.
In cohort study total population can be known,so we can calculate true RR.
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exposure(risk factor) in both cases. (if it present in both control and cases then it is not a true risk
factor, but if it present only in cases and not in control than it is a true risk factor for a disease)
OR gives us strength of risk factor with the disease.
.....
different risk factor has different OR for the same disease.
OR which has highest value is the NO 1 risk factor related to disease.
LARGER THE OR MORE IMPORTANT IS THE RISK FACTOR.
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just by seeing 2*2 table does not mean its a screening test.
it could be a presentation of observational study and it can either be any of three types,u cannot
say which one of the three is just by looking data cause all 3 present in the same way in 2*2 table.
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but can also be used for period
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for acute disease incidence is high and prevalance(at some point in time) is high too.
for chronic disease incidence is low but prevalence is high...
....
case fatality rate>> fatal case/total number of people with disease.
....
if incidence goes down prevalence automatically goes down.
....
Mortality>>>refers to incident
cases only.
Morbidity rate>>>>refers to both
incident and prevalent cases.
....
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if i say test is reliable than it tells nothing about the validity.
but if i say test has validity than it automatically understood that test is reliable cause reliability
comes first to validity and its a necessary thing.
......
in order to be valid we have to be reliable
Reliability is a necessary, but
insufficient, condition for validity(Accuracy)
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its a post test probability measure 2*2 table as a whole.
accuracy=(TP + TN)/(TP +TN + FP + FN)
accuracy=(true positives+ true negatives)/total screened patients(n)
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unlike random error systemic error is not affected by sample size page 92
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in a clinical laboratory, reliability is typically qunatified in terms of coefficient of variation (standard
deviation divided by a mean of repeated measurements), generally expressed as a percentage
1278
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Case-fatality rate>> Deaths from cause/Number of persons with the disease/cause>>>>death
given disease eg how many person with diabetes died due to this
Proportionate mortality rate (PMR)>>>Deaths from cause/

All deaths>>death as percentage of all deaths eg heart disease is leading killer in all causes of
death
...
attack rate is a type of incidence rate in which denominator shrinks down very much.
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who enter,who are already there and who are died
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beta error is a random error
1301
are unfortunate but ok and expected
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applies mostly to case-control study
1301
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different from random assignment(wihich is double randomization).....
randomization is same thing as random selection
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placebo effect>>patients expectations affecting an outcome.
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confirmation.
in case cant remember the past
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Double-blind RCT(Randomized controlled clinical trial)
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no group involved can remain
untreated. All subjects receive intervention, but at different times
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nbme>>>4,2,18 The advantages of proper randomization in Randomized controlled trial include: "It eliminates bias in
treatment assignment," specifically selection bias and confounding. "It facilitates blinding (masking) of the identity of
treatments from investigators, participants, and assessors." "It permits the use of probability theory to express the
likelihood that any difference in outcome between treatment groups merely indicates chance."
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Design bias:
Parts of study do not fit together
Non-comparable control group
Random assignment(different from random selection which is a solution to selection bias)
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1,referral bias, 2, susceptibility bias>>>treatment regime selected based on
severity of pte conditions. eg helathier person for PCI and sick person for medical
treatement page 63 ..... prevalence bias(neyman bias)>>>when incidence of diseae
is estimated based on prevalence, and data become skewed for selective survival
63..... ... Late-look bias: Severely diseased individuals are not uncovered Early mortality Stratify by severity type of selection
bias ..... selection
bias different from sample bias. Selection bias can occur if the subjects are
permitted to choose whether to go into a drug group or placebo group rather than being assigned
to one or the other randomly. In sampling bias(convenience sample) subjects who volunteer to
be in a study may not be representative of the population being studied. ...... random
missclassification bias: random (or nondifferential ) missclassificaiton effects all group to the same extent. eg using
baby size sphygmo to measure BP on all participants (treatment and control groups) as part of study in adult
patietns.however the resulting missclassification will likely affect both groups to he same extent(becasue the same
cuff was used)
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Interrater reliability is a measure of how similar test findings are when used by two different
examiners..
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Only a factor when there is no control group in a prospective
study
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length time bias>>>screening test detects less aggressive(benign form) form of
disease more often>>>increases survival time eroneously
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measure life expectancy (means total years one lived) not measure how many years one lived after diagnoses.
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stratified analysis (analyzing the cohort in different subgroups) to differentiate effect
modification(external variable positively or negatively impacts the observed effect of a risk factor
on disease status>>>>>>>stratifeid studies will reveal a significant difference in RR between th
estratified groups) and confounding bias(confounder are extraneous factors that correlate with
both the exposure and the disease>>>>>>>stratidfeis study will reveal no significant difference in
RR BETWEEN THE STRATIFIED GROUPS))
....
effect modification is not a bias, and is not due to flaws in design or analytical stage of study, its
just a natural phenomenon which need to be described not corrected
.....
common confounders>>>age, race, socioeconomic status, environment, smoking, gender
....
at design stage we use>>matching, randomization and restriction.
at analytical stage we use>>>stratified analysis
....
matching most commonly used in design stage of case-control studies
1189
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metanalysis compyling data from different studies to increase the power of analysis.
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have a Control group/placebo group>>>>thus in both group measurement is constant so any
difference would be real.
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such as case-control studies.
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weight data>>>strandardize it(means if we have 40%white males and 60% african american males in study than we
have to standardize our data to have 50% each)
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observer bias: occur in clinical trial when study participants or investigators are aware of indivivdual treatment
assignments. prevented by performing double-blind study so neither are aware of the treatment assignments .....
observer bias and ascertainement bias result from mislabeling esposed/unesposed or cases/control.
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attrition bias
1188
atrition bias:
type of selection bias>>>in prospective study,disproportionate loss to follow-up between the
esposed and unesposed group, and the lost group differ in their risk of developing the outcome
compared to the remaining subjects.
if the losses occur randomly between esposed and unesposed grou, no attrition bias results
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SD reflects the spread of individual values in a normal distribution.
SEM reflects the variability of means and helps estimate the true mean of the underlying
population.
....
most research is done on samples rather than on the the entire population.This introduce some
variability (when different samples are drawn from the same population, the results could be
slightly different).
.....
SE is defined as SD/ n and is a way to account from this variability due to sampling
.....
SD remains constant across changes in sample size. just like mean remains constant across
changes in sample size.
SD>>>> average of deviation.
Mean>>> average of central tendency
.......
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SD smaller and n larger would be better
....
Note that the sample size n is a component of the calculation of SE. As n increases, SE
decreases, so the Cl will become narrower and more precise.
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nbme,7,2,24
In the question we are asked about heterogeneity(variability)
-The distances between the scores and the mean (Xi-M) are called deviations
-The greater the variety or heterogeneity of the scores, the greater the deviations
-If the scores were clustered around the mean, the deviations would be small, but they would
increase as the scores became more spread out or more varied.
-And one way to measure variability (heterogenous population in this case ) is by calculating the
value of the Standard Deviation ..
-Generally SD - is an index of variability: the SD increases in value as the distribution becomes
more variable. The less the variability in the distribution, the lower the value of the SD.
In short when we get high SD that means high variabilty (high heterogenous population in this
case)....low SD means low variabilty (less hetrogenous population )...
So to check variabilty(hterogeneity) ...compare the standard deviation values not the mean of the
experiment...
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normal distribution has mean of zero and variance of one
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median often reflect central tendency better than the mean in such a situation.
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range>>>measure 2 extreme points.
regression toward the mean>>>extreme values when remeasured will tend to be less extreme
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in case of better scores>>>more SD above the mean is the better score.
less SD below the mean is the better score.
in better score measurement we actually want highest percentile.
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after statistical distribution wo do statistical inference(confidence interval and P-value)
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Meaning of the p-value

L Provides criterion for making decisions about the null
hypothesis
11. Quantifies the chances that a decision to reject the null
hypothesis will be wrong
111. Tells statistical significance, not clinical significance or
likelihood of benefit
iv. Limits to the p-value: the p-value does NOT tell us
- The chance that an individual patient will benefit
- The percentage of patients who will benefit
- The degree of benefit expected for a given patient
......
statistical significance(p-value)=is there a difference?
clinical significance=does the difference matter?>>>>clinician determine this by finding ratio from
the data
.......
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this is a computed p-value or computed alpha-criterion
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error of omission...
....
do not look p-value for type II error
....
beta error is a random error not a systemic error.
....
lower p-value criterion(alpha-criterion) is better for type 1 error but is worst for statistical power...
0.05 is at the cross point of curve b/w avoiding the type 1 error and have enough power
...
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how big the thing u looking for,eg elephant or mouse escape from the zoo
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nbme>>>2,3,44
decrease sample size, will decrease power, and increase error
SEM=sigma/√N, sigma=standard deviation
CI=(mean+or- Z(SEM))
So if N decrease ----- SEM increase
If SEM increase -----CI increas
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SEM = σ/√n.
we like this number smaller
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for 90% CI, Z=1.645
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means we are 95% sure that the true mean(if we measured the whole population) find b/w these
two interval value.
it does not mean that 95% class fall in this CI, for calculating this we have to know the exact mean
which we do not know (we know only interval in which true mean would fall)
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95% CI corresponds to the P valua <0.05
99% CI correspondes to the p value <0.01
......
CI + P-VALUE>>>>>100%
.....
If i want a smaller CI we need to increase the sample size.
Note that 99% CI would be wider than 95% CI, so to be confident that mean fall with in this range.
we are trading precision for the CI.
......
Z-score=standard score
It give you SD from the mean.
Z-score of +1 means i am 1 SD over the mean
.....
reality is not a mean but a confidence interval which have this mean is reality
.....
CI does not give u bell shaped probability distribution but gives u flat shaped probability
distribution (flat portion represents CI where along this line true mean would be present)
We are trading precision for the CI.
single mean value does not have CI but when we have range of number which is deducted by
using formula then it gives us Confidence that our real mean would fall in these numbers.
.....
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alpha criterion (not computed one but preset one) is easier. if it is easier to reject null hypothesis you have more
power,this is done by giving alpha crierion greater number. normally alpha criterion(also called p-value criterion)
value is .05 if u are willing to have more type 1 error(p-value) you have more power
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capacity to detect a difference if there is one
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alpha-criterion(also called p-value criterion) which is standard
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error of comission.
considered worse than type II error
.......
in general the smaller the computed p-value the better it is.
....
p-value is type 1 error
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NBME,11,2,4
Statistical significance= Is determined by P value.....and as see the p value is less than
.05....hence for sure there is a difference between the two interventions (NOT BY CHANCE
ALONE).....If the P Value is greater than .05 u can SAY the difference in the two interventions is
due to CHANCE ALONE .....So A is out
-Practical Importance means CLINICAL SIGNIFICANCE not Statistical....and clinical significance

MUST ANSWER THE QUESTION ...how effective is the intervention or treatment in the CLINICAL
SETTING....And the doctor made the CALL in this case not the researcher....And the way u
measure CLINICAL SIGNIFICANCE IS by some of the following methods...EFFECT SIZE
,Number Needed to treat,and Preventive fraction.....
-Already in the question u stated the magnitude of the difference was so small....How do they
know ? They calculated NNT....
as u know NNT= 1/49%-45 %=1/4%=25.....Taking Program A as a control (as u know control

groups can get placebo or as in this case STANDARD CARE)....
-This means if the health official decided to change Program B as a STANDARD of CARE .....to
treat HYPERCHOLSTEROLEMIA in 1 patient 25 should be INVOLVED .....
---NNT=25 is not clinical significant.....hence choice B......
about the other choices....
Choice D....once you find the difference is STATISTICALLY SIGNIFICANT ...the sample size
should be assumed LARGE and Enough...Only question sample size if the STUDY is not
STATISTICALLY SIGNIFICANT....i.e When Calculated P Value is greater than .05.....
Choice C....Many times the investigator will report the lowest COMPUTED P Value ....In general
the smaller the p the BETTER......
And I remember a question on NBME 7 where the computed P value was greater than .05.....and
the answer was ....Due to chance alone....but the scenario was almost the same as this
question.....
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ANOVA is used to determine whether there r any significangt differencve between the means of 2 or more
independent variable. ANOVA compares the means between the groups relative to the variability within groups and
determines whether any of those means are significantly differet from one another.. specifically it tests the null
hypothesis that all groups are simply random samples of the same populaiton (ie the means arte the same).the null
hypothesis is rejected and the alternate hypothesis is accepted when there are atleast 2 group means that are
significantly different form one another. 8519
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interval scale .... also called continuous data, or quantitative data ...... mean=average
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Types of correlations
i. Pearson correlation: compares two interval level variables
11. Spearman correlation: compares two ordinal level
variables
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linear regression:
is a method used to model the linear relationship between a dependent variable and an
independent variable. eg linear regression could be used to determine the relationship (describes
in terms of a trend line) between the number of cigarrete smokes per day and the number of
yearly hospitalization in COPD pateints
1283
.......
correlation coefficient is different from linear regression in that a single number is reported
describing the strength and magnitude of the association.
.......
NOTE: Correlation, by itself, does not mean causation.
A correlation coefficient indicates the degree to which two measures
are related, not why they are related
...
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DIT
physician autonomy:
physician have the right to choose which treatment would or would not provide to patient.
but physician should adhere to the standard of care eg aspirin not given to MI pte
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two sample T-test also called student t test>>>>means r independent paired t
test>>>means are dependent eg same individuals are followed over time compare
means (Base line BMI) before treatment and BMI after treatment) 82
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chisquare test for independence also known as chi-square test for association
1184 ................... 2 by 2 table is generally chi-squarre ............. Nominal data only Any
number of groups ( 2 X 2, 2 X 3, 3 X 3, etc.) Tests to see whether two nominal variables are independent e.g.,
testing the efficacy of a new drug by comparing the number of recovered patients given the drug with those who are
no ............... It can be used to evaluate whether the expected frequency of an occurrence is
consistent with the observed frequency of that occurrence (“goodness of fit”). For instance, a
study evaluating Mendelian inheritance of red and green seed colors would use a chi-square test
to compare the observed and expected proportions of each seed type. ..........
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2 independent sampke t-test is a aspecial case of F-test in ANOVA, the assumptions of bpth tests
and their resulting p-values are the same
8519
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correct statistical test always depends on the type of dependent and independent variables under
consideration.
in case of t-test and ANOVA require dependent variables (ie outcome) to be quantitative variables
unlike chi-square,
1184
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multiple logistic regression:
method used to predict the probablity of a binary outcome, (eg presence or absence of gastric
cancer) based on 1 or more independent variables, that can be either continuous or categorial, eg
test could be used to predict the probablity of gastric cancer based on alcohol consumption
tobacco usem and charred foor consumption.
8519
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fisher exact test in small sample size eg less than 10
82
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Legally, the designated health care proxy overrules all other decisions makers regardless of family
relationships.
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nbme>>>5,2,42
autonomous-Having independence or freedom from control by external forces or, in a narrow
sense,.
maleficence - doing or causing evil.
beneficence - the quality of being kind or helpful or generous.
Utilitarianism-defines morality in terms of the maximization of net expectable utility for all parties
affected by a decision or action.
deontology -is the view that morality either forbids or permits actions, which is done through moral
norms. For example, a deontological moral theory might hold that lying is wrong, even if it
produces good consequences.
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describes degree of variability in one variable as explained by the other.
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nominal scale(this or that)
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NOMINAL DATA male vs female, disease vs no disease. defined age groups (like 15-20, 20-30) ..........................
defference between frequencies of 2 groups
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Just as competent patients have the right to refuse medical care and interventions they also have
the right to refuse to receive diagnostic information.
Physician must respect their wish not to know, but should also explore the patient concerns to
better understand their preferences and maximize their involvement in subsequent medical
decision making.
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Physicians should always provide potentially life-saving therapy to a minor in an emergency,
regardless of parents’ wishes. In nonemergency situations, the physician should attempt to reach
an agreement with the parents and involve religious representatives and ethics committees when
necessary. Decisions that are clearly not in the child’s best interest should be challenged by
physicians who have the responsibility to advocate for the best interest of the child. if a resolution
cannot be reached after respectful discussion, seeking a court order for appropriate care may be
necessary,
adults patients with capacity have the authority to refuse any form of treatment, including life-
saving therapies
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dit
minor serving a sentence of confinement(juvenle attention under the supervision of government)
so parent dont necessarily have to give consent..
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blood levels above 100mg/dl (0.10% BAC) tend to result in intoxication. slurred speech, and impaired decision-
making capacity, while blood levels above 200mg/dl (0.20%) are associated with marked motor impairment, loss of
consciousness and memory blackout.
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its not mean public institution (eg school) give all these things, its only for physcians to prescribe
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Two-thirds of states require parental consent prior to abortion, one-third require parental
notification, but not consent.
once legally emancipated, minors do not need parental consent for medical treatment of any kind.
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The basic elements of informed consent are accurate description of the intervention and
alternative treatments and discussion of risks and benefits, followed by an assessment of the
patient’s understanding preference.
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advance directives consist of 2 main components a living will and a health care proxy. A living will
specifies the patient’s end-of-life wishes and often included specific directives regarding intubation,
cardiopulmonary resuscitation, enteral feeding and other life-prolonding interventions, A health care proxy
documents allow patients to designate a specific individual to make health care decisions should the patient
become incapacitated. The proxy decision aker must always make these decisions in accordance with the
patient;s wishes as outlined in the living will.
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under current law, a father has no legal right to know if a child is his unless he is ordered to make
child support payments.
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confidentiality breach:
in school transfer>>vaccination status.
employers (to some extent)
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The best initial approach is gentle, supportive,open - ended inquiry and identification of emergency
safety plans. Physician should confirm that violence is wrong and undeserved, but they should not
counsel the patient is a directive way. Confronting denial or pressuring the patient to disclose,
report the abuse or leave the partner should be avoided.
physician must assess the immediate and future safety of all patients presenting with IPV.
Although the patients currently denies feeling unsafe, she should be asked is she has a plan in
case of another emergency. She should be offered the opportunity to speak with a hospital or
community-bases domestic violence advocate and provided with information regarding shelters.
Educating the patient about IPV and offering support may help her feel comfortable disclosing and
seeking help in the future.............
Patients experiencing intimate partner violence should be assessed for safety and approached in
a supportive, nonjudgemental, open-ended manner, The physician’s priority should be ensuring
the patients’ safety through the use of referrals and developing an emergency safety plan.
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A “do not resuscitate” (DNR) order is placed by a physician and indicated that a patient should not
undergo cardiopulmonary resuscitation..this includes basic life support (mouth-to-mouth breathing,
chest compressions) as well as advanced cardiac life support (intubation, mechanical ventilation,
defibrillation and adminitering medications such as vasopressors or epinephrine).additionally
wishes such as the desire to not be fed artificially or any other limitations of care can be specified.
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A physician can respond to a family member’s request for information only if the patient has
specifically provided verbal or written authorization for release of information to the family member.
Rare exceptions may include disclosure of serious communicable disease sucha s HIV or
tuberculosis (human papillomavirus infection is not nationally reportable). In general, a written
(rather than verbal) release of information document is preferred to protect both the patient and
physician rom any misunderstanding, but this is not a HIPAA requirement. Without consent from
the patient, the physician is unable to provide any information regarding the patient.
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usually, the patient’s spouse is the next kin, although the children may sometimes have joint next-
of -kin status depending on state laws.
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Even cognitively impaired adults can frequently communicate useful information about their quality
of care.
once alone the following 3 questions can serve as a brief screen for elder abuse.
1- do you feel safe where you live?
2- who prepares your meals?
3- who handles your checkbook?
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Exceptions to confidentiality include the following:
・ suspected child or elder abuse (laws for spousal abuse vary by state)
・ knife or gunshot wounds.
・ diagnosing a reportable communications disease
・ threats to harm self or others and reasonable ability to carry out the threat in the near
future.
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if the patient has no family, the a person who cares about and knows the patient’s wishes can act
as a substitute...........
In the absence of an advance directive and designated health care proxy, a family member of an
incapacitated patient should be contacted to act as a surrogate decision maker, followed by a
person who cares about and knows the patient’ wishes. In an emergency the physician can treat
and incapacitated patient without obtaining consent.
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Advance care planning ideally should begin in the outpatient setting as a conversation between the patient
and the primary care provider. However, when a patient is hospitalized, it is essential to inquire about
advance directives in the event that the patient becomes unable to make decision.
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patient parents has the right to refuse immunnizations for their childrens.
state have the right to refuse to educate children unless they are immunized
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A learning disorder is characterized by difficulties with learning key academic skills (Reading,
writing or mathematics). Problems manifest at school age when these skills are being acquired
and performance is well below average for age. Many children display symptoms of anxiety,
inattention or hyperactivity when under stress to perform in an area of weakness.
Diagnosis of learning disorders requires comprehensive assessment, including educational testing
and ruling out intellectual disability, hearing, vision or neurological disorders. If a learning disorder
is confirms focusing on writing skills will help lower the boy’s distress stop the teasing and prevent
further absences.
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Language is the most commonly delayed milestone, with an estimated prevalence of
10%015% at age 2. Many children with isolated language delay will catch up in preschool
(Prevalence falls to 5% after age 3). However children with presistent language deficits are at
increased risk for writing and/or reading learning disorders in their school years. This child should
have a hearing examination as well as a speech and language evaluation, which can help to
assess and monitor her language development
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Intellectual disability begins in early development and includes deficits in general mental
abilities and adaptive functioning. Specific learning disorders occur in the presence of normal
levels of intellectual functioning
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A health maintenance organization (HMO) insurance plan has low monthly premiums, low
copayments and deductible and low total cost for the patient.
as a result, an HMO plan may provide this patient with the lowest monthly cost as long as she is
willing to see only provides within the limited panel approved by the plan
point of service (POS) plans are similar to HMOs in that they require patients to have a primary
care provider and obtain referrals for specialty consultations, However, unlike an HMO patients
may also see out-of-network provider.s POS plans typically have higher premiums than HMOs and
significants costs if patients choose to see out-of-network specialists.
Preferred provider organization (PPO) plans usually offer the most flexible choices for both in-
network providers. However, PO typically have higher premiums and deductibles than HMO plans.
...........................................
HMOs reduce utilization by confining patients to a limited panel of providers requiring referral from
a primary care provider prior to specialist consultations and denying payment for services that do
not meet established guidelines.
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Capitation is the payment structure underlying health maintenance organization (HMO) provider
networks. Under capitation, there is an incentive for the provider and patient to reduce
expenses,usually by restricting patients to a limited panel of providers within the pla, requiring
referrals from a primary care provider prior to specialist consultation, and denying payment for
services that do not meet established evidence-based guidelines.
capitation payment are often made to a private inscurance company, which then negotiates with
individual physicians or physician networks to provide care.alternatively a very large physcician
group (including priary and speciality physcicians) may contact directly with emloyes to prvovide
capitated care for their employes..
Discounted fee-for-service is a payment arrangement in which an insurer pays provider for each
individual service provided at a pre-arranged discounted rate. Employers would not generally
negotiate a fee-for-service contract directly with a provider.
global payment is an arrangement in which an insurer pays a provider a single payment to cover
all the expenses associated with an incident of care.this is most commonly done for elective
surgeries, in which the global payement covers the surgery as well as any pre- and post-operative
visits needed.
patient centered medical home>>>>payments for these services may be capitated or fee-for
service.
................
Capitation is an arrangement in which a payor pays a fixed, predetermined fee to provide all the
services required by a patient. Payors may negotiate a capitated contract with an insurance
company that then pays the providers, or a large medical group may negotiate with the payor.
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medicare>>It provide health insurance for patients age 65 and older who have worked and paid
into the system(ie, have paid taxes).
medicare also cover younger individuals with disabilities, end-stage renal disease or amyotrophic
lateral sclerosis,. Medicare consists of several parts with Part A covering inpatient hospital visits,
Part B covering a select number of outpatient services and medical devices, part C as an optional
capitated plan with additional benefits (vision, dental) and part D as an optional prescription drug
plan.
Medicaid, a state-run medical insurance program that cover homeless undocumented immigrants,
pregnant women and low-income families
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eg medicine should not be given untill we checked alergy status of the pateint.
.........................
of there are too much forcing functions then there is potential for workaround>obtain med without
using ordering system, potential harm
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EHR and EMR;electronic health/medical record:
pros
1,ease of sharing medical resords.
2, improving primary and secondary prevention through the use of system reminder
3, reduction of medical error in prescribing medication.
cons
1, does not imrove the quality of health care delivered
2,art of healing on therapeutic bed side healing is lost.
3, business of health care is lost.
4, physcician see few patient due to the burden of EHR.
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triggers and rapid response team>>>>pte that 'crash' often have sgns of impemding
decline hour before.
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nurses generally do SBAR for communication (eg with doctor)
situation, backround, assessment, recomendation
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1, airborn precautions>>isolated room, negative pressure ventilation and respirator
mask>>>>potential exposure to aerosolized particle (<5microns) that remain suspended in air for
extended period>>>tuberculosis, varicella...
2, droplet precautions>>>simple facemask>>>droplets (>5microns) remain suspended in air for
limited period only>>>neisseria, influenza, bordetella, mycoplasma, RSV
3, contact precautions>>>clostridium dificle, MRSA, VRE, scabies
..............
hand washing with soap and water is required for sprore removel, alcohol bases hand sanitizer do
not kill spore
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The checklist should provide instructions at the appropriate literacy level and patient education
materials to facilitate a successful transition from the hospital to the outpatient setting. Key
elements of the discharge checklist include detailed instructions regarding medication (their
purpose, dosing schedule and adverse events) follow-up appointments with the primary care
provider and any specialists, pending laboratory measurements or tests, and an emergency
contact number with specific directions on when to call. Medication changes that have occurred
during the hospitalization (eg, new medications, discontinued medications, changes is dose or
frequency) should be clearly identified on the checklist to reduce the risk of medication errors....
A discharge summary is prepared by the hospital physician to document the hospital course and
assist other medical provider and support staff in the care of the patient. It uses technical language
that may be confusing to the patient. In contrast, the discharge instruction checklist uses simple
and clear language intended to optimize patient understanding.............
A discharge checklist detailing medication and follow-up appointments can siginificantly facilitates
a pateitns transition from the hospital and improve adherence to outpatient treatment.individuals
who experience a smooth transition from the inpatient to the outpatient setting are at lower risk for
early rehospitalization.
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dit
quality improvement:
DMAIC
1,define>the problem
2,measure>establish an objective baseline
3,analyze>identify causes of the problem
4,improve>identify and implement intervention (remeasure,reanalyze and reintervene if needed)
5,control>maintain the improvement.
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.The process of transferring responsibility for medical care is referred to as a patient handoff, with “sign-
out” referring to the process of transmitting information about the patients and needed follow-up care.
Oversights and communication failures during the sign-out and handoff process have been linked to
adverse events in a range of hospital settings. Omission of key information during handoff can result in
medications errors, avoidable escalations in care (eg, transfer to the intensive care unit, redundancies in
care, and delays in diagnosis or treatment. Structured handoffs that include specified key elements (eg, a
systematic procedure for sign-out, checklists of tasks that need to be completed, a standardized
approach for each patient) have been shown to significantly reduce preventable adverse events.
Requiring more detailed sign-out notes will proved more information on each patient but often decreases
efficiency by causing the larger clinical picture to get lost in the details. Applying a systematic
organization method to sign-out notes is a more effective strategy to ensure that essential tasks are
not overlooked.
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Root cause analysis is a quality improvement measure that identifies what, how and why a
preventable adverse outcome occurred. The first step involves collecting data mainly through
interviewing multiple individuals involved in the steps leading to the outcome.
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The “dual identifiers” must perform the verification independently because 2 clinicans verifying
identifiers together can result in replicating an error
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preventable medical error that resulted in delayed diagnosis. Preventable medical errors involve
harm to the patient by an act of commission or omission rather than from the underlying disease
and are the result of failure to follow evidence-based best practice guidelines.
..
Malpractice is a legal determination, it involves situations in which the treatment provided is below
the accepted standard of practice and has resulted in injury or death to the patient. It is not a
category of medical error but rather refers to the consequences of many different types of error
that result in harm.
A near miss is a medical error that is recognized before any harm is done to the patient (eg,
patient is prescribed a lethal dose of medication, but the error is caught by the pharmacist).
A sentinel event is an unexpected occurrence involving death or serious physical or psychological

injury (eg, inpatient suicide, death of a full-term infants, retained object after surgery) that requires
immediate investigation.
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medication error plays a major role in patients morbidity and mortality, particularly in the hospital
setting.
Quality improvement measures such as checklists or medication reconciliation attempt to minimize
these preventable errors.
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dit
malpractice claim:
requirement for the claim,
duty, breach of duty, harm, damage
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crista terminales: a thick band of atrial muscle that seperates the smooth sinus
venosus form the right atrial appendage and atriium proper. it is the site of origin
of the atrial pectinate muscle.
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receives blood from the venae cavae........... common cardinal vein of developing embryo drain directly into the
sinus venosus.
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patent foramne ovale is variant of normal in adults.20-30% have this.suspect this if preset paradoxical embolization
and hypoxemia
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under normal condiiton coronary sinus is not visible on echocariography. it is visible in pulmonary hypertension.
............. the coronary sinus drains blood from the cardiac veins into the right atrium and runs transversely in the left
AV groove on the posterior side of the heart. .............. lower end of crista terminalis, coronay sinus present at
atrioventricular groove in posterior wall of heart
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receives blood from the sinus venosus.
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descending aorta is derived from fusion of embryonic left and right dorsal aorta
2023 ...... a portion of the aortic arch develop from the fourth aortic arch. ........ umbilical vein degenerate. vitelline
vein form the portal vein. cardinal vein form the veins of the circulatory system.
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The umbilical arteries originates from the fetal internal iliac arteries.
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dorsal aorta: 1, postero lateral branch>>arteries to upper and lower limb , intercostal, lumbar and lateral
sacral, 2, lateral branch>>>renal, suprarenal and gonadala, 3, ventral brancha: vitelline artery>>celiac,
superir and inferior mesenteric b:umbilicla artery>>part of internal iliac, superir vesicla and medial umbilical
ligament ...... ventral aorta>>>make heart ......................... venouys system:vitelline vein right and
left>>>portal system, and part of IVC umbilicla vein>>>right early degenrate, left>>ligamnetum teres cardinal
vein>>>>all main venous system, eg part of IVC, azygous and hemiazygous
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apex
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penetrating trauma at the left sternal border at the level of 4th intercostal injure right ventricle. pleura would be
injured but lung itself would not be injured. but if the penetrating trauma is in the mid clavicular line at the same
level it would injure lung along with left ventricle ......... the pulmonay truck could be pierced by a penetrating injury
to the second intercostal space at the left seternal border .............. the right middle lobe of the lung lies
immediately adjacent to the right border of the heart,and any condition that increases radiographic density in the
right middle lobe will abscure the adjacent cardiac silhoutte. on PA the right atrium composes most of the right
side of cardiac silhoutte. SVC is on the upper most border of the right side and IVC is on the lowest most border of
right side..... only the auricle of the left atrium is visible anteriorly(protruding between the pulmonat trunk and the
left ventricle .... RV wall thickness is 3-4 mm in diastole as compare to LV wall thickness which is 1cm in diastole.
normal diameter at the level of junction of mitral valve with its chordae tendineae is 5cm)
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courses in the coronary sulcus
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septal branches
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may provide collateral circulation in occluded LAD
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30% corononary flow in systole, 70% in diastole
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courses in the posterior interventricular sulcus
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diagonal branches
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descends in the anterior interventricular
sulcus
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courses around the left border of the heart in the coronary sulcus in atrioventricular groove on posterior surface
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pulmonary artery at lower level is anterior to aorta and at upper level lateral to
aorta ............... The ascending aorta lies posterior and to the right of the main pulmonary artery.
The aortic arch travels above the right pulmonary artery and the left bronchus. The
descending thoracic aorta the left anterior surface of the vertebral column and lies posterior to
the esophagus and the left atrium. ..... The main pulmonary artery ascends anteriorly and to the
left of the ascending aorta and is directed towards the left shoulder. Right pulmonary artery travels
horizontally under the aortic arch posterior to the superior vena cava. The left pulmonary artery
courses superiorly over the left main bronchus. The proximal 2-3 cm of the pulmonary veins
contain cardiac muscle within the media and function life sphincters during atrial systole.
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adenosine and NO play a very important role in coronary vessels dilations. ..... compliacne=diastolic volume/
diastolic pressure ..................... CO= (135*BSA) / (13*Hb)*(SaO2 - SvO2)
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obtained at the level of tissue O2 consumption.
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obtained from pulmonary artery
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during strenuous exercise, exercising muscle receive 85% of CO due to local release of vasodilatory factors.
although sympathetic discharge during exercise causes an increase in CO and increased contraction of blood
vessel, there is only modest blood pressure increase because of vasodilation within muscle so significantly
decreases the total peripheral resistance. ............ under normal condition in a healthy adult living at sea level.the
pulmonary circualtion is a low-pressure,low resitance and high flow system. bloof flow per minute in
pulmonary and systemic circiulation in all condition (rest and exercise) must be equal. the low afterload pressures
of the pulmonary circulation allow thin right ventricle to keep pace with the more substaintial left
ventricle...................... the arterial resistance in the systemic circulation is considerably higher than that in the
pulmonary circulation in all scenarios. the resistance of pulonary vasculatutre may be increased in individuals living
at high altitude, in patients with idiopathic pulmonary hypertewnsion ............. the mean arterial pressure,
diastolic pressure and systolic pressure. are considerably differetn in pulmonary and systemic circulation.the
pulmonart arterial blood pressure increases by only a few mmHg during maximal exercise despite the fact
that the rate of blood flow increase 5-7 fold ........ though TOTAL renal blood flow increases during exercise due to
significant increase in CO, but a slightly smaller portion of CO goes to kidney because of sympathetic stimualtion
causes vasoconstriction of the renal arterioles....... nbme 4,2,34 not sure. My explanation : coronary blood flow
doesnt change with exercise its only the duration of flow that changes due to tachycardia during exercise so
duration of diastole decreases ( coronary flow occurs during diastole) therefore the points must be parallel to
rest from Y-W . Perfusion pressure increases (not sure) coz resistance increases??
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highest for capillaries and shorter for aorta
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individual organ circulation
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total body circulation
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blood flow is directly proportional to the vessel radius raised to the fourth power. resistance to blood flow is
inversely proportional to the vessel radius raised to the fourth power. ...... when flow is reduced by a factor of 16, the
radius of the lumen is decreased to r/2 (50% of the original radius)
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highest for aorta,slowest for capillaries
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at this point all circulatory flow ceases, and the pressure through out the circulatory system equalizes... mean
systemic pressure is a measure of degree of filling of circulatory system relative to the circulatory capacity. this point
changes with increase or decrease in circulatory volume
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right atrial pressure increases during prolonged exercise due to increased return of blood to the heart and
decreased pooling of blood in the venous system.
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chronic anemia
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pressure-volume loop AV shunt increases preload and decreases afterload by routing blood directly form the
arterial system to the venous systme, bypassing the arterioles. eventually result in high output cardiac failure. .....
acutely AV fistula causes a decresae in TPR which results in an increased CO and an increased venous
return.However, the venous return curve does not immediately shift along the x-axis. Over time, the
sympathetic nervous system and kidneys will begin to compensate for a chronic fistula by increasing
cardiac contractility, vascular tone, and circulating blood volume. These changes further increase the
cardiac function curve as well as increase the mean systemic pressure, resulting in a rightward shift of
the venous return curve on the x-axis.
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TPR changes both venous return and CO.
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nbme>>>>4,4,34 in severe hemorrahge , adaptive reponse occur due to >>>>>fluid shift from intersticial to
vascular compartment. Physiologic compensation mechanisms for hemorrhage include initialperipheral and
mesenteric vasoconstriction to shunt blood to the central circulation. This is then augmented by a progressive
tachycardia and a fluid shift from interestitial to vascular compartment.
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systolic dysfunction>>>>effect both ventricular ejection and isovolumetric relaxation. isovolumetric relaxation line
shift to the right
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3 corners>>>starting from right bottom>>preload, afterload and contractitlity ....... COCO
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S3 also heared in the high output states (eg pregnancy and thrytoxicosis)........ it is due to sudden limitation of
ventricular movememnt during rapid passive ventricular filling. accentuated by having the patient in left lateral
decubitus position and fully exhale(end expirtion(which decrease the volume of lung and bring heart closer to
the chest wall.. it will intensify during expiration due to increase blood flow from lungs to the heart.................. it
may be heared on pateitns with chronic severe mitral regurgitation , chronic aortic regurgitation and heart failure
associated with dilated or ischemic cardiomyopathy ............ due to sudden deceleration of blood as ventricle
reaches its elastic limit, extra low frequency sound after S2 .......
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on left side of heart. On right side along lower left sternal border(tricuspid area) with the patient in supine position
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and restrictive cardiomyopathy
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in isovolumetric contraction and rapid ejection
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isovolumetric relaxation
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lost in aortic regurgitation
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rapid ventricular filling and reduced ventricular filling
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more pronounced in tricuspid and mitral regurgitation due to increase in atrial systolic pressure( unlike mitral
stenosis which increase atrial diastolic pressure) ......... mitral regurgitation has peak v wave, so can
be tricuspid regurgitation. 945 ............... in normal individual , left atrial pressure increases to about
10mmHg DURING SYSTOLE DUE TO PASSIVE FILLINg TO THE LEFT ATRIUM; THIS IS REFLECTED AS THE 'V
WAVE' ON LEFT ATRIAL pressure tracings
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prominent a wave in hypertrophic cardiomyopathy 2071
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due to sudden rise in end diastolic pressure following atrial contraction.
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require normal atrial contraction; absent in atrial fibrillation. its a sign of diastolic dysfunction. just prior to the S1
after the P wave on ECG (coinciding with the active phase of ventricular filling).
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when ventricular pressure exceeds the diastolic systemic blood pressure
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narrowing and upward shift of ventricular ejection phase (result of higher than normal pressures at the time of
aortic valve opening and closure).. would show elevated pressure during isovolumetric ventricular contraction
before the aortic valve opening
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rapid y descent becomes both deeper and steeper during inspiration is often observed in
constrictive pericarditis
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equalization of right and left atrial pressure minimizing the respiratory variation in left and right
ventricular flow
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carvallo"s sign
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since squatting simultaneously increases venous return and SVR, left ventricular stroke volume and mean arterial
pressure both rise, although there may also be a reflex bradycardia, the net effect of increased left ventricular
preload and afterload would likely be to increase LV work done perunit time.
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AS murmur decreases due to decrease tnasvalvular pressure gradient, as hand grip increases afterload.
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this is due to increase blood flow through the valve. it decreases by increasing afterload due to decrease in
tranvalvular pressure gradient
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related to left ventricular EDV
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but softer.MVP related to LV volume. decrease>>>>> early click increase>>>>> late click
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in severe aortic stenosis and concentric left ventricular hypertrophy>>>>atrial contraction (kick) become very
important in maintaining LV filling and CO>>>atrial fibrillation abolish this atrial contraction and decreases CO
and causes pulmonary edema
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especially carotid
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due to congestion of pulmonary vasculature.
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in 60s or 70s
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prominent v-wave. ....................... presence of S3 determines its intensity.(not intensity of holosystolic murmur)
................. ACUTELY:normal or near normal atrial compliance(so have pulmonary edema)CHRONICALY:
increased atrial compliance due to increased left atrial volume(so have atrial fibrillation and mural thombus
formation)
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this is a functional type due to dilation and/or papillary muscle ischemia.
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is US incidence of rheumatic heart disease is decreased to much,so mitral insufficiency due to myxomatous
degenraiton (mitral valve prolapse) is currently the major cause of siginificant mitral regurgitation in the US
..................... mitral annular calcification:degenerative calcific deposits in the fibrous ring of the mitral valveis
most common in individuals (especaiily females) over age 60, individuals with a prior history of myxomatous
degenration of the mitral valve, and individuals with chrinically elevated LVP. degenerative mitral annulus
calcification can occasionaly result in mitral regurgitaiton. mitral annular calcification generally does not impair
valuvlar funcitond,,on rare instances causes regurgitation or stenosis
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most common anatomical lesion producing mitral regurgitation
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at left sternal border (3rd and 4th intercostal space) ........ very loud murmur in asymptomatic patient(generally
loud murmur are indicator of severity but here is reverse) loudness is due to very small hole so blood has difficult
time to pass through it
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palpitation(due to increase stroke volume), head pounding (high amplitude intracranial pulsation,water hammer
pulses), head bobbing(due to high pulse pressure musset sign)
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in chronic severe AR as a consequence of infective endocarditis the regurgitant blood flow increases left ventricular
end-diastolic volume (preload) and wall stress, with resultant eccentric hypertrophy. the gradual increase in left
ventricular chamber size due to eccentric hypertrophy increase stroke volume and maintains cardiac output. in
contrast acute AR have a small left ventricular cavity and cannot significantly increase stroke volume to
accomodate for the regurgitant blood flow.this leads to a decline in CO, along with a rapid increase in LVEDP,
leading to acute PE
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generally A2
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presystolic(S1) acentuation of mitral and tricuspid stenosis is due to atrial contraction(increased transvalvular
flow) in severe mitral stenosis atrial fibrillation would eliminate this presystolic accentuation (which were produced
by atrial contraction). in mild mitral stenosis, the murmur may only be audible during the accentuation(presystolic)
phase in late diastole, .......... causes atrail fibrillation and left atrial thombus formation; also hoarsness due to left
atrail enlargement and impingement (causes neurapraxia >>failure of nerve conduction due to blunt injury) of left
recurrent laryngial nerve (loops behind the ligamentum arteriosum, underneath and around the aortic ach, and back
up alongside the trachea to the larynx)( (ORTNER SYNDROME)
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can have inspiratory splitting of S2
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small one>>asymptomatic>>>and have continuous murmur large one>>>dyspnea, cyanosis and frequent
respiratory infection,>>>generally dont have mumur .............. diagnosis is confirmed with echocardiography.
...................... ductus arteriosus>>normally closes during first 15 hours>>>remnant of 6th aortic arch
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world wide rheumatic heart disease MCC. In US calcinosis either on bicuspid or normal valve is MCC. ............. 3
etiology: 1, abnormal calcification of bicuspid valve. 2, calcified normal valve. 3, rheumatic heart disease. .........
May also arise as a consequence of chronic rheumatic valve disease; coexistingmitral
stenosis and fusion of the aortic valve commissures distinguish rheumatic disease from
"wear and tear.".......... rheumatic aortic heart disease usually produces combined aortic regurgitation and
stenosis. Acute aotic valve infective endocarditis tend to cause aortic regurgitation.
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in infective endocarditis
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An increase in LV preload and end-diastolic volume causes an increase in cardiac
contractility and LV ejection fraction. despite an increase in LV contractility ad ejection fraction,
a larger fraction of blood is ejected back into the left atrium across the incompetent mitral valve.
This reduces the effective forwrad flow and cardiac output and can lead to cardiogenic
shock. A decrease in effective forward cardiac output causes neurohumoral activation with a
reflex increase in systemic vascular resistance and cardiac afterload, which in turn can
further exacerbate MR. the goal of initial medical therapy in patients with acute MR is to
reduce systemic vascular resistance or afterload by using intravenous vasodilators
(nitroprusside) or intraaortic balloon counterpulsation as temporary stabilization measure
prior to valve surgery......... left ventricular preload reduction may decreased the regurgitant
flow fraction if the degree of mitral valve incompetence is volume dependent. however, non-
volume-dependent causes of mitral regurgitation(e.g., congenital defects, annular calcification)
would not be a affected.
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or have other cyanotic congenital heart disease... also with perinatal distress and fetal alcohol syndrome
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coarctation of aorta can also have continuous murmur due to persistent PDA and large collateral vessels. atrial
septal defect can also have when associated with mitral valve obstruction due to an elevated pressure across the
atria (Lutembacher syndrome)
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SEVERE mitral stenosis: 1, interval between A2 and OS decreases. 2, right side S3 or S4 can present. 3, absence of
presystolic accentuation (due to atrial fibrillation) 4, intensity of diastolic murmur may be increased or decreased
.......... the A2-OS interval is inversely correlated with the severity of mitral stenosis.
....... current standard for diagnosis and measurement of severity is done by transvalvular pressure gradient via
2-D Doppler echocardiography........ has near normal or decreased left ventricular diastolic pressure. Increased
LVDPmeans combined aortic valve dysfunction
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cause there is very high LA pressure.......................... intensity of diastolic rumbling depends on both transvalvular
pressure gradient and the amount of blood flowing through the valve.
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in developed countries mostly caused by aortic root dilation (in which murmur is best heard at right sternal border)
or bicuspid aortic valve.
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in severe state can be holodiastolic and present with absence of A2 heart sound. ........ the duration of the
diastolic murmur can provide information about the severity of aortic regurgitation. ..................... best heard at left
sternal border at the third and fourth intercostal spaces while the patient is sitting up and leaning forward with his
breath held at end expiration. ....... AR tends to elevate left ventricular diastolic pressure and decrease aortic
diastolic pressure. ......... loss of dicrotic notch .......... inhaled amyl nitrite produces marked vasodilation
causes reduction in systemic arterial pressure and decreasing this regurgitant murmur
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in developed countries sporadic myxomatous degenration is the most common cause. but inherited connective
tissue disease can also promote MVP. it is thought that subtle defects in connectie tissue protiens predispode
tissues rich in microfibrils and elastin (such as cariac valves) to damage by chronic hemodynamic stress.
histologically there is attenuation of the fibrosa (collagen) layer of the valve and thickening of the spongiosa layer
through deposition of mucoid (myxomatous) material. the chordae tendinae rutpure also develop due to thinning
of the collagenous core.
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by increasing LV <<<<volume>>>>> click goes further to S2 and murmur even disappear; note that with severe
MVP >>>>by increasing LV<<<<<<pressure>>>> holosystolic murmur will occur
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left lower sternal border..(unlike HOCM which is at left mid sternal border, 3rd or 4th intercostal space) changes
intensity with the inspiration.
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best heard with a patient in left lateral decubitus position.
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congenital aortic stenosis: present is childhood and produces systolic murmur as a result of severe subvalvular,
valvular and supravalvular anatomic defects. also associated with mental retardation and abnormal facies. .............
calcific aortic stenosis caused by chronic hemodynamic stress or atherosclerotic inflammation that eventually
leads to a progressive sortic valve leaflet thickening, calcification and stenosis.
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in 80s or 90s
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is due to decreased mean arterial pressure due to decrease CO.
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mid systolic ejection murmur. Dnt have S3 but when severe aortic stenosis(acutely) lead to HF produce S3. In
chronic aortic stenosis there is concentric LV hyoertrophy. ............. a longer and late peaking murmur indicates
severe AS. whereas a brief and early-peaking murmur indicates less severe stenosis. however, the intensity of
the mumur does not correlate with the severity of stenosis. ........ as stenosis get worsened peak goes closer to
S2 and S2 become silent cause stiff valve cant slam shut.
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time-dependent inactivation of L-type (long-lasting, large conductance) Ca channels reduces inward current
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ca dependent ca release
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is due to high K permeability and low Na permeability by leak currents(ungated) .................... theresting
potential of cardiac myocytes is approximately -90mV, while the resting potential of skeletal
myocytes is approximately -75mV. The highly negative resting potential of cardiac myocytes
reduces the risk of arrhythmias, as a larger stimulus is needed to excite the cells........... in
neuronal cell: resting potential is -70mV. binding of NT to ligand gated Na channel causes its activation and graded
depolarization of the neuronal cell membrane toward the threshhold for firing an AP(-55mV). once thrushhold is
reaches voltage gated Na channel open and make membrane potential to approach the equi;libirum potenatial for
sodium (+60mV). ..................... equibrium potential for Ca ion is (+125mV) ........ hyperpolarization is due to slow
closure of voltage gated K channel, it is -85 mV which is due to K equilibrium potential.... resting membrane
potential is -70mV
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nbme>>5,2,14 gap junction are most likely found with intercalated disk
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delayed rectifier current
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Ca gated K channel are one of four main types of K channels and are ubiquitous.
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L-type(long lasting) dihydropyridine sesnsitive Ca channel,causes slow but large influx of Ca into cell
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adenosine interacts with A1 receptors on the surface of cardiac cells, activating potassium channels and
increasing potassium conductance, causing the membrane potential to remain negative for a longer period.
adenosine also inhibits L-type Ca channels (long lasting) further prolonging the depolarization time. ACH behaves
similarly by increasing outward K conductance while decreasing inward Ca and Na currents during phase 4.
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by the slow influx of Na that begins at the end of repolarization. also has slow decrease in K efflux as the K
channels continue to close. once the membrane potential reaches approximately -50mV , the T-type (transient) Ca
channels open and allow Ca to enter the cell and contribue to depolarization. as the thrushhold reaches -40mV,
the L-type (long lasting) Ca channes open and trigger an AP. .............. early phase 4 inward Na current late
phase 4 transient inward Ca current. once the trushhold potential reached oppening of addictional calcium channel
is triggered and the resulting incrase in calcium influx begins phase 0 depolarization. ..........
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park.(2.2m/sec) at(1.1) ventura(0.3) avenue(0.15)
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60-100
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20 beats; ECG shows prolonged abnormally shaped QRS complexes due to aberrant impulse conduction through
the ventricles.
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in the right atrium near the septal cusp of the tricuspid valve. near the orifice of coronary sinus. 11956 ..............
nbme>>>6,2,24 AV node near the attachment of the septal cusp of the tricuspid valve.
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prolong in ventricular dyssynchrony or slowed intraventricular impulse conduction due to fasicular/bundle branch
block. <<<<<<<<<the heart rhythm remain same.>>>>>>>>>>>>>
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SA node is in subepicardial location and AV node is in the endocardial locarion
11956
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QT interval can be thought of as a rough estimate of APD (action potential duration) ................. QT interval generally
represent repolarization as ventricles prepare for the next beat.
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located at the junciton of the right atrium and SVC>>>upper part of crista terminales
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45-55; since ventricular depolarization proceeds nomrally QRS complex is narrow.
Becomes pacemaker in 3rd degree heart block
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slowest to ensure ventricular filling in diastole
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highest to ensure rapid ventricular contraction in bottom up direction(also endocardium to epicardium)
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is differentiated from other froms of polymorphic ventricular tachycardia by the facr that it it is always
associated with an underlying prolongation of the QT internal
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phenothiazine and methadone also
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unprovoked syncope in otherwise young healthy individual is QT syndrome provoked syncope(excerise) in
otherwise young healthy individual is HCM
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<0.12 seconds
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must be considered in any young healthy individual with sudden cardiac death .............. PSVT is a common
dysarrythmia that frequently occurs in pateitns with no other heart disease. the most common cause is re-
enterant circuit in the AV node...........................
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chronic, heavy alcohol use is one of the acquired causes besides drug uses. .......
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generally in wolf-parkinson-white syndrome there is widened QRS complex but reentery circuit causes paroxysmal,
narrow QRS complex
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as a result fo delta wave. ................ due to changes in geographic sequence of ventricular depolarization and
replorization as a result of pre-excitaiton, there may be variable ST segment/T wave abnormalities.however these
are found less consistently than the usuall WPW triad of ECG abonormalities
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K or Na.
majorly K channel protein that contribute to delayed rectifier current (Ik) of cardicac action potential
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quinidine, procainamide, disopyramide, ibutilide, dofetilide and sotalol
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fluoroquinolone
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Na and L-type Ca channel mutation
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most common tachyarrythmia ................... binge drinking ( holiday heart”),)>>>with chronic heavy alcohol
use QT interval prolongation results but atrial fibrillation is not as common as acute binge eating. ........... the area
aroud the opening of the pulmonary veins in the left atrium is frequently involved in the pathogenesis of atrial
fibrillation. ...... left atrial appendage (LAA) is a small saclike structure in the left
atrium that is particularly susceptible to thrombus formation. ........ factors contribute
to thrombus formation in atrial fibrillation: 1, left atrial enlargment 2, stasis of blood
due to ineffective atrial contraction 3, atrial inflammation and fibrosis. .....
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the isthmus between the inferior vena cava and the tricuspid annulus is the site
of radiofrequency ablation for atrail flutter 11956 .............. atrial fibrillaiton is most
often caused by reentrant currewnt that rotates aound the tricuspid annulus,, p
waves r replaced by regular , rapid fluttr wave
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dit
⅔ times QRS is narrow and ⅓ times QRS is prolonged
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also in proximal tubule along with in inner medullary collecting tubule. ................. ANP also decreases aldosterone
release>>>>leading to an increase in water and Na excretion by the kidney. ..... 28 AA polypeptide
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increase in both systolic(mostly) and diastolic HF
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dilation of internal carotid artery just above the bifurcation of common carotid artery.
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they are constantly firing in normal conditions. changes in pressure either increase or decrease firing
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used initially to treat PSVT(most common parosyamal tachycarida due to reenterent impulse from slow and fast AV
nodes)
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brain stem problem due to the increased ICP
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PaCO2 is the major regulator of respiration in the healthy individual. even a slight increase in PaCO2 result in
increased pulmonary ventilation .......... the medullary respiratory centers controls the depth and rate of respiration
based on input from central and peripheral chemoreceptors and airway mechanoreceptors.............. pulmonary
stretch receptor include myelinated and unmyelinated C fibers in the lungs and airways. these receptors regulate
the duration of inspiration depending on degree of lung distension (Hering-Breuer reflex) and act predominantly to
protect the lung from hyperinflation. ....... oxygen has relatively small effect on the respiratory drive if its partial
pressure in the arterial blood is >70 mmHg, as a result PaCO2 is the major stimulator of respiration in healthy
individual. in chronic COPD patient there is decreased sensitivity of PaCO2 and Ph, so arterial PO2 become
significant contributor to the respiratory drive. as a result when supplemenatal oxygen is given their level
increases rapidly which reduce peripheral chemoreceptor stimulation and decrease respiratory rate
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herings nerve
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lies just inferior to the hyoid bone.
lies at bifurcation of the common carotid artery
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BNP induces a diuretic, natriuretic and vasodilatory effect by antagonizing the actions of RAAS. ALSO
PROTECTS AGAINST THE DELETERIOUS MYOCARDIAL REMODELING AND FIBROSIS THET OCCUR IN
HEART FAILURE.. NEPRILYSIN INHIBITOR LEADS TO INCREASED LEELS OF ENDOGENOUS BNP. neprilysin
inhibitor improve outcome in patiensts with chronic systolic heart failure. .......... neprilysin is a metalloprotease
that inactivates several peptide hormone including bradykinin, glucagon, enkephalins and natriuretic peptides .
neprilysin inhibitor is sacubitril
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they counteract endothelin, sympathetic effects and angiotensin II
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also causes increase capillary permeability.
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precapillary sphincter can detect blood flow demand in target tissue and can dilate in response to local metabolites.
These sphincter are also responsive to sympathetic and parasympathetic.. ................ serotonin is produced by
gut neuroendocrine cell, platelets and serotonergic neuron in CNS>>>it has been shown to have both
vasoconstriction and vasodilation effects
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in large arteries and pre-arteriolar vessels ..... of these NO and adenosine are most important regulator >>>>both
are dilators. .......... nervous system has little effect on coronary blood flow
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in small arterioles ........ during stress and tachycardia>>adenosine from ATP increases coronary blood flow rate
by vasodilating coronary vessels, especialy during diastole>>increase blood flow by 5 times as compare to
resting state.
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due to increase in cytosolic Ca levels seondary to hypoxia-induced modulation of K channels and/or
decreased prodcuction of reactive oxygen species
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local tissue PO2
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NO synthesized from arginine and oxygen by eNOS>>>when there is increased intraendothelium <<<<Ca
concentration>>>>due to specific membrane receotro present on endothelial cells ....... released by coronary
endothelium in response to NTs (Ach and NE), platelet products ( eg serotonin ADP), thrombin, histamine, bradykinin,
endothelin. also released in response to pulsatile stretch and flow sheer stress in coronory arteries,>>>>> major
regulator of flow mediat4ed vasodilators in large arteries and prearteriolar vessels. ..... arginne level for NO
depends on exogenous food inake, endogenous synthesis, intracelluar storage and degredation, and the presense of
asymmetrical dimeethylarginine (endogenos analog og argine that work as competitive inhibitro of eNOS........
though endothelium of vessels dont have cholinergic innervation but theu have M3 receptros, so
cholinomimetic stimulates eNOS
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under normal condition LAEDP(PCWP) and LVEDP are normal except in MS. In all other pathologies (like dilated
cardiomyopathy, restrictive lung disease, cardiac tamponade. isolated aortic stenosis) their would be equal decrease
or increase in pressure but no difference exist.
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due to abnormal arteriolar dilation (eg use of dihydropyridine CCB) or impaiment in venous return ( eg enous
thrombosis and righr sided heart failure)
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filiariasis, invasive malignancies, and iatrogenic etiologies ( eg surgical lymph node disssection and radiation
therapy)
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reduces the amount of interstitial fluid reteurning to the circulaiton via capillary bed venules
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also depend on area of capillary available for filtration. Used to determine net fluid movement in a given area in ml/
min.
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does not cause any symptoms in older infants and children. overtime can lead to right ventricular enlargement
or hypertrophy
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transposition present with cyanosis at birth
TOF present with cyanosis sometime after at birth.
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when PDA present in these pateints, they pesent with continuous machine like murmur appreciated between the
scapula .......................
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asymmetric division of embryonic tuncus arteriosus produces significant stenosis .......... deviation of
interventricular septum>>>>>result from anterior and cephalad deviation of the infundibular spetum during
embryologic development, resulting in a malaligned VSD and an overriding aorta.
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is large enough and not restrictive.
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exercise intolerance is due to increase right to left shunt and resulting hypoxemia in response to active skeletal
muscle vessels dilation.
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harsh systolic ejection murmur over the mid-to-left upper sternal border and is due to presence of RVOT
(subvalvular, pulmonary artery stenosis, or supravalvular narrowing in the main pulmonary artery)............
repaired tetralogy has pulmonary regurgitation problem
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during septation of the truncus arteriosus. ........ due to abnormal primitive heart tube looping
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surviving neonates can present with a systolic-only murmur or even no murmur, depending upon the location and
size of any atrioventricular septal defects
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death due to congestive HF with in first year of life
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PG E2
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large one which has softer murmur due to lower pressure gradient
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small VSD have holosytolic murmur at the mid to lower left sternal border and no symptoms. the murmur becomes
audible arounf age 4-10 days when pulmonary vascular resistance declines, enablinf left to right shunt, most
small VSD are heodinamically insignificant and close sponatneously. in contrast moderate to large VSD usually
present with HF, failure to thrive and diaphoresis when feeding.lasrge VSD may have no mumur as right
ventricular pressure are similar to left ventricular pressure.large VSD rarely closes spontaneously and can result in
chronic pulmonary hypertension and cyanosis if the defect is not closed early in life.
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down syndrome
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failure of embryologic processes include 1, proliferation>>>unilateral aplasia of the fibula. 2,
apoptosis>>>autoimmune disease due to persistance of autoreactive T/B cells 3, obliteration>>brachial cleft cyst
4, migration>>hirschprung disease 5, fusion>>>hypospadias (failure of urethral folds to fuse)
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because PDA delivers unoxygenated blood distal to the left subclavian artery.
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cardiac examination shows bounding peripheral pulses and a palpable thrill over the left upper sternal border(left
infraclavicular region due to turbulent blood flow through the PDA)............... nbme>.3,3,32 As baby cries or takes
1st breath air enters in alveoli and there will be marked decrease in pulmonary vascular resistance -this cause
increase in left arial pressure more than rt atrial pressure and this leads to closure of foramen ovale ; Also
increase in O2 saturation and decrease in Prostaglandins --leads to closure of ductus arteriosus.
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RVH and right atrial enlargement due to eisenmenger is reversible(by transplanting lungs) unlike pulmonary arterial
hypertension which is irreversible
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pre in infants, post in adults. Can have continuous murmur due to collateral.
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laminated medial hypertrophy>>>>result in irreversible pulmonary vascular sclerosis and closure of cardiac
septal defect can no longer be hemodynamically tolerated by right ventricle>>>>>so we need lungtransplant.
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normally with in first 15 hours. Abnormal after 1st year. some patient may survive untill middle age with this
finding ................... pharmacologic closure of PDA can be achieved by PGE2 synthesis inhibitors (eg indomethacin)
in premature infants. however older patients usually require surgical ligation or percutabeous PDA occlusion.
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at infraclavicular region(upper sternal border. It is associated with prematurity ,perinatal distress ,rubella, fetal
alcohol syndrome and infant born with congenital cyanotic heart disease .............. clinical features vary
depending on the size. small PDA have a characteristic contiuous, machine like mumur.(left to right) with no
significant symptoms. large PDAs can present anytime duting childhood with progressive pulmonary
hypertension and reversal of the shunt to right to left.the characteristic continuous murmur decreases as the
pulmonary pressure rises and ultimately disaapears, typical consequeces are heart failure and
cyanosis(eisenmenger syndrome), ........ remnant of 6th aortic arch
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failed embryologic fusion is an endocardial cushion defect, resulting in ostium primum atrial septal defect.
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can have continuous murmur in rare instances when have mitral valve obstruction,due to pressure gradient
across atria (LUTEMBACHER SYNDROME) ............... have midsystolicpulmonary ejection murmur due to
increased flow across pulmonary valve ......... Diastolic murmur Atrial septal defect (↑ flow across
tricuspid valve)
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small ones which has low pitched holosystolic murmur
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although traditionally classified into preductal and postductal types, the signs and symptoms of aortic
coarctation depend more on the age at presentation, which varied according to the severity of the
stenosis. Severe coarctation usually presents in infancy with differential cyanosis affecting the lower
extremities as long as the ductus arteriosus remains patent. On ductal closure, these neonates can
develop signs of heart failure and shock. More moderate stenosis often presents in childhood or
adolescence with symptoms of lower-extremity claudication. .......... is a non-cyanotic congenital heart
disease that can present in infancy with shock when the patent ductus arteriosuscloses. children and adults who
present in later life tend to have milder coarctation that manifests as upper bosy HT and collateral intercosatal
vessels, and lower extremity claudication, limit lower extremity exercise tolerance
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It is usually an isolated abnormality; however it may occur in combination with other anomalies,
particularly aortic coarctation.
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ostium primum type: failure of endocardial cushions of AV canal to fuse completely during embryonic
development.
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MCC of death, death usually occur in b/w 30 and 40
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atretic aortic arch
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primary hyperaldosteronism>>>due to bilateral nodular hyperplasia or hyperfunctioning adrenal
adenoma.>>>>have normal sodium, low potassium and high bicarbonate.... despite the increase in sodium
reabsorption pedal edema and hypernatremia are rarely observed due to aldosterone escape. the increased
intravascular volume increases renal blood flow (with resulting pressure natriuresis) and augmented release of
atrial natriuretic peptide.
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associated wiht cystic medial necrosis of aorta, which may result in dissecting aortic aneurysm, aortic valve
incompetence and mitral valve prolapse.
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unilateral renal artery stenosis occur in 2-5% pf patients which causes HT. stenosis at the ostium of the artery.
causes decreased oxygen and nutrient supply>>>atrophy of kidney histologically atrophied kidney show crowded
glomeruli, tubulointersticial atrophy and fibrosis and often time focal inflammatory infiltrate ...............
abdominal and flank bruits, presents both during systole and diastole, are specific for RAS-
although bruits may not be present.
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other cuases of renovascular seclerosis are atherosclerosis and polyarteritis nodosa .............. less frequently,
RAS is a manifestation of fibromuscular dysplasia-a disease predominantly affecting women 20-
30 years old. in this case, the narrowing of multiple segments of he renal artery occurs (“string of
beads”)
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2nd MCC of death is cardiac failure secondary to aortic or mitral regurgitation
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Gestational diabetes causes: fetal macrosomia,caudal regression syndrome,postnatal hypoglycemia,
hypocalcemia, hypertrophic cardiomyopathy.still birth
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these patients usually also have a cleft in the anterior leaflet of the mitral valve as well as in the septal leaflet of the
tricuspid valve.causing regurgitation through the AV valves.
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on the medial eyelid
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can occur anywhere in arterioles but most commonly in kidney, retina and intestine ....... Hypertensive crisis, a
condition defined as a persistent diastolic pressure exceeding 130 mmHg that is often associated with
acute vascular damage. Hyperplastic arteriosclerosis, which can result from diastolic pressures >120-
130 mmHg
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muscular arteris: femur,tibia,rabius,ulna,and aterial supply to genital track
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often are palpable on PE
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generally occur >50 years and are thought to cause isolated systolic hypertension due to arterial hardening
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and reduplicated basement membrane
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hyaline material in the intima and media,underlying structure of vessel wall in maintained >>>but intima is
thickened and arterial lumen narrowed. hyaline material is thouggh to result from leakage of of plasma constituents
across the vascular endothelium, and from excessive extracellular matrixproduction by SMC. the SMC may be
stimulated by chronic/repetitiveendothelial injury caused by the hemodynamic stress of long-standing
hypertension or by the metabolic dearangements of diabtes .... in diabtics, development of hyaline
arteriosclerosis is related not only to the duration of the disease, but also to the degree of any concomintant
hypertension.
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benign appearing macrophages with abundant, finely vacuolated (foamy) cytoplasm containing cholesterol (free and
esterified), phospholipids and triglycerides.
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non-enhancing
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large elastic arteries>>>abdominal aorta, carotid and iliac arteries
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start as early as 2nd decade with formation of fatty streak and intimal thickening .......... fatty streaks, these
are the earliest lesions in the progression to atherosclerosis and can be seen as early as the
second decade of life. with advancing age, the chronic inflammatory process initiated by
endothelial injury transitions from fatty streaks within the intima (composed mainly of lipid-
laden foam cells) into atherosclerotic plaques, such as fibrous cap atheromas and fibrous
plaques ...... subendothelial collagen and subendothelial glycosaminoglycan form subendothelial fibrous cap
over the central core of an atherosclerotic plaque......... thin fibrous cap, rich lipid core and active inflammation
all correlate with decrease plaque stability. ......... more advance lesion develop lipid-rich necrotic core and regions of
calcification. ...... Abs to oxidized LDL have been detected in human serum and localize to atherosclerotic plaque.
titer of this rises following acute coronary event. although they play a role in atherosclerosis development , they do
not act as growth factors for SMc ....... total coronary artery calcium content correlate modestly with coronary
artery atherosclerotic plaque burden. but the presence of intraplque calcium could be consistent with either acute
coronary syndrome or with gradual occlusion without mycardial necrosis.
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injury due to hyperlipidemia and chronic hemodynamic stress.>>>> this leads to
increased expression of surface vascular cell-adhesion molecules (VCAM)>>>>that
allow adherence andmigraton of monocytes and T lymphocytes into the
intima>>>>the infiltratingleukocytes and dysfunctional endothelium release
cytokines and growth factor.( eg PDGF,FGF,endothelin-1, interleukin-1) that
promote migration and proliferation of VSMC from media within intima. VSMC
are also stimulated to synthesize extracellular matrix proteins (eg collagen,
elastin,proteoglycans) that form the fibrous cap typical of mature atheroma.
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the likely hood of plaque rupture or other acute plaque change has more to do with plaque stability than plaque
size. plaque stability depends upon mechanical strength of overlying fibrous cap. during chronic inflammatory
progression of an atheroma, the fibrous cap is continually being remodeled. the balance of collagen synthesis and
degredation determine the mechanical strength of the cap. activated macrophages in thr atheroma contribute to
collagen degredation by secreting metalloproteinases.thus a high degree of ongoing intimal inflammation can
destabilize the mechainical integrity of plaque through release of the metallopreoteinases. ......... macrophage
also produce matrix metalloproteinases and tissue factors that degrade the
extracelular matrix,causing the formation of a large, soft lipid-rich core with
thinning of the fibrous cap.such vulnerable plaques have an increased propensity
for rupture.
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mostly at carotid sinus at the origin of internal carotid artery. in the last occur in circle of willis
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which progressively weakens the underlying media of the aortic wall
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result in thoracic AA. the infrarrenal abdominal aorta lacks a vasa vasorum
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thigh claudication is due to occlusion of external iliac artery or common femoral artery and/or superficial femoral
and profunda femoris artery . aortoiliac atherosclerosis can cause decrease blood flow to pudendal arteries which
are branches of internal iliac artery and causes erectile dysfunction.
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Signs of embolism (blue toe, livedo reticularis with normal peripheral pulses) following an
invasion vascular procedure (eg, angiography, aortic surgery) is suspicious for atheroembolic
disease ............
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characterized by the fragmentation of elastic tissue and by the separation of the elastic and fibromuscular
components of the tunica media by small cleft spaces(mucoid spaces)>>>>predispose to ascending AA, and
dissection .......... most frequent histopathological abonormality (other than intimal tear) found in association with
aortic dissection
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perivascular fibrosis with as extensive lymphoplasmacytoc infiltrate and
thickening of the adventotia is characteristic of inflammatory aneurysm AAA.
however this is a rare (usually not associated with) cause of AAA that is typically
associated with systemic symtoms (eg fever, fatigue) .......... microbial infection
(usually ) can cause localized dilaiton of an artery due to destruciotn of the vessel
wall by infection. trauma , bacteremic seeding, or septic emboli (mycotic
aneurysm) can cause INFECTED ANEURYSM.>>>>>>>>typically present with
painful pulsatile masses and systemic signs such as fever and malaise. ..... AAA
result form transmural inflammation,chronic inflamamtion leads to degredatin of
elastin and collagen by proteases, resulting in loss of elastin and smooth
muscle cells and abnormal collagen remodeling and cross-linking ..............
AAA most commonly occur below the renal arteries, risk factors are advance age
>60, smoking, hypertesion and male sex
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severe, complicated intimal atheromas can destroy and weaken the underlying media, resulting in aortic
aneurysm.
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released by activated platelets(locally adherent), disrupted endothelial cells, and infiltrating macrophages
promotes migration of SMs from media into the intima and increase SMCs proliferation. platelets also release
TGF-beta which is chemotactic for SMCs and induces interstitial collagen production. ........ fibroblast are
found infrequently in the tunica intima of blood vessels and are not significantly
ivolved in atherosclerosis pathogenesis. .... VSMC are directly responsible for the
synthesis of new collagen and extracellular matrx
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turbulent arterial flow>>>endothelial injury>>>atherosclerosis. turbulent arterial flow also associated with
pathogenesis of neointimal hyperplasia and aneurysm disease
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popliteal and coronary arteries
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most prominent around the ostia of major arterial branches. The upper limb arteries is usually spared.
mesenteric and renal arteries tend to be spared except at their ostia (opening from the aorta).. pulmonary artery
and its major branches are relatively thin walled, compliant vessels which are usually but not always spared
from atherosclerosis. ............ internal mammary artery is relatively resistant>>>use in bypass surgery. Bends and
branch point are more susceptible due to turbulent blood flow
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stable and variant are episodic pain. unstable is constant pain.
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75% of artery occlusion
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may occur at the site of atherosclerosis.................... in some cases, spasm may cause Q-wave transmural MI,
even in the absence of atherosclerotic lesions on coronary angiography. ....... nbme, 6,2,22 31 year old women
has had severla episodes of retrosternal chest pain while at rest, during past 6 months.the most recent epidsode
occur while she was asleep and produced severla minutes of ST segment elevation on home cardiac monitor.she has
no known risk factors.event in a large epicardial artery most likely responsible is>>>>endothelial cell dysfunction
not plaque rupture and coronary emolization.
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ergonovine is an ergot alkaloid that constricts vascular smooth muscle by stimulaiton both alpha-
adrenergic and serotonergic receptors...
ergonovine also aid in the diagnoses.
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unstable angina is defined as new onset angina, existing angina with increasing frequency, durationa and intensity
or angina at rest. ................ an ulcerated atherosclerotic plaque with partially obstructive thombus with would tend
to produce unstable angina, subendocardial MI, and sudden cardiac death.
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So whenever we give coronary dilator in ischemic patient(to treat it)we should give preload reducer to
decrease cardiac work otherwise coronary steal syndrome results
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sudden plaque change causes MI
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hibernation refers to the state of chronic myocardial ischemia, in which both
myocardial metabolism and function are reduced to match a concomitant
reduction in coronary blodd flow(due to moderate/severe flow-limiting stenosis).
this new equilibrium prevents myocaridal necrosis. chronically hibernating
myocardium demonstrates decresaed expression and disorganization of
contractile and cytoskeletoal proteins, altered adrenergic control, and reduced
calcium responsiveness.. these cahnges lead to decreased contractility and left
ventricular sytolic dysfunciton,.however, coronary revascularization and
subsequent restoaration of blood flow to hibernating myocardium improves
contractility and LV function. ................... ischemic preconditioning: is a
phenomenon in which brief repetitive episodes of myocardial ischemia , follwed
by reperfusion, protect the myovardium from subsequent prolonged episodes of
ischmeia. ................ the clinical manifestation of myocardial reperfusioninjury
include arrythmias, microvascular dysfunciton with myocardial stunning and
myocyte injury and death. ......... from 60sec to 30 min there is period of Myocardial stunning which is
reversible reduction of function of heart contraction after reperfusion, not accounted for by tissue
damage or reduced blood flow.hibernation in which there is still ongoing ishemia but this is reversible too,
this is a repetitive or chronic ischemia. repetitive stunning can result in hibernation. ...... early biochemical
consuquence of total myocardial ischemia is cessation of aerobic glycolysis and initiaiton of anaerobic glycolysis.
this transition occur within seconds and result in inadequate produciton of high-energy phosphates (eg ATP and
creatine phosphate) and the accumulaiton of deleterious metabolites.including lactate. although total ATp levels
remain relatively normal during the first few minutes of ischemia, ATP is rapidly depleted from areas of the cell
with high metabolic demand, such as cytosol surrounding the contraction fibers and electrolyte transport
pumps.the depletion of ATP in critical cellular areas and the accumulaiton of toxins result in loss of contractility
within about 60 seconds of total myocardial ischemia. when ischemia last less than 30 minutes loss of contraction is
reversible but with the effect of myocardial stunning. after 30 minutes it is irreversible. under hypoxic condition
ATP is degraded to ADP, AMP and eventually adenosine. adenosine is able to cross cell membrane and function as
a vasodilator. after 30 minutes of ischemia about half of the cellular adenine stores are lost and ischemic injury
become irreversible.
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chronic ischemic heart disease tend to result in progressive HF and ventricular <<<<dilaiton.>>>>> histologically
the major findings are diffuse subendocardial vacuolization and fibrosis
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The majority of sudden cardiac deaths are due to ventricular fibrillation (VF) or ventricular
tachycardia that deteriorates to VF
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myocardial contusion: after chest wall trauma typically presentss with mid-anterior chest wall pain, shotness of
breath, persistent tachycarida, and new conduction defects on ECG (eg bundle branch block)
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simulate the generalized coronary vasodilation due to exercise(cause of NO and
adenosine).>>>>>>>>
allows detection of ischemic area that would otherwise not be seen in resting heart.
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and adenosine; all are selective vasodilators of coronary vessels
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also used for prevention
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transient transmural ischemia
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mid night to early morning
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nbme>>>>2,3,6>>cardiac catheterization for angina.
femoral artery to apex of left ventricle
femoral artery ---iliac artery --to --descending aorta--to arch aorta -ascending aorta then -AORTIC
VALVE- ---enter in left ventricle --to the apex.
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The “septum” is actually the tunica intima of the aorta, which has been torn from the reminder of
the aortic wall. develop between the intimal flap and medial wall, creating a false lumen.
.................. most frequent histopathological abonormality (other than intimal tear) found in association with aortic
dissection>>>>>>cystic medial degeneration. .................. Aortis dissection occurs in patients with long-
standing hypertension and those with Marfan and Ehlers-Danlos syndromes (the 2 latter
conditions cause cystic medial necrosis of the aortic wall).
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slowly developing atherosclerosis causes collateral arterial formation in the case of LAD involvement collateral
develop from RCA(right marginal branch) to supply area which normally supplied by LAD.
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MCC of death pre-hospital phase
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variable waviness of myofibril at the border of the infarct (due to myofibril relaxation) might be observer before 4
hours ....................... 4-12 hours>>edema and wavy elongated myocyte fibers with normal appearing nuclei. 12-
24>>cytoplasmic hypereosinophilia with pyknotic(shrunken) nuclei
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3-7 days due to extensive cogulative necrosis,neutrophilc infiltration and enzymatic lysis of CT(mean 4-5 days;range
1-10 days)
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cause hypotension,biventricular failure and new murmur
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and resulting cerebral thromboembolism does not develop untill atleast 48 hours after MI
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RVMI is seen in 30%-50% pf patients with acute inferior wall MI due to occlusion of the proximal right
coronary artery before the origin of the RV branches. Patients typically with hypotension, distended
jugular veins, and clear lungs due to RV dysfunction. RV dilation and elevated diastolic pressure also
cause a shift of interventricular septum toward the LV cavity. normal or decreased pulmonary
capillary wedge pressure (PCWP).
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at day 7 scar has type III collagen at final stages of healing 2 weeks>>>it is replaced by type I
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cause extracardiac obstructive shock>>>>pulseless electrical activity
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begins at day 7 and most prominent through 10-14 days
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MCC of death in-hospital phase
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patients with noncoronary atherosclerotic disease, DM, or chronic kidneys disease are at the sae risk of
cardiovascular events(eg MI, stroke) as patietns with known coronary heart disease. coronory heart diease is the
most common cause of death in pateitns with DM
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complete ischemia for >30 min causes MI............. the ventricular remodeling that occurs after an acute MI involves
expansion(dilation) ,thinning and fibrous healong of the infarcted zone of myocardium.at the same time,
regional dysfunction of the infarct causes volume overload for the remaining viable myocardium.
Hypertrophy(eccentric) of the remaining myocardium compensates for the loss of contractile function
of the infarcted region. ......... nbme>>>5,4,19 accumulation of metabolic products in heart tissue
(lactic acid/bradykinin) which causes the pain during angina / MI. ............. nbme3,3,36
development of major depressive episode is a sequela of myocardial infarction that is associated with decreased
survival
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peaked T-wave are the first ECG sign (reflecting localized hyperkalemia), and ST-segment elevation follows with
in minutes to hours. With in hours to days, Q-waves appear in the involved leads.............. a. Inverted T waves •
areas of ischemia at the periphery of the infarct b. Elevated ST segments • injured myocardial cells surrounding
the area of necrosis c. New Q waves • area of coagulation necrosis
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mainly (SEPTAL)..
Infranodal(mobitz type 2) 2nd and 3rd degree heart block can also result
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with bradycardia and hypotension due to sinus supply
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INTRAMURAL ARTERIS: in the substance of myocardium are unlikely sites of occlusion. unlike epicardial arteries
they are rarely affected by atherosclerosis, if occur it would cause subendocardial (ST depression)infarction not
transmural.
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may be due to LEFT MAIN CORONARY ARTERY.septal V1-V2; anterior V3-V4;lateral V5-V6 or may be I and aVL
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combine will be caused by proximal LAD>>>and according to uworld>>V1-V4
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generally present in less than 10% of cases. rsik factors are, age greater than 60, female gender, pre-existing
hypertension and absence of left ventricular hypertrophy.. risk increases if this is the patient first MI.
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the frequency of early death (within first 24 hours of MI) is actually increased by myocardial reperfusion via
fibrinolytic therapy, though there is survival benefit overall
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Aspirin use significantly reduces the risk of death from coronary heart disease in diabetic patients,
at level similar to smoking cessation. however when all cause mortality is compared, smoking
cessation has a greater effect on reducing mortality than daily aspirin therapy
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increase venous capacitance ,decrease SVR, causing CNS sympatholytic effects to cadiovascular system
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polyserositis .......... Dressler’s syndrome generally responds to aspirin, NSAIDS, and/or
glucocorticoids.
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generally resolves spontaneously, if not we give aspirin with colchicine 714
...................... the exacerbation with swallowing indicated that the posterior pericardium may
be involved, and the radiation into the neck suggests involvement of the inferior pericardium,
which is adjacent to phrenic nerve afferents supplying the diaphragm.
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viral myocarditis>>prdominantly lymphocytic intersticial infiltrate, with focal necrosis of myocytes adjacent to areas
of inflammatory cekks. most commonly caused by adenovirus , coxsackie B virus and parvovirus B 19 ...........
viral dilated cardiomyopahty results from direct viral injury as well as an autoimmune reaction to virally altered
myocytes. these myocoardial inflammation leads to dilation of all 4 chambers and resultant decrease in contractility.
...... Mural Thrombi can be formed in Dilated Cardiomyopathy.*As we see in "Post-MI", ischemia
produce "Akinetic region" that cause STASIS of Blood promoting development of Mural
thrombi....... and in the same way a Dilated "HYPOKINETIC" heart promote thrombus
formation in DCM. .......... A patient with DCM would probably not be capable of participating in
activities as strenuous as soccer
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X linked with involving gene for dystrophin. .................... mutations affecting cardiac cell cytoskeleton
proteins and mitochondrial enzymes of oxidative phosphorylation are thought to cause the genetic
form of dilated cardiomyopathy (DCM). an example would be X-linked DCM involving the gene for
dystrophin, which normally links the internal myocyte cytoskeleton with the external basement
membrane. (remember that dystrophin mutations are also found in the common skeletal myopathies i.e,
Duchenne and Becker muscular dystrophies).
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on biopsy patchy fibrosiswith vacuolization and lysis of myocytes are evident.
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eccentric hypertrophy: volume overload>>>>in aortic/mitral regurgitation, MI, and dilated cardiomyopathy
concentric hypertrophy; pressure overload>>>chronic HT and aortic stenosis.
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MCC of VF before 30s
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subaortic stenosis. ............. Bifid carotid pulse with brisk upstroke (spike and dome) is characteristic of this.
microscopic examination shows extreme myocyte hypertrophy,disorganized myocyte bundles, and myofiber
disarray... both upstroke is in systole......... harsh crescendo-decrescendo systolic type. accentuated by
standing
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normal aging>>.decrease left ventricular chamber size, particualrly in the apex-to-base dimensiton. this decrease
in chamber length causes the ventricular septum to acquire a sigmoid shape, with the basilar portion buldging
into the left ventricular outflow tract. atrophy of myocardium reesults in increased interstitical connectove
tisssue, often with concomitant extracellular amyloid deposition, also progressive accumulation of cytoplasmic
granules (lipofuscin)
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lately. earlier restrictive .......... hemochromstosis can produce a restrictive cardiomyopathy (with a
morphologically normal LV) or lead to dilated cardiomyopathy (with increased LV cavity size).
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MCC of death is CHF
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specifically these are predominantly single point missense mutations in the genes for bet-myosin heavy
chain [MHC] (35%-50%), myosin binding protein C (15-25%) cardiac troponin T(15-20%) pr tropomyosin
(<5%)
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dilated cardiomyopahty is generally a diagnoses of exclusion once other etiologies of HF are ruled out, namely
pericardial disease, valvular defects, coronary artery disease and cardiac rhythm disturbances. both
primary(idiopathic) and secondary (eg due to exogenous cardiotoxic agents) dilated cardiomyopathy may exist in the
absence of coronary artery disease. ...... it is important to note that the term "dilated cardiomyopahty" excludes
cardiac chamber dilation that is due to coronary artery disease, valvular pathology or congenital disorders.
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many patinets are asymptomatic and may be diagnosed with an abnormal ECG or murmur during rotuine
evaluaiton. they can also present with exertional dyspnea, chest pain, fatigue, palipations dizziness, syncope or
sudden cardiac death (due to ventricular arrythmia) examination show harsh crescendo-decrescendo systolic
murmur at the apex and left lower sternal border.which chnages in intesnisty with physiologic maneuvers...........
(with Supranormal EF i.e. above 55%) ....... high voltade QRS complex ................ thickness of RV in
diastole 3-4mm. thickness of LV in diastole 1cm.diameter at the level of junction of mitral valve with its its chordae
tandinae is 5cm
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dicrotic pulse: pulse with 2 distinct peaks (one during systole and other during diastole) due to an accentuated
diastolic dicrotic wave after dicrotic notch. occurs in patient with severe systolic dysfunction and high systemic
arterial resistance. ................ pulsus alternans>>>beat to beat variation in pulse amplitude due to
change in systolic blood prerssure Generally most commonly seen in patients with severe LV
dysfunction.
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concentric hypertrophy uniformly thickens the ventricular wall with the outer dimensions of the ventricle
remaining almost unchanged.
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" Loeffler endocarditis —associated with hypereosinophilic syndrome, histology shows eosinophilic infiltrates in
myocardium
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also caused by product of inborn metabolic error.
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Echocardiogram will show "SPECKLED Pattern
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dynamic LVOT obstruction occur in 25% of patients
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almost always
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with variable expression
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also due to chronic supraventricular tachycardia and diphetheritic myocarditis.
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on biopsy distention of individual myofibers with intracellular trypanosomes.
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hypersensitivy myocardits>>> histopathology show perivascular and intersticial inflammatory infiltrate of
mononuclear cells and abundant eosinophils>>>most cases are beleived to occur due to initiaiton of new drug
therapy, against which the body mounts an atopic response................ mutation of the calcium binding
sarcoplasmic reticulum protein might underlie some cases of arrythmogenic right ventricular cardiomyopathy
(ARVC), a progressive fibrofatty replacement of the right ventricular myocardium of uncertain pahtigeneis.
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also increase diastolic filling pressure
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orthopnea is a specific find of LVHF. wheezing on exertion may occur in LVHF (cardiac asthma) but is non-
sepcific. chest tightness can also present with LVHF but is non-specific. pink frothy sputum ca be seen with
LVHF, it is due to rupture of bronchial veins. this is also a non-specific finding of LVHF.
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2ndry pulmonary hypertension due to reactive vasoconstriction due to venous congestion
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Granulomatous lung disease such as tuberculosis, fungal infections, and sarcoidosis may
increase net pulmonary vascular resistance by destruction of lung parenchyma. However, any
resulting pulmonary hypertension would predominantly be proximal to the pulmonary capillary
bed. Pressure within the remaining capillaries is usually normal or only slightly elevated ....... in
asthma or COPD Acute airway obstruction could lead to pulmonary hypertension due to hypoxic
vasoconstriction of small pulmonary arteries. However, the vasoconstriction occurs primarily in
the small arteries proximal to the pulmonary capillary bed, so congestion is unlikely
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patient with corpulomanr have elevated level of aldosterone. although the increased atrial/brain natriuretic
peptide levels in these patients tend to inhibit RAAS,but there is often net sodium and water retention, which
exacerbates edema formation. ............. RHF rises capillary hydrostatic pressure, netplasma filtration pressure and
interstitial fluid pressure.as the interstitial fluid pressure increases, so does lymphatic drainage.
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In the Prussian blue reactions, colorless potassium ferrocyanide is converted by iron to blue-
black ferric ferrocyanide. gloden cytoplamsic granules in macrophages that turn ble with
prussian blue staining are consistent with hemosiderin laden macrophages (siderphages)
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chronic ischemic heart disease tend to result in progressive HF and ventricular <<<<dilaiton.>>>>> histologically
the major findings are diffuse subendocardial vacuolization and fibrosis ..... yhese pte are typically tachypneic
and may be using accessory muscle
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but increase diastolic filling pressure
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is non-enterococcal, ....... enterococcal (faecalis and faecium ) causes subacute endocarditis (following GI/GU
procedures).
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due to redistribution.... ......... cutaneous
vasoconstriction may occur in states of circulatory shock
but does not occur during hypoxemia in the absence of shock.
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vasopressor is of little benefit because intravascular volume is low and sympathetic system is already maximally
stimulated.so we dnt use
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immunollogiic phenomenon>>>>edematous and hemorrhagic lesions of the retina
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diffuse proliferative glomerulonephritsis,deposition of circulating IC in glomerular capillary wall resulting in
capillary wall thickening with eubendothelial and subepithelial deposit formation. hypercellularity similar to
PSCGN and MPGN is revealed on ligh micrsoscopy ............ glomerulonephritis is common. but ATN can occur if
endocariditis is caused by rare gram negative bacteria which produce endotoxin. renal failure may be seen if the
emboli is large enough to cause renal infarct(which is very rare cause emblolus are small enough)>>>>renal
infarct causes pain in flank.
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IC mediated, like roth spot
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and jameway and this are sign of microembolism
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underlying host endothelial damage is the key predisposing insult in the development of endocarditis. valve posses
this type of minor endothelial damage on otherwise normal appearing valve. S,aureus can also invade intact
endothelium ( unlike other endocarditis-causing pathogen) due to the expression of multiple surface adhesions.
.......... s.aureus settles on valves because of the turbulance of the blood flow at these sites. it has ability to cause
perforations in the heart valves, rupture of the cordae tendinae and send septic emboli
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native valve bacterial endocarditis (NVBE) involve the mitral valve in most cases, and mitral valve prolapse is
the most common cardian abnormality predisposing to NVBE among 15-60 years old americans. it si
hypothesizzed that paltelt and fibrin deposition occur spontaneously in persons with valvular disease, causing
non-bacterial thombotic endocarditis. these deposits may then colonized by microorganisms during episodes of
bacteremia, causing NVBE..................... rheumatic valvular disease is also a potential, although less commin,
precipitant of NVBE
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mitral regurgitation can predispose to mitral valve endocarditis in multiple pathologies ...... aortic valve less
commonly involve cause of relatively high blood flow. ............. hemodynamic factors that injure the valve or
endocardial endothelim or totherwise promote nonbacterial endicardial thrombus formaiton include: 1, high
velocity-jets strking the endothelium 2, turbulen flwo frm a high -to a low-pressure chamber across a narrow
orifice (as in mitral regurgitation) ...... isolated atrial septal defect cannot predispose to endocarditis because low
pressure differential between the atria and absence of high velocity intracardiac flow jets.
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They are typically the result of hypercoagulable state, although they may also have been
caused by endothelial injury. When caused by hypercoagulable, NBTE is most often related to
some underlying disease, such as a cancer. There is particularly strong association of NBTE with
mucinous adenocarcinomas of the pancreas and adenocarcinomas of the lung, which may
relate to procoagulant effects of circulating mucin. NBTE associated with disseminated cancer
is termed “marantic” (or “marasmic”)endocarditis, dervied from the term for cancer-related
wasting of body tissues (“marasmus”). By a similar mechanism, tumor-associated release of
procoagulants is thought responsible for the migratory thrombophlebitis (Trousseau
syndrome) sometimes seen in patients with disseminated cancers.
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due to loss of sympathetic input
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progressive fatigue. no new mumur cause already has affected valve
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in patient other than IV drug abusers, dissemination of staph aureus occurs from a primary disease process such
as surgical I&D of abscess or from infected IV catheters such as central lines, and it moves hematogenous
spread to the endocardium
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early in coarse are regurgitant(most commonly mitral) Aortic valve less commonly involve due to relatively high
blood flow.
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mycoplasma,histoplasma,chlamydia
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are nontender, macular and erythematous lesions typically located on the palm and soles.they are the result of
septic embolization form valvular vegetations and are composed of bacteria, neutrophils (microabscesses),
necrotic material and subcutaeous hemorrhage.
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early sepsis in characterized by increased CO, peripheral vasodilation and warm extremities>>>when sepsis
progresses the stroke volume decreases, CO decreases and distal hypoperfusion becomes evident.. in advanced
septic shock cool and clammy extremities, delayed capillary refill, altered mental status and decreased urine output
are observed
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TPR and contraction velocity are high due to sympathetic stimulation. fluid resuscitation decrease both these
parameters
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human body sustain normal BP and stroke volume upto 10% of blood loss.after this sympathetic stimulates
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most common acquired valvular heart disease.MOST COMMON 5-15 years................ with in first few
decades>MR middle-age>MS older age> mixed MR and MS................... Rheumatic heart disease
almost
always affects the mitral valve, but both mitral and aortic valves are affected in about 25% of
cases. Rheumatic heart disease typically causes combined aortic stenosis and regurgitation,
both of which can increase LV diastolic pressure.
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clinical features: acute/subacute>>>migratory arthritis, pancarditis,sydenham chorea chronic>>> mitral regurgitation/
stenosis ............ most organ are mildly and transiently affected in ARF, with the exception of the heart. ........
cause of death severe myocarditis >>>>cardaic dilation>> HF .......... pregnancy will uncover rheumatic heart
disease cause of hyperdynamic state
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hyperkinetic extrapyramidal movemment disorder,most common acquierd chorea of childhood. cross reacting Ab
againt BASAL GANGLIA ................. jerky movement of face arms and legs(1-8 months after). unlike
parkinson(except in levodopa toxicity)
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can be present in any of the 3 layers.later replaced by fibrous scar tissue. acchoff bodies contain plump
macrophages (antischow cells/caterpiller cell)......... bopsy shows intersticiaL fibrosis with central lymphocytes
and macrophages as well as scattered multinucleated giant cell. this intersticial myocardial grnuloma or aschoff
body is pathognomonic fot RF myocarditis. plump macrophages with abundant cytoplasm and central slender
chromatin ribbons called anitshcow (or caterpiller) cells are also often present.. over several year aschof bodies
are replaced by fibrous scar causing stenosis.
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on cardiac,CNS, joints and cutaneous
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with in first few decades>MR middle-age>MS older age> mixed MR and MS................... Rheumatic heart
disease almost always affects the mitral valve, but both mitral and aortic valves are affected in
about 25% of cases. Rheumatic heart disease typically causes combined aortic stenosis and
regurgitation, both of which can increase LV diastolic pressure.
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fibrinous and serofibrinous pericarditis is the most common and caused by MI, rheumatic fever, and uremia. also
be caused by viral infection ................. nbme>>>1,3,48>>>>in fibrinous pericarditis or pleuritis>>enzyme required to
eliminate the exudate and restore normal anatomy>>>is plasmin
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and often pulse less electrical activity.
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and COPD are the most frequent causes of paradoxus in the absence of pericardial diseases. nomrally
intrathoracic pressure vary minimally during respiration>>2-4 mmhg drop in inspiration from atmospheric
pressure..but in these disease there is exageration in this inthrathoracic pressure drop which is transfer to
extrathoracic structures>>this lead to excessive drop in blood prressure with inspiration.
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restrictive cardiomyopathy, cor pulmonale:Acute core pulmonale as might result in severe asthma attack. Chronic
core pulmonale in COPDs
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nbme,11,4,31 Breast cancer is the second most common cause of malignant pericardial effusions (15).
Approximately one in four patients with malignant pericardial effusions has breast cancer, and autopsy findings
indicate that of all patients with breast cancer, approximately one in four had malignant pericardial effusion.
Hematologic malignancies such as leukemia, Hodgkin disease, and non-Hodgkin lymphoma make up the third largest
group (15% of cases). the primary. Lung cancer, the most frequent source of neoplastic pericardial disease,
accounts for about one-third of cases. "http://radiographics.rsna.org/content/21/2/439.full";; PLEASE check this
video:http://radiographics.rsna.org/content/21/2/439.full On both sides the phrenic nerve runs posterior to the
subclavian vein and posterior to the internal thoracic artery as it enters the thorax.[1] Both of these nerves
supply motor fibres to the diaphragm and sensory fibres to the fibrous pericardium, mediastinal pleura, and
diaphragmatic peritoneum. Open to more explanations
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reduced intrinsic ventricular wall compliance (eg restrictive cardiomyopathy) is a cause of S3. in contrast,
constrictive pericarditis reduces ventricular compliance via an external force, results in pericardial knock, a
sharper, more accentuate sound heard earlier in diastole than the S3 sound.
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constrictive(chronic, require months to years to produce constriction sufficient to cause tamponade) also have
pericardial knock just after S2 in early diastole and before S3. may be confused with opening snap of mitral
stenosis................. Serous viral perocarditis(after URI) causes significant acute pericardial effusion and produces
tamponade. Fibrinous viral pericarditis(after URI) would only be expected to cause pleuritic chest pain and a
pericardial friction rub.
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in very large percardial effusion and cardiac tamponade beat to beat variation in amplitude of QRS complex.
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due to serous viral pericarditis after Upper respiratory viral infection 1-2 weeks before.
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specifically antibodies directed against GAS antigens, M protein and N-acetyl-beta-D-
glucosamine. subsequently attack myosin, a cardiac protein, and lysoganglioside, a neuronal cell
surface protein.
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no penicillin resistant strain have yet been detected
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normal are <300 todd units/mL
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fibrous thickening and fusion of valve leaflets in chronic rhematoid heart disease following acute rheumatic fever is
the most common of MS, accouting for upto 99% of cases. mitral stenosis cause strial enlargement>>>atrial
fibirillation>>>aterial mural thombosis>>emboli formation. cardiac ausculation often reveals a loud first heart
sound (S1), an early diastolic sound (opening snap), followed by a mid-diastolic murmur form turbulant flow across
the mitral valve.
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presents as faintly erythemaotus circular lesions with central clearing that come and go on the trunk and
extremities.
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generally have sterile synovial fluid
........
the initial manifestation is often a migratory arthritis. the lower extremities are usually the first
involved, followed by the upper extremities; symtoms last for a days to a week.
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in RHD>>>their is fibrous thickening and distortion of mitral valve leaflets along with commisural fusion at the
leaflet edges.. in IE>>>their is large friable vegetations in the valve cusps along with destruction (rather than
fibrosis) of the valve leaflets.
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in tricuspid stenosis and rarely in cardiac tamponade
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nbme>>>2,2,24>>> amorphous extracellular matrix. myxoma cells are frequently stellate with eosinophilic
cytoplasm and indistinct cell borders.the ovoid nuclei are typically pale with open chromatin. nucleoli may be
prominent.
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due to radiation,surgery and tuberculosis. pericardium 4-20mm (normally 1-2mm),rapid y descent, present with
progressive dyspnea, peripheral edema and ascitis.
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produce VEGF and IL-6........................... Histologically, these tumors are composed of scattered cells within
a mucopolysaccharide stroma (arrow), abnormal blood vessels and hemorrhaging. Myxomas produce
large amounts of vascular endothelial growth factor, which contribute to the angiogenesis,
hemorrhaging (seen as hemosiderin deposition [brown]), and friability seen in these tumors. Myxomas
also produce large amounts of interleukin 6, thus patients frequently present with constitutional
symptoms 9e.g, weight loss, fever). myxomas are often pedunculated and gelatinous and can become
quote large. They tend to present with emboli and/or cardiovascular symptoms. The cardiovascular
symptoms are secondary to valve obstruction by the myxoma, which accounts for why symptoms are
position dependent.
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Leukocytoclastic vasculitis (microscopic polyangiitis, microscopic polyarteritis, hypersensitivity
vasculitis) is characterized by segmental fibrinoid necrosis of the small vessels (i.e, arterioles, capillaries,
venules). Aside from their localization to small vessels, the lesions of microscopic polyangiitis are foten
histologically similar to those of polyarteritis nodosa (PAN).
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foal pain over the tample or tenderness on palpation may be present.sometimes accompanied by scalp
tenderness especially during hair combing......... superficial inflammed temporal artery may cause pain,
nodularity and thickening found on palpation of temporal area.
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painless.. ......... GCA can cause sever ischemic optic neuropathy due to ophthalmic artery occlusion. other optic
complicationss are amaurosis fugax, central or branch retinal artery occlusion and cerebral infarction leading to
central visual field defects
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T-cell mediated inflammatory process of medium-to-large arteries. may occur diffusely but predominantly affects
arteries of the head and neck, especially temporal artery.
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almost always >100mm/hr
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uncommon form of vasculitis
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mononeuritis multiplex
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necrotizing hepatic arteritis can be seen in many autoimmune diseases such as rheumatoid arteritis and
polyarteritis nodosa.
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this differentiate it with scarlet fever. in scarlet fever tonsillar exudate is common
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causes inflammatory thrombosis and ischemia involving small to medium arteries of the exremities. ............
common in israel, japan and india
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pulmonary-renal syndrome (glomerulonephritis with acute pulmonary hemorrhage) seen in goodpasteur
syndrome, granulomatosis with polyangitis and microscopic polyangitis. .......... Focal necrosis of alveolar
walls and intra-alveolar hemorrhages are more typical of pulmonary hemorrhage syndromes
such as Goodpasture syndrome and vasculitis-associated hemorrhage (as seen in
hypersensitivity angiitis, granulomatosis with polyangiitis [Wegener’s], and lupus
erythematosus.
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pauci immune. associated with type 3 RPGN
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(leukocytoclastic angiitis or hypersenstitivity angiitis) is the most common vasculitis asscoiated with antibiotic
use. it is due to type III immune reaction. ......... drug induced antineutrophil cytoplasmic antibodies-associated
vasculitis is commonly linked to medication with hyperthyroidism(eg propylthiouracil and methimazole) and
hydralazine
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nbme>>>1,2,19>>>autopsy shows nodular areas of chrinic pneumonitis with necrotizing arteritis and focal
collection of epitheloid histiocytes.
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kawasaki associated with MI in children. associated with coronary aneurism and subsequent thombosis.
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mononeuritis multiplex ia a peripheral neuropathy of multiple individual nerves. it is associated with a variety of
diseases, including granulomatosis with polyangitis and polyarteritis nododsa.
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autoantibodies directed against lysosomal enzymes of human neutrophil and monocytes
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these granulomas some time coalesce into nodules or undergo cavitation.
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principally radial and tibial arteries endothelial cell injury due to hypersensitivity to tobacco products or direct
injury from products.>>>>extend to contiguous vein and nerves>>.encompass all three structures in fibrous
tissue ................ severe distal pain may be seen at rest and may result from neural involvement
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persistent fever
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diagnoses require fever for >/5 days plus 4 of the following: 1, bilateral non-exudative conjuntivitis. 2, cervical
lymphadenopathy. 3, mucositis:erythema of the palatine mucosa, fissured erythematous lips, strawberry tongue, 4,
extremity changes: edema of hands and feet, erythema of palms and soles, desquamation of the
fingertips(periungual) 5, rash:polymorphous (usually urticarial) erythematous rash on the exremities that spreads
centripetally to the trunk.
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episodic "mutlisystem" involvement ..............kidney , heart, GI tract and liver involvement are most common,
and clinical features are due to ischemia of the involved organs.
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in these cases, hepatitis B surfaceantigen/antibody complexes can be demonstrated in affected tissues.
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GCA is histologically identical to takayasu arteritis, which involves the aortic arch and affects primarily younger
pateitns.................... Medial granulomas may also be seen in Takayasu arteritis, though less frequently.
Thus, the distinction between giant cell lesions of the aorta is often times based on the patient’s age.
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biopsy show scattered, focal ganulamotous inflammation scntered on the media with intimal thickening,
fragmentation of the elastic lamina, and giant cell formation (without distinct grnulomas) in the medium to
smaller branches of the carotid artery. ((((((((((( consisting of mononuclear infiltrate and multinucleated giant cell.
segmental involvement)))))))))))?????? ................. although both humoral and cellular immune
mechanisms have beed implicaed in the pathogeneisi of GCA, cell mediated
processes are of primary importance. the inflammatory infiltrate in affected vessels
is composed of lymphocytes (predominantly CD4 positive T cell) and
macrophages and frequently contains multinucleated giant cells. the produciton
of cytokines, in particular interleukin-6 (IL-6), appears to closely correlate with
the severity of the disease; a monoclonal antibody against IL-6 (tocilizuzmab) is
effective in treating GCA
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more than 50% of patient also complain of muscle pain (neck,torso,shoulder and pelvic girdle) and morning
stiffness due to this. fatigue,fever and weight loss may also occur.
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in the middle of the meal is characteristic. tongue claudication,and facial pain can also occur
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mean age of onset is 65years. almost exclusively in patients age >50 most common form of vasculitis in persons of
northern europena descent. .................... the most common form of systemic vasculitis in adults.
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PAN is segmental transmural necrotizing inflammation of medium to small-sized arteries. In PAN, the
necrotic tissue and deposits of immune complexes, complement, and plasme proteins produce a
smudgy eospinophilic deposit ( fibrinoid necrosis) to give a histologic pattern consistent with immune
complex vasculitis.
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boys2-10 years of age ........... self
limited disease as circulaitng IC clear. treatment is
supportive unless specific complications (eg intessuseption) occur ........... usually
benign and self limited but can cause acute glomerulonephritis/renal failure as a complication
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in 100% of patient with 85% having colicky abdominal pain and 70% has polyarthralgias
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along with bleeding. also have increased risk of intussusception.
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have mesangial proliferation and crescent formation.
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the granulomas seen with Churg-Strauss syndrome typically have a central necrotic zone.
............................. vascular lesions in this syndrome may be histologically similar to those of PA but ypically occur
in smaller vessels. they are characteristically accompaied by granuloma with eosinophilic necrosis. ..........
vascular lesions are necrotizing granulomas which can cause a coronary
arteritis.
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small vessel leukocytoclastic vasulitis of dermis and GI track>>>IgA and C3 deposition.
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self limited migratory arthralgia or arthritis most commonly of large joints of lower extremities
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viral or streptococcal>>>symptoms generally develop few weeks after the associated illness resolves.
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adult onset asthma. also have migratory or tansient pulmonary infiltrates
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directly blocks the lumen of ion channel. amiloride(Na channel blocker at DCT) also function like this
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dihydropyridine CCB causes peripheral edema>>>>this is due to preferential dilation of precapillary vessels
(arteriolar dilation) which lead to increased capillary hydrostatic pressure and fluid extravasation in the intersticium,
ACEI and ARBs causes post-capillary venodilation and can normalize the the increased capillary hydrostatic
pressure, reducing the risk of peripheral edema in patients taking CCB
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nicardipine has a longer half life compared to other agents, the hypetensive effect may be
prolonged and rapid titration of the agent is difficult
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is a newer novel intavenous agent that is benazepine derivative of dopamine. in contrast to dopamine, it is a
selective dopamine-1 receptor agonist with no effect on alpha or beta receptors. D1 stimulation >>>increase
adenylyl cyclase>>increase intracellular cAMP>>dilation. in kidney not only improve renal blood flow, but also
leads to increased sodium and water excretion. thus fenoldepam is the only available IV agent that improves
renal perfusion while it lowers blood pressure. it can be used for short term managment of severe HT and can be
used saferly in all HT emergencies. it may be exceptionaly beneficial in patietns with concomitant renal
insufficiancy
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this is with non-dihydropyradine
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consider most effective agent for most cases of HT emergency. is has slight reflux sympathetic activation(unlike
hydralazine and diazoxide).only limitation is cyanide posioning. ......... it can cause coronary steal syndomre, if pte
has CAD. ............. hydralazine and diazoxide are consider third line agents and are not recommended in
hypertensive emergencies with aortic dissection, because of significant reflux aympathetic activation, resulting in
increased HR and Na and water retention......... hydralazine is consider safe and useful in preganancy related
hypertensive emergency
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constipation occur with both verapamil and diltiazem but verapamil > diltiazem
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non-dihydropyridine also decreases proteinuria but these are not superior to ACEI or ARB in the diabetic patients
who have progressive nephropathy (microalbuminuria 30-300 mg/day)
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also have ANCA associated vasculitis like pripylthiouracil and methimazol 508
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inhibits Na inward current, so have low intracellular Na , which causes
upregulaiton of Na/Ca exchanger, so more Ca goes out as Na gets in,>>>>this
occur in late phase of repolarizaiton in ischemic myocardial cells
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undergo extenscie first pass metabolism by glucuronidation
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venodilators increases peripheral venous complaince, reducing cardiac preload and LVEDP and LVEDV>>>>this
is the primary mechainsm of action for symptoms relief in pateitn with acute pulmonary edema. lower LVEDP also
leads to a reduction is LV systolic wall stress and a decrease in myocardial oxygen demand, resulting in relief of
angina symtoms,... nitrates also have a modest effect on arteriolar dilation. higher doses can lead to a significant
drop in systemic blood pressure, thereby decreasing cardioac afterload. reducing left ventricular wall stress and
causing a further decrease in myocardial oxygen demand.
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decreased inrtracellular Ca and cause myosin dephosphorylation
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at high doses arteriolar dilation which causes headache and skin flushing
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vasodilation(arteriolodilation) in skin and meninges repectively at high doses
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Phosphodiesterase inhibitors: inamrinone and milrinone - increase cAMP in heart muscle;
results in increase inotropy(cAMP increases intracellular Ca, by releasing it from sarcoplasmic
reticulum) - increase cAMP in smooth muscle; results in decrease TPR (a well known side
effect of phosphodiesterase inhibitor)>>>>>limit their use in hypotensive patient
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tachyphylaxis describes dereased drug responsiveness in a short period following
one or more doses (ie rapidly developing tolerance) ........ tachyphylaxis in nitroglycerin is
explained by the diminished release of NO from the target cells. ............. tolerance can occur by multiple
mechainism such as change in cellular response to drug (decreased receptors, decreased response to receptor
stimulaiton), as well as increased rate of drug elimination by the body........... tachyphylaxis or receptor
downregulation is one mechanism by which the body develop tolerance to drugs on a cellular level.
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sunlingual nitroglycerin is the therapy of chice in acute episodes for immediate relief of angina and for prevention
of angina prior to engaging is strenuous physcial activity. chronic nitrate therapy with long-acting oral
formulation (isosorbide) is used to prevent recurrent anginal episodes in patietns with chronic stable angina.
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at low doses
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nitrates are metabolized into NO in this region.
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active metabolite of dinitrate,which has almost 100% bioavailability
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the increase in coronary blood flow is limited with nitrates as they dilate the large epicardial
arteries more than the smaller resistance vessels (e.g arterioles). coronary arterioles in an
area of low-limited stenosis are typically maximally dilated to maintain resting blood flow.
medications that cause dilation of arterioles within the normal myocardium (e.g,
dihydropyridinecalcium channel blockers ) can divert blood away from the ischemic area
(coronary steal phenomenon).
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its due to this drug K channel blocking effect, it causes dose dependent QT
prologation, but does not cause tdp.
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Niacin reduces serum triglyceride concentrations. Additionally, niacin decreases VLDL conversion to
LDL, thus decreasing serum LDL concentrations as well. Nicotinic acid also increases HDL by 25-30%,
making it the most effective HDL- increasing agent currently available. ................ decreases HDL
clearence
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omega 3 fatty acid decrease serum TGs and a slight increase in HDL
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competitively inhibits... ....... statins are indicated for secondary prevention in all patients with known atherosclerotic
CV disease, regardless of baseline lipid levels. ............. activated macrophages in an atheroma contribute to
collagen degradation by secreting metallopreinases.. where there is high intimal infammation , release of these
metaloproteinases is increased ,which can destabilize the mechanical integrity of plaque. statins dcreases this
inflammation are used in acute coronary syndrome to stabilize plaque. ........... statins theoratically can decrerase
adrenal and gonadal steroids,practically no. but we have to take caution if patient is already taking adrenal enzyme
inhibitor eg ketoconazol,aminogluthetimide.
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myopathy or myalgia with or without myonecrosis (elevated creatine kinase) rarely renal failure due to
rhamdomyolysis can be ...... Myopathy is a rare complication of statin use, clinically defined as muscle pain
with serum creatine kinase over 10 times the upper limit of normal ..... statins decrease levels of
CoQ(ETC) by decreasing farnesylPP>>>>myopathy
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also called cationic exchange resin....................... DIT cholestyramine bind clostridium difficile.
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depletion of bile acid causes upregulation of 7-alpha hydroxylase which convert cholesterol into bile acid
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first agent used for hypercholesterolemia. also has antinflammatory and immunomodulatory properties. drug is
rapidly absorbed and glucuronidated to form active metabolite. genetic polymorphism effect pharmacokinetic of
this drug. its a metabolism dependent inhibitor of CYP3A4. ........ Ezetimibe is modestly effective at reducing
serum triglycerides and increasing serum HDL concentrations. This medication is primarily used in
conjunction with statin therapy. ......... benefits over statin monotherapy are likely minimal
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only when used with statins>>>>hepatotoxicity
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uworld says it increases lipoprotein lipase activity ............. Lipoprotein lipase (LPL) hydrolyzes
triglycerides in chylomicrons and VLDL to release free fatty acids, which can be used for energy
or converted back to triglycerides for storage in adipose tissue. it also facilitates the transfer
of triglycerides from these lipoproteins to HDL. Fibrates (e.g, gemfibrozil, fenofibrate)activate
peroxisome proliferator-activated receptor alpha (PPAR-a), which leads to decreased hepatic
VLDL production and increased LPL activity. They are able to decreased triglyceride levels by
25%-50% and increased HDL by 5%-20%. Fish oil supplements containing high concentrations of
omega-3 fatty acids also decreased VLDL production, and inhibit synthesis of apolipoproteinB
as well. alternate treatment for patients with moderate hypertriglyceridemia
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decreased renal excretion of uric acid ................. other durgs causing this are hydrocholothiazide, cyclosporine
and pyrazinamide
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due to tachyphylactic response
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325mg aspirin 30 -60 min before niacin.. administration of niacin with meals also improves flushing. hot liquids
exacerbate this symptom.
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because fubrate inhibit rate limiting step of bile acid synthesis (cholesterol 7-alpha
hydroxylase). cholesterol/bile acid ratio increases.
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fibrates are inferior to statins and are primerily used to prevent pancreatitis in patients with very high TG levels.
fibrate are often combine with omega 3 FA to lower TGs to prevent pancreatitis. statins have smaller but
significant effect in lowering TGs.
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inhibit niemann pick C1 LIKE 1(NPC1L1) transpoter protein which normally transport dietary cholesterol.
NATURALLY OCCURING MUTATION that disrupt THIS TRANSPOTER ASSOCIATED WITH REDUCED LEVEL OF
LDL cholesterol ....................... also increases cholesterol transport form blood to liver due to upregulation of
LDL-receptor on hepatocytes.
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bile acid resins increase cholesterol content of bile increasing the risk of gallstone formation. ...........................
Bile acid-binding resins are primarily used in combination with statins. Concurrent administration of these
two drugs types results in decreased statin absorption. For this reason, it is recommended that agents be
administered at least four hours apart.
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can significantly increase in patients with pre-existing hypertriglyceridemia.
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gemfibrozil increases the concentration of many statins accounting for increase risk of myopathy.
fenofibratedoesnotalter pharmakokinetic of statins but itself cause myopahty , thus compunding the risk for
myopathy associated with statins alone.. simvastatin is a statin with highest associated risk of myopathy.
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mild elevation is normal. severe elevation occur only in 15 population. discontinue drug only when ALT/AST
increase by 3folds ..... most liver toxicity occur with in 3months of time. with discontinuation of drug liver enzymes
normalizes ...... significant hepatitis after statins generally does not produce significant symptoms and jaundice
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TGs lossely reflect caloric balance: a calorie-restricted diet with increased exercise and reduced alcohol intake
can provide a rapid and significant drop in TGs levels.
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low HDL (men <40, women <50) are at increased risk of cardiovascular disease.
nonpharmacologic measures such as exercise, weight loss and smoking cessation help to raise
HDL and have significant CV benefits.
in contrast use of medication to raise HDL levels does not improve CV outcomes.
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proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors are monoclonal antibodies that reduce
LDL receptor degradation in the liver. These drugs are used primarily in patients with elevated
cholesterol levels but have minimal effect on triglyceride levels.
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Digoxin is renally cleared agent with a half-life of approximately 1.5 days in patients with
normal kidney function. As patients age, renal function decreases progressively. This decrease in
renal function is often not accompanied by a concomitant rise in serum creatinine, since
creatinine is derived from muscle tissue and lean body mass also decreases with age. liver
enzyme activity plays little role in the elimination of digoxin, as this agent is primarily excreted
unchanged by the kidney. the patients lean muscle mass is important to consider when
dosing digoxin is stored in the body.lean body mass does tend to decrease in an age related
fashion, but age related renal insufficinecy is most directly related to toxicity of this agent in the
elderly.
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Sympathomimetics: dobutamine and dopamine(beta-1 receptor)
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txicity mostly present with non-specific GI and neurologic symptoms. changes in color vision are more specific but
rarer. life threatening are cardiac symptoms.................. hypotension can occur with digoxin cause of
bradycarrythmiaas and severe vomiting and diarrhea, but digoxin is also an inotropic>>so hypotension is a variable
finding
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elevated potassium is a sign of digoxin toxicity
..............
calcium gluconate should not be given for hyperkalemia in digoxin toxicity
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amiodarone can cause visual disturbances but does not causes increase in extracellular
potassium
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rapid IV verapamil is absolutely contraindicated>>>>Exaggerate AV block
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delayed after depolarization: occur after complete repolarization and is due to increased intracellular calcium or
increased chatecholamine stimulation states. digoxin toxicity can lead to delayed depolarizations via its mechanism of
increasing intracellular calcium. this is how digoxin can lead to ventricular tachycardia and death
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2nd line agent(adenosine,CCB,BB are 1st line)
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nbme,11,3,3 Digoxin toxicity......inc.parasympathetic activity..nausea,vomitingdiarrhea,blurry yellow visionand
arrhythmia may cause inc.PR and dec QT, scooping of ST and T-wave inversion Antidote...slowly normalize K+and
Mg+,lidocain,anti-dig fragments..
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digoxin also decreases action potential duration and shortens QT-interval.
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the QRS complex duration is typically slightly reduced during exercise in response to the increase in cardiac
conduction veocity (dromotopy) slightly that accompanies faster heart rates.
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use dependence in which tissue undergoing frequent depolarization become more susceptible to blockage. use
dependence occur because sodium channels in rapidly depolarizing tissue spend more time in the activated and
inactivated states, thus allowing more binding time for the drug. Na channel binding strength is 1C>1A>1B. use
dependence is more pronounced in class 1C antiarrythmics because of their slow dissociation from the sodium
channel, which allows their blocking effects to accumulate over multiple cardiac cycles. this effect is enhanced
with tachycardia, and the resulting increase in sodium channel blockage helps to slow conduction speed and
terminate tachyarrythmias. the prominent use dependence effects of class 1C drugs can cause a delay in
conduction speed that is out of proportion to prolongation of the refractory period. this can promote arrythmias,
especially in patients with ischemia or structural heart disease. ............... use dependence describes the
phenomenon in which higher rates of depolarization lead to increased sodium channel blockage due to the channels
spending less time in the resting states.
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binds less avidly to sodium channels than other class 1 Anti arrhythmic.
dissociation from the channel occur so rapidly that there is minimal cumulative effect over multiple
cardiac cycles, resulting in little use dependence
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Oral formulations
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little effect on phase 0 depolarizaiton due to rapid binding and rapid release
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class 1B does shorten phase 3 repolarization (by blocking sodium window
current) and the action potential duration
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lidocaine reduces phase 4diastolic depolarization causing a decrease in automaticity.
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moricizine
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this class of drug prolongs QRS duration in a rate-dependent manner, which is consistent with a
drug that exhibits strong use-dependence
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occasionaly used in management of SV arrythmia in patients with structurally normal heart.
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prolong QRS complex but has little or no effect on QT interval>>>unlike class III drug which
prolong QT interval bus has no effect on QRS complex
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block Na channels and exhibit slow rate of dissociation during diastole (thus being
more effective(Vmax) at higher rates of depolarization, termed as use dependence)
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are characteristically nonfocal neurological signs,such as tremor drowsiness and change in mental status.also can
lead to generalized seizure
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class 1 use dependence in cardiac myocyte cell and pacemaker. class 4 use dependence only in pacemaker/nodal
cell???????????????
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these drugs are more selective for ischemic myocardium because the reduced resting membrane potential delays
sodium channel transition from the inactivated to the resting state, resulting in increased drug channel binding.
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tocainide
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Side effects: CNS toxicity (seizures); least cardiotoxic of conventional anti-arrhythmics IV use
because of first-pass metabolism. currently amiodarone replaced the lidocaine in the
management of ventricular tachycardia.
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prolong QRS complex and QT-interval.
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preferentially bind to and block activated and inactivated voltage gated sodium channels in cardiac
pacemaker cells and myocytes.
dissociation of the drug from the channel occurs during resting state, a conformational state
distinct from the inactivated state the occurs following repolarization.
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mainly used in the setting of postoperative HT and may be preferred in critical patients where rapid
withdrawal pf the drug effects is needed.
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broadest antiarrythmic:supraventricular(atria,nodal,junctional) and ventricular
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rare but life threatening
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in iodine depleted region>>>due to excessive thyroid hormone production.
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Because of the reverse use-dependence of class III agents, at low heart rates class III
antiarrhythmic agents may paradoxically be more arrhythmogenic.
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(Reverse use-dependence). This means that the refractoriness of the ventricular myocyte
increases at lower heart rates.............
demonstrate reverse use dependence( the slower the heart rate, the more the QTc interval is
prolonged)
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in iodine sufficient region>>>due to excess iodine and occur in 5-20% of patient.. can cause prolactin increase due
to hypothyroidism but amiodarone doesnt effect directly prolactin.... this is treated with levothyroxine and amiodarone
is continued..
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does not predispose to torsades de point>>>due to having a more homogenous effect of ventricular repolarization
compared to other drugs (ie less QT dispersion)
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work independently of adrenergic receptors by his own G-coupled receptors.
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dnt affect QRS and QT interval..
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L-type>>>after 40mv
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CCB such as diltizem are most selective for rapidly depolarizing cells (use
dependent)
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by blocking the SA and AV node calcium channels, verapamil slows the depolarization that occurs
in phase 0 and the latter part of phase 4.>>>>>this decreases the rate of SA node firing and slows
AV node conduction.
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CCB blocks AV node(calcium sensitive tissue of the heart)
unlike B-blocker dnt have effect on SA node.
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verapamil: gingival hyperplasia
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digoxin also can cause AV nodal conduction delay like CCB but would not cause constipation.which is a differentiating
feature beside others
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act on A1 receptors
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automaticity occur above the ventricle >>>>>ie in the atrium or AV node
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chest pain is due to brocnsospasm.
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adenose acts by slowing conduction through the AV node>>>>>by hyperpolarizing the nodal cell
and conducting cell
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IVADRABINE: inhibits the Na funny channel>>>prolonging the slow depolarization phase and slow sinoatrial node
firing rate. has no effect on inotropy and/or relaxation (lusitropy). indicated in chronic HF with reduced ejection
fraction and persistent symptoms despite medical therapy. it reduces the risk of hospitalization due to HF.
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and/or relaxation(lusitropy) ........................ shown to reduce the risk of hospitalization due to HF
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under hypoxic condition ATP is degraded to ADP then AMP and finally into the
adenosine>>adenosine crosses the membrane and result in coronoary
vasodilation(compensatory).
adenosine store depleted in 30 min and injury become irreversible
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also have high grade AV block.
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this is the drug also used for chemical stress test.
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characteristic side effect
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other constipation causes are opioid analgesics,iron supplementation,and anticholinergic(atropine)
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if it is given for ventricular tachycaria for prolonged period of time it can lead to ventricular fibrillation and death. so
we have to differentiate supraventricular by ventricular tachycarida.
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increases refractory period in nodal tissues by reducing cacium influx and slowing the recovery of inactivated
calcium channels
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verapamil besides it effect on nodal tissues also decreases the amount of intracellular calcium
available within cardiomyocytes(fast-response tissue) which can reduce myocardial contractility
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nbme>>>3,3,35
primarily affect AV nodal cells.
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from foramen cecum on the dorsal surface of tongue to the superior border of thyroid isthmus
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adrenal cortex venous drainage goes to adrenal medulla which is rich in cortisol. cortisol produced by fasciculata
increases the transcription of medullay enzyme phenylethanolamine-N-methyl transferase, which convert norepi
to epi.
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as a hormone it mainly acts to work on attention and impulsivity.
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Thyroid follicular cells are derived from endoderm; parafollicular cells (aka, C cells, produce C alcitonin) are derived
from neural crest.”
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acetylcholine.
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and extracellular potassium level, only in the case when there is hyperkalmeia
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pharyngeal epithelium evagination or outpouching>>>>lower end of evaginaiton form gland, remaining portion form
duct. ............................ formation of mature thyroid by fusion of thyroid follicles (derived from pharyngeal epithelium
evagination) with parafollicular C-cells (derived from ultimobrachial bodies)
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both belong to somatotrophic hormone family????? prolactin is lactotroph
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magnocellular. hypothalamic axons terminate into herring bodies>>>specialized nerve terminal that act as storage
sites for the secretory vesicles.
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involved in postranslational hormone processing and stabilization of hormones during transport to posterior
pituitary ........ neurophysin bind oxutocin and vasopressin and acut as chaperone. involved in the transport
and packing of vasopressin through the endoplasmic reticulum (ER) and Golgi apparatis into
neurosecretory granules.
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derived from posterior wall of rathke pouch>>>not a significant source of secretory product but can form Rathke's
cleft cyst.
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hpl is secreted by syncitiotrophoblast (placenta)>>>structural and biological properties are similar to GH and
prolactin>>>>increases maternal insulin resistance and secretion.
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mediates low level basal glucose uptake. dont require insulin
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in skeletal muscle(3/4) and liver(1/4)
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increases lean body mass
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GLUT-4 is translocated to cell membrane and transverse tubules (deep invvaginations in the cell
membrane) in response to insulin.
GLUT-4 translocation also occur during muscle contraction by an insulin-independent mechanism,
which is mediated by several cellular factors, including AMP-activated kinase, nitric oxide, and
calcium-calmodulin-activated protein kinase.
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TNF-alpha, catecholamine, glucagon and glucucorticoid induces insulin resistance through the activation of serine
kinases, which then phosphorylate serine residues on the beta subunit of insulin receptor and insulin receptor
substrate>>>this inhibits tyrosine phosphorylation of IR and IRS-1 and hinders downstream signalling.
phosphorylation of threonine residue also has same function. activation of PPAR-gamma results in improved
insulin sensitivity
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phosphorylation of tyrosine causes activation of protein phosphatase 1 which dephosphorylates glycogen
synthase(activate it) and fructose 1,6 bisphosphotase(inactivate it) ...................... insulin receptor is a tetrameric
structure, two alpha extracellular subunit which provide binding sites for insulin and two beta membrane spanning
subunits contain the intracellular tyrosine kinase domains.
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insulin release by parasympathetic M3 stimulation by smell or sight of food. sympathetic stimulation has both
inhibitory or stimulatory effects>>> inhibitory is prominent in nomral condition which is mediated by alpha-2
receptor. beta-2 stimulation causes release of insulin. glucagon and glucagon like peptide also release insulin.. H2
receptor causes increase in insulin release and somatostatin 2 cause decrease in insulin release.
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by directly inhibiting the alpha cells of pancreas.
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leading to increased blood volume and blood pressure.
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production of insulin begins in ER with the synthesis of proinsulin., where it is folded and its disulfide bonds are
oxidized. it is subsequently transported to golgi apparatus, where it is packed into secretory vesicles. .........
unlike insulin, C-peptide does not undergo significant first-pass metabolism by the liver. As
a result, circulating levels of C-peptide can be used as a marker of endogenous insulin
secreting capacity.
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Transmembrane carrier proteins that belong to the GLUT family transport glucose by facilitated diffusion.
These proteins are stereoselective and preferentially catalyze the entrance of D-glucose rather than L-
glucose into cells. GLUT2 it facilitates export of glucose from the liver, small intestine and kidneys
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skeletal muscle is not a target tissue for glucagon but liver is...................... amino acid sequence of glucagon is
similar to gut hormone secretin so increases insulin secretion.
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glucagon(increases hepatic gluconeogenesis and glycogenolysis) is the primary hormone increases, epinehrine
(increases hepatic and renal glycogenlysis and gluconeogeneis,also causes release of gluneogenic substrates
from muscle and fat) is the back up of glucagon. cortisol and GH contribute to glucose homeostasis during
prolonged fasting by altering transcription of many key enzymes
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synthesized and released by corticothophic cell in anterior pituatary .............POMC is a polypeptide precursor that
form all 3. there may be a close physiologic relationship b/w the stress axis and the opioid system.
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also menstrual abnormalities and sexual dysfunction
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vasopressin acts as a potentiator for CRH, enhancing the release of ACTH.
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increases ureagenesis by indirectlyactivating transamination of alanine to pyruvate(which go for
gluconeogenesis). the amino group released as urea
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tonic inhibition. structurally related to GH and hpl ..................... some of hormone that may increase prolactin level
are TRH, vasoactive intestinal peptide, oxytoxin and vasopressin. ......... tuberoinfundibular pathway disruption
causes increase in prolactin release
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nbme>>>>2,3,22>>>>during a marathon young women initially has pain and distress but suudenly
feel well>>>>>its due to beta-endorphin release.
β-endorphin is an endogenous opioid peptide neurotransmitter found in the neurons of both the
central and peripheral nervous system.
It is an agonist of the opioid receptors, with evidence suggesting it serves as the endogenous
ligand of the μ-opioid receptor, the same receptor to which the chemicals extracted from opium,
such as morphine, have their analgesic and addictive effects
effects
It is used as an analgesic in the body to numb or dull pains. That is the reason why humans start
to feel better immediately after an acute physical trauma even though the symptoms are still
present. The reason the pain dulls is because it binds to and activates opioid receptors. β-
endorphin has approximately 80 times the analgesic potency of morphine.
β-endorphin is believed to have a number of other benefits, including:
Boosting the immune system[citation needed]

Slowing the growth of cancer cells
Promoting feeling of well-being
Increasing relaxation
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inhibit acetyl-CoA carboxylase>>>decreases formation of malonyl CoA>>>when concentration of malonyl CoA
decreases kitogenesis favors over lipogenesis
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has both anabolic and catabolic actions simultaneously ............. IGF-1 and IGF-II are synthsized by
various tissues, including the liver and bone.. IGF-I increases the osteoblastic replication and collagen synthesis,
it also decreases collagen degredation by inhibiting the enzyme metalloproteinase 13 (MMP-13). the net effect of
the IGF-1 on bone is anabolic. ........ hypothalamic IGF-1 locally regulate CNS activity and does not contribute
significantly to bone and soft tissue growth......... IGF-1 binds cells membrane-associated receptors with tyrosine
kinase activity to produce anti-apoptotic and anabolic effects.
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level increase in fasting state and decrease after food intake.
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leptin decreases food intake in the following ways. 1, decreases the production of neuropeptide y, a potent apetite
stimulant,in the arcuate nucleus of the hypothalamus. 2, leptin stimulates the produciton of POMC in the arcuate
nucleus. alpha-melanocyte-stimulating hormone (alpha-MSH) is produced by cleavage of POMC and inhibits food
intake. .................. Leptin is a hormone secreted by fat cells that acts on the hypothalamus to
decrease appetite. Although PPAR-y activation increases fat cell mass, circulating leptin levels
remain unchanged or decreased due to the inhibiting effect of PPAR-y on leptin gene
transcription........ homozygous mutation of the leptin receptor (db/db),result in ineffective leptin
signalling>>>>individual is hyperphagic and obese, and leptin level are high as production is normal.
homozygous mutation for leptin production (ob/ob)>>>individual is hyperphagic and obese but leptin levels are
low. most obese pte dont have these mutation but they have sustain elevation of leptin from the enlarged fat
stores result in leptin desensitization>>>>>individual besome resistant to leptin just like insulin in type 2
diabetes.
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in proportion to the quantity of fat stored. large fat cells produce more leptin...................... low BMI correlate with
low adipocyte store and low leptin level.
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loran dwarfism>>>GH receptor defect>>>decreased linear growth>>patient have high serum GH concentration with
low level of circulating IGF-1,
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antenatal diagnoses of fetal adrenal disorders accomplished via amniocentesis. this analysis may involve
measurement of amniotic fluid 17-hydroxyprogesterone levels, gene linkage analysis
involving the HLA region of chromosome 6, or detection abnormal genes via molecular probes.
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cholesterol side chain cleavage enzyme. rate limiting enzyme of cortisol synthesis. ........ desmolase catalizes the
formation or destruction of carbon-carbon bonds within a molecule.. this enzyme plays a significant role in
respiration and fermentation. ........ this enzyme deficiency causes cholesterol esters to accumulate in the
adrenal and gonads>>causes progressive damage
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converted by Oxidoreductase .................................................. DHEA and ASD are called 17-Ketosteroids (17-KS)
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also called 18-Hydroxylase
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3,beta-hydroxysteroid dehydrogenase is the rare form of CAH>>>>in which all steroid hormone are deficient.
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three degrees: 1, classic salt wasting 2, classic non salt wasting (male with this variety typically present during the
first few years(2-4 years) of life with early virilization and accelerated linear growth) 3, non classic, delayed
(premature pubarche or sexual precocity in school age children, young women can present with menstrual
irregularities , acne and hirsutism). female with classic form (with or without salt wasting present with ambiguous
genitalia at birth ......... has variable presentation depending on the severity of the enzyme deficiency.
Neonates typically have virilization and life-threatening hyponatremia (salt wasting). Late-onset 21-
hydroxylase deficiency usually presents as hirsutism, oligomenorrhea and acne. ............... along with
vomiting, hypotension, hyponatermia and hyperkalemia, severe enzymatic defects can also result in significant
cortisol deficicncy, which can cause hypoglycemia and further impair blood pressure maintenance (leading to
circulatory collapse)
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treatment of CAH involve administering low (ie physiologic) doses of exogenous corticosteroids to suppress
ACTH secretion. .................. female diagnose at birth>>virilization male diagnose later>>>sall wasting(these
symtopms appear 1-2 weeks after birth)/or precocious puberty symptoms.............. Maternal virilization does
not occur due to intact placental aromatase activity. unlike in aromatase deficiency patient. ......... growth
of facial and pubic hair along with enlatged genitalia in a boy younger than 9 years old signifies precocious
puberty, for girls this syndrome is defined as an appearence of secondary sexual characteritics before age 7.
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this is diagnostic (increase level in serum)for this cause of CAH
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all will born with female phenotype. affected individual do not undergo puberty...................................... hypertension,
hypokalemia and low renin are usually detected around the time of expected puberty
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Angiotensin II acts synergistically with potassium, and the potassium feedback is virtually
inoperative when no angiotensin II is present
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last two are called 17-Hydroxycorticoids (17-OH)
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/isomerase .............................. epostane and trilostane inhibit the formation of progesterone from pregnenolone by
inhibiting the enzyme 3-beta hydroxysteroid dehydrogenase.
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is a trophic hormone.
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steroidogenic acute regulatory protein>>>>regulates cholesterol transfer with in
mitochondria 1163
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also increase glycogenesis, 548 ......... glucucorticoid are predominantly catabolic, causing muscle
weakness, skin thinning, impaired wound healing, osteoporosis and immunosuppression. however they increase liver
protein synthesis, specifically the enzyme involved in gluconeogenesis and glycogenesis. this along with
peripheral antagonism of insulin result in hyperglycemia ........ overall glucucorticoid inhibit RNA and protein
synthesis in many tissues such as muscle,however hepatic RNA and protein synthesis are stimulated
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corticosteriod inhibit monocyte differentiation into macrophages, thereby decreasing the rate of antigen
presentation by macrophages to T lymphocytes
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an effect previously used as the basis for bioassay for corticosteriods
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glucucorticoid causes proximal muscle weakness secondary to both cortisol direct catabolic effect and the
hypokalemia induced by cortisol's mineralocorticoid effect.
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cortcosteriod decreases peripheral lymphocytes count within minutes as a result of inhibition of immunoglobulin
synthesis, stimulation of lymphocyte apoptosis and lymphocytes redistribution (from the intravascularr
compartment to the spleen, lymph nodes and bone marrow) . T lymhocytes counts are typically reduced to a
greater degree then B lymphocyte count ............... high doses of cortticosteriod can sometimes cause
corticosterid-induced psychosis (confusion, hallucinaiton)>>>>hypoalbuminemia is a risk factor.
neuropsychiatric symtoms typically resolve with discontinuation of therapy .........
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convert calcidiol to calcitriol
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bone turnover increases when ratio of rank-ligand to OPG (osteoprotegrin) increases. similarly over expression of
RANK receptor on osteoclasr also increases bone turnover.
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99% circulating thyroid is bound, 70% with TBG and other with albumin and transthyretin .................... at normal
level>>>protein anabolism at higher level>>>protein catabolism ........... T4 converted in peripheral tissue to T3
(most active) and rT3 (inactive form) ...... circulating T3 and intracellular T3 (from deiodination of T4 to
T3)>>>>have negative feedback control on hypothalamus and pituitary.
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iodothyronine deiodinase is inhibited by propylthiouracil, glucucorticoid, amiodarone, iopanoic and and non-
selective beta blocker(propanolol) ............. ipodate(contrast agent) also inhibit peripheral conversion. ........... T3
mostly produced in peripheral tissue by the removal of iodine from T4, which is catalized by iodothyronine
deiodinase
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synthesis inhibited by PTU and methimazole. release inhibited by the pharmacological doses of the iodine
........................ after nuclear reactor accident, potassium iodide is given which competitevely inhibit radioactive
iodine uptake. levothyroxine due to its negative effect on TSH can eventually decrease radioactive iodine uptake
(cause TSH increases iodine uptake) but it takes several days to weeks... By inhibiting iodine organification through
prophythyouracil(by inhibiting enzyme thyroid peroxidase) decreases idoine uptake but its not an efficient way.
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only small amount of DIT and MIT are secreted because iodotyrosine deiodinase removes the iodine groups from
the MIT and DIT for recycling
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occur at apical-colloid interface
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COLLOID>>>consists mostly of thyroglobulin a high molecular weight glycosylated protein. TSH increases the
synthesis of thyroglobulin by increasing its gene transcription.
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the thyroid follicular cell than engulf the thyroglobulin, which now contains multiple iodinated tyrosine compounds
(mono and diiodotyrosine, triiodothyronine and thyroxine). thyroglobulin is than digested with in lysosomes,
releasing T3 and T4 in circulation.
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basolateral surface. through energy dependent>>>Na-I cotransporter. iodide uptake is positively upregulated by
TSH
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retinoid, PPAR and fatty acids also have nuclear receptor
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increase its synthesis and also causes sialylation of TBG which leads to decrease clearance>>>>>leads to
transient increase in TSH for restoration of homeostasis.
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nbme>>>5,4,11 TBG deficiency does not cause thyroid disease.First, any decrease in TBG levels
initially increases the concentration of the free hormone. Subsequently, the tendency to
cause hyperthyroidism is counterbalanced by the tendency to shut off TSH secretion and
hence decrease the TH secretory rate from the thyroid gland. Finally, the total TH
concentration in the serum decreases until the concentration of the free hormone is
restored to normal. This equilibrium is achieved extremely rapidly and on a
physicochemical level. If chronic, the decreased extrathyroidal pool of TH may lead to small,
transient declines in circulating free TH levels, thus resulting in transient TSH stimulation of
the thyroid. The latter mechanism may explain the moderate elevation in serum
thyroglobulin levels observed in up to one third of patients with TBG deficiency. Because
TBG deficiency is not an acute process, a state of resultant hypothyroidism does not occur.
Total T4 and T3 may be low in states of TBG deficiency, but the free T4, free T3, and TSH
remain normal.*** Thyroid function tests (TFTs) in patients with TBG deficiency show normal
TSH and free T4, but low total T4 and, occasionally, low total T3 serum
concentrations.Thyroid binding protein deficiency states :***Inherited causes include the
following:•TBG gene defects - Partial deficiency (X linked) and complete deficiency (X
linked)•Other genetic defects - Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1),
which is autosomal recessive.***Acquired causes include the following:•Hyperthyroidism•Nephrotic
syndrome •Chronic renal failure•Chronic liver disease•Severe systemic illness (except human
immunodeficiency virus/acquired immune deficiency syndrome [HIV/AIDS] and acute intermittent
porphyria)[2] •Malnutrition•Acromegaly (in very rare cases only)[3, 4] •Cushing syndrome•Drugs
(eg, androgens, glucocorticoids, L-asparaginase)
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nbme>>5,2,17 stem is simply asking that "Once the Cytokine(PDGF) provided the signal , Which intracellular Enzyme
is, that Inhibit (oppose/antagonize ) the Transmission of This Mitogenic Signal" Mitogenic Signal transmission uses
"MAP Kinases".......it is the "Phosphatases" that oppose the signal at all levels where kinases are used.
Kinases............. promote Mitogenic SignalPhosphatases..... oppose Mitogenic signal -so the signal
transmission is controlled by the balance b/w the above two enzymes activity
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examples of signal transduction systems include
1, MAP-kinase pathway
2, PI3K/Akt/mTOR pathway
3, inositol phospholipid pathway
4, cAMP pathway
5, JAK/STAT pathway
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free in cytosol
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relaxation of SM, platelet activation, sperm metabolism and cell division. ........................... cGMP gated sodium
channels play a role in vision.
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AT I receptor.
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acts via a type 1 nuclear receptor, that on binding progesterone translocates to the nucleus and bind directly to
DNA to influence protein synthesis.
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is a specific intracellular tyrosine kinase associated with receptor that dimerize upon ligand binding ............. the
action of GH are mediated through transmembrane receptors that recruit janus kinase, which is found in the
cytoplasm. this non-receptor tyrosine kinase causes phosphorylation and activation of STAT transcription factor.
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antigen specific receptor on B and T cells.
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mitogen-activated protein>>>which enters the nucleus to influence gene transcription RAS-MAP pathway>>>ras is a
G-protein that exists in two form active(GTP bound) and inactive(GDP bound)>>.active form activate RAF
kinase>>>which causes activation of MAP kinase ......... (associated with phospholipase C which activate
PKc)....??????
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PI3K/Akt/mTOR pathway is an intracellualr signalling pathway that is important for cellular proliferation. activated
when a GF binds to its tyrosine kinase receptor, causing autophosphorylation of sepecific tyrosine residues within
the receptor. these phosphotyrosine residues activates phosphoinositide 3-Kinase (PI3K), which then
phosphorylates PIP2 found in the plasma membrane to PIP3, this lead to activation of protein called Akt (or
protien kinase B), a serine/threonine-specific protein kinase. subsequently Akt activates mTOR (mammaalian
target of rapamycin), whihc translocates to the nucleus to induce genes involved in cell survivial, aniapoptosis and
angiogenesis. mTOR activation is inhibited by PTEN (phosphatase and tensin homolog), a tumor suppressor
protein that removes the phosphate group from PIP3. the PI3K/Akt/mTOR pathway is highly active in many cancer
cells as a result of mutations causing increased activirty of PI3K or Akt or loss of funciton of PTEN.mutations
involving certain GF receptor (eg epidermal growth factor) can also enhance activity. several drugs targeting this
pathway ( eg mTOR inhibitors including rapamycin (sirolimus) have shown benefit in treating certain cancers.
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M1, M3, a1:
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transmembrane
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b1. b2. D1,prostacyclin. protein kinase A causes phosphorylation of certain serine or threonine
residues causes activation or deactivation. Also phosphoryles several protein that bind to regulatory
regions of genes on DNA molecule itself
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nbme>>> 5,2,26 1-STEROID HARMONE RECEPTARS STRUCTURE Steroid harmone receptars are present
INTRACELLULARLY * They are composed of polypeptide contain one ZINC atom which bound to four cystein
residue . They also have gene regulatory proteins that have one harmone binding domain and one DNA binding
region [which activates transcription]. Mechanism of gene transcription --- these inactive steroid receptars are
present in the cytoplasm and bound to heat shock protein 90 ie hsp90 and immunophillin hsp56.[these hsp
covers DNA binding regions] * When steroid harmone diffuses across the cell membrane and bind to harmone
binding site of receptar hsp90 and hsp56 are relased ---------this now leads to exposure of DNA binding site or
region. ----Now this steroid -receptar complex is transported to the nucleus where it binds to DNA and activates
transcription of small number of specific gene within 30 seconds -[this is primary response] ----gene product of
primary response activates other gene to produce secondary response . eq of streoid receptars- 1-glucocoticoids
2-estrogen 3-progesteron 4-thyroid harmones ie T3/T4 5-Retinoic acid receptar 6-vitamin D3.
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nbme Cytoplasmic receptors(steroid hormons) (once activated they migrate to nucleus) .andrgen .estrogen
.progesteron .glucocorticoids(cortisol) .mineralcorticoid(aldosterone) Nuclear receptors: .vit A .vit D .retinoid
.Thyroid .Fatty acids .PPAR(peroxisomal proli. AR)
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its mean negative test
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The ACTH stimulation test is used in the evaluation of adrenocortical insufficiency, not
adrenocortical excess
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Biochemical investigation comes first in the workup before any imaging as brain MRI will show
small masslike lesions 5%- 10% of the time even in normal subjects (incidentalomas). .......
measurement of cortisol levels in the evening is more sensitive and specific for Cushing
syndrome screening, since levels are normally the lowest at this time.
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adrena medulla is spared in this disease.
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Primary hyperaldosteronism does not directly cause edema due to aldosterone escape mechanism . However, certain
2° causes of hyperaldosteronism (eg, heart failure) impair the aldosterone escape mechanism, leading to edema."
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metyrapone blocks cortisol synthesis by inhibiting 11-B-hydroxylas, which converts 11-deoxycortisol to
cortisol serum 11-deoxycortisol and urincary 17-hyrdoxycorticosteriod levels will normally rise in response
to metyrapone, indicating an intact HPA axis.
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mean age of onset is 2 years
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on ch 2
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neuritic process also called neuropil are pathognomonic finding. NSE,chromogranin,synaptophysin, and S-100
immunohistochemical stains are usually positive.
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paraneoplastic syndrome
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most common extracranial childhood tumor
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can have hypokaelmia due to high epinephin levels which via bet-2 receptor stimulaiton and the resulting
intracellular K shift. ............ also have orthostatic hypotension (due to low plasma volume)
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25% inherited
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similar tumors arising from chromaffin cells outside the adrenal medulla are called paragangliomas
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thyroid hormone play a role in the conversion of beta carotene to vit A.
hypothyroidism become deficicent of vit A and can have yellowing of skin,
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myoedema>>>focal mounding of muscle after percussion. myoedema is characteristic finding in hypothyroid
myopathy secondary to slow Ca reabsorption by the sarcoplasmic reticulumn. serum CK elevation can
precede many years before overt hypothyroid myopathy. .......... elevated CK may be first manifestation of
hypothyroidism
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hyperthyroidism can cause irregular menses or amenorrhea along with weight loss ...... can cause hypercalcemia
due to bone teurnover(increased osteoclastic bone resorption)...but this hypercalcemia is not very severe
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atrail fibrillation is directly proportional to the severity of hyperthyroidism. hand
tremors are due to sympathetic overactivity
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although beta blockers can cause fatigue and depressive symptoms, they help reduce fatigue and mood lability in
patients with grave disease by ameliorating sympathetic overactivation.
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alopecia areata, and hyperhidrosis.
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TSH increases before any decrease in T3/T4. T3 is last to decrease in hypothyroidism ............. synthetic T3
(liothyronine) is not typically used for hypo cause it has short half life, require multiple daily dosing due to wide
flactuation of plasma T3.
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the speciifc symtoms not cuased by increased thyroid hormone levels but are
instead due to the autoimmune response directed against the TSH receptor.this
receptor is widely distributd throughout the body, particularly on adipocytes and
fbroblasts. patient with grave disease develop lymphocytic infiltration of the
orbital and peritibial connective tissue due to increased TSH reeptor expression
in these regions. cytokines released by activated T cells increase fibroblast
proliferation and secretion of glycosaminoglycans , resulting in mucinous
edema and tissue expansion.
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hypo can cause hypertension due to increase peripheral resistance. ........ depression, myalgia (myopathy with
increase CPK) and arthralgia.
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hyperthyroidism can produce a constellation of clinic features similar to Pheochomocytoma, but
the symptoms of hyperthyroidism are usually continuous and do not remit and recur
spontaneously.
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congenital hypothyroidism. Affected neonates appear lethargic, feed poorly, exhibit prolonged jaundice,
and demonstrate constipation, muscle hypotonia, and a hoarse cry. Physical examination of the infant
with congenital hypothyroidism reveals pale, dry cool skin; myxedema (edema of skin and subcutaneous
fat) and macroglossia (large tongue). coarse facial features and umbilical hernia are commonly present as
well. These infants also have an increased incidence of congenital heart defects such as ASD and VSD.
T4 is essential for normal brain development and myelination during early life.
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biopsy is typically not required for diagnoses.
diagnoses is made with clinical symptoms, elevated TSH and lowT4/T3 and elevated antithyroid
peroxidase.
occasionaly the thyroid gland is nodular on examination.
the presence of thyroid nodules may be an indication for fine-needle aspiration to rule out
malignancy
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transient hypothyroidism and eventually become euthyroid.
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a hard, fixed thyroid gland can simulate a malignancy
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a large portion of patients have postive antithyroid peroxidase antibody titers. suggesting an autoimmunity role
in the develpopment of riedel;s thyroiditis.
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mixed cellular infitraiton with occasioanl giant cell. .................. though it is not a true immune disorder, it is
thought to be due to a cross-reacting response against viral or tissue antigens following cellular
injury. decreased radioiodine uptake. early neutrophilic infiltrate with micro abscess formation. As the
disease progresses, this is replaced by a predominantly lymphocytic infiltrate with macrophages and
multi nucleated giant cells. It usually follows a viral illness. Biopsy is characterize by a lymphocytic
infiltrate with macrophages and multinucleated giants cells. .......... original insult is viral.
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microscopically has intense mononuclear infiltration consisting of lymphocytes and plasma cells. several germinal
center also present. the thyroid follicular epitheelial cells undergo a metaplastic cchange, leading to the formation of
large, oxyphilic cells with granular cytoplasm called hurthle cells. ............... Biopsy reveals diffuse
lymphocytic infiltration with formation of germinal centers. ..... nbme>>>>1,2,20 >>>>50 year old women
with visible painless lump in her neck for the past 6 month>>>enlarged non-tender thyroid gland>>>initial thyroid test
normal than increased TSH and low thyroxine>>>diagnoses on biopsy>>>heavy lymphocytic infiltrate with
germinal center formattion.
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Pathogenesis (multifactorial) (1) Cytotoxic T cells destroy parenchyma (type IV hypersensitivity reaction [HSR]) •
Initial thyrotoxicosis, eventual hypothyroidism (2) Blocking antibodies against TSH receptor (type II HSR) • Decrease
hormone synthesis; type II hypersensitivity (3) Helper T cells release cytokines attracting macrophages that
damage tissue (type IV HSR) (4) Antimicrosomal and antithyroglobulin antibodies destroy parenchyma (type II
HSR)
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nbme, 3,4,48 6 month old infant is sluggish and appears edematous. has course immature facies and poor
muscle tone.>>>>>diagnoses is congenital hypothyrooidism ............. nbme forum causes ...in brief for neonatal
hypothyroidism 1-Drug-induced hypothyroidism can result from use of thioamides, lithium, amiodarone, and excess
dietary iodine by the mother . Exposure to these substances most often results in biochemical evidence of
hypothyroidism in the absence of clinical symptoms. 2-Congenital hypothyroidism: Approximately 75% of infants with
congenital hypothyroidism have defects in thyroid gland development, 10% have hereditary defects in thyroid
hormone synthesis or uptake, 5% have secondary (pituitary) or tertiary (hypothalamus) hypothyroidism, and 10% have
transient hypothyroidism The reason I'm so persistent is that other forums have concluded that the answer to the
question is T4 or T3. While I don't believe this is the answer, I'm looking for someone to argue that it is. levothyroxine
is FDA class A which has no significant placental crossing ability so the T3,T4 is out.
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radioactive idoine is generally the preferred treament for Graves disease in the US, antithyroid
thionamide drugs are used in select cases, particualarlt patietns with mild disease.
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which are activated by cytokines released form Th1 lymphocytes infiltration of extraocular muscles and orbital
connective tissues>>>>>fibroblasts then produce excessive glycosaminoglycans. glucucorticoids are used to treat
this inflammation. glucucorticoid are also used to prevent worsening of ophthalmopathy induced by radioactive
iodinetreatment (especially in the smokers)... glucucorticoid can also decrease peripheral conversion of T4 to T3
but it has no effect on ophthalmopathy
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nbme>>1,4,32>>>.circulating antibodies against thyrotropin receptor are found
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pathogenesis: (a) Stimulating type of antibody as opposed to a blocking antibody (b) Type II HSR (2) Antimicrosomal
and antithyroglobulin antibodies are present. (3) Inciting events that may initiate onset of the disease • Infection,
withdrawal of steroids, iodide excess, postpartum state
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graves disease during pregnancy can be complicated by neonatal hyperthyroidism caused by
placental transfer of maternal thyroid-stimulating antibodies.
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when damage is unilateral. bilateral damage causes inspiratory stridor and respiratory distress due to vocal
cord paralysis. ....... The recurrent laryngeal nerves innervate all of the intrinsic muscles of the
larynx except the cricothyroid muscle. Paresis of vocal cord muscles innervated by left
recurrent laryngeal nerve cam cause hoarseness. newly present
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arises form thyrocervical trunk and courses posterior to the carotid artery and jugular
vein to supply the infrior pole of the thyroid gland. it runs adjacent to the recurrent
laryngeal nerve
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cells are characteristically enlarge with overlapping nuclei containing finely dispersed chromatin, giving them a
groung glass appearance(orphan annie eye). numerous internuclear inclusions and grooves can be seen due to
invagination of nuclear membrane ........... on light microscopy revelas branching papillae, which are composed of
a fibrovascular stalk covered by neoplastic cuboidal cells. ........ the tall cell variant of papillary thyroid cancer is
characterized by follicular hyperplasia, lined by tall epithelial cells.this variant of papillary thyroid cancer is seen in
older individuals and carries a relatively worse prognosis when compared to weel-differentiated papillary thryoid
cancer(whihc ae lined by cuboidal cell) ...... the diagnoses can easily be made by FNA biopsy
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histologically>>>polygonal to spindle shaped cell with a slightly granular cytoplasm that stains for calcitonin,
.......... microscopically, there are uniforms polygonal or spindle-shaped cells with extracellular
amyloid deposits. Amyloid stains with Congo Red
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inactivating mutation of P53 is fairly common in anaplastic thyroid cancer. .................... cytologic
features>>>pleomorphic cells, including irregular giant cell and biphasic spindle cell.
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often metastasize to lung and bone, patients typically present with an asymptomatic neck mass. voice changes
may occur if there has been involvement of larynx and recurrent laryngeal nerve.
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RAS gene mutations are found in follicular thyroid cancer and some follicular adenoma.
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80% medullary thyroid cancer are sporadic and 20% familial.
>95% of familial cases has RET gene mutation.
RET mutation are also commonly found in sporadic cancers
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thyroid follicular adenoma and carcinoma cannot differentiate by FNA ....................... the presence of colloid-
containingmicrofollicless suggests a benign follicular adnemona. in some cases, benign follicular
adneoma can be difficult to distinguish from well-differentiated follicles thyroid cancer, which can also
have the appearance of normal thyroid follicles. The tip-off is that capsular and vascular invasion occurs
only with follicular thyroid cancer.
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internal larygeal accompany superior larygenal artery external larygeial nerve accompaniyes
Internal laryngeal nerve – sensory;
superior thyroid artery .........
supplies floor of piriform recess and mucous membrane of
larynx above of the vocal folds
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external branch of superior laryngeal nerve courses along with superior thyroid artery (branch of external carotid
artery)>>>>>innervate on cricothyroid muscle of larynx
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important causes are humoral hypercalcemia of malignancy, vitamin D toxicity, excessive ingestion of calcium,
thyrotoxicosis and immobilization(Ca reabsorbed from inactive bone) ......... in this PTH is appropriately
suppressed by high calcium levels.
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Tertiary hyperphosphatemia
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nbme>>>2,2,25 (confusing)>>>familial hypoparathyroidism in which there is constitutive activation of Ca+2
sensing receptors in parathyroid gland which suppresses PTH secretion, leading to increased phosphate levels,
hypocalcemia, increased Ca+2 loss in urine. And the constitutive activation of the Ca+2 sensing receptors makes it
seems as though the Ca+2 levels are normal/high and so that is why PTH is not secreted
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signs of neuromuscular hyperexcitability become clinically apparent with serum calcium levels <_ 7.0 mg/
dL. ........................ other causes of hypocalcemia are sepsis, tumor lysis syndrome, acute pancreatitis and
severe bitamin D or magnesium deficiency....... glucocorticoid can worsen hypocalcemia by decreasing
expression of vit D receptor.
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PTH acts to increase serum calcium concentrations, the calcium levels often remain low in vitamin
D deficient states (especially when bone stores becomes depleted, as in this osteomalacic patient)
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both secondary hyperparathyridism and pseudohypoparathyroisiam are problem of
kidney.
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85% of cases
hyperplasia most remaining, cancer is very cause
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due to chronic stimulation ............................. less common and is usually seen with end stage renal disease (ie on
dialysis )
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the high bone turn over due to high PTH level increases bone resorption more than bone formaiton, causing
osteopenia, and pathologic bone changes similar to those seen in primary hyperthyroidism (osteitis fibrosa
cystica). patients also develop PTH resistance, resulting in low turn over adynamic bone disease and
osteomalacia.... dearanged siganlling between renal cells and bone osteoblasts and osteoclasts (eg FGF-23,
Klotho) also contributes to the skeletal chnages that occur in CKD
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most common presentation now a days is asymptomatic hypercalcemia due to routine calcium measurement in
chemistry profile
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familial hypocalciuric hypocalcemia::::
calcium sensing receptors are transmembrane G-protein coupled (metabotropic) receptors that
help to regulate the secretion of PTH is response to chainges in circulating calcium levels.
binding of calcium to CaSR leds to inhibition of PTH release, where low calcium levels lead to
increased release.
FHH is a benign autosomal dominant disorder caused by a defective Casr in the PT gland and
kidneys.. in FHH higher serum calcium levels are required to suppress the secretion of PTH. this
raises the set point of calcium-induced regulation of PTH secretion.
patients have mild asymptomatic hypercalcemia, reduced urinary excretion of calcium and high
normal or mildly elevated PTH.
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unlike osteoporosis (tabecullar bone), hyperparathyroidism causes cortical bone involvement of appendicular
skeleton(pectoral girdle, pelvic girdle and limbs) >>>>subperiosteal erosions in phalanges of the hand, "salt and
paper" skull and osteolytic cyst in long bones (osteitis fibrosa cystica)
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but this hypercalcemia does not suppress PTH due to autonomous gland function.
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Most prolactinomas detected in women are <10mm (microadenoma); men are often diagnosed at a
more advanced stage (>10mm) due to having only mild, nonspecific symptoms. Even without
treatment, the risk of a microadenoma enlarging rapidly is low. ........... Because the symptoms of
elevated prolactin in men are often mild and nonspecific, patients may not seek care until the
tumors are large and cause mass effect symptoms. ............. Gonadotroph adenomas may
produce FSH or LH. however most of these tumors overproduce the biologically inactive
gonadotropin a-subunit and present with mass effect and hypopituitarism. Most
nonfunctioning adenomas arise from the gonadotrophs. ....... Thyrotroph adenomas are very
uncommon.
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we use just in lithium induced diabetes mellitus
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in complete form.
in partial form less than 50% and greater than 10% increase.
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thiazide causes mil hypovolemia thus increases proximal Na and water reabsorption.
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normally prostaglandin inhibit ADH.
so it decrease the synthesis of prostaglandin
212
.......
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lymphocytic hypophisitis is the most common inflammatory condition of teh pituiatery and typically
occurs during late pregnancy or the early postpartum period.
in contrast to sheehan syndrome presentaion is acute with severe headaches and visual field
defects
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in pregnancy induce estrogen-induced hyperplasia of lactotroph
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non-malignant infiltrative lesions such as sarcoidosis and histiocytosis X
mainly involve the suprasellar region, where they compress the hypothalamus and
pituitary stalk. this disrupst the normal hypothalamic dopamineric suppression of
prolactin secretion, leading to increased prolactin levels and possible gaalctorrhea.
central diabtes inspidus may also be seen with resulting hypernatremia ............
primary pituitary cancer is extremely rare. although the pititary is prone to
metastases due to its high vascularity. the patient present with tumor mass effects
(eg headache, bitemporal hemianopsia)
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Patients with pituitary apoplexy can develop cardiovascular collapse due to ACTH deficiency and
subsequent adrenocortical insufficiency. Pituitary apoplexy is a medical emergency that requires urgent
neurosurgical consultation and treatment with glucocorticoids. ............. The rupture of a saccular
aneurysm near the optic chiasm can present similarly to pituitary apoplexy. However, this patient’s
chronic history of decreased libido and acute cardiovascular collapse are more suggestive of a pituitary
etiology. ......... most common manifestation is failure of lactation due to prolactin
deficincy. also causes hypothyroidism and hypocortisolism. thryoid deficicny
may take a few weeks to develop due to long circulaintg half-life of thyroxine (5-
7) days and peripheral conversion of thyroxine (T4) to T3. cortisol deficiency
manifest rapidly, with nausea, postural hypotension, fatigue and weight loss.
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loss of pericytes in the retinal microvasculature is one mechanism for diabetic retinopathy......... nbme,11,2,39
Diabetic retinopathy is retinopathy (damage to the retina) caused by complications of diabetes mellitus, which can
eventually lead to blindness. It is an ocular manifestation of systemic disease which affects up to 80% of all patients
who have had diabetes for 10 years or more. Diabetic retinopathy is the result of microvascular retinal changes.
Hyperglycemia-induced intramural pericyte death and thickening of the basement membrane lead to
incompetence of the vascular walls. These damages change the formation of the blood-retinal barrier and also
make the retinal blood vessels become more permeable. Small blood vessels – such as those in the eye – are
especially vulnerable to poor blood sugar (blood glucose) control. An overaccumulation of glucose and/or fructose
damages the tiny blood vessels in the retina. During the initial stage, called nonproliferative diabetic retinopathy
(NPDR), most people do not notice any change in their vision. Some people develop a condition called macular
edema. It occurs when the damaged blood vessels leak fluid and lipids onto the macula, the part of the retina that
lets us see detail. The fluid makes the macula swell, which blurs vision.
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The risk of MI-associated mortality begins to decrease immediately upon smoking cessation.
However, it takes several tobacco-free years before the risk returns to baseline. It appears that
smoking not only worsens the complications of diabetes but also increases the likelihood of
developing diabetes in the first place, thus highlighting the importance of prevention and early
cessation. ............. Early in the pathogenesis of type 2 diabetes, glucose tolerance is thought to remain
normal because of a compensatory increase in insulin secretion from beta cells. This compensatory insulin
response by beta cells ultimately fails, causing poor glucose tolerance. Amylin is stored in insulin
secretory granules and is co-secreted with insulin from pancreatic beta cells. Amylin may play a
causative role in beta cell apoptosis and defective insulin secretion; however this theory is still
controversial.
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glucose convert into sorbitol and sorbitol convert into fructose. both sorbitol and fructose are osmotically active.
.................... polyol pathway impairment occur in tissues that do not depend on insulin for glucose transport (lens,
peripheral nerves, blood vessels and kidneys)>>>sorbitol and fructose causes osmotic damage >>>>result in
cataract formation and peripheral neuropathy (due to schwann cell injury) ............. nbme>>>4,3,29>>>wrong QN
intermittent nausea and vomiting of undigested, bile stained food for the past 3 months in a patient which have 10
year history of type 1 DM is due to>>>>>>autonomic dysfunction and not by either peptic ulcer or chronic gastritis.
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HbA1c is formend when glucose attaches irreversibly to HbA inside erythrocytes. glucose freely diffuses across
the red blood cell membrane, as a result the degree of HbA1c elevation is directly correlated to the average blood
glucose levels over the total eythrocyte lifespan.. changes in red blood cell survival can influence HbA1c levels.low
and high turnover states can slightly incease or decrease HbA1c levels respectively. for this reason HbA1c should be
interpreted cautiously in patients with conditions that alter red blood cell turnover ( eg anemia, chronic kidney
disease, certain hemoglobinopathies) ................ nutrictional deficiencsies>>>vit b12, folate and
iron>>>>>preponderence of old erythrocytes>>>>flasely increase hbA1c treatment of vitmain def>>>>falsely
lower hbA1c>>>>young red cel rapidly release into circulation chnoic renal disease>>>no
erythropeotin>>>no new red cell>>>falsely high hbA1c scike cell trait>>>>relative normal hbA1c>>>due to
normal eruthro turnover beta thalasmeia trait>>>falsely low hbA1c>>>>due to increase cell
turnover>>>due to increase hba2
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glycosylation refers to the attachment of glucose to amino acid residues in various proteins forming reversible
glycosylation products that slowly stabilize to irreversible products. glycosylation products accumulate and
cross-link with collagen in blood vessels and interstitial tissues contributing to microangiopathy and nephropathy.
cross linking of proteins by glycosylation products also facilitate inflammatory cell invasion and deposition of
LDL in vascular walls leading to <<<<<<<atherosclerosis.>>>>>>>
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endoneural arteriole hyalinization (diabetic microangiopathy)>>>distal symmetric peripherall neuropathy that
usually start in legs
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non-enzymatic glycosylation interfere with binding of 2,3-BPG by altering the physical structure of binding pocket,
which is compensated by increase red cell2,3-BPG levels in patient with diabetes.
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complication are due to two mechanism: 1, non-enzymatic glycosylation 2, polyolo pathway impairment ..............
Common dermatologic manifestation of diabetes mellitus include skin tags, acanthosis
nigricans, and necrobiosis lipoidica diabeticorum. ......... in DM type 2 moratality rate form coronary
heart disease is 40% from cerebrovascular accident is 10%........
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diabetic nephropathy: The earliest morphological change is glomerular basement membrane (GBM)
thickening with resultant mesangial matrix expansion. Normally, the GBM has negatively charged
heparan sulphate moieties that form a charge barrier preventing leakage of negatively charged proteins,
like albumin, into the Bowman’s capsule. In diabetes, there is progressively loss of this negative charge
due to upregulation of heparanese expression by renal epithelial cells, which results in leakage of
albumin and other plasma proteins. Early administration of ACE inhibitors in patients with diabetes and
albuminuria has been shown to reduce urinary albumin excretion and slow progression to overt diabetic
nephropathy. Low molecule weight (LMW) proteins (eg, beta-2-microglobulin, immunoglobulin light
chains) are normally filtered by the glomerulus and reabsorbed in the renal tubules. Damage to the
tubular cells can cause loss of these tubular proteins in urine. Ischemic tubular damage may be seen
in advance DN Waxy casts are seen in advanced renal disease (chronic renal failure). They are shiny,
translucent tubular structures formed in the dilated tubules of enlarged nephrons that undergo
compensatory hypertrophy in response to reduce renal mass....... nbme>>6,2,10 Diabetic
glomerulopathy occurs in both type 1 and 2 DM.pathogenesis- 1)Non enzymatic glycosylation of
GBM(glycosylation means-glucose attach to aminoacids, increases vessel and tubular cell
permeability to proteins. 2)Nonezymatic glycosylation of afferent and efferent arterioles produces
hyaline artreosclerosis- involve efferent b4 afferent cause hyperfiltration. 3)hyperfiltration causing
damage to mesangium-increases GFR damage mesangial cell-hyperfiltration njury. 4)diabetic
microangiopathy:increase deposition of type 4 collagen -GBM, tubular basement
memb,mesangium.
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the dyslipidemia seen with insulin resistance is charatterized by high TGA and low
HDL, LDL levels do not increase with insulin resistance 1327 ......... hypoglycemia in the
neonate of a diabetic mother typically resolves within 3-7 days of birth as the hyperinsulinemia remits. persistent
hypoglycemia can be due to inborn metabolic abnormalities or genetic defects affecting insulin secretion (eg
persistent hyperinsulinemic hypoglycemia of infancy)
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MODY>>>autosomal dominant>>>mutation that causes impair glucose sensing and insulin release>>>non-
insulin dependent diabetes in <25 years of age, and accounts of <5% of all diabetes.
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lymphocyte. also have fibrosis of islet of langerhans found in patients with rapidly developing DM 1 ...............
although auto-antibodies against beta-islet antigen are present, but they have permissive role in pathogenesis,
cell mediated immunity has primary role in pathogenesis>>>infiltration of islets by inflammatory infiltrate called
insulitis, and is more prominent during early course of disease................ nbme>>>1,3,37>>>20 year history of
DM 1 and 3 years history of microalbuminuria>>>>finding on examination of tissue on renal biopsy>>>is diffuse
glomeruloscelrosis, not a glomerular luekocytic infiltration.
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generally have hyperventilation to compensate metabolic acidosis. however sever DKA can cause pulmonary
edema or significantly decreased mental status , which may lead to subsequent respiratory failure. if PaCO2
persist above the expected compensatory rande PaCO2= (1.5"HCO3)+8+-2>>>>it indicates superimposed
respiratory acidosis
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causes glucose utilization by cells thus decreases lipolysis and ketone production. which ultimately increase
bicarbonate. insulin shift K into the cell
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In the general population, DR3 and DR4 are saeen in approximately 40% of subjects; however in
patients with type 1 diabetes mellitus, DR3 and DR4 haplotypes are seen in more than 90% of subjects.
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therapy result in decrease glucose, osmolarity, and potassium, as well as increase in serum bicarbonate and
sodium.
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normalize the serum Na concentration and decrease serum osmolarity
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generally it is normally secreted along with insulin from beta-cell
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present with overt symptoms of diabetes when >90% beta-cells are destroyed.
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hypoglycemia in type 1 pateints is either due to: excessive insulin dose, inadequate food intake and physical activity/
exercise. ............... in normal individual overt hypoglycemia does not occur with exercise because a drop in blood
glucose will stop insulin release. however patients taking exogenous insulin are vulnerable to exercise-induced
hypoglycemia as insulin will continue to be releases form the injection site despite failing glucose levels. in addition
strenous exercise may cause changes in skin perfusion that can lead to increased insulin absorption (especially if
the insulin is injected into an exercising limb rather than the abdominal area) .............. In a medical setting,
severe hypoglycemia is treated with intravenous glucose (eg, 50% dextose ampule). In a
nonmedical setting, emergency glucagon kits may be needed for rapid correction of
hypoglycemia. Glucagon can be injected intramuscularly or subcutaneously. Glucagon is not
available, buccal or sublingual glucose or surcose ( eg, glucose paste cake frosting sugar packets)
may be attempted, but absorption of glucose from oral mucosa is slow and erratic and may be
ineffective.
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normocytic normochromic anemia resembling anemia of chronic disease is present in the majority of patients
........................... insulin level tend to be normal but can be increased secondary to the hyperglycemia and
glucagon-induced stimulation of the pancreatic beta-cell
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painful and pruritic rash typically affecting the face, groin and extremities>>>overtime small erythematous
plaques/papules coalesce to form large lesions with central clearing of bronze colored induration. rash also
commonly affects the mucous membrane and causes glossitis, cheilitis and blepharitis. ....... most common
location of nacrolytic migratory erythema is groin .......
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common in appendix. ilium or rectum. ..... most common ilial tumor. ....... nbme>>>>4,3,8 carcinoid
tumor metastasis to liver by blood.
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enterochromaffin.
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causes hyperplasia of parietal cell, gastrin has trophic effect on it,causes visible enlarging fundic mucosal cell.
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found in 50% of patients gastric acid presence make pancreatic and other intestinal enzymes inactive. so body
cannot proper digest nutrient
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diazoxide>>>>k channel agonist>>>>inhibit insulin release
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so patient with ZES should udergo tesitng (eg serum calcium, prolactin levels) to exclude MEN
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this location make this syndrome diagnoses likely
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fibrous intimal thickening with endocardial plaques limited to the right heart but not in left side cause degraded by
pulmonary endothelial monoamine oxidase(bradykinin,serotonin,kallikrien) .......... pulmonic stenosis and
restrictive endocarditis ultimately develop ........................... the degree of endocardial fibrosis seen in this
syndrome correlates with the plasma levels of serotonin and urinary excretion of the serotonin metabolites (5-
HIAA)
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easily recognized as there is minimal to no variation in shape and size of tumor cells Glands,nests,rows or sheaths
may be formed. tumor cell have eosinophilic cytoplasm and oval to round stippled nuclei, on electron microscope
multiple small dense granules are seen in cytoplasm, these contain secretory products, eg vasoactive amine
(histamine, serotonin and brdykinin) or hormones ( eg gastrin)
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extraintestinal carcinoid tumors (eg brinchial carcnoid) can cause syndrome without metastasizing as the
vasoactive substances are secreted directly into systemic circulation (again bypassing hepatic metabolism)
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acts on the liver to produce amino acid oxidation and gluconeogenesis from amino acids. circulating level of
amino acids are low and thought to be the cause of the necrolytic migratory erythema skin lesion.
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unlike MEN-1 only 10-20% of patients have hyperparathyroidism.
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inherited mutation
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early recongnition is important as almost alll patietns will develop MTC and prophylactic thyroidectomy can be
life-savings. ................. history of total thyroidectomy is clue patient were have medullary throid carcinoma (benign
thyroid masses are usually treated medically or with partial thyroidecctomy) ...................... mucosal neuromas
are encapsulated, thickened proliferations of neural tissue. .... intestinal ganglioneuromas (often causing
associated constipation)
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peptic ulcer disease may occur in MEN 1 (wermer syndrome)....................... hyperparathyroidism is the most
commmon manifestation of MEN 1 and is caused by parathyroid chief cell hyperplasia............... in MEN
1
primary hyperparathyroidism is often a initial manifetation an usually presents with
asymtomatic hypercalcemia or renal stones. prolactin secreting adenomas are
the most common pituitary adenoms>>>in premenopausal women present at an
early stage with menstrual irregularities and galactorreha. in men present later
when large prolactinomas lead to mass effect symtoms such as headache or
bitemporal visual field defects due to compression of optic chiasm. gastrinomas is
the most common followed by insulinoma and non-functional tumors.these
tumors are often metastatic and are frequent cause of tumor-related death in
MEN1
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Orthostatic hypotension is occasionally seen with insulin therapy, though the mechanism is not clear.
599 ................ regular insulin and NPH are only 2 human recombinant insulin without any amino acid
modification. all other preparation are properly referred to as insulin analogue .............. normal pancreatic insulin
secretion is biphasic and includes. 1, continuous low-level (basal) secretion 2, a postprandial insulin spike
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regular insulin can be used for mealtime bolus insulin but is not preferred. Regular insulin forms dimers
due to hydrogen bonding between the C termini of the B chains and can form hexamers in the
presence of zinc ions. .......... SC has onset of action in 30 min. peak in 2-4 hours and lasts 5-8 hours. not good
for postprandial hyperglycemia ............. intravenous infusion begins to lower serum glucose and ketones with in
minutes of adminitration., has half life of 5 min, allowing rapid adjustment of infusion rate based on glucose
level
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the main side effect of TZDs is fluid retention due to increased sodium reabsorption in the renal
collecting tubules. This can lead to <<<<water weight gain>>>>, peripheral edema, and
decompensation of underlying congestive heart failure. Fluid retention is often worse when TZDs are
given in combination with insulin. TZDs also cause <<<<adipose weigh gain>>>>>, likely due to a
combination of increased fat storage in adipocytes and an increased number of adipocytes in
subcutaneous tissue. Hepatic toxicity has been associated with an older TZD troglitazone, which is no
longer available ........ long term use of pioglitazone may be associated with urinary bladder cancer
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shot given twice a day. ..... crystalline suspension with protamine and zinc..that delays absorption. start
working within 2 hours, peak 4-12 hours and last 18 hours.
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metformin is a non-competitive inhibitor of mitochondrial glycerol-3-phosphate dehydrogenase and complex 1
(first electron transport chain enzyme)>>>>the resulting decrease in cellular energy stores causes AMPK
(adenosine monophosphate activated protein kinase) activaion>>leading to decreased hepatic gluconeogenesis.
....... also decreases intestinal glucose absroption.
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and meglitinides (repaglinide and nateglinide) are insulin secretagogues. meglitinides are functionally similar to
sulfonylureas. have similar efficacy and, their short half life require frequent dosing, typically with each meal, but
may reduce the risk of hypoglycemia. meglitinides are well studied for patients who have postprandial glucose
excursions.
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also in cardiac and GI diseases.
risk increases with exercise, missed meals, chronic malnourishment
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PPAR-gamma/RXR(retinoid X receptor) heterodimer complex binds to transcriptional regulatory sequence of various
genes responsible for glucose and lipid metabolism, 1, increase fatty acid uptake 2, increase adiponectin production 3,
increase insulin sensitivity (muscle and liver) 3, decrease TNF-alpha production 4, decrease leptin production.
RXR>>>>retinoid X receptor. ......... important genes that are upregulated by TZDs include>>>>GLUT-4 and
adiponectin ........ one of the most important genes regulated by PPAR- gamma is one the codes for adiponectin, a
cytokine secreted by fat tissue that enhances insulin sensitivity and fatty acid oxidation. adiponectin levels are
low in obese pateitns and those woth type 2 DM. treatment with TZDs increases adiponectin levels, improving
insulin sensitivity. ........ The PPAR family appears to play a significant role in the pathogenesis of
metabolic syndrome (obesity, hypertension, dyslipidemia, and insulin resistance). PPAR-y
activation leads to an increase in fat mass 1, secondary to the increased differentiation of
preadipocytes into mature adiocytes. 2, The increased movement of free fatty acids into fat
cells, along with increased fatty acid oxidation (adiponectin effect) cause circulating free fatty
acids levels to decrease.
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"(thus use with caution in renal insufficiency)."
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due to osteoporosis>>>>due to decrease bone formation
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by increasing glucose utilization and decreasing glucose produciton in adipose tissue, muscle and liver.
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these 3 are equally effective in lowering blood glucose, but have different durations of action. glyburide and
glimepiride are long acting and have a higher incidence of hypoglycemia, especially in the elderly. in contrast,
glipizide is short-acting and has a significantly lower incidence of hypoglycemia.............. glyburide>>>>renal
excreted glipizide>>>hepatic excretion
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normally lactate produced in intestine is converted to glucose by hepatic gluconeogenesis>>>>but as
mitochondrial enzyme are inhibited lactate production increase (due to increased anaerobic glycolysis) and
reduces hapatic metabolism of lactate (due to decrease hepatic gluconeogenesis)>>>>this increase the risk of
lactic acidosis particularly elderly or with renal/hepatic failure, CHF and alcoholics............ recent IV contrast
administration may reduce metfromin excretion>>may predispose to lactic acidosis
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has a pH 4 and form microprecipitate in the SC tissue after injection,(precipitates in SC tissue).resulting in slow
release of insulin., last for 24 hours and does not hava a pronounced peak.
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pharmocological targets:
1, intracellular mitochondrial enzyme>>metformin
2, intracellular nuclear receptor>>>thiazolidindiones (eg pioglitazone)
3, membrane ion channel>>sulfonylureas and meglinitides.
4, surface adenylate cyclase-coupled receptor>>GLP-1
5, surface membrane bound enzyme>>acarbose,
6 , surface tyrosine kinase reseptor>>>insulin.
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determir has a covalently bonded fatty acid, which promotes self-aggregation and reversible
binding to albumin, allowing for slow sustained release ............ detemir is long-acting insulin analogue
with fatty acid bound to one of the lysine aino acids on the insulin molecule, fatty acid allow detemir to bind to
albumin and slowly dissociate,resulting in prolonged action. start working within 2 hours,peak 3-9 hours and last
upto 24 hours.
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alteration of the amino acid structure at the C terminal of the insulin B chain can prevent
polymerization and allow rapid absorption from the injection site. ....... do not polymerize into dimer or
hexamer like regular insulin>>>these are monomeric>>>>allowing absorbed rapidly after SC injection onset of
action 15 min and peak 45-75 min. not usually given intravnously.
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log acting insulin is usually secreted by kidneys and can predispose CKD pte to hypoglycemia
11945
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is an incretin hormone secreted by the intestinal L cells in response to food. GLP-1 act through cell surface
receptors that are coupled with a G protein-adenylyl cyclase system
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nasopharyngitis
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renal failure can cause decrease effectiveness and increase risk of side effects>>>>so serum creatinine and
blood urea nitrogen is monitered before and after starting drug.. although it cause UTI but urinalysis are not done
before or after starting drug 604
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methimazoel also have an adverse effect of cholestasis ........................... ANCA develop in about 50% of patinests
taking propylthiouracil. most patients are asymtpmatic, but some can develop arthralgias and glomerulonephritis
as a result of ANCA-assicated vasculitis. ........... nbme>>>1,3,49>>>>chonically use causes PTU crosses the
placenta and result in hypothyroidism in neonates.
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adiponectin: Expression & release of "adiponectin" ->Stimulated by: Insulin & inhibited: TNF-a INC
weight/adiposity -> INC: FFA/TNF/Resistin/& DEC adiponectin -> Insulin resistance-> INC insulin*
-> DEC liver syn/blood tissue & DEC IGFBP 1 & 2 -> INC IGF-1** bioavailably ====> Target cell /
DEC apoptosis/ INC cell proliferation that tickle by IR* and IGFIR** -> sad path for tumor dev.
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both can produce agranulocytosis( absolute neutrophil count <500). this serious complication occur in about 0.5% of
patienets, usually within first few months of therapy. patient typicall y present with fever, sore throat, oral
ulcerations or other signs of infection. if agarulocytoosi is suspected drug should be stoped immediately and a
white blood cell count with differential obtained to confirm the diagnosis.
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this receptor reabsorb 90% of filtered glucose in proximal tubule.
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DPP-4 inhibitors effect is glucose dependent and diminshes as glucose levels approach normal. as a result, it
does not usually cause hypoglycemia. .................... dipeptidyl peptidase. this enzyme decreases
glucose utilization by peripheral cells. ......... oral glucose increases endogenous GLP-1 and GIP
levels...................
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glucocorticoid bind to cytoplasmic receptors that then translocate to the nucleus where the expression of anti-
inflammaotry peptides is upregulated. glucucorticoid decrease COX-2 transcription but do not inhibit its function
directly.
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may cause hyponatremia, extracellular volume expansionhypoglycemia.
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esophagus normally collapsed with no visible lumen in CT which present b/w vertebral column and trachea.
trachea has radiolucency,function as a landmark b/w great vessels anteriorly and esophagus posteriorly
.............. CT represents the lumen of the second part f the duodenum, which classically lies at the
level of L2 (on the left side of screen.) also at the level of T12-L1 suprarenal gland present on the left side of
screen.
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differential diagnosis of billous vomiting is midgut volvulus (surgical emergency) which must be excluded .... the
more distal the atresia the more likely it present with abdominal distension and less likely with billous vomiting
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imperforate anus is commonly associated with anovesical, anorectal or anovaginal fistulas.. urogenital track
anomalies being the most common
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during midgut development in the first trimester, the abdominal contents undergo physiological
herniation,followed by a rotation of the midgut and physiologic reduction. failure of extraembryonic gut to return
to the abdominal cavity results in either emphalocele or gastroschisis
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midgut in the frst trimester involves a physiological occlusion of the intestinal lumer follwed by recanalization.
failure of recanalization results in duodenal atresia............. after endothelial proliferation in 8-10 weeks of
gestation..>>>failed apoptosis>>>is the mechanism).....billous or non-billous vomiting.
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associated with hirschsprung disease. constipation and abdominal distension
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failure of partition in 4-5 week of gestation
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hind gut develop after midgut return to the abdominal cavity. ascending and descending colon pressed against
posterior abdominal wall.
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or christmas tree deformity. obstructed superior mesenteric artery. proximal segment>>>blind pouch followed
by an area of absent small bowel and its dorsal mesentery. distal segemt>>spiral configuration around iliocolic
vessel
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associated with gastroschisis. billous vomiting and abdominal distension
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containing mutliple organ. umbilical cord at apex
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associated with jejunum and ilium atresia
..........
gastroschisis is a full-thickness abdominal wall defect.
umbilical cord to the left of defect.
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septum transversum>>>composed of mesodermally derived tissue that extends ventral to the gut tube from the
umbilicus to the pericardium. it give rise to the myoblasts that form the diaphragm and exists as vestige as the
central tendon of the diaphragm. additionally liver grows into the septum transversum as an outpouching of the
embryonal foregut.
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normally umbilical ring or the congenital fascial opening for the umbilical cord, closes and forms the linea alba, a
midline band of fibrous tissue. umbilical hernias are caused by an incomplete closure of the umbilical ring, therby
allowing protrusion of bowel through the abdominal musculature. most umbilical hernias are reducible,
asymtomatic, and resolve spontaneously in the first few years of life. it is associated with down syndrome,
hypothyroidism and backwith-weidmann syndrome.
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nbme>>>2,4,42
The most common foregut cysts, the bronchogenic cyst and the esophageal duplication
representing abnormal budding of the vertebral and dorsal primitive foregut, respectively,
indicating their common origin from the primitive foregut and close embryologic relationship
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PYLORIC hypertrophy of muscularis mucosa
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proximal portion degenerate(may persist as a functional lesser pancreatic duct) and the remainder portion fuses
with ventral duct to form main pancreatic duct of wirsung
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contribute most of the head.
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cleaves into two parts with subsequently form a ring,
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dominant dorsal duct (of santorini) opens into duodenum via the minor papilla and drain majority of pancreas. the
smaller ventral duct (of wirsung) opens into major papilla and drain inferior/posterior portion of head and
uncinate process
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incidental finding
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and bladder.
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non-expanding hematoma in this location treated conservatively ( i.e no operatively)
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Secondary Retroperitonealization: Parts of the gut tube (most of the duodenum, pancreas, ascending colon, descending colon,
part of rectum)
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dorsal
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5 % of population
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recurrent billous vomiting soon after birth or asymptomatic.
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rare anomaly.
usually asymptomatic.
.................
Half of cases are not diagnosed until
symptoms occur in adulthood.
shelf
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inferior/posterior portion of the head.
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of wirsung
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ligamentum teres hepatis called round ligament also
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the lesser omentum is the double layer of peritoneum.between 2 layers of the lesser omentum on right free side
present hepatic artery, common bile duct, portal vein, lymphatics and hepatic plexus. the right and left gastric
arteries and gastric veins also lie between the 2 layers, near where the lesser omentum attaches to the stomach.
anatomically lesser omentum is divided into the hepatoduodenal and hepatogastric ligaments ............ the
greater omentum is the large fold of visceral peritoneum.
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gastrocolic ligament form part of the anterior wall of the lesser sac and is often divided during surgery to provide
access to the anterior pancreas and posterior wall of the stomach
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nbme,11,3,7
to encircle the stomach, the band will pass through>>>lesser omentum not hepatoduodenal
ligamanet.
The lesser omentum (small omentum; gastrohepatic omentum; omentum minus) is the double
layer of peritoneum that extends from the liver to the lesser curvature of the stomach and the start
of the duodenum.
The lesser omentum is extremely thin, and is continuous with the two layers of peritoneum which
cover respectively the antero-superior and postero-inferior surfaces of the stomach and first part of
the duodenum.,
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345
the teniae coli begin as a continuous layer of longitudinal muscle that surrounds the rectum just
below the serosa.
at the erctosigmoid junciton, this layer condenses to form 3 distinct longitudinal bands that travel
on the outside of the entire colon before converging at the root of the vermiform appendix.
the teniae coli has a similar function as the outer layer of musculairs externa in other portions of
the digestive tract.
the teniae coli run the length of the colon and contract lengthwise to form hasutra, colonic
sacculations causing the colon's segmented appearence. compared to the circumferential small
intestinal folds,the distance between the haustra is wider and they do not span the entire colonic
circumference.
these differences help distoinguish the colon from the small intestine on abdominal x-ray
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also dont have plica circularis but have microvilli
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paneth cells occur in small groups at the base of intestinal crypts. these have both phagocytic and secretory
properties and thus privide the first line of immune defense against intestinal microorganisms. paneth cells secrete
lysozyme, an enzyme capable of dissolving the cell wall of many bacteria, and defensins, polypeptides that have
antimicrobial and antiparasitic properties. ...... innate immune response
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345 proximal colon responsible for water and electrolyte absorption.distal colon is responsible for storage of feces.
ilium is responsible for dietery lipids (triglyceride, phospholipid and cholesterol esters) absorption. duodenum is
responsible for dietery lipid digestion (vie the action of lipase, phospholipase A2 and cholesterol esterase)
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The arcuate line is a horizontal line located below the umbilicus that demarcates the lower limit of the
posterior rectus sheath. Above the arcuate line, the rectus abdominis is surrounded by posterior sheaths
below. the muscle is covered only by the anterior sheath. The superior and inferior epigastric arteries
(branches of the iliac artery) supply the superior and inferior portions of the rectus abdominis muscle,
respectively. The epigastric artery ascends the posterior surface of the rectus abdominis muscle and
enters the lateral aspects of this muscle at the arcuate line. Because there is no supporting posterior
sheath, trauma to the inferior epigastric artery below the arcuate line can result in significant
hemorrhage. The lateral femoral cutaneous nerve travels under the inguinal ligament. It provides
sensory innervation to the anterolateral thigh. Entrapment (meralgia paresthetica) most common occurs in
obese or pregnant persons or in those who wear garments that are tight around the hip. Horizontal
transection of the rectus abdominis muscle must be performed with great caution as in the inferior
epigastric arteries enter this muscle at the level of the arcuate line. The inferior epigastric arteries below
the arcuate line are susceptible to injury (eg, hematoma) due to lack of supporting posterior rectus sheath.
......... The inferior epigastric artery is 1 to 2 branches of the external iliac artery and takes off
immediately proximal to the inguinal ligament (the external iliac artery becomes the common femoral
artery once it passes the inguinal ligament). As the inferior epigastric artery runs superiorly and medially
up the abdomen, it provides blood supply to the lower anterior abdominal wall. The other main branch
off the external iliac artery is the deep circumflex iliac artery, which branches more laterally but also
supplies blood to the lower abdominal wall.
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supply the diaphragm and provide branches to the suprarenal glands.
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pudendal artery and obturator artery are brances of internal iliac artery. pudendal artery supplies>>>scrotum, penis
and anal canal obturator artery suppplies>>>pelvis, bladder, parts of femoral head and medial thigh muscles.
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only rectum, which particularly drians via the middle and inferior rectal veins
direclty in to the IVC,, all other intestinal structures drian via portal vein
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SMA and IMA are anastomosed by: the marginal artery of drummond(marginal
artery). which is the principal anastomosis, and the inconsistently present arc of
riolan (mesenteric meandering artery) ......... unlike SMV,IMV donot course with IMA
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causes are diminshed mesenteric fat, low body weight, recent weight loss, severe burns, or other inducers of
catabolism and prolonged bed rest. also occur with pronounced lordosis or after surgical correction of
scoliosis, as this procedure lengthen the spine resulting in decreased mobility of the SMA
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normally have 45* angle,if it reduce to
20* cause this
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distal sigmoid colon has also watershed are b/w IMA and hypoogastric artery
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celiac trunk supply blood to most foregut stuctures with the exception of mouth,part of pharynx and upper
esophagus
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at the L3 level
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blood supply to the proximal ureter>>>branches of renal artery. distal
ureter>>>superior vesical artery in between>>>arterial supply is anastomotic and
highly variable, with possible afferent branches from the gonadal, common and
internal iliac, aorta and uterine arteries... in a kidney transplant patient the native
kidneys are typically left in place, and the donor kidney is placed retroperitoneally in
the right iliac fossa. blood supply is established by anastomosing the donor renal
artery with the recipients external iliac aretry. the proximal ⅓ of the donor ureter is
preserved and used to establish continuity form the colelcting system of the kidney
to the recipients bladder. although the transplanted ureter will continue to receive
blood supply through the donor renal artery, the most distal portion may be
susceptible to ischemia due to lack of anastomotic connections. distal ureteral
ischemia is a recognized complication of renal transplant and causes leakage of
urine 5-10 days following transplant. brancehes form the common iliac, internal
iliac and superior vesical arteries supply more distal segments of the ureter,
which are not typically retained in the transplanted specimen
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chronic mesenteric ischemia: severe pain 30-40 min after meal. PE normal, endoscopy does not reveal anything
abnormal, light microscopy shows mucosal atrophy and flattened villi. atherosclerotic plaques in vessels.
angiography is gold standard but expensive and time consuming. mesenteric duplex ultrasonography is non-
invasive and alternative to detect blood flow.
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internal iliac artery supplies portions of the gut through branhes like the middle rectal artery and the inferiro rectal
artery (a branch of the pudendal artery, which arises from the internal iliac artery).. the branches of the internal iliac
artery supply the bladder, uterus, vagina, ad part of the rectum.
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lumbar arteries arise directly from the aorta to supply the lumbar vertebrae and
surrounding atrutures.
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structure passes at L1 level: pylorus of the stomach (variable), fundus of gallbladder, neck and body of the pancreas, hila of
kidneys, first part of the duodenum, and origin of the superior mesenteric artery
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azygous vein drains blood form the esophageal veins into the superior vena cava. azygous vein also provides
collateral circulation between the superior and inferior vena cava and can become enlarged with caval obstruction.
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supply blood to pylorus, proximal duodenum and head fo pancreas.
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posterior to pylorus:common bile duct posterior to 1st part of duodenum:gastrodudenal artery posterior to 2nd part
of duodenum:right ureter courses retroperitoneally posterior to pancreas:portal vein form ............. right
gastroepiploic>>>distal greater curvature left gastroepiploic>>>middle greater curvature short gastric>>>proximal
greater curvture .................. the branches of splenic artery are (dorsal pnacreatic, short gastric,, left
gastroepiploic, and greater pancreatic arteries)......... Inferior pancreaticoduodenal arteries(branch of SMA) which
anastomose with the superior pancreaticoduodenal branches of the gastroduodenal artery in the head of the pancreas
....................... inferior pancreatoduodenal artery(branch of SMA)_supplies blood to the lower duodenum and to the head of the
pancreas.
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pancreatoduodenal vein drians the pancreas and dudenum into the superior mesenteric veins. the SMV also
drains blood from the lower stomach (via the right gastroepiploic vein) and small intestine. blockage of SMV could
lead to varicela formation in the lower stomach, but not the upper regions ................. left gastric veins drains blood
from the upper stomach and lower esophagus>>>portal hypertension causes both esophageal and gastric varices
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The major arterial blood supply to the anterior wall is derived from the superior epigastric branch of the internal thoracic
artery(subclavian vessel) as well as the inferior epigastric and the deep circumflex iliac branches of the external iliac artery.
...... superior epigastric artery and vein anastomose with internal thoracic and inferior epigastric ............
superficial epigastric vessel bracnhc of femoral vessel anostomose with
thoracoepigasttic vessel which is a branch of lateral thoraci vein(axillary
vessel)..... .............
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right gastroepiploic vein drians venous blood from the lower parts of the antero-superior and postero-inferior
surfaces of the stomach.
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distal lesser curvature
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Splenic cyst formation typically occurs due to infection. ................ courses superior to the pancreas
and separated by posterior surface of stomach by the pancreas so that rarely affected by penetrated stomach
ulcer
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hepatic artery occlusion is compensated by portal vein and retrograde arterial flow from accessory arteries (eg
from inferior phrenic adrenal, intercost alarteries etc)
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anal carcinoma
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Branches of the deep external pudendal artery supply the scrotum (labia majora in females)
and the perineum. The external iliac vein receives drainage from the inferior epigastric and
deep circumflex iliac veins, which serve the anterior abdominal wall and iliac crest, respectively.
The superior vesicle artery and its branched supply portions of the urinary bladder and ductus
deferens. ................ superficial and deep external pudendal vessels are branches of
femroal vessel
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autonomic innervation from the inferior hypogastric plexus, whihc is only sensitive to stretch and not pain,
temperature or touch.
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anal fissure: mostly in posterior midline distal to the dentate line. associated with constipation and low fiber diets.
acute lesion only involve epithelium of anal mucosa. chronic causes spasm of internal anal sphincter, causing
the presence of an enlarged anal skin tag distal to the fissures. ......
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are covered by modified squamous epithelium.
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are covered by columnar epithelium
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The venous component of internal hemorrhoids drains into the middle and superior rectal
veins, which communicates with the internal iliac and inferior mesenteric veins, respectively.
External hemorrhoids drain via the inferior rectal vein into the internal pudendal vein, which
communicates with the internal iliac veins. With the breakdown of connective tissue (due to
advancing age or prolonged straining), the cushions bulge into the anal canal become inflamed,
thrombose or prolapse.
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colon cancer
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hepatic centrilobular necrosis is the deth of hepatocytes immediately surrounding the terminal
hepatic vein. Ischemic injury (as in right sided heart failure), drugs, toxins, and fulminant
hepatitis can be responsible. ................... Periportal hepatic fibrosis is a pathologic finding found in
chronic viral hepatitis.
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block at ilioiguinal crease lateral to femroral artery. ............ femoral artery is located at the
midinguinal point (midway beyween the pubic symphesis and anterior superior ilic spine, femoral vein 1cm below
inguinal ligament and 0.5-1.1 cm medial to the femoral artery pulsation. femoral nerve 1cm lateral to femoral
artery pulsation.
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contains ilioinguinal nerve(L1)
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femoral branch of genitofemoral nerve(L1-L2) cutaneously innervate triangle.
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anterior abdominal wal has followng layers .skin .superficial fascia of camper(fatty layer) . superficial fascia of scarpa
(membranous layer) . external oblique muscle/aponeurosis . internal oblique muscle/aboneurosis . transversus
abdominis muscle/aponeurosis . fascia transversalis . extraperotoneal fatty tissue . pertoneum
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maintain posture and increases intra-abdominal pressure during forced expiration, defecation and parturition.
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nbme>>>2,2,18
external oblique in bilateral contration result in flexion of the trunk.
external obliqwue in unilateral contration >>>posterior pelvic tilt, same side flexion and rotation of
the trunk to the opposite side.
the external oblique are the largest of the abdominal muscles.
this muscle originate form the external surface of the lower 8 ribs and insert into the anterior half of
the outer lip of the ilialc crest and the aponeurosis of the anteriro abdominal wall.
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tunica albuginea is a fibrous tissue that overlies the corpus spongiosum and corpora cavernosa of the penis
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form parts of the posterior wall of the inguinal canal.
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outer most layer of spermatic cord and lies deep to the dartos muscle and scrotal fascia
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immediately overlies the spermatic cord and tunica vaginalis
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aponeurosis of internal oblique contributes to the formation of conjoint tendon and rectus sheath. internal oblique
muscle itself form cremaster muscle .................. the rectus muscle sheath is formed by the aponeurosis of
interna and external oblique and the transversus abdominis muscle
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superior surface of bladder is covered with peritoneum and is related to coils of ilium or sigmoid colon. along the
lateral margins of this surface, the peritoneum is reflected onto the lateral pelvic walls. the bladder is therefore
extraperitnoeal
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opening in tranversalis fascia>>>located superior to the mid inguinal canal.( midway between superior iliac spine
and the pubic tubercle) ...... mid inguinal point = deep inguinal ring
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transervasalis fascia lies posteriorly to indirect inguinal hernias.
indirect inguinal hernial sacs are located along the anteromedial aspect of the spermatic cord.
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best felt with the pulp of fingers on deep palpation.
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medial to femoral sheath (contain femoral artery and vein) and lateral to lacunar ligament and pubic
tubercle.............. coopers (pectineal) ligament will be posterior to a femoral hernia. ........... coopers ligament is a
thickend part of the pectineal fascia, it overlies the pectineal ridge of the pubic bone and is located posteriorly to
the femoraal canal
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(hernias cannot be reduced) causing nausea, vomiting , abdominal pain and
distention.>>>>>>>>>
if blood supply is compromised causes strangulation which have systemic findings scuh as fever
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due to weakness in transversalis fascia (which make floor of triangle)either due to acquired connective tissue
disease or due to chronic abdominal wall injury
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palpated by the tip of finger during deep palpation at external ring.
indirect inguinal are more common than direct inguional hernias.
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have trophic effect(proliferation)
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somatostatin inhibit both glucagon and insulin but has more effect on insulin so patient with somatostatinoma most
often present with hyperglycemia as compare to hypoglycemia, ....... patient with somatostatinoma present with
abdominal pain, gallbladder stone,constipation, hyperglycemia and steatorrhea. .... GH, TSH, CCK, gastrin,
secretin, VIP
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lanreotide>>>both have longer half-lifes as compare to somatostatin.
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by pancreatic ductal cell which produce isotonic fluid(Na and K), bicarbonate rich and chloride poor as compare
to plasma. when secretin secretion increases pancreatic flow rate increases and fluid become further more in
bicarbonates and less in chlorideregarless of flow rate or hormonal stimulation, the sodium concentration of
pancreatic secretion is identical to the plasma remember that pancreatic juice is an isotonic secretion in
pancreatic duct chloride is exchanged for bicarbonate. ............ has no function on pancreatic acinar cell. (means
enzymatic secretion)
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and convert into NaCl and carbonic acid
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and also by pancreas.
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VIP stimulates pancreatic bicarbonate and chloride secretion, and its binding to intestinal epithelial cells leads to
adenylate cyclase activation and increased cyclic AMP produciton, causing sodium, chloride and water secretion
into the bowel.(secretory diarrhea often >3 litters/day) ........ patients are usually hypotensive due to dehydration and
the vasodilatory effects of VIP. ........ increases intestinal chloride loss into stool and causes excess losses of
accompanying water, sodium and potassium
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just like gastrin but counteracts gastrin in the stomach.
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mainly amylase and lypase(these two are secreted in active form)
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starts when Ph fall below 5 and dramatically increase when Ph drops below 3
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by pancreatic acinar cell
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decreases gall-bladder motility (stones) and GI motility (steatorrhea).
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and also by hypothalamus.
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due to inhibition of histamin and pentagastrin stimulated acid secretion
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cleaves polypeptide at the site of aromatic amino acid,which later further degraded by pancreatic protease. pepsin
is helpful but not absolute requirement for protein digestion. after gastrectomy protein digestion can still
continue.
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pink(eosinophilic) and superficial. round plate like. these cells have abundant mitochondria and an intracellular
tubulovesicular system that allows them to secrete large quantities of gastric acid and intrinsic factor .... are
oxyntic(pale pink) round, plate like found on superficial layer of gastric glands..
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basophilic,small granular cell ..... found in deeper aspect of gastric gland, are basophlic, small, granular,
synthesize and secrete pepsinogen
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and in the presence of small amount of preexisting pepsin
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not a hormone (like all other here) but a NT which also increases gastric acid.
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into maltose (glucose-glucose disaccharide), trisaccharide maltotriose and limit dextrin.
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medium chain triglyceride can be passively diffuse into enterocytes,but they would better absorb when converted by
lingual and pancreatic lipase to monoglycerides and free fatty acids .......... lipid digestion occur in duodenum
but absorption occur in jejunum. transporter protein are not required to absorb fatty acids,cholesterol and
monoglycerides in enterocytes. inside the cell TGs and cholesteryl esters are reconstructed and combine with protein
to form chylomicrons
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deficiency of this enzyme results in diarrhea,growth retardation and hypoproteinemia
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vit C absorption at distal small bowel by active transport. B6 absorb passively in jejunum and ileum. ...............
biotin B7 and pantothenic acid B5 absorbed in small and large bowel by Na-dependent multivitamin
transporter.
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also affect fat soluble vit and calcium.
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also work as its own inhibitor. ....... serine peptidase inhibitor kazal-type 1(SPINK1), secreted by pancreatic
acinar cell, inhibits activity of trysinogen molcules that become prematuraley activatedwithin the
pancreas .................. herediatary pancreatitis is due to SPINK1 mutation
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cholecystectomy has little affect on secretion and absorption of bile but only increase enterohepatic circulation
....... 0,5 gram synthesize everyday 0.5 gram secretes every day in feces. pool is 4 grampool circulate 6-8 times ......
,bile salts can inhibit bacterial growth, downstream biliary flow helps to wash organism away from
the biliary tree, and bile secretory IgA helps prevent bacterial adherence.
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billroth 2 gastrojejunostomy affect its absorption either by decrease acidity (antral resection,no gastrin) or by
resection of duodenum or proximal jejunum,
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is a monosacharide.
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and converted to activated form by trypsin
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along with lipases
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gives green color to tissue after few days. along with biliverdin, also produce CO, ferrous iron while consuming
oxygen and electrons provided by NADH and NADPH-cytochrome P450 reductase.
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yellow pigment.
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tightly bound to albumin
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3 steps: carrier mediated passive uptake of bilirubin at the sinusoidal membrane(basolateral
side)>>>>conjugation with glucuronic acid in EPR>>>>actively biliary excretion of water soluble,nontoxic bilirubin
glucuronide
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loosely bound to albumin
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by biliverdin reductase
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and 2nd most common overall
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DES>>>because the food bolus is inefficiently propelled toward the stomach,patients typically
present with intermittentsolid/liquid dysphagia, chest pain,heart burn, and food regurgitation.
the pathogenesis of DES likely involves impaired inhibitory neurotransmission within the
esophageal myenteric plexus. ....... DES: corkscrew esophagus. disorganized,non peristaltic contractions
causes crampy pain.(unlike GERD burning pain) mimic unstable angina. cardiac workup should be done in this patient
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are shallow in the lower esophagus that sometimes diffusely involve esophagus.biopsy shows
enlarged cells with basophilic or eosinophilic intranuclear inclusion bodies..... .. both intranuclear and
cytoplasmicviral inclusions. commonly in the distal esophagus.
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can be nonprogressive intermittent type
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pill induced esophagitis: tetracycline, potassium chloride, bisphosphates. ................................. oral ulcer can be
associated with>>pemphigus vulgaris, paraneoplastic pemphigus, bechet disease and crohns
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on erythematous base.
yeast cell and pseudohyphae penetrate the mucosa
candida MCC of infectious esophagitis.
light microscopy demonstrates pseudohyphae and budding spores embedded in necrotic debris
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patietns can have extraesophageal symptoms (eg nocturnal cough, hoarsness) in the absence of heartburn. (silent
GERD) .......... GERD MCC of esophagitis. ................ GERD most commonly presents with symptoms of heartburn,
regurgitation and dysphagia (difficulty swallowing without pain), but cardiac like chest pain, globus (sensation of lump
in the thraot) and odynophagia can also occur, the presence of odynophagia usually indicated the progression to
erosive esophagitis and the formation of an ulcer, which can be confirmed by upper esndoscopy......... esophageal
stricture can also occur and usually produces dysphagia to solid foods and intermittent esophageal obstruction.
barrett metaplasia is another complication of chronic GERD, but the produce no symptoms untill a malignant
transformation has occured and characteristically presents with weight loss and dysphagia.
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and ts repetitive will cause metabolic alkalosis ....... can also be occur by straining during defecation or heavy
lifting,seizure,blunt abdominal trauma and upper GI endoscopy
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systemic sclerosis may involve the lower two-third of the esophagus, resulting in smooth
muscles atrophy and gut wall fibrosis. patient can develop dysphagia with acid
reflux,however, manometry typically shows absent peristaltic waves with decreased lower
esophageal sphincter tone.
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almost never life threatening,10% of UGI bleeding are due to this
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longitudinal tear ................ hiatal hernias are found in about half of patients and are considered a strong
predisposing factor.ethanol abuse is a common predisposing factor.
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eosinophilic intranuclear inclusions(cowdery type A) in multinuclear squamous cells at the margin of ulcer
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reflux esophagitis is histologically characterized by elongation of the lamina propia papillae, basal cell
hypertrophy and scattered eosinophils and neutrophil. ............................. diagnosis require endoscopic and
microscopic studies
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cricophryngeus dysfunction results from a failure of cricopharyngeus to relax during swallowing and causes a
choking and or ''food sticking'' sensation and pain with swallowing. a video fluoroscopic swallowing study is
used for diagnoses. .............. after the content of the oral cavity are collected on the tongue and propelled into the
pharynx. involuntary contraction of the pharyngeal muscle pushes food into the esophagus. cricopharyngeus
muscle contract behind the food bolus, initiating the peristalsis
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causes intramural,parasympathetic denervation of smooth muscles
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eosinophilic esophagitis typically presents in atopic patients with solid food dysphagia and/or food
impaction. findings on esophageal manometry are nonspecific. ........ histologically by nuemrous
superficially located intraepithelial eosinophils, which can help differentiate if from reflux esophagitis.
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generally poor prognosis as many patients present with incurable locally advance or metastatic disease. .....
chronic GI blood loss is frequently seen in these patients causing iron deficiency anemia... ...... esophageal
leiomyoma are most commonbenign tumor of esophagus.is is slow grwoing. fascicles of spindle cell with variable
amount of fibrosis on light microscopy.
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SCC>>>solid nests of neoplastic SC with abundant eosinophilic cytoplasm and distinct borders. areas of
keratinization identifies as keratin pearls and presence of intercellular bridges is also characteristic of squamous
differentiation. ..... SCC>>flattened polyhedral or ovoid epithelial cells with eosinophlic cytoplasm, keratin nests or
pearls within or between cells, and internuclear bridgning. large hyperchromatic cells with bizzare nuclei and
atypical mitoses are commonly seen.
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ulcerated/exophitic lesion in the lower one-third of the esophagus.
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alcohol and cigarettes most common cause in US for squamous, .... iran and russia>>>hot food and
beverages>>SCC ...... cheweing of betel nuts and consumption of N-nitroso containing food (squamous) common
in ASIA.
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plaque-like thickening of the mucosa that may become ulcerated.
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majorly squamous
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histology typically shows tongue-like projections of gastric columnar epitheliumextending from the proximal
esophagus to the gastroesophageal junction .
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erosive type>>>>limited to muscularis mucosa. gastric pits or foveolae (which are invaginations of gastric
mucosal surface that lead to the gastric mucosal glands) and gastric glands (located in the lamina propia of
gastric mucosa) are affected in this .... cause upper gastrointestinal hemorrhage that can lead to melena. symptoms
subside within few days with full re-epithialization after removing offending agent .........
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reduces mucin and bicarbonate secretion, gastric epthelial cell proliferation, and gastric perfusion. also
increases gastric acid secretion and can penetrate the cells of the gastric mucosa, causing direct cell damage.
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particularly prone to perforation. occur in esophagus,stomach,duodenum
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histologically show loss of parietal cell with lymphocytic and plasma cell infiltration. CD4+T cell mediated parietal
cell destruction.
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exogenous secretin differentiate b/w ZES and other causes of hypergastrinemia (eg atrophic gastritis/fundus,body
type). in ZES>>>>gstrin increases after secretin test in atrophic gastritis(fundus/body)>>>gastrin decreases after
secretin test
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undiagnosed or untreated, gastric carcinoma will eventually extend through the gastric wall to serosa. involovemnet
of regional and distant lymph node is common. with metastasis to virchows node frequently the first clininal
manifestation of occult gastric cancer. ....... important factor that influence survival: 1 depth of invasion through the
gastric wall 2 regional lymph node involvement. ......... blood group A association. Arise from precursor lesion.
........ signet-ring carcinoma.Cells often contain abundant mucin droplets that push the nucleus to one side
and lead to the characteristic appearance of a signet ring. diffuse involvement of the stomach wall (due to
loss of the cell adhesion protein E-cadherin). They have a plaquelike appearance, are ill-defined and
often infiltrate large areas of the stomach wall, causing a “leather-bottle stomach” (linitis plastica).
intestinal-type adenocarcinoma of the stomach closely resemble colon cancers, showing well-formed
glands that consist if columnar or cuboidal cells. they tend to grow as nodular, polypoid, and well-
demarcated masses that rapidly expand within the gastric lumen(choice D). these lesions often
ulcerate/bleed and must be differentiated from peptic gastric uclers by biopsy. the most important
factors that influence survival rate with gastric adenocarcinoma are the depth of invasion through the
gastric wall and regional lymph node involvement.
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seen with diffuse type ............. metastatic spread of adenocarcinoma to one or both ovaries may occur in
associattion with primary cancers of the stomach, breast, pancreas and gallbladder. but most commonlt with
stomach
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have elevated risk of duodenal ulcer formation
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seen with intestinal type
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dnt form gland.
not projected into stomach lumen but infiltrate stomach wall
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TGF-alpha is a potent stimulator of epithelial growth and is secreted by carcinomas, macrophages and epithelial
cells. is mentrier disease overprodcution of TGF-alpha rsulting in mucosal cell hyperplasia with gastric fold
enlargement. however this condition causes hypoplasia of parietal/chief cells, resulting in glandular atrophy with
reduced gastric acid secretion........... cituzimab (monoclonal antibody against EGFR) is used for
treatment.. in this disease there is overexpression of TGFa .......... Rugal thickening with acid
hypersecretion is a characteristic finding in the stomach of a patient with Zollinger-Ellison syndrome.
Rugal hypertrophy with parietal cell atrophy and decreased acid secretion occurs with Menetrier
disease. ..... MC Gram (-) rod, Urease (+) is virtually ALWAYS associated with those gastritis & MC
thickened gastric fold. Cases 3/4 with gastritis.. so thickened gastric fold is not characteristic
of menetrier disease
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antrum type typically do not have elevated gastrin level. fumdus/body type has increase gastrin level
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atrophic gastritis is commonly associated with chronic gastritis>>>caused by H.pylori, pernicious anemia, radiation
and granulomatous conditions ............. long standing inflammation of the gastric mucosa can lead to diffuse
gland atrophy and intestinal metaplasia.
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in proximal duodenum>>>>>localized ischemia
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surgical stress(ulcers due to impaired oxygenation), smoking, alcoholics physiolic stress>>>patient often has
multiple small (<1cm) lesions ranging from superficial erosions to full thickness ulcers. ulcers may perforate or
bleed
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granulomatous gastritis: is most often idiopathic but can be associated with crohn disease, sarcoidosis, and
mycobacterium. charaterized by intramucosal epitheloid granulomas that cause narrowing of antrum secondary to
transmral inflammation
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non-invasive bacteria found atatched to the gastric mucosa or deep in the mucus
layer overlying the gastric epithelium.. are susceptible to gastric acidity but are
protected by the mucus layer and endogenous urease production.
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2nd MCC of gastric ulcer after H pylori
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ulcer formation due to increase acid production.main mechanism
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The splenic artery may be
subject to erosion by a
penetrating ulcer of the
posterior wall of the stomach
into the lesser sac.
shelf
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derived from C3-C5 nerve root>>>delivers motor innervation to the diaphragm and carries pain
fibers from the diphragmatic and mediastinal pleura.
sensory innervation of the remainder of the pleura (costal and cervical) is accomplished by
intercostal nerves and is typically felt closer to the source of pain.
the visceral pleura does not carry pain fibers.
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chronic antral inflamamtion(antral gastrotis) leads to a decrease in the number of
somatostatin-producing cells (delta cells)>>>>very low pH that is not adequately
neutralized by duodenal bicarbonate production leading to duodenal ulceraton and
duodenal gastric metaplasia ............ H-pylori can onlycolonize area of gastric
metaplasia
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ulcer results from local destruction of mucosal layer and subsequent local inflammation. decrease or normal
level of gastric acid. normal level is sufficient to cause gastric ulcerarion when the mucosal layer is degraded
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most gastric ulcer are usually located at the transitional zone between the acid-secreting epithelium of
the gastric corpus and gastrin-producing epithelium of the antrum. The predilection of ulcers for the
transitional zone may be due to the microenviornment having an optimal pH of Helicobacter
pylori proliferation, or perhaps non-optimal local conditions induce the expression of
inflammatory bacterial stress proteins
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overgrowth of bacteria causes deconjugation of bile acid by removing glycine and taurine making it a less
soluble,causing lipid malabsorption
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because the concentraiton of gluten is high there
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an enzyme that participates in metabolism of gluten.
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also called beta-galactosidase(lactase-phlorizin hydrolase)
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stool osmotic gap is increased.normally it is <50 and composed of electrolytes(Na,K) and some colonic
fermentation products abnormally it is >100 and composed mainly of poor absorbable substances.
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caucasian
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done sudan stool test for screening and for confirmaiton do quntitative test for fat(more than 7g/day fat)
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org only proliferate within macrophages of these tissue, preovoking no inflammatory response as a
consequence. Distended macrophages with rod shaed bacilli and PAS + and diastase resistant garnules(which
consist of lysosomes and partially digested bacteria)............. AB therapy is usually successful ........both
whipple and tropical sprue can have villous atrophy
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actinomycete(bacillus)
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done with 50 g lactose and check at 0,60 and 120 mins
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histologic changes and symptoms disappear after gluten free diet ......................... manisfestated as delayed
puberty and growth failure in children, difficulty gaining weight and anemia in adults ................ IgA anti tissue
transglutaminase and IgA endomysial antobody are very sensitive and specific for the diagnoses. small bowel
biopsy is confrimatory... .......... anti-reticulin antibodies are also found
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IgA antibody to gliadin (a mixture of polypeptide extracted from gluten)........ is a typical finidng in these patietns
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barley and rye. oat and rice dnt contain
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These antibodies appear to cause clinical disease by cross reacting with epidermal
transglutaminase. DH is strongly associated with celiac disease, A gluten-free diet tends to
improve both the enteropathy and dermatitis. ........ appear bilaterally and symmetrically on
the extensor surfaces (e.g, elbow, knees) upper back and buttocks. Histologically dermatitis
herpetiformis is characterized by microabscesses containing fibrin and neutrophils at the
dermal papillar tips. The overlying basal cells become vacuolated, and coalescing blisters
form at the tips of the involved papillae. ........ on extensor surfaces, knees elbows, buttock and back.
symmetrically distributed and highly pruritic
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intestinal serosa looks dull gray.edematous and granular. the mesentery of involved segment may be edematous
or fibrotic
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DTHR and granuloma formation. secrete IL-2 and INF-g to stimulate macrophages which secrete TNF-alpha
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perianal disease other than fistulas is also common and may include skin tags and fissures .........
gallstone>>due to ileum involvement .impaired bile acid absorption.bile acid wasting occur..cholesterol/bile acid
ratio INC cholesterol deposits causes gallstones
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canker sore apart from crohn seen in physical trauma,stress,food alergies,citrus fruits,B12
deficiency.
but exact etiology is unknown
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duration and extent of colitis are most important risk factors.
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IL-4,5,6,10
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granular mucosa.. ........... pseudopolyps>>>>>>isolated areas of regenerative mucosa
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due to neuromuscular degeneration of intestinal wall.(((inflammatory mediators, bacterial products and increased
NO, which contribute to colonic smooth muscle paralysis))) associated with intestinal perforation. diagnose with
plain X ray film. barium enema and colonoscopy are contraindicated.. toxic megacolon can akso associated with
clostridium difficle infection and other forms of infectious colitis. ................ Toxic megacolon is a potentially life-
threatening complication of both Crohn’s disease and ulcerative colitis. it occurs due to neuromuscular
degenration of the intestinal wall and its rapid dilation.Abdominal pain and distention are common
symptoms. Toxic megacolon is associated with bowel perforation, but not with intestinal fistulas.
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main symptom versus abdominal pain of crohn. also have tenesmus and abdominal pain. ............. bloody
diarrhea, with or without abdominal pain, is the hallmark of ulcerative colitis. (In Crohn’s
disease, there may also be bloody diarrhea, but abdominal pain is virtually always present).
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positive for occult blood test.grossly bloody stool is less commonunless the colon is involved. ...............
typcially present with prolonged diarrhea(SECRETORY TYPE) and abdominal pain.. constitutional symptoms
(eg low grade fever, fatigue) malabsorption and weight loss are also common.
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its a common manifestation.but not as common as abdominal pain
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in crohn patient typically present insidiously (over the course of years) with bouts of crampy abdominal pain. ........
affected area appears hyperemic and edematous. ......... Transmural inflammation explains the two most
common complications of Crohn’ disease: strictures and fistulas. Chronic inflammation causes edema
and fibrosis, Inflammation and necrosis of the intestinal wall causes ulcer formation.
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NOD2 mutation>>>impair innate immune response>>>>exaggerated adaptive
immune response. ....... numerous genes (including those in the HLA family) have
been implicated in this disorder, but mutation in the NOD2 gene have shown a
particularly strong association with crohn disease. NOD2 is exreressed in epitheial
cells and macrophages and helps resulate innate immunity. it encodes an
intracellular microbial receptor that recognizes bacterilal lipopolysaccharides
and subsequently activates the NF kb pathway. NF kb is a proimflammatory
transcription factor that increases cytokine production. in crohn disease. mutation in
NOD2 RESULT DECREASED ACTIVITY OF nf KB, which impairs the innate
immune response of the intestinal mucosa (eg antimicrobial peptide synthesis
and mucin secretion). the loss of this natural barrier defense allows luminal
bacteria to penetrate submucosal tissue, causing an exaggerated respnse by the
adaptove immune system that result in chronic gastrointestinal inflammation. .........
multifactorial inheretance. NOD 2. NF Kappa B
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nbme>>2,1,16>>>histologic finding in acute appendicitis is neutrophilic infiltrate of the muscularis.
dont choose lymphoid hyperplasia which is an etiology in a children.
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depending on its orientation of appendix ther ecan be additional clinical findings.
an inflammed appendix lying agaisnt the right obturator internus muscle can
cause right lower quadrant pain with internal rotation of the right hip. if the
inflammed appendix lies against the right psoas muscle, there can be pain with
hip extension. the patient with retrocecal appendix may not have significant
right lower quadrant tenderness, as the infallamed appendix does not contact the
anterior parietal peritoneum and the cecum (distended with gas) acts as a cushion
that blocks the examiners hand
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through areas of focal weakness in the muscularisexterna.
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most common presentation. painless. It is due to disruption of arterioles adjacent to diverticulum
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pulsion
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due to excessive mucus production which causes venous drainage obstruction resulting ischemia,necrosis and
ultimately perforation.
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visceral pain (dull, non-localized) parietal pain (severe, well localized) visceral pain
is most often due to luminal distension and stretching of the smooth muscle and
is carried by general visceral afferent .. patient can also develop nausea, vomitig or
sweating due to autonomoic stimulaiton. the afferent pain for the appendix,
proximal colon and overlying visceral peritoneum cross through the superior
mesenteric plexus and enter the spinal cord at the T10 level to prodcue vague,
referred pain at the umbilicus. as the appendix becom emore inflammaed, it
irritates the parietal peritoneum and abdominal wall and cause a more sever
somatic pain that shift from the umbilical region to McBurney point.the abdominal
wall becomes very sensitive to gentla pressure or sudden release of deep pressure
(rebound tenderness) ........ cecum is innevated by the superiior mesenteric
plexus and has only visceral sensation
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occur in all age group but more commin in 6-10 years old children.. ..... bacterial infection plays role in
pathogenesis but is not an initial event .......... also caused by foreign particle.nematode and
carcinoid......................
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nbme>>>5,3,33
10 year old boy with chronic iron deficiency anemia, test of stool for occult blood is positive.barium
enema with air contrast shows no abnormalities.upper endoscopic normal.condition improves with
H2 receptor antagonist.most likely cause is >>>>>meckel, not arterovenous malformation.
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cecum is found in right upper quadrant, fixed with fibrous bands (Ladds band) to the second portion of
duodenum. the entire midgut is fixed with SMA>>>results in two condition 1, intestinal obstruction ( bilious
vomiting in 1st day due to adhesion bands) 2, midgut volvulus ( impaired perfusion can cause gangrene and
perforation)
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upper dysphagia
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can present only with painless type bleeding
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peptic ulceration is implicated in the development of lower abdominal bleeding due to meckel diverticulum ............
most common and significant because gastric epithelium produces acid that can
cause ulceration of adjacent tissues and lower GI bleeding
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hirschprung disease. neural crest cell migrate to the intestinal wall very early during embryonic development(these
are precursor of ganglion cells of intestinal wall plexi), they move caudally along the vagal nerve fibers. they are
present in the wall of the proximal colon at 8th week of gestation and in the rectum by the 12th weeks. the rectum
is always involved in hirschprung disease.the bowel is filled with stool but the rectum is empty, the tone of anal
sphincter is usually increased. sigmoid colon is involved in 75% of cases, the rectum and anus however are
always involved.
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food aspiration may lead to pneumonia
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retention cysts from due to accumulation of trapped secretios following obstruction
of a glands duct. chronic rhinosinusutis frequently causes mucus retention cysts
in the maxillary sinus
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these are an example of ectopy (heterotopy)
can have other type also like colonic, jejunal, duodenal and endometrial
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most common ectopic tissue.2nd most common is pancreatic.
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traction diverticulum is true,occur due to inflammation and subsequent scarring.
occur in mid esophagus.after mediastinal lymphadenitis( tuberculosis,fungal infection)
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nbme>>>5,4,41
persistance of remnant of proximal portion of yolk sac.
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weak point is in posterior hypopharynx (killian triangle) this disease is due to cricopharyngeal dysfunction,which
doesnt relax
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can be palpated as a lateral neck mass
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the distal sigmoid lies between the areas supplied by IMA and hypogastric arteries.
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nbme, 3,4,38 tUBULAR ADENOMA IS MOST COMMON NEOPLASTIC POLYP. STALKED POLYP....LOOKS LIKE
A MUSHROOM
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other 2 non-neoplastic polyps are
inflammatory>>>>>seen in UC and crohn>>>composed of regenerative intestinal mucosa.
lymphoid>>>seen in children>>consist of intestinal mucosa infiltrated with lymphocytes
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these polyps can cause bleeding and intussuseption.
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smaller and pedunculated
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the maliganant potential of an adenomatous polyp is partially determined by the degree of
dysplasia.
mildly dysplastic cells are elongated and hyperchromatic and show loss of mucin from the
cytoplasm.
with continued proliferation, dysplastic cells display increased variation in shape/size
(pleomorphis) and the nuclei become enlarged and deeply stained (hyperchromic). other findings
include an increase in number/size of nucleoli, nuclear-to-cytoplasmic ratio, and number of mitotic
figures.
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also associated with increased risk of adrenal adenomas and thyroid cancer
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also in marfan syndrome
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5q21
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these 3 features determine malognant potential of adenomatous polyps: 1, degree of dysplasia. 2, histology: villous
more than tubular 3, size: >4 cm has more malignant potential than <1 cm mostly benign ................. adnomas <1 cm
ar)unlikely to undergo mailgnanat transformation, while those >4cm are very likely (40%) to progress to
adenocarcinoma.
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has fibrovascular stalk with tubular glnads and villous components.the glands are lined with dysplastic columnar
epithailial cells
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sometime have valvety or cauliflower like projections, generally are larger and sessile. these polyps cause
MUCOUS secreting diarrhea(secretory diarrhea), bleeding and partial obsturction.
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composed of mucosal glands, smooth muscle and connective tissue.
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composed of well differentiated mucosal cell that form glands and crypts.
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the duration and extent of colitis are the most significant risk factors .......... colitis
associated carcinoma have following features: 1, affect younger patients 2,
progress from flat and non-polypoid dysplaisa 3, histologically appear mucinos
and/or have signet ring morphology 4, develop early p53 mutations and late APC
gene mutations, opposite that of sporadic 5, be distributes with in proximal colon
(especially with Crohns disease or concurrent primary sclerosing cholangitis) 6,
be multifocal in nature 7, tend to be of higher grade, and are more likely to be
anaplastic.
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due to occult blood
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liver and lung are common site of metastasis. ............................. lymph node metastasis typically occur sequentially
through the epicolic/paracolic, intermediate and paraaortic lymph node. later in the disease course spread via the
thoracic duct to the supraclavicular lymph node (virchow node) ................ if tumor conifned to the mucosa the
patient has 90%+ chance of 5-year suvival. if it involves the muscular layer, 5 year survival rate is 70-80%. lymph
node involvement and distant metastasis have poor prognosis
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distal colon cancer>> "napkin ring" constriction of the bowel, with heaped-up
edges and an ulcerated central region.
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glycoprotein involved in cell adhesion.
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are smaller one.
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are larger one
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adnocarcinoma arise from both,mucus secreting and absorptive epthelium
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inherited mutation in one gene out of four responsible for mismatch repair.(MLH1, MSH2, MSH6, and PMS2) inherit
a mutation in one allele of the gene and 2nd mutation of other allele occur during adult life and disease
manifests ....... lynch 1 is characterized by predisposition to colon adenocarcinoma. lynch 2 is characterized by
predisposition to colon cancers and increased incidence of extraintestinal cancers
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severe cirrhosis causes high-output heart failure (peripheral edema/ascites, bilateral bibasilar
crackles,jugular venoous distension, and hepatomegaly from venous congestion) due to splanchnic
vasodilation and intrahepatic or mesenteric arteriovenous shunts.
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results in accumulation of genetic errors
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on CH 5. found in most cases of sporadic colon cancer and in all cases of familial polyposis syndrome .............. APC
tumor suppressor ggene is reponsible for regulating cell growth/adhesion. found in all patients with familial
adenomatous polysposis
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regulates apoptosis
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due to ammonia and dimethyl sulfide
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in alcoholic liver disease SHBG also increases so it bind to free testosterone and thus ratio of free testosterone/
estrogen decreases ................... due to hyperestogenism their is also decreased body hair. ......... increase
estrogen >>>androstenedione is not catabolized(in liver) so estradiol accumulate. also have increased adrenal
production of andreostenedione with aromatization to estrone and eventual conversion to estradiol. estradiol
induces SHBG production (primarily in the liver but also in uterus and testes) which results in increased
testosterone binding and a decreased free testosterone/estrogen ratio.
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in hepatorenal syndrome>>>>the renal involvement is due to renal vasoconstriction.
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alcohol-associated hepatic inury evolves through the stages of alcoholic steatosis (reversible),
alcoholic hepatitis (reversible), and alcoholic cirrhosis (irreversible).
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hypoalbuminemia
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are subcutaneous lesion.
blanch with pressure and refill centrifugally upon release.
they are dilated cutaneous arterioles that present as a central papule with radiating blanching
capillaries.the number and size of these skin lesions generally correlate with the severity of liver
disease.
........................
acquired spider angiomata may also occur with ither hyperestrogenic states (eg pregnancy)
possibly due to estrogen effects on arteiorlar dilation.
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it is defined as reversible decline in neurological function..
is due to increased inhibitory neurotansmission (GABA) and decreased excitatory
neurotansmission (glutamate and acetylcholine)
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that causes unregulated cell growth and responsible for increase in size
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K-RAS proto-oncogene and DCC gene mutations lead to unregulated cell proliferation and avoidance of
apoptosis, respectively. they are usually onserved in larger adenomas (>1 cm) or carcinomas. ............... p53 are
found in most colon carcinomas but rarely adenomas.
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Factor VII, part of the extrinsic pathway, has the shortest half-life of all coagulation factors.PT
assesses the extrinsic and common pathways of coagulation and is the first to become abnormal in liver
disease. ............. hypoalbuminemia, elevated bilirubin levels, and prolonged PT are signs of
inadequate liver function (eg, liver failure) and indicate a poor prognosis in cirrhotic patients.
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encodes for a protein that regulates cell cycle by stimulating and inhibiting it as necessary.
mutation of K ras causes it to become oncogene,which encodes for a protein that has lost its
ability to inhibit the cell cycle, but can still stimulate it .................. Mutated ras inhibits the
activity of GTPase activating protein. This prolongs the activated state of ras, resulting in
increased growth signals.
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It is especially pronounced in viral-infected cells and causes mitochondrial dysfunction. The two
components of Reye’s syndrome include: 1, Hepatic dysfunction manifests with vomiting and
hepatomegaly, but jaundice is rare. Liver function tests reveal increased levels of ALT, AST,
ammonia and bilirubin and a prolonged PT and PTT. Light microscopy of a liver biopsy shows
microvesicular steatosis, the presence of small fat vacuoles in the cytoplasm of hepatocytes (
Choice C). No necrosis or inflammation is present in the liver. Electron microscopy findings
include swelling, a decreased number of mitochondria and glycogen depletion. 2,
encephalopathy.
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differentiation b/w liver and bone source can be done by electrophoresis, specific monoclonal
antibodies,
heat denaturation causes bone specific to denature (heat>bone=boil)
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frequently after upper respiratory infection, influenza, measles, varicella or another viral disease.
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helps convert gluthatione to glutamate
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increase in biliary disease,pregnancy(placenta),bone disease(osteomalacia), malignancy(CML) and total
parenteral nutrition(intestine)
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micro in reye syndrome .......................... fatty change (steatosis) occurs in reversible
hypoxic, toxic, or metabolic injury (eg. protein malnutrition, diabetes, obesity). it affects cells
involved in and dependent on fat metabolism. the most common cause of hepatic steatosis is
alcohol abuse.
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macrocytosis is specific for alcoholic liver disease, it can occur in the absence of anemia,B12 and folate def
............. DIT histologically in alcoholic hepatitis we see 1, fatty infiltration (although it is not specific, we also see in
non-alocholic fatty liver disease and steatohepatitis. 2, mallory bodies. (also non speific, see in alcoholic
cirrhosis,wilson,PBC, hepatocellular carcinoma but most often in alcholic liver disease. 3, necrosis and
hepatocyte swelling. ............
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also have fibrosis
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sedative use and metabolic dearrangement (eg hypokalemia)
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the PPAR famiky apperars to play a significant role in the pathogenesis of
metabolic syndrome...
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altered mental status: is due to impaired neurotransmittor release, astrocyte dysfunction, neuroinflammation
and/or edema
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ascitis due to mechanical compromise to portal vein and also by vasoactive mechanism which causes dilation of
splanchnic arteries and futher constricting arteries intrahepatically. hepatorenal syndrome is the cause of
activation of RAA system........ Thrombocytopenia in alcoholism develops due to both direct toxic
effect of alcohol on the bone marrow and hypersplenism with splenic sequestration of platelets
...... first line treatment is furosemide and spironolactone
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nbme,11,1,19 In alcohol consumption AST and ALT both are high but AST is 2 times higher than ALT. Nonalcoholic
steatohepatitis or NASH is a common, often “silent” liver disease. It resembles alcoholic liver disease, but occurs in
people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and
damage. Most people with NASH feel well and are not aware that they have a liver problem. Diagnosis NASH is
usually first suspected in a person who is found to have elevations in liver tests that are included in routine blood test
panels, such as alanine aminotransferase (ALT) or aspartate aminotransferase (AST). When further evaluation shows
no apparent reason for liver disease (such as medications, viral hepatitis, or excessive use of alcohol) and when x
rays or imaging studies of the liver show fat, NASH is suspected. The only means of proving a diagnosis of NASH
and separating it from simple fatty liver is a liver biopsy. For a liver biopsy, a needle is inserted through the skin
to remove a small piece of the liver. NASH is diagnosed when examination of the tissue with a microscope shows fat
along with inflammation and damage to liver cells. If the tissue shows fat without inflammation and damage,
simple fatty liver or NAFLD is diagnosed
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common in china(asia) and africa most common and severe type is B1. classic G:C>>>T:A transversion on codon
249>>>causing mutation in P53. aspergillus flavus and parasiticus.
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increased level present in 50-75% of patient................... hep C also have slightly elevatyed alpha-feto protein, but
continuous rise should alert more towards the hepatoellular carcinoma.
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hepatoblastoma is the most common liver neoplasm of children and is associated with familial
adenomatous polyposis and beckwith-wiedmann syndormes.
this neolasm is usually fatal within a few years if not surgically resected.
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dilated vascular spaces with thin walled endothelial cells.>>> soft blue compressible masses upto few centimeters
in size.>>>may appear on skin, mucosa, visceras and deep tissues. when appear on skin most frequently based in
the dermis. cavernous hemangioma of brain and visceras are associated with VHL syndrome .............. these
benign tumor are though to be congenital malformations that enlarge by ectaisa , not hyperplasia or
hypertrophy.. hemongiomas may occur in singly or in multiples and are well circumscribed masses of spongy
consistency, typically measuring less than 5cm in width.. microscopically consist of cavernous, blood filled vascular
spaces of variable size lined by single epithelial layer, collagenous scar or fibrous nodules may be seen in
association with thrombosis. most are asymtopatic, although some will complain of abdominal pain and right
upper quadrant fullness.. prognosis is excellent with surgical resection an option for those who are
symptomatic or who have compression of adjacent structure
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most common benign liver tumor
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cells express CD 31, which is PECAM1 (pletelet endothelial cell adhesion molecule), PECAM is a member of the
immunoglobulin family of proteins, is expressed on the surface of endothelial cells and functions in leukocyte
migration through the endothelium.
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20 times more common than hepatocelluar caricnoma, liver is the 2nd most
common site of metatstatic spread (after the lymph nodes) because of its large
size, dual blood supply, high perfusion rate, and the filtration functio of kupffer
cells.
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liver disease in first 2 decades of life present with hepatomegaly or heptasplenomegaly, cholestasis and elevation of
liver enzymes. neonatal hepatitis with cholestatic janundice in common. attack of hepatitis in childhood and
adolescense may appear to completely resolve, or may become chronic and silently progressive. it is not
uncommone for patients to be asymtopmatic untill they have developed end-stage liver disease. .........
diagnoses of disease is established by measurement of the serum A1AT level. followed by confirmatory genetic
testing. the test is infdicated in all patietns with premature onset (<50 years) of chronic bonchitis, emphysema and
dyspnea as well as in nonsmokers suffering from COPD. a history of neonatal hepatitis shold highten suspicion
for A1AT deficiency.............. 75-80% of individual eventually develop severe panacinar emphysema. liver disease
occur in 10-15% of patients and is of greater concern during the first 2 decades of life because pulmonary
dysfunction takes decades to develop........... smoking plays a synergistic role in the disease process by
permanently inactivating A1AT through oxidation of a crucial methionine residue. thus smoker with A1AT
deficiency tend to develop dyspnea at a median age of 36 years versus a median age of 51 years in nonsmokers
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intracellular granules representing globules of unsecreted A1AT are seen within the periportal
hepatocytes of afflicted individuals.
these globules also resist digestion by diastase.
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an autosomal codominant disorder.
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Type: Highlight Author: LENOVO Subject: Highlight Date: 6/25/2017
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liver becomes grossly, reddish purple and develops a tense capsule.
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typically have mutliple nodules through out the liver that may replace more than
80% of the hepatic parenchyma, often resulting in marked hepatomegaly(non
tender) the nodules frequently outgrow their vascular supply and become centrally
necrotic and umbilicated. even with significant metastatic involvement, patient
may have no clinial or laboraotry signs suggestive of hepatic insuffiiany. once
majority of liver parechya is destrpyed or the major bile ducts become obstrycted
with tumor, patient tend to present with jaundice or abnormla hepatic enzyme.
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metastic initially nontender
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2nd most common cause of death in this population. ............... liver involvement causes cirrhosis and
hepatocellular carcinoma.
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inhibit several different proteolytic enzymes (including neutrophil elastase). most individual are homozygous for the
Z allele, which causes decreased secretion of A1AT secondary to abnormal protein folding
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and/or the intra or suprahepatic inferior vena cava
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arsenic (in insecticides), vinyl chloride (in plastic industry), thorotrast (a former radioactive contrast medium)
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predominantly in young or middle aged women who have a lengthy history of OCP. these are typically identified
when pateint complain of abdominal oain in the epigastrium or right upper quadrant, when imaging is obtained
for unreleated issues, or when an individual suddenly collapses because of rupture and intrabdominal bleeding
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hepatic abscess in underdeveloped countries>>>>parasitic infection (eg entamoeba, echinococcus) hepatic
abscess in developed countries>>>bacterial infection which depends on the route of infection. traumatic cause has
mixed aerobic anaerobic etiology, staphylococcus has hematological spread, other causes are gram negative
bacilli
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cholangiocarcinoma is a rare maligannacy that arises form the intra and
extrahepatic ble ducts. intrahepatic cholangiocarcinma appears grossly as a
treelike mass that grows along the biliarysystem, typically resulting in extensive
intrahepatic metastasis. risk factors include primary sclerosing cholangitis,
fibropolycystic liver disease, and infection with liver flukes in endemic areas.
the prognosis is very pure.
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can present unifocally, multifocally or as a diffusely infiltrative cancer.
.................. individuals with stable, compensated cirrhosis who suddenly decompensate without appaaretn
reason should be carefully evaluated for hepatocellular carcinoma, especially when serum AFP levels are also
elevated. ............... serum AFP levels do not correlate well with the size, stage, or prognosis of
HCC chronic liver disease (eg, viral hepatitis). the sensitivity of AFP in detecting HCC ranges from
41- 65%, whole its specificity ranges from 80-94% A rise in serum AFP to level exceeding 500
mcg/L in a high-risk patient is considered diagnostic of HCC sudden surge in AFP above their
baselines
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less common, also cause anemia of chronic disease (TIBC low). so patient can be anemic or polycythemic
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HCC is strongly associated with hep B and is often preceded by HBV-induced cirrhosis. it is due to integration of
viral DNA in to host genome,>>>>>causes increase synthesis of insulin-like growth factor II and receptor for
insulin-like growth factor I, thereby stimulating cell proliferation. another effect is suppression of p53 tumor
suppressor/cell cycle regulatory gene in host cell. chronic inflammation and regeneration also facilitates
accumulation of mutations.
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biliary atresia: extrahepatic biliary atresia is a congenital obstruction of extrahepatic bile ducts. by the 3rd week of
life, there is total obstruction. affected children will have the characteristic cholestatic picture of acholic (light) stool
and dark urine. on physical examination there is a firm, enlarged liver. laboratory findings include increased levels
of direct bilirubin, alkaline phosphatase and gamma-glutamyl transferase. liver biopsy is usually diagnostic:
showing 1, marked intrahepatic bile ductule proliferation 2, portal tract edema and fibrosis 3, parechymal
cholestasis. if biliary drainage is not restored surgically, bile stasis will cause development of biliary cirrhosis
by 6 months of life.
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grossly, the liver appears black due to impaired excretion of epinephrine metabolites that
accumulate within lysosomes
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febrile illness, physical exertion
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overgrowth of bacteria(anaerobes and staphylococcus aureus) causes deconjugation of bile acid by removing
glycine and taurine making it a less soluble,causing lipid malabsorption
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AR, absence of MRP2 (multi drug resistance protein 2) used for bile excretion to bile canaliculi
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normal bilirubin level. 0.2-1 mg/dl
direct one <0.2
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micronodular>>>>pigement cirrhosis with hepatomegaly............. mildly elevated liver fucntion tests
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eventually progressive hepatic damage secondary to the obstruction in intraheaptic bile flow is observed.upstream
portal tracts undergo bile ductular proliferation, inflammation and necrosis of adjacent parenchyma. generalized
cholestasis develops, and the liver gradually grossly stained green and uniformly micronodular. ultimately the
end-stage liver findings in PBC cannot be distinguised from those in seconndary biliary cieehosis or chronic
hepatitis. ............. dense portal track infiltrate of macrophages, lymphocytes, plasma cells and eosinophils that
results granulomatous destruction of intrahepatic,interlobular bile ducts (florid duct lesion)>>>>>>>>>>>.similarity
of these finding also seen in graft versus host disease.
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exocrine pancreatic function is usually preserved inpatients with hemochromatosis. Therefore,
fat malabsorption and osteoporosis (due to decreased vitamin D) would not typically be
seen.
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ethanol (also cause redistribution of bosy iron), Vit c and citric acid (of inorganic iron) increase intestinal
absorption of iron>>so exacerbate hemochromatosis
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missense mutation in the HFE gene (eg, C282Y), which is most common found in Caucasian.
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and is insidious in onset. ............ pruritis (usually worse at night) is normally the first symptoms. fatigue is also
often reportedas the disease progresses hepatosplenomegaly and cholestasis (eg jaundice, pale stool and dark
urine) can develop. reduce bile flow result in malabsorption .reduced biliary cholesterol excretion may also
promote hypercholesterolemia with xanthemasma formation. late manifestation include cirrhosis and portal
hypertension. ......... chronic cholestatic processes including obstrutive biliary lesions ans primary biliary
cirrhosis result in subsequent hypercholesterolemia, leading to the formation of xanthelasma. correction of
underlying lipid defect can lead to slow resolution of these lesions. ....... abnormalities on laboratory testing ae
consistent with cholestasis and include elevated ALK phosphatase and cholesterol, as well as elevated IgM.
ALT and AST are normal ........... also has kayser fleisher ring
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likely diagnose in a patient with youngar than 30 years old with unexplained chronic hepatitis. ................ causes
cystic degeneration of putamen.............. many progressive neurologic diseases may be associated with
cystic degeneration of the putomen, but Wilson’s disease is the most likely
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Inactivation of the HFE protein results in decreased hepcidin synthesis by hepatocytes and
increased DMT1 expression by enterocytes, leading to iron overload. ......... the increased iron
accumulation in the bodu through the 2 mechanism, 1, enterocytes repsond by increasingapical expression of
divalent metal transpoter 1(DMT1), increasing iron absorption from the intestinal lumen. 2,
Hepatocytes respond by decreasing hepcidin synthesis, low hepcidin levels result in increased
ferroportin expression on the basolateral surface of enterocytes. This allows increased iron
secretion into the circulation, leading to iron overload. ......... This HFE protein normally
interacts with the transferrin receptor o increase endocytosis of the iron-transferrin
complex. once inside the cell, transferrin is degraded and the released iron is added to the
labile iron pool, which controls the expression of proteins involved in iron absorption and
storage. Mutations that inactivate the HFE protein cause enterocytes and hepatocytes to
detect falsely low iron levels. .......
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transferrin>>>>more than 50% saturation.
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removal of excess cholesterol from the body occurs via 2 mechanisms; excretion of free cholesterol into
bile and conversion of cholesterol into bile acids. In the liver, free cholesterol is converted into cholic
and chenodeoxycholic acids through a series of chemical reactions beginning with cholesterol 7a-
hydroxylase (rate limiting step in bile acid synthesis). These bile acids are then conjugated to either
glycine or taurine (improving solubility and emulsifying ability) to create the bile salts that are
actively secreted into the bile canaliculi, As water-insoluble cholesterol is secreted in bile it is rendered
soluble in small amounts by the detergent action of these amphipathic (eg, hydrophobic and
hydrophilic) bile salts and phosphatidylcholine (a phospholipid).. when there is more cholesterol than
can be made soluble, it precipitates into crystals that eventually grow and merge to form gallstones.
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normally chlolesterol is solubilized by bile acids and phospholipids. medical treatment in patients who do not go for
cholecytectomy is hydrophilic bile acids (ursodeoxycolic acid) which reduce bile cholesterol secretion and
increase biliary bile acid concentration, which promotes gallstone dissolution.............. nbme>>>3,339
Ursodeoxycholic acid helps regulate cholesterol by reducing the rate at which the intestine absorbs cholesterol
molecules while breaking up micelles containing cholesterol. Because of this property, ursodeoxycholic acid is
used to treat (cholesterol) gallstones non-surgically. The drug reduces cholesterol absorption and is used to
dissolve (cholesterol) gallstones in patients who want an alternative to surgery. The drug is very expensive,
however, and if the patient stops taking it, the gallstones tend to recur if the condition that gave rise to their
formation does not change. It is the only FDA approved drug to treat primary biliary cirrhosis
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clofibrate, octreotide or ceftriazone, ...... drug induced cholestasis with OCPs , anabolic steroid and
chlorpromazine ....... 7-alpha hydroxylase convert cholesterol (insoluble) to bile acid (soluble). fibrate medication
(as bezafibrate, fenofibrate, and ciprofibrate) reduces the conversion of cholesterol to bile acids by inhibiting 7-alpha
hydroxylase resulting in increased concentration of cholesterol with in bile.. when gall bladder is hypomotile or there is
more cholesterol than dissolve into bile salts, the cholesterol precipitates into insuloble crystals.
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very low calorie diet with decreased caloric intake and rapid weight loss can lead to bile stasis and increased
cholesterol mobilization,
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chronic extravascular hemolysis (sickle cell, beta thal, hereditory spherocytosis
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greater than 2.5cm
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disease of middle age or elderly,young people only when have a predisposing condition eg sickle cell deisease.
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the presence of echogenic stucture within gallbladder can be suggestive of acute cholescystitis in
the setting of fever and abdominal pain but is not diagnostic>>>>>it can be an incidental
asymptomatic finding in the setting of other abdominal pathology>>>more specific US signs for
acute cholecystitis are gallbladder wall thickening, pericholecystic fluid, and positive sonographic
murphy sign
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although patient are asymtomatic, some may present with right upper quadrant pain, or with a firm non-tender
mass in the right upper quadrant.
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Acalculous cholecystitis most commonly, occurs in critically ill patients (eg, those with sepsis, severe
burns, trauma, immunosuppression) and is associated with high mortality, The condition is thought to
arise secondary to gallbladder stasis and ischemia, which causes inflammation of and injury to
gallbladder wall.
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in 11-33% of patients.
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or from chronic irritation from gallstone
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mechanical disruption of gallbladder mucosa and release of infammatory mediators (eg lysolecithin, PGs) cause the
obstructed gallbladder to be inflammed and edematous>>>blood supply to the distended organ is compromised and
secondary bacterial infection results.>>>causes gangrene or perforation>>formation of pericholestetic abscess or
generalized peritonitis ................... Persistent gallbladder outflow obstruction promotes hydrolysis
of luminal lecithins to lysolecithins, which disrupts the protective mucus layer. The luminal
epithelium is then exposed to the detergent action of the bile salts, resulting in chemicals
irritation and prostaglandin release. Inflammation of the mucosa and deeper tissues causes
gallbladder eventually result in ischemia. Finally, bacteria (eg, Escherichia coli, enterococcus,
Klebsiella, Enterobacter) invade the injured and necrotic gallbladder wall, causing an
infection. The gallbladder is vulnerable to ischemic injury as the cystic artery lacks collateral
circulation
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generally not needed, only treated with stone removal and left fistula to be healed itself.
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this is due to production of beta-glucuronidase by the infected hepatocytes and bacteria. this enzyme causes
hydrolysis of bilirubin glucuronides and increases the amount of unconjugated bilirubin in bile. therefor biliary
infection with E.coli, ascaris lumbricoides or the liver fluke opisthorchis sinesis significantly elevates the risk of
developing brown pigment stone.
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most common in rural asia, with an increased incidence in women and elderly. only 10-25% in US.
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hypomotility associated with pregnancy, advanced age, fasting, hypertriglyceridemia and prolonged total
parenteral nutrition. also associated with glucose intolerance .......... gallbladder actively absorbs water from bile.
hypomotility of gallbladder results from pregnancy, rapid weight loss, octreotide,prolonged use of TPN and
high spinal cord injuries>>>>results in biliary sludge (due to precipitation of cholesterol monohydrate crystals,
calcium bilirubinate and mucin)>>>>>increases the risk of cholesterol stone formation
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increase cholesterol synthesis by upregulating hepatic HMG-CoA reductase enzyme. progesterone causes
hypomotility of gallbladder and also causes decrease bile acid production .......... decrease the activity of
aromatase enzyme would indirectly reduce the cholesterol gallstone formation. cause androgen is not converted to
estrogen, and estrogen does not stimulate HMG CoA reductase.
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Choledochal cysts are congenital dilations of the common bile duct that typically present during
childhood (age<10) with recurrent abdominal pain and jaundice.
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heredetitary pancreatitis: is a rare disorder that results form mutations involving
the trypsinogen or SPINK1 genes.the most common mutation leads ti the
production of abnomral trypsin that is not susceptible to inactivating cleavage by
trypsin.since there is always a small amount of trypsinogen that activates
prematurely within pancreatic acini and ducts, these protective mechanisms are
critical for preventing pancreatic autodigestion......................... multiple protective
mechanisms exist to limit the amount of trypsinogen that becomes prematurily
activated. 1, serine peptidase inhibitor kazal type 1(SPINK1) is secreted by
pancreatic acinar cells and functions as a trypsin inhibitor.it impedes the activity of
trypsinogen molecyles that become prematurely activated within the
pancreas,preventing trypsin-mediated activation of other proteolytic enzmes and
autodigestion of pancreatic tissue. 2, in addition to functioning as its own activator,
trypsin can also serve as its own inhibitr by cleaving other trypsin
molecules(rendering them inactive).this process is critical in preventing large
amouns of trypsin from forming within pancreatic tissue............. ....... after acinar
damage(either direct or indirect "due to obstruction") trypsinogen is activated by lysosomal enzyme with in
pancreas causes autodigestion
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coxsackie virus, mycoplasma pneumonia
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azathioprine,sulfasalzine,furosemide and valproic acid
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common in lesser sac(behind the stomach), bordered by stomach,duodenum and transverse colon. wall closely
adherent to surrounding hollow organ.
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acute intersticial pancreatitis (macroscopically>>edematous, microscopically>>intersticial edema, focal fat
necrosis and calcium deposits) can progress to acute necrotic pancreatitis (acini defect, can have hemorrhage ,
macroscopically>>white chalky fat necrosis, black areas of hemorrhage can also be seen grossly).......................
acute necrotizing pancreatitis has a high propensity for secondary bacterial infection.
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by 70% of colorectal and pancreatic cancer.
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due to release of procoagulant(mucin) causing hypercoagulable state.similar mechanism of MARANTIC
endocarditis(NBTE)..???? it occur especially with adenocarcinomas that secrete thrmboplastin-like substance that
is capable of causing chronic intravascular coagulation that is both disseminated and migratory.
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is an indicative of an adenocarcinoma in the head of pancreas.
cancer in body and tail do not obstruct common bile duct and usually do not produce symptoms
untill they invade the splanchnic plexus and cause midepigastric abdominal pain.
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genetic predisposition; hereditary pancreatitis,MEN,HNPCC,FAP
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carbohydrate antigen elevated in 74% of patients,
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fibrosis,thickening and organization of wall occur with time.take about 4-6 weeks........................... glycogen-
rich cubodial epothelium is seen is serious pancreatic neoplasms. Columnar mucinous epithelium is
typically found in mucinous cystic neoplasm Atypical cells forming papillary projections are seen in the
papillary variant of pancreatic adenocarcinoma.
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degree of hypocalcemia can be used as a marker of severity of acute pancreatitis.............. hyperglycemia:
indicator of severity. hypernatremia: due to third spacing and decrease fluid intake
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high levels of circulaitng triglycerides lead to increased produciton of free fatty acids within the pancreatic
capillaries by pancreatic lipase. normally, fatty acids exist in serum bound to albumin. however, if serum TGs
level rise to >1000 the concentration of free fatty acids exceeds the binding capacity of albumin and leads to
direct injury to the pacncreatic acinar cells. this hypertriglyceridemia causes acute pancreatitis via direct tissue
toxicity.
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causes pancreatic secretion to have more protein content and less fluid which form plugs. causes spasm of sphincter
of oddi and direct injury of acinar cell. MACROCYTOSIS is often seen with alcoholism due to B12 and folete
def(malnutrition) or direct toxic effect of alcohol to bone marrow. INDICATOR OF THIS ETIOLOGY: AST/ALT ratio
increases, GGT increases (may in part be a marker of the oxidative stress associated with
ethanol metabolism), macrocytosis (even in the absence of anemia), increase IgA to IgG ratio macrocytosis
can occur independently of folate or cobalamin deficiency
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1 structural abnormalities of duct (strictures, cancer, pancreas divisum) or ampullary region(choledochal cyst,
stenosis of sphincter of oddi) 2 surgery of stomach,biliary track or after cardiac surgery.
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phases of gastric acid secretion. 1. cephalic phase>>>due to cholinergic and vagal stimulation after seeing food
items 2, gastric phase>>>chemical stimulation and stomach distention thourgh ECL cells 3, intestinal
phase>>>downregulate by producing peptide YY from ilium and colon, which bind ECL cells and inhibit gastrin
dependent histamine release.
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Patients treated with PPIs showed a modest increased risk of hip fracture due to osteoporosis
(caused by decrease Ca absorption)
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increases level of warfarin,phenytoin,propanolol, metoprolol, quinidine and theophylline.
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bismuth subsalicylates, probiotics and octreotide are used for secretory type of diarrhea
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kaolin-pectin and attapulgite, absorbs fluid, toxins, nutrients and digestive juices to make stool less watery>>>used
for symptomatic relief of diarrhea
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sponataneous abortion.
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and prochlorperazine 261 and prochlorperazine. phenothiazine and benzamide ............................... the
drug which is antagonist form both Dopamine and H1 is>>>>promethazine
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granisetron and dolasetron.
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in the GI track there are presynaptic vagal nerve terminal with 5HT-3 receptor that initiate vagus nerve activity in
the medulla oblangata's "vomiting center"
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acts on both central and peripheral dopamine receptor. ................... has both prokinetic and antiemetic
properties.
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Promotes incorporation of water and fat into stool. "
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are effective in treating central nausea (seen in acute migraines) and also reduce migraine headache pain. also
mainly used for chemotherapy induced and post operative emesis
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effective in reducing nausea and vomiting caused by gastrointestinal upset (eg infection, chemotherapy and
distention) and general anesthesia.
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in the GI track, the area postrema and the solitary nucleus and track.
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subsrance P receptor (neurokinin receptor 1 NK1) antagonist in area postrema>>>>>antiemetic in both acute
vomiting and delayed emesis associated with chemotherapy. aprepitant and fosaprepitant
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antimicrobial enzyme that can be found in many secretion including saliva and tears as weel as within granules in
neutrophil.functions by hydrolyzing bond in peptidoglycan cell wall of bectrial organism
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also n-formylated peptide
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nbme>>>2,4,38>>>
in PSCG C5a is responisible for cellular infiltration not n-formylated peptide.
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and its precursor 5-HPETE
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also found in lysosomes of most cells and hydrolyzes organic phosphates
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also with collagen vascular disease, acute intersticial nephritis and drugs
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the inhibition of mast cell degranulation by cromolyn and nedocromil occurs independently of any stimuli. These
agents are very effective prophylactic agents for patients with seasonal symptoms, aspirin
hypersensitivity, and exercise-induced asthma, though in general, they are less efficacious than
inhaled glucocorticoids.
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and its larvae by ADCC using MBP (by degranulation) and reactive oxygen intermediates ............ complement
does not play a prominent role in destruction of parasite by eosinophil. ................. eosinophil can phagocytose
parasite and present them in association with MHC 2 to helper T-lymphocyes
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trichinella,trichura.toxicara,ancylostoma, ascaris,strongyloides, shistosoma>>>>>upon entery into
the blood are coated by IgG or IgE that bind the Fc receptor of eosinophil cell surface.
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immediate type.... in late type eosiophil are involved
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disorders of mast cell include urticaria pigmentosa and systemic mastocytosis ............... in systemic
mastocytosis, associated with mutation in KIT(CD117) receptor tyrosine kinase>>>>result in prominent
expression of mast cell tryptase.>>>mast cell proliferation in the bone marrow and in other organs. increased
histamine secretion ensues; as a result, many clinical symptoms of this disease are mediated by histamine.
gastric acid secretion increases, which inactivates pancreatic and intestinal enzymes, causing diarrhea. other GI
symptoms include nausea, vomiitng and abdominal craamps. gastric ulceration may occur. other histamine-mediated
symtpms of mastocytosis are syncope, flushing, hypotension,and tachycarida and bronchospasm. skin
manifestations, scuah as pruritis, urticaria and dermatographism are typical ................. gastric hypersecretion is a
common finding in systemic mastocytosis (CD117)>>>>KIT receptor tyrosine kinase. ..... mastocytosis>>>
benign, pruritic infiltration of teh skin by mast cells that is more common in children. scratching of the lesions
causes degranulation of teh mast cells, associated urticaria and in rare cases, severe flushing or syncope.
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Activated by (1) tissue trauma, (2) complement proteins C3a and C5a, or (3)cross-linking of cell-
surface IgE by antigen . in non-immune mediated mast cell degranulaito, there is direct activation of mast cells
independent of IgE cross-linking. these pseudoallergic reactions can be caused by chemical, heat, and certain
drugs (eg opiates, vancomycin) and are clinically similar to hypersensitvity and allergic reactions.
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acute allergic reaction>>>basophil and mast cell. chronic allergic reaction>>eosinophil
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by having its role in Type 1 HS reaction>>>>eosinophil also synthesizes PGs, LTs, and cytokines that contribute to
the inflammation. seen in LATE PHASE type 1 HS and CHRONIC allergic reaction
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Antibody dependent cell mediated cytotoxicity (ADCC) besides eosinophil is also used by
macrophages, neutrophil and natural killer cell
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basophils contain granules that stain dark blue, are irregular sized and usually obscure the nucleus.
SRS-A (slow reacting substances of anaphylaxis, a mixture of leukotrienes).
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also with churg strauss syndrome
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antigen presenting cells include dendritic cells, macrophages and B-lymphocytes. dendritic cells are professional
APC.they take up antigen by endocytosis, constitutively express MHV class II and B7 molecule and are able to
activate all forms of T-cells (naive, effector and memory). macrophages are phagocytes that only inducably
express MHC II and B7 and can only activate effector and memory T cells, not naive T cells. B lymphocytes
take up antigen by receptor-mediated (membrane bound antibody) endocytosis and constitutively express MHC II.
these cells are able to stimulate all forms of T-lymphocytes
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langerehans cells are commonly found in skin and mucous membrane. dendritic cell are the most effective form of
APC because they constitutively express MHC class II and the co-stimulatory B7 cell surface molecules. they take
up antigen by contact endocytosis and pinocytosis for thier environment. they are derived from myeloid cell line.
myeloid stem cell>>>granulocyte-monocyte progenitor cell>>dendritic cell they have chaarcteristic racquet
shapedintracytoplasmic granule noted in the question stem is a birbeck granules.
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different form langhans cells, a form of multinucleated giant cell with horse shoe-shaped arrangement of multiple
nuclei.
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6*3=18
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Synthesize (by liver) from 10-12 weeks then by spleen and finally bone marrow as Hb matures until term. The
gamma-chain does not bind with 2,3-BPG due to replacement of histidine(+charge) by serine.
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familial erythrocytosis>>> due to mutation in beta-globin chain resulting in reduced binding of 2,3-BPG which
increases hemoglobin oxygen affinity.
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two alpha and two delta>>>>expressed at very low level.
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glassy shiny cytoplam adjacent to the nucleus,nucleus is at border.
abundant basophilic cytoplasm>>eccentrically placed nuclei>>wagon wheel chromatin
distribution>>perinuclear pale zone due to weel developed golgi and centrioles
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positively charged histidine and lysine combine with negative charged phosphate group of 2,3-BPG
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called GOWER globin>>two zeta and two epsilon>>>>produced by embryonic yolk sac. replaced by Hb portland
and subsequently Hb gower 2 before Hb fetal production begins at 10-12 weeks of gestation.
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3*2=6
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in Rh hemolytic disease The severe anemia also stimulate release of immature, nucleated
erythrocytes and leads to persistent extramedullary hematopoiesis in the liver, spleen, and
other tissues hepatosplenomegaly). ABO- mediated hemolytic disease is less severe because
maternal anti-A or B antibodies are mostly of the IgM class and fetal A/B antigens are less
developed at birth.
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fetomaternal blood exchange increases with gestational age and is highest during delivery.
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by opsonizing fetal Rh+ RBCs which results in sequestering and clearacne by mother spleen.
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formation of memory B-lymphocytes is first pregnancy against D-antigen called Rh
alloimmunization.
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at 28 weeks and immediately after birth
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which is anti-D IgG
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Rh antigen are a group of non-glycosylatedtransmembrane protein. the D antigen is the most immunogenic.
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The association of a type A or B fetus with a type O mother occurs in approximately 15% of
pregnancies; however HDN occurs in only 3% of these pregnancies. Unlike Rh disease, ABO disease
can occur with the first pregnancy because anti A and anti B antibodies are formed early in life from
exposure to A- or B- like antigens presents in foods, bacteria and viruses.
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hageman factoe (XII) defciency is an autosomal recessive disorder that does not typically cause
clinically significant bleeding despite aPTT prolongation
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along with bradykinin PGE2 also mediate pain.
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LMWH has very little effect on thrombin due to very short saccharide side chain
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oral
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direct factor Xa inhibitor have most specific activity against factor Xa without inhibiting thrombin. so they prolonged
the aPTT and PT but not TT
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trinucleotide expansion>>>large unstable protein>>>move less on electrophoresis non-sense mutation>>>small
protein>>>move more on electrophoresis frame shift mutation>>>alpha thalasemia>>>beta tetramers>>>move
more on electrophoresis due to more negative charge
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rare autosomal recessive disease. sponataneous bleeding is rare, but affected patients are at increased risk for
bleeding following surgery or trauma.
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also idraparinux
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mainly prolongs the TT but little effect on tha aPTT and PT
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unfractioned
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also stimulates non vascular smooth muscle contraction.
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nbme.5,2,21
sequence specific cleavage of protein plays a role in>>>>inititation of coagulation not by activation
of G protein by hormone receptor
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the most common cause of acquired dysfibroginemia is liver disease.
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vWF>>>>besides platelet adhesion also enhance platelet aggregation, particularly under condition of high sheer
stress (such as in small vessel)..
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adhesion is done by GP Ia/IIa between platelet and vessel collagen.
strengthened by binding of platelet with GP Ib/IXb with vWF on vessel wall..
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released by dense granules
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biopsy show normal intestinal mucosal architecture, but enterocytes contain
clear or foamy cytoplasm which is more promiennt at the tips of the villi,
chylomicron and VLDL particels are synthesized within the endoplasmic
reticulum as lipids accumulate around a single apoB molecule. apoB48 (a
truncated version without the LDL receptor ligand) is presnet in chylomicron.
during the synthesis of apoB containing lipoproteins, microsomal TGs transfer
protein (MTP) functions as a chaperon protein necessary for proper foldng of
apoB and also participates in the transfer of lipids to newly formed chylomicrons
and VLDL particles. abetalipoproteinemia is most commonly caused by an
autosomal recessive, loss of funciton mutation in the MTP gene.
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burr cells are erythrocytes with short, evenly spaced projections. they can occur
as an artifact or in association with uremia, pyruvate kinase deficiency,
microangiopathic hemolytic anemia or mechanical damage
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due to Vit E deficiency also
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due to inhibition of erythrocytes 5" nucleotidase>>>>ribosome aggregation due
to inability to degrade RNA ...... basophilic stippling results from the abnormal degradation of
ribosomal RNA (due to lead-induced inhibition of a 5' nucleotidase)
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iron deficiency anemia
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autoimmune hemolytic anemia, burns and un-fresh blood sample.
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iron-deficient individuals on replacement therapy should experience hemoglobin level increases of
approximately 2g/dL per week for the first three weeks. the reticulocyte is an immature RBA that is
slightly larger and bluer than a mature RBC. it lacks a cell nucleus but retains a basophilic,
reticular (mesh-like) network of residual ribosomal RNA. the ribosomal RNA appears blue
microscopically after the application of the Wright-Giemsa stain
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malaria
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myelophthisic anemia: caused by space occupying lesion in bone marrow.. all hematopoietic series are affected
and present with pancytopenia.. the most common cause is infiltration by metastatic carcinoma with associated
fibrosis.fibrosis, granuloma or other space occupying lesions may also be responsible
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increase MCV can be seen in hypothyroidism and myelodysplasia.
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treatment is oral iron supplements along with Vit C (to increase its absorption)
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nbme>>>2,4,43>>> iron tablet toxicity>>>>microscopic examination of hepatic tissues shows lysosomal
degredation>>>mechanism is Peroxidative decomposition of cellular membrane lipids is a postulated mechanism
of hepatocellular injury in parenchymal iron overload. Peroxidative degradation of the lysosomal membrane and
the resultant release of hydrolytic enzymes may be responsible for hepatocellular injury in iron toxicity.. iron
tablet toxicity>>>also causes gastric bleeding
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HbH and Hb Barts tetramers hava very hight affinity for oxygen (resembling myoglobin) and are ineffective in
delivering oxygen to tissues.
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iron absorption occurs predominantly in the duodenum and proximal jejunum,
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on chromosome 164 genes code for 2 chains
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laboratory testing: 1, decreasdd bone marrow iron stores (ferriti and hemosiderin)
2, decreased serum ferritin>>>>most specific detector of anemia 3, increases
serum TIBC, reflecting increased serum transerrin, 4, decreased serum iron
conentration>>>>>least useable for detecting iron def anemia 5, decreased blood
hemoglobin 6, appearence of microcytic, hpochromic red blood cell
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also called patterson kelly syndrome
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chronic alcoholism which is the 2nd most common cause of pancreatitis can cause macrocytosis even in the
absence of anemia due to malnutrition( eg folate deficiency), liver disease or direct toxic effect of alcohol to
bone marrow. .......... Alcohol related macrocytosis can occur independently of folate deficiency.
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the anemia of chronic liver disease is usually normocytic or slightly macrocytic
with target cells in the peripheral blood smear. microcytic anemia occurs in <25%
of cases, and most patietns only have mild anemia with hemoglobin level of 10-11
g/dl
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nbme,11,4,6 Body store iron deficiency is diagnosed by diagnostic tests as a low serum ferritin, a low serum iron level,
an elevated serum transferrin and a high total iron binding capacity (TIBC). A low serum ferritin is the most sensitive
lab test for iron deficiency anemia Serum iron levels (i.e., iron not part of the hemoglobin in red cells) may be
measured directly in the blood, but these levels increase immediately with iron supplmentation. The diagnosis
of IDA requires that a patient be anemic and show laboratory evidence of iron deficiency. Red blood cells in IDA are
usually described as being microcytic (i.e., mean corpuscular volume less than 80 μm3 [80 fL]) and hypochromic,
however the manifestation of iron deficiency occurs in several stages.
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nbme>>>5,1,24
18 month old boy who is "chubby" and have weight above the 90th percentile.>>>>>has iron
deficiency anemia.
diminishes both growth and learning in children.
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nbme>>>3,4,1>>> Decrease in β-globin chain synthesis Mild anemia is most often due to DNA splicing defects.
Severe anemia is due to a nonsense mutation with formation of a stop codon. Premature termination of β-globin
chain synthesis or absent β-globin chain synthesis. Normal synthesis of α, δ, γ-globin chains. β-Thal minor (β/β+) Mild
microcytic anemia Mild protective effect against falciparum malaria RBC life span is shorter than normal.
Decreased MCV, Hb, and Hct Increased RBC count Normal RDW and serum ferritin Hb electrophoresis Decreased
HbA (2α/2β) Increased HbA2 (2α/2δ) and HbF (2α/2γ) There is no treatment. β-Thal major (Cooley's anemia; β0/β0)
Severe hemolytic anemia RBCs with α-chain inclusions are removed by macrophages in the spleen. Causes an
increase in unconjugated bilirubin RBCs with α-chain inclusions undergo apoptosis in the bone marrow
(ineffective erythropoiesis). Extramedullary hematopoiesis Increased RDW and reticulocytes Hb electrophoresis
No synthesis of HbA Increase in HbA2 and HbF Long-term transfusion requirement danger of iron overload (called
hemosiderosis)
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Kozak consensus>>>play a role in initiation of translation (ie mRNA binding to ribosomes)>>>>gccgccRccAUGG
where R is either G or A>>>purine located three bases upstream from the start codon is key determining factor for
translation>>>its mutation (replacement by G to C at position 6) causes>>thalasemia intermedia >>>> form of
beta-thal which is clinically less severe than beta thal.
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cooleys
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Severe hemolytic anemia (a) RBCs with α-chain inclusions are removed by splenic macrophages • Marked
increase in unconjugated bilirubin (UCB; jaundice) (b) RBCs with α-chain inclusions undergo apoptosis in the
bone marrow (ineffective erythropoiesis).
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occupationally inhalation is the main route at consumer level, gastrointestinal absorption is the most significant
means of exposure.
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constipation,headache,impaired concentration and deficits in short-term memory ...... when venous blood sample
increased by 10microg/dl(0.48micromol/dl) ............... homemaid alcoholic beverages(moonshine) has lead
content
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rate limiting step in heme synthesis
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(2) Sideroblasts die in the marrow (ineffective erythropoiesis) • Phagocytosed by macrophages, which leads to
excess iron stores
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iron is transported to developing erythrocytes that cannot form heme,and its
granules accumulate circumferentially around the nucleus, forming ring
sideroblasts
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by 5' nucleotidase inhibition
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also with other drugs like chloramphenicol, linezolid ..................... isonizid
directly inhibits the enzyme pyridoxine phosphokinase, which normally converts
pyridoxine ( vit B6) to its active form, pyridoxal 5'phosphate
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microcytic hypochromic. cause lead inhibit mitochondrial iron transport.
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without hepatitis and cirrhosis
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lead has strong affinity for sulfhydryl group.so inhibit these two enzymes
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seen with chronic hemolytic anemias>>>>such as Beta-thalasemia
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elevated to compensate for the decreased synthesis of HbA due to beta-globin chain underproduction.
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on chromosome 112 genes code for 2 chains
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Beta-thalassemia is the most common thalassemia in patients of Mediterranean descent; alpha-
thalassemia is more common in individuals from Southeast Asia. Beta-thelassemia affects beta-
chain production and can be caused by a variety of DNA mutation affection the transcription,
procession, and translation of beta-globin mRNA. Most commonly, these mutations cause
aberrant precursor mRNA splicing or premature chain termination during mRNA the
promoter region. The resulting beta-globin deficiency occurs in the setting of normal heme and
alpha-chain synthesis, leading to increased formation of hemoglobin A2 and (in some patients)
hemoglobin F (a2y2). Decrease beta-chain synthesis in beta-thalassemia results in the formation
of insoluble alpha-chain tetramers that precipitate within red blood cells. This can affect the
membrane cytskeleton and reduce membrane stability. However, the initial pathogenic
abnormality in beta-thalassemia is a deficiency in beta-chain synthesis. In patients with beta-
thalassemia, the DNA replicated normally despite the mutations in the beta-globin gene. It is
not until the DNA is transcribe into mRNA that hemoglobin production becomes abnormal.
Anemias due to DNA synthesis defects include the megaloblastic anemias (vitamins B12 or folic
acid deficiency), which are characterized by an elevated MCV (>100um3).
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RNA and protein synthesis may continue relatively unaltered, leading to a state of unbalanced
cytoplasmic growth with impaired cell division. Pancreatic insufficiency is also associated with
vitamins B12 deficiency as pancreatic enzymes normally cleave R factor from B12 allowing B12 to bind to
intrinsic factor and be absorbed.
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and also inhibit rate limiting step of pyrimidine synthesis. CMP-II
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orotic acid increase due to urea cycle enzymes defect.eg
1, OTC deficiency,
2, cirullinemia
3, argininosuccinic aciduria
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"Treatment: uridine triacetate
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hypochromic
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bone marrow biopsy>>hypercellular with erythroid and granulocytic hyperplasia
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hereditary orotic aciduria occurs due to a defect in uridine 5’-monophosphate (UMP) synthase, a
polupeptide containing 2 enzymatic domains (orotate phosphoribosyltransferase and OMP
decarboxylase) that catalyze the final conversion of orotic acid to UMP
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HUS>>>>has decrease heptoglobin, increase LDH, increase indirect bilirubin, increase bleeding time
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transmembrane iron transport.
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in myelofibrosis>>>unlike in aplastic anemia, massive splenomegaly is expected because the patient
compensate for the loss of bone marrow hematopoiesis with extramedullary hematopoiesis ................. the absence
of splenomegaly is key in diagnosing aplastic anemia. pancytopenia and splenomegay is very unlikelu to hasve
aplastic anemia. other causes of pancytopenia without splenomegaly include severe vit B12 and folic acid
deficiency, acute leukemias and certain forms of myelodysplastic syndrome.
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transform into AML
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fat and marrow stroma.
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alpha 2 globulin produce by liver ...................... Haptoglobin is a serum protein that binds to free hemoglobin
and promotes its uptake by the reticuloendothelial system.
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have gross hematuria and proteinuria
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patients with sickle cell traits typically have normal RBC indices and reticulocyte counts,
Individuals with sickle cell anemia (Eg, no normal Hb A) will have an elevated reticulocyte count
but will maintain a normal mean corpuscular volume ............. Extramedullary
erythropoiesiscan occur un SCD and can lead to an elevated MCV (as the reticulocytes
produced are, on average, larger than the erythrocytes). However, this patient’s low reticulocyte
index (RI), representing the reticulocyte percentage corrected for degree of anemia. an
elevated RI, reflecting an adequate marrow response (ie, reticulocyte production), would be
expected with erythropoiesis and can also be seen with hemolysis or acute blood loss.
Conversely, a low RI suggests inadequate response to anemia and lack of erythropoiesis.
Furthermore, accelerated erythropoiesis often results in an only mildly increased MCV; an
MCV > 115 um3 (as seen in this patient) is more suggestive of folic acid or vitamin B12 deficiency.
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In infants, splenic congestion can be sen with splenic sequestration crisis (10%-15%
morality), which develops due to vasoocclusion and splenic pooling of erythrocytes.
Manifestations include marked hemoglobin decrease, rapidly enlarging spleen, and
hypovolemic shock. However, by early adulthood, repeated infarction leads to functional
asplenia............ at birth infants who are heterozygous for sickle cell trait typically have the greatest
amount of fetal hemoglobin (Hb F) followed by hemoglobin A (Hb A) and the smallest amount of
hemoglobin S (Hb S) they may develop hematuria priapism and increased incidence of urinary tract
infections, Splenic infarction at high altitude has also been reported
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autosomal dominant (75%). northern eurorpean descent. age of diagnosis varies considerably but many have
jaundice and fatigue in times of increased hemolysis in the setting of viral infections
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have negative comb test
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on crystal voilet stain>>small, irregular dark purple granules.
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nbme>>>2,4,28>>>decreased production of ATP from glucose. Pyruvate kinse deficiency leads to decrease in ATP
formation.- The def of ATP causes the erythrocytes to loose its characteristic biconcave shape and signal its
destruction in spleen. The Na/K ATP ase result in loss of ion balance and causes osmotic fragility leading to
swelling and lysis PK def -present with-- hemolytic anaemia increase in 2;3 BPG absence in heinz bodies
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form hexagonal crystal and promotes red cell dehydration, causing mild chronic hemolytic anemia.
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glycosylphosphatidylinositol (GPI) anchor>>>glycolopid necessary for the attachment of several
cell surface proteins, including CD55 (decay accelerating factor) and CD59 (MAC inhibitory
protein)
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due to stem cell disorder. also associated with aplastic anemia
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it is gold standard.. also use HAM test positive.
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A to T mutation at position No 6 of beta-globin gene. nucleotide substitution (GTG>GAG) at the
sixth codon of the beta-globin gene, leading to the production of a defective form of Hb,
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hemolysis>>>repeated sickeling>>>permanent deformation>>>premature desrtruction by macrophages and
mechanical stress. causes intravascular and extravascular hemolysis.>>>>>increased indirect billirubin, LDH and
decreased heptoglobin ................ initially sickeling is reversible later on become irreversible(loss of cell
membrane)
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gardos channel (Ca dependent potassium channel) blocker hinder the efflux of potassium and water from the
cell, perventing dehydration of erythrocytes and reducing the polymerization of HbS
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stiffening of erythrocite membrane and hemolysis in the microvasculature due to an inability of erythrocyte to
deform and fit through the capillaries
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the chronic anemia in SCD can result in cardiomegaly due to chronically increased CO (systolic
function is largely preserved due to an increase in SV).
however this typically does not occur until after infancy
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microvascular occlusion typically involve the bone marrow, periosteum and deep muscle but can
occur in other organs..
dactylitis is common during first few years of life as the affected bones still contanin hematopoietic
bone marrow
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the glu (acidic)>>>>valine (neutral) substitution leads to alteration of a region on the beta-globin SURFACEthat
interacts with the complementary site on another Hb molecule. as a result of the charge difference,the hydrophobic
interaction that occur cause aggregation of Hb molecules (under anoxic condition) and subsequent erythrocyte
sickling ............. normally globin chain of Hb tetramer in compactly folded due to nonpolar hydrophobic residues in
the interior and charged polar residues on the surface. .... a glu>val substitution affects the 3 dimensional
(tertiary structure) of Hb, but it does not result in a change in alpha-helical secondary structure. introducing
proline into the primary structure could distort the alpha-helix due to prolines rigid cyclic structure
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on chromosome 11. beta gene has been mapped to chromosome 11p,15.5 indicating its locus,
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due to release of free hemoglobin and other prothrombotic factors from lysed RBCs and platelets.
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somatic mutation in the PIGA gene within the clonal population of multipotent hematopoietic stem cell.
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despite the name it is neither nocturnal nor paroxysmal. low level base line hemolysis occur through out the day
and exacerbated by many conditions. hematuria only appears to be nocturnal as the urine normally become more
concentrated at night.
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glutamic acid is replaced by basic polar (positively charged lysine) residue..
because lysine is charged (athough it has opposite polarity to glu), hydrophobic interactions
between Hb molecules do not occur..
the presence of lysine causes HbC to have decreased mobility on electrophoresis.
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heinz bodies also with diabetic ketoacidosis.
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clinical presentation: hemolytic anemia, jaundice(extravascular) and splenomegaly(accumulate in the spleen).
complications:pigmented stones and aplastic crisis
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or acidified glycerol lysis test
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Patients with sickle cells disease (SCD) or other hemolytic anemias are predisposed to
develop folic acid deficiency due to increased erythrocyte turnover. Low folic acid levels
impair DNA synthesis.
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possible mechanism include increased sickling of parasitized sickle cell trait RBCs and accelerated
removal of these cells by the splenic monocyte macrophage system
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bypass phosphoglycerate kinase>>>no atp production
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has thrombocytopenia but typically no purpura or active bleeding
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also occur in cancer chemotherapy eg cisplatin and cyclophosphamide
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congenital neutropenia>>>> bone marrow aspirate>>arrest in promyelocytes ............... G-CSF receptor
mutation is found in 80 percent of pateint
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Acute intermittent porphyria can cause attack of abdominal pain (without abdominal tenderness)
due to autonomic neuropathy. Erythropoiesis is not affected, and the peripheral blood smear
is normal.
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loss of developmental milestones (in infants)
learning problem in older children
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which uses heme stores in liver. eg phenobarbital, griseofulvin, phenytoin. progesteorn (eg in puberty), low caloric
diet and smoking
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thought to be mediated by the formation of porphyrin-mediated superoxide free radicals from oxygen upon
exposure to sunlight,
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uroporphyrinogen 1
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coproporphyrinogen oxidase
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mitochondria is necessary for the 1st and the last 3 steps.... heme is synthsized in virtually every organ but hte
prinical site of synthesis are erythrpcyet precursor cell(located in bone marrow) and hepatocytes (use heme in
microsomal cytochome P450 system)
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stimulated by alcohol, barbiturates and hypoxia.
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also called uroporphyrinogen 1 synthase and HMB synthase.
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dit though an enzyme deficiency but is an AD
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Elevated urinary porphyrin levels (uroporphyrin, heptacarboxyl porphyrin) are seen in porphyria
cuctanea tarda.
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actually in decreased Ferrochelatase activity zinc(abnormal) is seen within protoporphyrin
instead of iron.It is classic finding of Ferrochelatase deficiency ????????????????????
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contain zinc
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deficiency will result in decrease heme symthesis and concurrent hypochromic, microcytic anemia.
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increased protoporphyrin can be caused by 1, EPP (erythropoietic protoporphyria = Ferrochelatase
deficiency) 2, lead poisoning 3. iron deficiency anemia
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uroporphyrinogen 3 synthase.
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photosensitivity caused by defect in URO decarboxylase, COPRO oxidase, PROTO oxidase, and
Ferrochelatase.
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no photosensitivity. also have hyponatremia
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color change>>>>darken>>on exposure to light and air due to oxidation of excess PBG>>>>it is a key feature of
acute porphyrias
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have increased activity of enzyme gamma ALA-synthase in blood and urine,
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also have intramuscular hemorrhage.
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((((((((a single injection can result in therapeutic response, that's the characteristic of hemophilia
B.))))))))))))
confusing some say hem A.
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this is used for moderate to severe form of disease
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iron poisoning has 4 stages
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only this (solely) is used for mild form of hemophilia A
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patient with hemophilia have normal platelet function and can form a pletelet plug, so bleeding after procedure can be
delayed rather than immediate, in contrast to patient with platelet disorder.
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all other clotting factors are produced by liver.
only VIII is produced by endothelial cell
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platelet funciton analizer (PFA-100) monitor time needen for a patients blood to form a platelt-based hemostatic
plug in an in vitro environment.
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IgG
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in children , ITP is typically acute and self-limited, whereas it tends to run an insidious and chronic course in
adults. a peripheral blood smear with isolated thombocytopenia and no other platelets abnormalites wuld help
confirm diagnoses(megakaryocytes can sometimes be seen) ......... platelets can undergo splenic sequestration
in ITP, but the primary mechanism responsible for the thrombocytopenia is immune destruction.
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hall mark of the diagnoses are microangiopathic hemolytic anemia (nonimmune hemolytic anemia with schistocytes)
and thrombocytopenia without any other obvious cauuse
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normally circulating vwf (produced by megakaryocytes and endothelial cells) is released as large vwf multimers
that are cleaved to their regular si by the ADAMTS
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is life saving and sholud be consider who have disease or in whom TTP is suspected
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in arteriolar and capillary microvasculature.
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HIV and Hep C
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It is the most common cause of thrombocytopenia in children 2 to 6 years of
age.??????????????????/
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toxin injure the endothelium of preglomerular arterioles and glomerular capillaries, leading to platelet activation
and aggregation and the formation of microthombi. platelet consumption causes thrombocytopenia but there is
typically no purpura or active bleeding.
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thrombocytopenia and microangiopathic hemolytic anemia.
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autosomal dominant
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thrombosis develop through 2 pathophysiological meshanism. 1, inability of inactivation of factor Va and VIIIA. 2,
Va participation in conversion of prothombin to thrombin. this combinaiton of increased coagulaiton and decreased
anticoagulaiton produces hypercoagulable state
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mutation is single amino acid substitution(glutamine for arginine) near the protein C cleavage site in her coagulaiton
factor 5 gene product.
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detected in approximately 20% (range 12-40%) of patients with abnormal venous thrombosis. ....... clinical
manifestations are DVT, cerebral vein thomboses and resurrnet pregnancy loss. 1-9% caucaisan are heterozygote
and have 5-10 times more risk of thrombosis. while homozygote carrier has 50-100 time the risk of thombosis.
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inherited causes of hypercoagulability must be considered in all patients under age 50 who present with
thromboses in the absence of any obvious explanation for an acquired prothrombotic effects. factor V leiden
mutation and mutation in prothombin gene are the most common inherited causes of hypercoagulability.
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retianed dead fetus more than 6 weeks. release of tissue factor (thromboplastin)
from the placenta>>overwhelming activation of intravascular coagulation.
subsequent production of plasmin from plasminogen activates the seconday
fibrinolysis (thrombolysis), open up the ocluded blood vessels, and release fibrin
degredation product
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and vitronectin (which involve in hemostasis tumor malignancy)
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and Mg chelator.
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nbme>>>2,2,7>>>>16 year old boy with respiratory distress.
examination show a large mediastinal mass ans 3-cm firm cervical lymph node
bilateral>>>>>diagnoses is hodgkin lymphoma
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ample cytoplasm, bilobed or double nuclei and inclusion-like eosinophilic nucleoli.. seen against the background of
lymphocytes, histiocytes and eosinophils in classical HL ............... RS cells are derived from germinal
center B-lymphocytes and are the neoplastic cells of Hodgkin lymphoma (HL).
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also present on granulocytes.
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double stranded DNA viruses that are oncogenic and associated with non-hodgkin lymphoma are EBV and HHV-8.
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the typical presentation is either non-tender lymphadenopathy or lymphadenopathy incidentally detected on
routine chest X-rays
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monomorphic cell polulation is indicative of malignancy and is characteristic of NON-hodgkin Lymphome.
HODGKIN lymphoma does demoanstrate an admixture of several lymphoid cell type within lymph node just like
lymphoid hyperplasia
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especially when transfused(packed or whole blood) 5-6 liters in a period of 24 hours.
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Non-Hodgkin lymphoma can invade the bone marrow, causing myelopthisic anemia. A
peripheral blood smear would show leukoerythroblastosis (immature granulocytes and
nucleated teardrop-shaped erythrocytes).
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t(2:8) and t(8:22) are typical for burkitt. ........... Translocations between chromosome 8 and chromosomes
coding for the immunoglobulin heavy chain (14) the kappa light chain (2) or the lamba light chain (22)
may result in Burkitt lymphoma.
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monomorphic, intermedium size, with round nuclei and multiple prominent nucleoli, and vacuolated basophilic
cytoplasm.
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histology describe>>diffuse uniform ,round,medium sized lymphocytes and a high proliferation index represented
by the high Ki-67 fraction(approaching 100%)................ high mitotic index and high cell death rate (apoptotic
bodies) are typically seen
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as a B-cell neoplasm>>tumor cell express pan B cell antigen (CD19, CD20, CD79a) CD21 and CD10.
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two major cell types: 1, centrocytes (small cleaved cells) with increased nuclei to cytoplasmic ratio 2,
centroblasts (large non-cleaved cells)
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prednidoe is a part of the CHOP therapy used in the treatment of non-hodgkin
lymphoma, including diffuse large B cell lymphoma, it induces lymphocyte
apoptosis. contributing to tumor lysis syndrome
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EBV is the etiologic agent most strongly associated with burkitt lymphoma, with infection being present in 40% of
immunodeficiency-associated Burkitt lymphoma and nearly all cases of endemic Burkitt lymphoma. a crucial step
in the transformation of infected cells is tha balanced t(8;14) tranlocation, which causes overexpression of c-MYC,
a transcriptional regulator that controls cell proliferation. chronic EBV infection increases B-cell proliferation and
is thought to increase the risk of c-MYC translocation. pre-existing immunodeficiency secondary to HIV
infection can potentaite EBV antigen-induced B cell proliferation.
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proliferating CD4 lymphocytes infiltrate the dermis and epidermis, where thet form pautrier microabscesses. this
condition manifests with plaques (often on trunk or buttock) that may be confused with eczema or psoriasisi.
generalized erythema and scaling and thickening of the skin (erythroderma) may result
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non-tender, nodular pattern>>>>show aggregates of closely packed lymph node follicles. ..... patient present with
persistent painless fluctuating lymphadenopathy. follicular lymphome is the most common indolent non-hodgkin
lymphoma in adults and the second most common NHL overall. the condition most often presents in middle-aged
patients with painless lymph node enlargemement or abdominal discomfort from the abdominal mass. histology is
notable for a mixture of cleaved and non-cleaved follicle center cell in a nodular pattern.
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diffuse sheets of large lymphocytes with nuclei at least 5 times the size of small lymphocytes.................. presents
with rapildy enlarging nodal (neck, abdomen, mediastinum) or extranodal symptomatic mass. the waldeyers ring
(orophayngeal lymphoid tissue) and GI tract are commonly involved and systemic "B" symtoms (fever, weight loss,
drenching night sweats) can also be seen.
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benign, tingible body macrophages
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clear spaces that surround macrophages contribute to to characteristic starry sky appearance.
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is a highly aggressive (but generally chemotheraoy-responsive) B-cell NHL. patients typically develop rapidly
growing tumor masses in the facial bone, jaw and abdomen. tumor doubling time is very rapid and
<<<<<spontaneous>>>> tumor lysis can occur. ............. although it is very aggressive, the tumor
responds well to short term high-dose chemotherapy. Patients with limited disease have an
excellent prognosis.
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Multiple myeloma (MM) should be suspected when an elderly patient has one or more of the following ・
fatigability (due to anemia) ・ constipation (due to hypercalcemia) ・ bone pain, most common in the back
and ribs (bone lysis due to production of osteoclast-activating factor by myeloma cells) ・ elevated
serum protein (monoclonal proteins) ・ renal failure. myeloma cast nephroparhy ("myeloma kidney"
bence jones proteins are filtered by the glomerulus in small amounts and them reabsorbed in the
tubules, when levels exceed reabsorptive capacity, light chains precipitate with Tamm Horsfall protein
and form cats that cause tubular obstruction and epithelial injury, leading to impaired renal function. On
light microscopy, numerous large, glassy cats that stain intensely eosinophilic are seen. deposition of
light chain fragments in the glomerular mesangium and capillary loops can also renal failure in MM
(AL amyloidosis).
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eosinophilic extracellular deposits on H and E stain.
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is a more specific laboratory tetst
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due to: infiltration by plasma cell, deposition of amyloid, bence jones casts is tubules, hypercalcemia leading to
metastatic calcificaiton and inflammation by macrophages and gaint cell......... renal insufficeincy is due
to hypercalemia and ALamyloidosis.
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bortezomib is a proteasome inhibitor used in the treatment of MM and waldenstorm macoglobulinemia...
bortezomib binds and inhibits the 26S proteasome. in MM bortezomib can facilitate apoptosis of neoplastic cells by
preventing degradation of pro-apoptotic factors.
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hypercellular marrow with megaloblastic hematopoiesis can be seen in MDS or megaloblastic anemia. MDS
typically occur in elderly and has a male predominance. ......... ringed sideroblasts are abnormal erythrocyte
precursor found in MDS and characterized by mitochondrial iron accumulation surrounding the nucleus.
patients with MDS typically have petechia , weakness and recurrent infection; splenomegaly is uncommon
............. bone marrow biopsy show disordered (dysplastic) differentiation affecting all non-lymphoid lineages. also
may include ringed sideroblasts and megaloblastoid maturation ....... Myelodysplastic syndromes usually
present with cytopenias, hypercellular bone marrow, abnormal maturation of cells, and
increased blasts (< 20%).
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normocytic normochromic anemia due to replacement of bone marrow by malignant plasma cell which affects
normal hematopoesis.
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causes fatigue, confusion and constipation.
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increase IL-1 (osteoclast activating factor) and IL-6 by malignant plasma cell.
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neoplastic B lymphocyes mature into plasma cells that synthesize abnormal
(typiclaly large) amounts of monoclonal immunoglubilin or immunoglobulin
fragments (eg light chains) ................. greater than 30% of plasma cell in bone marrow sample is
diagnostic
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dohle bodies (basophilic oval inclusion in mature neutrophil) commonly seen in toxic
systemic illness but can also be seen in burns or myelodysplasia ... peripheral blood show
dohle bodies, toxic granulation and cytoplasmic vacuoles. .... occur in response to underlying
condition >>>severe infection/hemorrhage,malignancies, acute hemolysis, .. bone marrow
can be normal on hypercellular and responds with increrase band and mature early neutrphil
precursor (eg myelocyte) in contrast to increase immature cell ( eg myeloblasts, and
promyelocyte) seen in acute leukemia
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accounts for 15-17% of ALL. B-cell type is most common and accounts for 70-80%
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(CALLA) suggest a good prognosis. also CD 19 and CD 20
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ALL is a primarily a diseae of children (75% occurs in children under 6 years). most patiens wirh precursor B-ALL
present with evidence of bone marrow failure: thrombocytopenia and/or anemia and/or neutropenia. the leukocyte
count may be normal, decreased or increased ............ precursor T-ALL acounts for about 15% of all chilhood ALL
and is more common in adolescents than younger children. patient typically present with a high leukocyte count
and often a large mediastinal mass. the lymphblasts is precursor T-ALL variable express CD1a and T-cell amrkers
like CD3, CD4 and CD8 .............. acute lymphoblastic leukemia is the most common leukemia in children. generally
present with fever, fatigue, palllor petechiae and bleeding. leukemic spread can cause lymphadenopathy,
hepatosplenomegaly and bone pain. ......... t-all>>>>>increae lekocytes count, b-all>>>>normal, decrease
or increase leukocyte count .... immature cell neoplasm
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has indolent course
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neoplastic cell resemble mature B-lymphocytes.
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mainly T type patient has panhypogamaglobulinemia>>>death due to infection
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indolent course middle age men ........... cells often described as having a fried egg appearance
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WHO diagnostic criteriara require the presence of >20% myeloblasts in the bone marrow. ........... acute
myelogenous leukemia is the most common acute leukemia in adults. However, the mean age to
diagnose is around 65, and most patients will have a WBC count of about 15,000-20,000/mm3 with a
sigificant increase in blast cells (eg, >_ 20%) ....... functional neutropenia despite leukocytosis. the median
white blood cell count is around 15,000/mm3 at diagnosis............. immature cell of myeloid origin proliferate in the
bone marrow and suppress the growth and multiplication of other hematopoetic cells>>>clinically manifested due
to anemia, thrombocytopenia and neutropenia(recurrent infection) >>>due to marrow replacement by leukemic
cells ..... it is divided into eight types, M0 through M7 the clinical manifestation of AML result from
marrow replacement by leukemic cells. ..... a chromosome 16 inversion is observed in the M4Eo
(eosiniphilic) subtype of AML
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M4-M5 monocytic precursors M6 erythrocytic precursors (typically affects elderly people) M7 arises form primitive
megakaryoblast and in associated with T(1;22) and down syndrome in children
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retinoic acid receptor alpha (RARalpha) is transfered from ch17 to ch15
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myeloid precursors in different stages of differentiation proliferate.
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platelet derived growth factor receptor mutation play a role in chronic myelo-monocytic leukemia. ..... reciprocal
translocation between the long arms of chromosome 9 and 22. This translocation fuses the BCR geen on
chromosome 22 to the ABL gene on chromosome 9 shortened chromosome 22. Karyotype analysis
shows elongated chromosome 9 and shortened chromosme 22 ....... uncontrolled mature granulocyte
production, mostly neutrophils but also basophils and eosinphils. leulocyte alkaline phosphatase is
decrreased because the WBCs are cytochemically abnormal. other clues to the diagnosis of CML are the
predominance of myelocytes compared to more mature forms such as metamyelocytes (“myelocytic
bulge”) and the absolute basophilia and eosinophilia.
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the majority of CLL exhibit increased expression of the protooncogene BCL-2 similar to follicular lymphoma and
DLBCL
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"Bcell ALL associated with Down syndrome."
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severe form
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where promyelocytic leukemia (PML) gene present.
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large cell with abundant basophilic cytoplasm, nuclei are often bilobed or folded, containing multiple nucleoli.,
contain auer rods also and peroxidase positive
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needle shaped cytoplasmic inclusions (fused lysosomal (deformed azurophilic) granules)... the cell cytoplasm also
has numerous coarse azurophilic granules. on bone marrow biopsy>>>promyelocytes (immature myeloid cell)
with auer rod
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have bone marrow and reticuloendothelial infiltration. patient often manifest with pancytopenia(marrow infitration
and cytokine production cause fibrosis) and splenomegaly (splenic red pulp infiltration>>crossing midline or
extending into left lower duadrant)
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rituximab, fludarabine and prednisolone is used for treatment. .... fludarabine
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warm and cold both
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is a T-cell marker
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deletion of 13q is one of the molecular defects seen in chronic lymphocytic leukemia........ lymphocytic leukemia
(like thymoma) can cause pure red cell aplasia ................... mature T cell leukemia is a group on uncommon
neoplasms that are derived from the mature or post-thymic cells. findings would include more mature lymphocytes
(not blastc) expressing T-cell markers. ................ both CLL, SLL are mature B-cell leukemia of small, round
monomorphic B-lymphocytes in the peripheral blood, bone marrow and lymph node. these neoplastic
lymphocytes express CD 19 and coexpress CD5 (T cell marker) on their surafec .........
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precursor B-ALL are positive for Tdt, CD10, and almost always CD 19 precurosr T-ALL are TdT positive and
variably express CD1a and the T-cell markers CD2, cd3, cd4,, cd5, cd7, cd8
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ataxia telangiectasia and neurofibromatosis type 1.
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down syndrome, patau syndrome, ataxia telangiectasia, bloom syndrome and fanconi anemia are at increased risk of
developing acute leukemias.
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Treatment of AML M3 can release Auer rods..........>DIC
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peripheral blood smear shows the presence of myelocytes,metamyelocytes, nucleated erythricytes
and teardrop erythrocytes.a bone marrow specimen shows marked thickened trabeculae with
replacemnt of marrow by cellular fibrosis tissue with admixed marrow elements..
explanation
Abdominal fullness related to an enlarged spleen (splenomegaly).
Bone pain
Bruising and easy bleeding due to inadequate numbers of platelets
Fatigue
Increased susceptibility to infection, such as pneumonia or diarrhea
Pallor and shortness of breath while doing physical work due to anemia
Because of a high rate of cell turnover, hyperuricemia and gout may also complicate the picture
The bone marrow is replaced by collagen fibrosis, impairing the patient's ability to generate new
blood cells resulting in a progressive pancytopenia
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clonal myeloproliferative disease of pluripotent hematopoietic stem cell ...... diagnoses is conformed by decrease in
EPO and bone marrow asipration cytogenetic studies showing a JAK2 mutation. ................ Patients frequently
present with nonspecific symptoms (eg, headache, weakness, diaphoresis), aquagenic pruritus, facial
plethora, and splenomegaly. Associated conditions include peptic ulcer disease (altered mucosal
blood flow due to increased viscosity) and gouty arthritis (higher red cell turnover). Polycythemia
vera is caused by abnormal transduction of erythropietin growth signals. The erythropoietin recepto has no
intrinsic kinase activity and must interact with Janus kinase 2 (JAK2), a cytoplasmic tyrosine kinase, to
initiate downstream signaling. Virtually all patients with polycythemia vera have a mutation in JAK2 that
causes constitutive activation of its kinase domain, resulting in clonal proliferation of myeloid cells. JAK2
mutations have also been implicated in essential thrombocuthemia, primary myelofibrosis and other
myeloproliferative disorders.
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95% have V617F or exon 12 mutation>>>JAK2>>replaces a valine with phenylalanin at position 617>>rendering
hematopoietic cell more sensitive to growth factor eg eryhtropoietin and thrombopoietin.
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in response to proliferation of monoclonal cell lines>>>caused by atypical megakaryocytic
hyperplasia>>which activate fibroblast proliferation>>>resulting in progressive replacement of
marrow space by collagen. initially there is hypercellularity in bone marrow with minimal
fibrosis, as disease progresses pancytopenia results. hematopoesis is compensated by
extramedullary hematopoesis.
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the mutation V617F substitutes a bulky phenylalanine for a conserved valine at position 617, resulting in
constitutive tyrosine phosphorylation activity and consequently cytokine independent activation of JAK-STAT
pathway.
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plasma volume increases due to pooling of RBCs in spleen. these patient have some degree of hypersplenism.
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polycythemia is less common
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with the exception of CML
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cerebellar hemangioblastoma are often associated with polycythemia.
fibroids can also produce erytho and cause polycythemia
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more often than HCC produce polycythemia
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>52% in males, and >48% in females
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due to extramedullary hematopoesis.
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increase basophill>>>>>increase histamine release
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also manifest with increase in WBCs and platelets. thombotic events due to blood hyperviscosity. gout due to
increase cell turnover.
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hypercellular marrow with increased blasts can be found in myeloproliferative disorders such as primary
myelofibrosis (would present with splenomegaly and fatigue) or chronic myelogenous leukemia ( would present
with leukocytosis), MDS (would present in older pateitns) and certain leukemias (eg acute myeloid leukemia-
blasts would be seen on peripeheral smear)
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also in neuroblastoma
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fusion gene encodes a protein that inhibit apoptosis,while promoting mitogenesis and increased tyrosine kinase
activity
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apoptosis inhibitor protein bcl-2 is overexpressed
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may develop eosinophilic granuloma
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increased production of cyclin D1 , a promoter of G1>S phase transition during the cell cycle.
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is a nuclear phosphoprotein that function as a transcription activator controling cell proliferation, differentiation
and apoptosis
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cutaneous involvemnent present as erythematous papules, nodules, and/or scalling plaques.
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primarily by argatroban(parenteral) and hirudin dabigatran primarily used for
prevetion and treatment of venous TE and for stroke prevention in atrial
fibrillation 1077
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unfractioned heparin binds to ATIII via a pentasaccharide in the heparin chain.results in conformational change of
ATIII which subsequently inhibits factor Xa and neutralizes thombin, promoting anticoagulation. .................. LMWH
act on factor Xa, not thrombin ..... unfractioned heparin has activity against both thrombin and Xa but LMWH has
activity against only factor Xa... both has pentasaccharide sequence but the difference exist in length of the
saccharide side chain.
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causes significant reduction in death and recurrent MI when used in acute treatment of MI as compare to
unfractioned heparin.
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they do not require antithombin III
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Heparin is the most important cause of thrombocytopenia in hospitalized patients. HIT more commonly
leads to paradoxical thrombosis rather than bleeding. HIT is a serious disorder caused by antibodies to
heparin and platelet factor IV. Both high molecular weight heparin and LMWH should be avoided
in these patients.
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dabigtran is an oral direct thrombin inhibitor that inactivates both circulating and clot-associated thrombin. It
has the same uses as the factor Xa inhibitors.
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lepirudin also
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VTE in pregnancy is complicated by the nedd to balance the risks and benefits to both mother and child. LMVH
currently provide the best balance. LMWH has a simple mode of administration, better bioavailability and
short elimination time(meaning that they can be stopped shortly priro to delivery, thereby reducing the risk of
intra or postpartum hemorrhage................ direct thrombin( dabiatran) and factor Xa (apixaban) have fetal
toxicity and are not used in preganancy clopidogrel and aspirin have no role in acute VTE treatment.
recombinant plasminogen activator is ised as thrombolytic therapy in acute VTE.however due to a significantly
increased risk of maternal hemorrahge, it shuld be reserved for the life-threatening VTE.
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drug that causes isolated thrombocytopenia inlcude heparin, beta-lactam antibiotics and vancomycin.
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rodenticides contain brodifacoum, a long acting 4-hydroxycoumarin derivative.
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barbituates may also increase heptic synthesis of clotting factor. besides
increase in metabolism of warfarin
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desired is 2-3 >3 has increased risk of bleeding.
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although PT should theoratically be prolonged by the action of on the final common pathway, in practice PT reagent
contains heparin neutralizers that minimizes this effect.
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not effective against low molecular weight heparin.
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P450 2C9
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aspirin and other NSAIDs when used concurrently with warfarin increases the risk of bleeding due to antiplatelet
effects and GI ulceration. these drugs also displace warfarin from its protein-binding site (increasing the
concentration of free warfarin). acetaminophen can interfere with vitamin K metabolism and inhibit P450.
cimetidine and amiodarone inhibit metabolism. the interection between amiodarone and warfarin is important as
some patients with atrail fibrillation may be prescribed both medications. the commonly used antiobiotics
metronidazol and TMP-SMX also inhibit warfarin metabolism. ..... spontaneous retroperitoneal hematoma (in
front of psoas major muscle) due to warfarin toxicity may result in femoral nerve injury
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They are used for venous thromboembolism treatment as well as for stroke prophylaxis in patients
with atrial fibrillation (who are at risk for embolic stroke).
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most effective if given within 6 hours of the onset of symptoms and in the absence of contraindication. emergent
cardiac catherterization id preferred to thrombolytic therapy. .............. if properly selected decreases mortality
significantly.
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and tranexamic acid. both inhibit plasminogen activation, and to a lesser extent has antiplasmin activity.
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ADP receptor require for platelet activation, aggregation and fibrin binding
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is superior to aspirin in the treatment of peripheral vascular disease...
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direct vasodilator
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useful following percutaneous cronary intervention and for treatment of unstable angina and non-ST segement
elevation myocardial infarction.
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have synergistic effects when used with aspirin
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also suspected dissecting aneurysm, and ischemic stroke with in one year.
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non-fibrin specific(also destroys fibrinogen and clotting factors V and VII. ........... other three are fibrin
specific. .......... streptkinase is a foreign protein derived from streptococci and can induce hypersensitivity
reactions.
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irreversible competitive
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5-deoxyuridine also inhibit thymidylate synthase 2018 .................... overdose of 5-
fluorouracil drug is treated with>>>>uridine ...... MTX and 5-FU both effectively inhibit
thymidylate formation.
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methottrexate indirectly inhibit thymidylate synthase.
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are inactivated by XO and thiopurine methyltransferase (TPMT) in the liver. allopurinol does not impact 6-TG in
the same manner. some physicians prefer to assess TPMT enzyme activity levels in their patients before
administering 6-MP.
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fludarabine is a deamination-resistant purine nucleotide analog that exertes its
cytotxicity by many mechainsms, including inhibition of DNA polymerase, DNA
primase, DNA ligase and rionucleotide reductase. fludarabine is used to treat CLL
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5-FU requires the presence of reduced folate in order to form complexes with
thymidylate sybthetase. 5-FU has a reduced cytotoxic effect in cells that are
deficient in THF. for this is reason, leucivarin can be utilized to potentiate the
toxicity of fluropyrimidiens such as flurouracil by strengthening the association
of the drug with thymidylate synthase. ............ thymidylate synthase is the only de novo pathway
of dTMP production. there is salvage pathway using thymidine kinase that normally accounts for 5-10% of dTMP
synthesis. activation of this pathway by thymidine supplementation can partially compensate for diminshed dTMP
synthesis
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also called folinic acid (5-formyl derivative) which is pre-reduced form of folic acid that can be used for the
synthesis of purine and thymidylate without first being converted to by DHF reductase. ................
leucovorin(N5-formyle-tetrahydrofolate) does not require reduction by
dihydrofolate reductase before it can function as a cofactor for thymidylate
synthase and other enzymes invovled with purine and amino acid syntheis.
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resistance to methotrexate can be due to: a) amplification (production of additional copies) of
the gene that codes for dihydrofolate reductase resulting in increased levels of this enzyme b)
diminishing dihydrofolate reductase affinity for MTX c) reduced influx of MTX, caused by a
change in the carrier-mediated transport responsible for pumping methotrexate into the cell... "
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structurally similar to folic acid, after gaining access into the target cell converted to polyglutamate form.
polyglutamation prevents the movement of MTX out of the cell, in a similar fashion folate and DHF stored
within the cell. ...... disrupting the synthesis of thymidine and to a lesser extent to purines ............. THF is a single
carbon group donor (typically in the form of methyl or formyl group) in the synthesis of purines ..........
contraindicated during pregnancy
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due to GI track mucosa disruption.
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risk of opportunistic infection; B-cell lymphoma
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that is incorporated into DNA leading to stand termination. it does not affect
folate metabolim. gemcitabine is antother pyrimidine analog that functons much
like cytarabine, it differs for cytarabine in that it is not S-phsae specific, likely owing
to additional cytotxic functions such as inhibition of ribonucleotide reductase.
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result in opportunistic infection (due to marrow suppression their is decrease lekocytes) and death
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cytotoxic.
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inhibition of thymidylate synthase after enzymatic conversion to its nucleotide floxuridine
monophosphate
1892
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resistant to degradation by ADA. 1890
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cholestasis and hepatitis in fair number of patients
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P450 2B 1890 .. cyclophosphamide require bioactivation by cytochrome P450 2b
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nbme>>>4,1,11>>>
fibrosis but there is no change in FEV1/FVC.
diffusion capacity and lung volume decreases

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G2 phase. DNA is checked for errors in this phase. drugs active in this phase include drugs that interclalate with
DNA and induce free radical formation. examples are bleomycin and doxorubicin.
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Anthracycline chemotherapeutic agent(epirubicin,idarubicin along with other two) ....... resistance to drug is due to
P-glycoprotein over expression
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nbme>>>1,2,25>>resistance to vincristine, doxorubicin and dactinomysin but not to methotrextae and various
alkylating agents>>>due to altered drug traansport out of the cell.
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or adequate hydration
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are non-cell cycle specific
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acrolein that is formed by these agents
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b/w hydrogen bonded bases(AT GC) causing defective base pairing and splitting of DNA. transcription and
replication failure and mutagenesis ultimately result.
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nbme>>>>2,4,13>>>non-productive cough, fever and gradually progressive dyspnea,
an X ray film shows alveolar-intersticial infiltrates, negative culture of bronchiolar lavage.>>>>>all
are sign pf pulmonary fibrosis
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the anthracycline (daunorubicin, doxorubicin, epirubicin and idarubicin).the generations of free radicals
is implicated inthe unique ability of these agents to cause cardiotoxicity. dilated cardiomyopathy is
cumulative dose-dependent and may present many months after discontinuation of the drug. swelling
of the sarcoplasmic reticulum is the morphologic sign of an early stage of doxorubicin-associated
cardiomyopathy. it is followed by loss of cardiomycytes (“myofibrillar dropout”). The most effective
method of preventing doxorubicin cardiomyopathy is dexrazoxane. It is an iron-chelating agent
that decreases formation of oxygen free radicals by doxorubicin and other anthracyclines
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also called 2-mercatoethanesulfonate 1816 ............. also by aggressive hydration and
bladder irrigation.
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both positve and negative supercoil 2018
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microangiopathic hemolytic anemia with cisplatin and cyclophosphamide 508
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in metaphase of M phase
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resutls from desruption of neuronal microtubules, which are responsible for transoporting oraganes and other
cellular products between the neuronal cell body and the axon terminals.
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semisynthetic drivative of plant alkaloid podophyllotoxin, which targets topoisomerase II. podophyllin is used
topically to treat genital warts.
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etoposide killed cancer cells show a high number of double-stranded DNA fracture>>>>these fracture are due to
dysfunction of topoisomerase II. etoposide and podophyllin specifically inhibit the topoisomerase 2 ability to seal the
strand breaks it induces, causing chromosomal breaks to accumulate and eventual cell death.
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taxanes
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irinotecan and topotecan inhibit topoisomerase 1, an enzyme that induces single strand breaks in DNA to relieve
negative supercoiling during replication.
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decrease cumulative toxicity with platinum containing and alkylating chemotherapeutic agents and to decrease
xerostomia (dry mouth)
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resistance to drug is due to P-glycoprotein over expression
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by binding to beta-tubulin
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only negative supercoil 2018
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inhibit sealing activity>>>breaks accumulates>>>cell death 2018
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inhibits cellular proliferation of cells expressing BCR/ABL without inducing apoptosis.
1628
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26 protesome inhibitor
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EGFR inhibitor eg erlotinib and gefitinib are used to treat advanced non small cell lung cancer.
7721
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due to androgen excess 7585
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acneiform eruption like methyltestosterone and lithium
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mutated KRAS is ressistant to anti-EGFR therapy( cetuximab and pantimumab).
as such genetic testing aimed at identifying tumors with wild type (normal0 KRAS
or mutated KRAS is recomeneded prior to initaitng therapy ...................... use in
menetrier disease
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also we give busulfan
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also we give fludarabine
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by preventing degredation of pro-apoptotic factors
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it depletes B cells (and abnormal antibody production) through multiple pathways, including complement mediated
lysis, antibody dependent cytotoxicity (via NK cells) and induction of lymphocyte apoptosis.
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causes hypoxia and necrosis at target
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active stage 7721
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borionic acid containing dipeptide 11584
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has tyrosine kinase receptor 11585
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crizotinib>>>in non-small cell lung cancers 8281
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inhibit MAPK, and PI3K/Akt signaling pathway
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inhibit proliferation and apoptosis both
11585
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" Prevention and treatment
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osgood-schlater disease is an overuse injury of the secondary ossification
center (apophysis) of the tibial tubercle. common in adolescet atheltes after
recent growth spurt. tibial tubercle is the insertion point of patellar ligamnet (where
quadrciepps muscles converge). repetitive quadriceps contraction (eg jumping)
and chronic avulsion casue the proximal patellar tendon to seperate from the
tibial tubercle. during the healing process, callous formation causes the tubercle
to become elevated and prominent.
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arise form the anterior intercondylar area (fossa).
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patellar ligament>>>inferior projection of quadriceps femoris tendon>>>>injury>>difficulty with leg extension
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tendon of biceps femoris (part of hamstring) inserts at the styloid process of the
head of the fibula. the medial condyle of the tibia is the insertion site for the
semimembranous muscle, the most medial of the hamstring muscles.
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meniscal injury is diagnosed by joint line tenderness while the knee is flexed
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satorius muscle is the longest muscle in the body, originats form the anterior iliac
spine and inserts into the pes anserinus of the anteromedial tibia shaft near the
tibial tuberosity. pes anserinus bursitis commonly occurs in runners and causes
anteromedial knee pain
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oblique popliteal ligament>>>>is wide fibrous band that connects the posterior distal femur to posterior proximal
tibia>>>>it has small opening for vessel, nerves and muscle insertions.
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meniscus and collateral opposite effect,
cruciate same one
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nbme,7,1,43
in football players ossification of medial collateral ligament is very common.
not tendon of adductor magnus.
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The rhomboid major is innervated by the dorsal scapular nerve (C5). It originates on the
spinous processes of T2-5, inserts on the medial border of the scapula, and draw the scapula
upward and medically. The serratus anterior originates on the first 8 ribs and inserts on the
medial border of the scapula. It rotates the scapula upward, allowing abduction of the arm over
the head. Paralysis (due to injury of the long thoracic nerve) results in impaired abduction and
winging of the scapula, but not should droop.
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the teres major arises from the inferior scapula and inserts into the medial intertubercular
sulcus of the humerus.the muscle helps with homoral extension and internal rotation.
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ACL often injure in sudden acceleration or deceleration in non-contact athletic injuries.
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suprapatellar bursa located anteriorly between distal femur and quadriceps. bursitis here is caused by most often
from direct blow to distal thigh or prolonged/repetitive quadriceps activity (eg running)
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anserine bursitis>>>pain along the medial knee and well defined tenderness approximately 4 cm distal to
anteromedial joint margin of the knee.. frequently result from obesity or overuse in athletes. anserine bursa is
made up of semitendinosus, gracilis, and sartorius ............ bursa become inflamed due to infection (septic
bursitis) crystalline arthropahty (eg gout) and autoimmune disease (eg RA) ........... because bursa are located in
prominent and exposed positions, the pain of bursitis is may be exquisite and point tenderness is typical. active
range of motion is often decreases but passive motion is usually normal due to less pressure on inflammed bursa
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the soleus and gastrocnemius muscle combine to form the achilles
tendon.which insert on the posterior calcaneous and acts in ankle flexion. the
tendon can be injured with sudden forces during strenous activities ( eg sudden
pivoting on a foot or rapid acceleration)
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repeated impingement between humerus head and acromion especially during abduction. ............ impingement b/
w head of humerus and acromioclavicular joint
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1:medial rotation of the arm also bythoracodorsal nerve(latissimus dorsi muscle) this muscle also causes extension of
arm. 2:adduct and medial rotation(pectoralis major)
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adduction>>latissimus dorsi, perctoralis major, coracobrachislis, subscapularis and teres minor and major.
extension>>primerily by latissimus dorsi, posterior deltoid and teres major. flexion>>pectoralis major, biceps brachi,
anterior deltoid and coracobrachilis, internal rotation>>>insertion of subscapularis with contribution from teres
major, perctoralis major, anterior deltoid and latissimus dorsi on the lesser tuburcle of head of humerus
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with shoulder drop
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nurse maid elbow>>>>annular ligament
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all these along with biceps tendon stabilizes glenohumeral joint
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abducted at 90 then flexed at 30, thump pointing ground, pressure downward produces pain in the shoulder along with
weakness
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abduction of the arm above 90°.the long thoracic nerve (serratus anterior muscle AND trapezius(cn11)
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ankle is stabilized laterally by the anerior inferior tibiofibular, anterior
talofibular, posterior talofibular and calcaneofibular ligaments. the most
common ankle sprains (inversion and plantar-flexed foot) involve only the
anterior talofibular ligament and ecchymosis at the anterolateral aspect of the
ankle. however stronger forces can injure multiple ligaments. ..............................
dorsiflexiona and/or eversion of the ankle can cuse a high ankle sprain affecting
the syndesmotic structures (interosseous membrane and anterior, posterior and
transverse tibiofibular ligaments) which connect the tibia and fibula.injury to these
structures are uncommon as they can withstand sever forces, patient usually have
an unstable ankle join with tenderness at the distal tibiofibular joint, but no
significant swelling. ......... the medial deltoid ligament complex is stronger than
the other ligaments and is not commonly injured. forcedeversion of the ankle can
damage the deltoid ligament but more commonly causes an avulsion fracture of
the medial malleolus. ........ the subtalar joint is at the psoterior junction between
the talus and the calcaneus and is reinforced by the talocalcaneal ligaments, the
joint is involved with inversion, eversion, dorsiflexion and plantar flexion of the
foot, but is infrequently injured.
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caused by swelling of gastrocnemius or semimembranosus bursa, often from due to extrusion of synovial fluid
from the knee joint into the bursa in patients with osteoarthritis or inflammatory joint disease (RA)
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other profession associated with prepatellar or infrapatellar bursitis include carpet layers, mechanics and plumbers.
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according to uworld>>> PCL (it is least injured knee ligament) most commonly injured in contact support and car
accident following a direct blow to the anterior proximal tibia. generally ACL is more commonly injured. patellar
fracture also occur in direct blow due to car accident>>>inability to extend leg
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the pectoralis major arises from the anterior clavicle, sternum, costal cartilages and aponeurosis of the
external oblique muscle. It attaches on the lateral lip of the bicipital groove of the humerus and serves
to adduct and internally rotate the humerus. The muscle is anterior to the chest tube insertion site.
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abduction of the arm at angles below the horizonatl plane.
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medial epicondyl is the site of wrist flexors.
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thumb swing on this
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from articulation with scaphoid and lunate bone
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is the largest bone of the proximal carpal row. the dorsal scaphoid branch of the radial artery supplies the
majority of the scaphoid after entering near the bone's distal pole. blood supply to the proximal pole proceeds in a
retrograde manner.
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synovial sheaths of the flexor digitorum superficiales and pofundus tendons extends from the palm,through
the carpal tunner to a a point 1cm proximal to the transverse carpal ligament. the median nerve lies outside the
sheath.......... the deep fascia of the palm (palmar aponeurosis) spans from the flexor retinaculum at the wrist to
the fibrous flexor sheaths of the digits. the fibrous flexor sheaths are thick, blind-ended tunnels on the palmar
surface of the fingers that contain the flexors digitorum profundus tendons........... dupuytren's contracture is a
slowly progressive fibroproliferative disease of the palmar fascia. nodules form on the fascia, eventually resulting in
contractures that draw the fingers into flexion.
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motor involement causes weakness of thumb abduciton and opposition, and atrophy of the thenar eminence.
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in pregnancy due to fluid accumulation. in RA due to tendon inflammation in hypothyroidism due to
glycosaminoglycan buildup in hemodialysis patient due to beta2-microglobilin deposition (dialysis associated
ayloidosis)
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carpal tunner is an anatomic space in the wrist defeined by carpal bones on the dorsal aspect and the transverse
carpal ligamnet (flexor retinaculum) on the volar aspect. the ligament attaches to the hamate and pisisform on
the ulnar side and to the trapeziuma nd scaphoid tuberosity on the radial side. the carpal tunnel contains the
flexor digitorum profundus tendond, flexor digitorum superficiales tendons, the flexor pollisis longus tendon,
and the median nerve. ....... often occur bilaterally...................
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bounded medially by the tendon of the extensor pollicis longus and laterally by the tendons of the abductor pollicis
longus and extensor pillicis brevis.the scaphoid and trapezium bones form the floor of the snuffbox.
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together with lunate form small articular surface b/w distal ulna and the carpal bones
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central bone
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lateral epicondyl serves as the primary attachment point for the extensor carpi radialis brevis and extensor
digitorum, which are involved in wrist extension. repetitive use lead to microtrauma and cause angiofibroblastic
tendinosis (ie excess fibroblasts and neovascularization) at its origin on the lateral epicondyle. there is generally
little to no true inflammatory infiltrate. .... angiofibroblastic tendinosis with little to no true
inflammatory infiltrate 11684
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nbme,11,2,12 wrong number patietn present 6 weeks after an open carpal tunnel release operation..percusion of the
area between the flexor carpi radialis and palamaris longus tendons at the distal palmar wrist crease produces a
painful shock-like sensation radiating into the affected area of the palm, nerve injury most likely occur in this
patinet due to operation is>>>>> palmar cutaneuos branck of the median nerve. explanation The palmar branch of
the median nerve is a branch of the median nerve which arises at the lower part of the forearm. It pierces the palmar
carpal ligament, and divides into a lateral and a medial branch; The lateral branch supplies the skin over the ball
of the thumb, and communicates with the volar branch of the lateral antibrachial cutaneous nerve. The medial
branch supplies the skin of the palm and communicates with the palmar cutaneous branch of the ulnar. Unlike
most of the median nerve innervation of the hand, the palmar branch travels superficial to the Flexor retinaculum of
the hand. Therefore, this portion of the median nerve usually remains functioning during carpal tunnel syndrome
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the latissimus dorsi is a large thoracolumbar muscle that contributes to forceful movement of the
humerus.it originates in a broad area spanning from the illiac crest and lumbar fascia to the
spinous processes of T7-T12 and lower ribs.it inserts at the bicipital groove of the
humerus.innervated by the thoracodorsal nerve, with fibers originating from the C6-8 nerve
roots.primary function include extension, adduction and internal rotation of the humerus. due to
broad area and exposed location,is vulnerable to injury from external trauma. also frequently
injured in sports requiring forceful downward movement of the humerus , such as throwing,
climbing, or swinging a tennis racket overhead.
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the clavicular fracture only occasionaly causes neurovascular compromise. usually involving the subclavian
vessels and supraclavicular nerve ........... clavicular fructure>>>in the middle third of
clavicle>>local swelling and tenderness.
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runs through the quadrangular space
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acromioclavicular joint subluxation typically results from a downward blow on the
tip of the shoulder and produces swelling and upward displacement of the
clavicle.not associated with the nerve injuries.
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before this supraspinatus
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due to paralysis of elbow flexors (biceps brachii, greater part of brachialis and coracobrachialis)
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largest branch. courses through the supinator muscle near the head of the humerus
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(lateral epicondyle or radial head dislocation) effect this nerve aslo. midshaft injury>>>>sparing
of triceps brachii and sensory innervation to the posterior forearm/dorsolateral hand
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arise from medial and lateral cord fibers of brachial plexus>>courses with the brachial artery in the groove between
brachialis muscle and biceps brachii, gain access to the forearm in the medial aspect of the antecubital fossa and
immediately courses between the humeral and ulnar head of pronator teres muscle. the nerve then travel between
flexor digitorum superficialis and flexor digitorum profundus muscles before entering the wrist/hand within flexor
ratinaculum .... the axiallary artery gives off the PCHA and becomes the brachial artery.>>>it courses anteromedially
in the arm and branches into the radial and ulnar arteries in the forearm. supracondylar fracture may injure
brachial artery. the common interosseus artery is the short branch of the ulnar artery that gives rise to anterior,
posterior and recurrent branches within the proximal forearm.
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both when lesion is at elbow.
only ape when lesion is at wrist
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courses between olecranon and the medial epicondyl of the humerus before entering the forearm, where it lies
between flexor carpi ulnaris and flexor digitorum profundus muscle .... the aponeurosis of the flexor carpi
ulnaris at the elbow spans from the olecarnon to the medial epicondyl and forms the roof of the cubital tunnel,
the ulnar nerve runs throgh this space.compression causes ulnar lesion.
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superficial branch of ulnar nerve provides senstion to medial 1 and half fingers and hypothenar prominence. deep
motor branch of ulnar nerve supply most of the intrinsic muscle of the hand ... in the forarm innervate fleoxr carpi
ulnaris and medial portion of flexor digitorum profundus.
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b/w hook of hamate and pisiform bone which from guyons canal.
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other location is>>>entrapment between the pronator teres. ........................ normally pronation is done by median
nerve.
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repetitive supination/pronation>>causes injury to the radial nerve passing through the supinator canal
(screwdriver)>>>> finger drop, (triceps brachii which causes elbow extension and extensor carpi ulnares longus
which causes wrist drop does not occur), sensory innervation is also preserved.
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midshaft fracture is associated with injury to the deep brachial/profunda brachii artery. deep brachial artery is
branches off the brachial artery high in the arm, passes inferior to the teres major muscle, and courses
posteriorly along the humerous in close association with the radial nerve.the deep brachial artery give rise to radial
and middle collateral arteries. the radial collateral artery also courses with the radial nerve, but injury to this
artery from the midshaft fracture is less likely because it originates at the lower end of the spiral
groove.................. at lateral epicondyle radial nerve divide into deep branch of radial nerve(motor) and superficial
branch of radial nerve(sensory), posterior interosseus nerve>>which is branch of deep radial branch>>innervate
muscle involve in finger and thumb extension.
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due to biceps brachi muscle.
supination is also caused by supinator muscle innervated by radial nerve.
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generally rarely affect. penetrates the coracobrachialis muscles and initially courses between biceps brachii and
coracobrachialis muscles before descending toward the elbow between the biceps brachii and brachialis muscle
........... injured instrenuous upper extremity activity (eg, baseball, pitching) Innervates the major
forearm flexors (eg, biceps brachii, brachialis,) and coracobrachialis (flexes and adducts the
arm). After innervating these muscles, the remaining fibers become the lateral cutaneous
nerve of the forearm and provide sensory innervation to the skin of the lateral forearm......
coracobrachialis muscle lie deep to the biceps brachi and overlies the median nerve and brachial artery.
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protrusion of the acromion, and anterior fullness (due to humeral heads
movelmemtn into this location)
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follow a blow to an externally rotated and abducted arm (eg throwing a football)
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fracture of coracoid process of the scapula is rare. often occur who engage in
shotgun or rifle-related activite
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the interosseous membrane is a thick connective tissue sheet that runs between the radius and ulna. it serves as a
muscular attachement point and contributes to stability of the forearm. disruption can lead to instabilty to the
forearm.
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compression of the subclavian vein can cause upper extremity swelling. whereas compression of
the subclavian artery can cause exertional arm pain. TOS most commonly occurs within the
scalene triangle, which is formed by the anterior and middle scalene muscles and the first
rib. the brachial plexus trunks and subclavian artery pass between the anterior and middle
scalenes; the subclavian vein runs anteromedial to the triangle. TOS can be due to an
anomalous cervical rib, scalene muscular anomalies or injury (e.g, repetitive overhead arm
movements, trauma).
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innervated by musculocutaneous
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median and ulnar nerve
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hypertrophy of the scalene muscles
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originates on the surface of the first 8 ribs and inserts on the medial border of the scapula. it function to stabilize
and rotate the scapula upward.
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Homer's
syndrome and recurrent laryngeal nerves ( hoarseness) can be due to compression
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nbme>>>3,1,24
erbs palsy C5 due to stretch between neck and shoulder -
Klumkes paralysis T1 results due to stretch between hand and lower trunk..
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the nerve root combine into 3 trunks and pass between the middle and anterior scalene muscles (scalene
triangle) in the posterior neck. the brachial plexus controls all motor activity in the upper extremity, except for the
trapezius muscle, which in innervated by CN 11. the interscalene nerve block is a regional anesthesia for shoulder
and upper arm, administered in the scalene triangle and affects the brachial plexus roots and trunks. interscalene
nerve block also causes transient ipsilateral diaphragmatic paralysis in nearly all patients by anesthesizing the
roots of the phrenic nerve (C3-C5) as they pass through the interscalene sheath. the nerve block should therefore
be avoided in patients with chronic lung disease or with contralateral phrenic nerve dysfunction ... omohyoid
muscle originates from the upper scapular border and travels along the front of the neck to insert into the hyoid
bone. the muscle is innervated by cervical plexus branches (ansa cervicales) originating from C1-C3 and is not
usually affected by interscalene block ... the platysma is a superficial neck muscle covering the clavicle and
sternocleidomastoid before inserting around the mandible. the muscle is innervated by cervical branch of the facial
nerve, not the brachial plexus
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nbme,11,1,23 if severed tendon of the flexor carpi radialis cannot be sutures then we use tendon of the palmaris
longus to bridge the gap between severed ends because functional loss would be inginficant. The palmaris
longus is seen as a small tendon between the flexor carpi radialis and the flexor carpi ulnaris, although it is not
always present. The muscle is absent in about 14 percent of the population Absence of palmaris does not have
any known effect on grip strength
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overuse of the abductor pollicis longus and brevis can lead to De Quervain tenosynovitis, which
causes thumb and wrist pain.
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interosseous muscles, which originate on the metacarpals
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due to weakness of thenar and flexor digitorum profundus muscles of the 2nd and third digits.
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transection may cause loss of skin sensation or muscle paralysis.
entrapment can cause burning /shrp pain due to continuous stimulation of pain fibers.
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lymph node dissection
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spontaneous retroperitoneal hematoma due to warfarin therapy. clinically may present with severe pain in the
groin, lower abdomen or back may also occur if neuropathy is caused by retroperitoneal hematoma.
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qudriceps muscle
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superficial peroneal nerve>>>lateral compartment muscle>>eversiondeep peroneal nerve>>>anterior
compartment muscle>>dorsiflexion and toes extension
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The common fibular nerve may be compressed by the piriformis musclewhen the nerve passes through the piriformis
instead of inferior to the muscle with the tibial nerve. Piriformis syndrome results in motor and sensory loss to the lateral
and anterior compartments of the leg.
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due to prolonged lying after surgery. legs crossed and leg casts
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mediate by peroneus longus and peroneus brevis muscle (lateral compartment muscle) which are innervated by
superficial peroneal nerve
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due to superficial peroneal nerve injury
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between flexor ratinaculum and medial surface of talus and culcaneus>>>here tibial nerve divide into to medial
and lateral plantar nerve. lesion at this site result in sensory loss on plantar surface and intrinsic foot muscle
weakness with preservation of foot plantar flexion and inversion.
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function of tibialis posterior muscle.
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besides other causes also caused by irritation by bone spurs and irritation by the piriformis. L5 and S1 most
commonly involve. L5>>>posterior and lateral thigh, and leg pain shooting to the inner foot. S1>>pain stricktly
to the posterior thigh and leg shooting to the foot accompanied by wekness of the plantar flexion and loss of the
ankle jerk reflex. ...... sciatic nerve course just below the biceps femoris in the posterior thigh........ A positive
straight leg raise test (pain elicited in the supine patient when the leg is held straight while raised
off the examining table ) s a sing of sciatic nerve root (L4-S3) irritation. The straight leg raise test is
most sensitive of intervertebral disc herniation causing sciatica.
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sciatic foramen is a pelvic opening serving as the major pathway for pelvic neurovascular strutures to the lower limbs.
it is divided into greater and lesser sciatic foramina by the sacrospinous ligament. the greater sciatic foramen is
bordered anterolateraly by the greater sciatic notch of the ilium, inferiorly by the ischial spine and sacrospinous
ligament,superiorly by the anterior sacroiliac ligament and posterolaterally by the sacrotuberous ligament.the
piriformis originates on the anterior aspect of the sacrum and occupis most of the space in the greater sciatic
foramen. it inserts on the greater trochanter of the femur and acts to externally rotate the thigh when extended
and abduct the thigh when flexed. structures running above the prirformis include the superior gluteal vessels and
superior gluteal nerve.strutures crossing below the piriformis inclue inferior gluteal vessels, internal pudendal
vessels and multiple nerve (most notably sciatic nerve). muscle injury or hypertonicity can compress the sciatic nerve
to cause scitica like syndrome know as piriformis syndrome. muscle can be tender with deep palpation or on
streching with adduction and internal rotation
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function of gastrocnemius, soleus and plantaris muscle.
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function of flexor hallucis longus and flexor digitorum longus
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compression of tibial nerve under the flexor ratinaculum and posterior to the medial maleolus (tarsal tunnel
syndrome) can cause numbness and pain in the sole of the foot. compression of saphenous nerve anterior to the
medial maleolus can cause numbness and paresthesias at the medial foot.
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mediate by tibialis anterior muscle which innervated by deep peroneal nerve (innervate the anterior compartment of
the leg)
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also loss of extrinsic extensor of the toes>>hallusic longus and hallusis brevis
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lateral sural cutaneous nerve is a branch of common fibular nerve>>>sensory innervation to posterolateral leg
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begin in the proximal popliteal fossa where sciatic nerve divide into common peroneal and titbial nerve
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injury of femoral nerve results in knee buckling and loss of patellar reflux. they often complain of difficulty with
stairs and frequent falling secondary to 'knee buckling'. sensory loss over the anterior and medial thigh and
medial leg is typical.
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by iliopsoas muscle
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largest branch. femoral nerve fibers descends through the fibers of psoas major muscle, emerges laterally
between the psoas and illiacus muscle, and then runs beneath the inguinal ligament into the thigh.
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only nerve that exit pelvis through obturator foramen. divide into anterior and posterior branches anterior will
innervate pectinius, gracilis, adductor longus and brevis. posterior will innervate adductor magnus and obturator
externus
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acute compartment syndrome: the deep fascia of the leg, the fascial intermuscular septae, and the interosseus
membrane divide the leg into 4 compartemtns( anterior, lateral, and superficial and deep posterior), early fasciotomy
is necessary ro prevent permanent and disabling injury (eg myonecrosis, nerve damage,amputaiton). the most
common site of ACS is anterior compartment, which include the foot extensor muscle, anterior tibial artery and
deep peroneal nerve. ...................... the great saphenous vein starts in the dorsum of the foot and runs along the
medial leg and anterior thigh before merging with the common femoral vein in the femoral triangle. it is outside
the deep fascia and is not vulnerable to ACS. ....................... peroneal veins accompany the peroneal artery and
drain blood from the lateral compartmetn into the deep posterior compartment and eventually into the posteriro
tibial vein................ the deep posterior compartment contain the posteior tibial artery, peroneal arterty and tibial
nerve, ACSa involving this compartment may cause decreased sensation in the plantar surface, decreased toe
flexion, and pain with passive toe extension........ the laterla compartment of the leg contain the superficial
peroneal nerve and the proximal part of the deep peroneal nerve. ACS in this compartment can produce loss of
sensation in the lower leg and dorsum of the foot as well as foot drop.
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femoral nerve is the largest branch of the lumbar plexus the nerve emerges between the psoas
and iliacus muscles and passes under the inguinal ligament (;lateral to the femoral artery) into
the thigh before branching in the femoral triangle into an anterior and posterior division. the optimal
site for femoral nerve block is in the inginal crease at the lateral border of the femoral artery.injecting at this
site anethesizes the skin and muscles of the anterior thigh, femur and knee. the block also anethesizes the
saphenous nerve (terminal extension of the femoral nerve) to decrease sensation in the medial leg below the knee.
.............................. the adductor hiatus is an opening in the aponeurosis of the adductor magnus at the distal one-
third of the femur that allows passage of the femoral vessels into the popliteal fossa. the saphenous nerve
passes near the hiatus , but injection at this level would not anesthesize the multiple sensory branches that arise
proximal to this level ............ obturator canal is a small gap in the obturator membrane (fibrous sheet coverign the
onturator formane) that allows the obturaotr artery, vein and obturator nerve to travel from the pelvis to the thigh.the
obturator nerve innervates adductor muscles of the thigh and the skin of the medial aspect of the thigh.
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The blood supply to the femoral head derives mainly from the ascending cervical and retinacular
branches of the medial circumflex artery. These vessels are especially vulnerable to damage from
fractures of the femoral neck due to their close association with it. The deep femoral artery gives rise to the
medial and lateral femoral circumflex arteries. Branches of the lateral circumflex and superior and
inferior gluteal arteries join with the medial circumflex artery to form the trochanteric anatomosis. The
obturator artery gives rise to the artery of the ligamentum teres, which supplies a minor portion of the
femoral head. This vessel is important in children because it supplies the region of the femoral head
proximal to the epiphyseal growth plate, but it is of minimal clinical significance in adults.
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inferior rectal nerve is a branch of pudendal nerve.. branches of pudendal nerve supply the perineum and external
genitalia in males and females and are very sensitive to touch, temperature and pain
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iliohypogastric>>>arises from L1 nerve root>>emerges from the lateral border of the upper psoas major, and
passes behind the kidney anterior to the quadratus lumborum.provides motor function to the anterolateral
abdominal wall muscle. its anterior branch emerges above the superficial inguinal ring to innervate the skin above
the pubic region.the lateral branch descends over the iliac crest ti innervate the gluteal region.injury to the
anterior branch during appendentomy (macburny point) causes decreased sensation at the suprapubic region.
ililioingional nerve>>>L1 nerve>>>this nerve accompanies the spermatic cord thorugh the superficial inguinal
ring.mostly a sensory nerve and provide sensation to the upper and medial thigh and parts of external genitalia(the
root of penis and upper part of scrotum in males,and the mons pubis and labia majora in
females)genitofemoral>>>>L1-L2>> provide senation to the upper anterior thigh and motor function to the part of
genitalia(eg, cremasteric reflex in men, mons pubis in women.((((((((((((((((.scrotum/labia majora and skin of
femoral triangle)))))))))))))???????? lateral femoral cutaneous>>>>L2-L3>>>provide snsation to the skin on the
lateral thigh. obturator nerve>>>L2-L4>>innervates the skin of the medial thigh(sensory) and provides motor
innervation to medial thigh(adductors)
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psoas muscle arises form the transverse processes and lateral aspects of the 12th thoracic through 5th lumbar
vertebrae. it then courses downward across the pelvic brim anterior to thw hip joint capsule and deep to the
inguinal ligament to insert into the lesser trochanter of the femur via a tendon shared with the illiacus muscle. the
illiacus muscle and psoas muscle act as the major flexor of the hip. psoas abscesses can occur due to direct spreasd
of infection from an adjacent stucture( eg vertebral bodies, appendix, or hip joint) or from hemtogenous or lymphatic
seeding from a distant and pssible unknown site risk factor include diabtes mellitus, IV drug abusers, HIV , and
other forms of immunosuppression. sign and symtoms include fever, back pain,inguinal mass, and difficulty
walking. pain is exacerbated by movements that cause the psoas muscle to be stretched or extended, such as
extension of the hip. (ie the psoas sign). patietns frequently position themselves to minimize psoas stretching
and discomfort, particularly with hip flexion and lumbar lordosis
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the rectus femoris is 1 of the 4 quadriceps muscles that attach to the patella via a shared quadriceeps tendon. it
fucntions to extend the knee and flex the thigh. a pateient with an abscess involving this muscle would most likely
complain of thigh or knee pain and favor extension of the knee
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the quadratus lumborum courses posterior to the psoas muscle.it connects the 12th rib and upper lumbar
vertebra to the iliac crest, contratction of this muscle assists in extension and lateral flexion of the vertebral
column
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thigh sensation. 1, upper thigh and inner leg>>femoral 2, upper anterior thigh>>>genitofemoral 3, upper and
medial thigh and parts of external genitalia>>>ilioinguinal. 4, lateral thigh>>laterla femoral cutaneous nerve, 5,
medial thigh>>obturator nerve
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obturator internus is a fan shaped muscle originating from the medial surface of the obturator membrane, ischium,
and pubic rim. it exit the pelvis through the lesser sciatic foramen and inserts on the greater trochanter of the
femur, where it funcitons similarly to the piriformis ................. obturator externus runs from the obturator
foramen of the pelvis to the trochanteric fossa of the femur. it acts to externally rotate the thigh.
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patient will lean toward the affected site(ipsilateral side) to compensate for hip drop (gluteus medius lurch)
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trochanteric bursitis causes sharp, intermittent pain at the lateral hip and thigh, pain in increased on the affected
hip (eg lying on the side) and with walking. restricted joint movement is not usually present
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NBME,7,1,41
25 year old women with increase severe pain of the right hip during the past week, she runs 5
miles and recently changed her route becasue of construction, she now runs on uneven ground
rather than pavement.range of motion of the thigh is full.the pain is exacerbated by flexion and
internal rotation of the hip and by direct palpation over the lateral aspect of the hip. most likely
involved is >>>>>trochanteric bursa not sciatic nerve not anserine bursa not ischial bursa.
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nbme,6,4,10
lumbar disc herniates into the spinal canal causes PLL to push into the spinal root nerves.
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tibial nerve L4–S3)
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Ankle jerk reflex: tests
spinal nerves S1-S2.
shelf
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" S1–S2 "
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Knee jerk reflex:
tests spinal nerves
L2-L4.
shelf
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femoral nerve L2–L4)
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nbme>>>4,3,30
54 year old man with 3 month history of severe pain that radiates from his right thigh to the bottom
of his right foot., most likely cause by >>>>>disc herniation, not by sacroileitis or vertebrall body
compression fracture.
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The uniform distribution of T-tubules in skeletal muscle fibers ensures that a depolarizing signal
reaches each fiber at the same time. This coordination is necessary for muscle contraction.
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nbme>>>4,4,28 person trained for merathon during the past 6 months runs 15 miles daily. indurance training of
normal skeletal muscle result in>>>>increase capillary to fiber ratio. explanation Muscle possesses the capacity to
alter its structural and enzymatic protein content according to changes in use and environment Changes can occur at
the level of: – Structure – e.g., changes in fiber size, – Type – e.g., myosin heavy chain type – Metabolism – e.g.,
mitochondrial density, activity of oxidative enzymes – Energy storage – e.g., intracellular lipid content – Capillarity
(external to fiber) – capillary density or capillary:fiber ratio – Function – e.g., force production, speed of contraction/
relaxation, resistance to fatigue
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T-tubules are a communocation of the extracellular space that permits a more rapid spread of depolarization
through skeletal and cardiac muscle.
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skeletal muscle contratcs in response to acetylcholine, it does not have tha capability to depolarize itself as is
seen in tissues demonstrating automaticity. however smooth muscle cells is specialized tssues (GI track, uterus,
ureters, bladder and vasculature) do display automaticity regulated by outside stimuli
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first glycogenolysis and then subsequent glycolysis.
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type II b>>>>anaerobic glycolysis. type II a>>>is in between type I and type IIb and have aerobic glycolysis.
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composed of overlapping filaments, (actin and myosin) along with structural and binding protein
such as titin and alpha-actinin
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calcium efflux from cytoplasm causes relaxation, and this efflux results from Ca ATPase (to sequester calcium in
sarcoplasmic reticulum) and NA/Ca exchange mechanism (does not require ATP) on sarcolemma which accept
three extracellular Na ions in exchange for one intracellular Ca ion. calmodulin binds and activates plasma
membrane Ca -ATPase which removes Ca from the cell by hydrolyzing ATP. calmodulin is therefore an indirect
contributor to calcium efflux from the cell.
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nbme>>>5,1,35
after 3 month of weight lifting, change in muscle on biopsy are>>>increase number of
mitochondria and amount of actin per myocyte but no change in total number of myocytes.
explanation.
Wt lifting is a "Resistance Exercise"(AN-aerobic).
-the large change occur in number of Actin per myocyte and small change in mitochondria..
-Change in the # of Mitochondria
(which would otherwise Inc in "Endurance Exercises" (Aerobic) e.g Long Distance Running......
sarim explanation:
increase in myoFILAMENTS(Actin n Myosine) per myoFIBRIL
increase in myoFIBRILS per myoFIBER
# of myoFIBER does not change but their cross sectional area increases as new sarcomeres are
added in parallel (due to load stress) and it will increase the muscular tension(Force).
Note that there will be "NO change in muscle length" which is limited by it's origin and insersion.
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Troponin T binds the other troponin components to tropomyosin, troponin I binds the troponin-
tropomyosin complex to actin, and troponin C contains the binding sites for Ca2+
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Estrogen maintains bone mass in premenopausal women. Low estrogen levels lead to increased
production of inflammatory cytokines (especially interleukin-1 and tumor necrosis factor-a),
increasing expression of the receptor activator of NF-kB ligand (RANKL) and resulting in increased
osteoclast activity.
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in skeletal muscle:depolarization of cell membrane triggers the opening of L-type cacium channels present within
the myocytes T-tubule system.this directly results (through physical interaction) in the opening of the RyR1 calcium
channels present within the sarcoplasmic membrane.thsi is referred to as L-type channel-RyR mechanical
coupling. there is NO significant flux of calcium across the L-type calcium channel. skeletal muscle does NOT
require calcium to enter from the extracellular space to cause calcium release from within the cells.this is for this
reason that CCB do not affect skeletal muscle... in cardiac muscle: the L-type channel-RyR mechanical
coupling mechanism does not exist. in this case depolarization causes L-type calcium channels on the plasma
membrane to open and allow influx of extracellular calcium. the calcium binds to and activates sarcoplasmic RyR
channels by a mechanism known as calcium-induced calcium release,which then allows calcium to move out of
the sarcoplasmic reticulum.contraction then proceed in the similar manner to the skeletal muscle. in smooth
muscles:calcium enter the cell from the extracellular space durig depolarizaiton through voltage-gated L-type
calcium channels. similar to cardiac muscle, the calcium then causes a release of calcium from the sarcoplasmic
reticulum via a caclium-dependent RyR calcium channel in the sarcoplasmic membbrane. calcium then binds to
calmodulin
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IP3 binds to its receptor on the endoplasmic reticulum and leads to the release of Ca into the cytoplasm. in
vascular smooth muscle cells, this increased conentration of cytoplasmic Ca results in incmreased smooth
muscle contraction.
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TGF-beta increases the replication of osteoblast precusors, leading to increased formation of mature osteoblast.,
also increases collagen synthesis and decreases bone resortion by increasing osteoclastic apoptosis.
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for differentiaiton. M-CSF and RANK-L are produced by osteoblast and bone marrow stromal cells. ....... are
formed when severeal mononuclear precursor cells fuse ro create a multinucleated mature cells. nomral
osteoclast has 2-4 nuclei.
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in smooth muscles these are inhibited by diltiazem,>>causing vasodilaiton.. these channels are also presnt
in cardiac muscles>>verapamil causes decreased contractility
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deoxypyridinoline measure osteoclastic activity,pyridinoline covalently cross link with collagen which are most
commomly use method to detect osteoclastic activity;; tartarate resistant acid phosphatase and urinary
hydroxyproline can be used also ............. hydroxiproline not commonly used marker>>>several commonly used
meat products cause a high hydroxyproline concentration in the blood ....... this acid phosphatase (lysosomal
enzyme) present in osteoclast is resistant to degradation by tartrate.not commonly used marker becuase tartrate
resistant acid phosphatase is unable to in frozen serum samples.
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and bone marrow
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Depolarization of the T tubules in SKM fibers/sensor DHP -> Ca channels of SR/ryanodine ->
OPEN ( Unleash Ca -> myoplasm).
In SM -> SR Ca channels opened by IP3.
In cardiac M an ↑ in intracellular Ca conc (Ca dependent Ca release)
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nbme 6,1,32 In younger women, drop in estrogen production can occur if the menstrual cycle
becomes irregular or if it stops completely. The menstrual cycle can be interrupted due to over
exercising, extreme dieting or maintaining a low body weight. Female athletes and those
with anorexia nervosa or bulemia are at the highest risk. Surgically induced menopause can
also cause this condition in younger females.
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hip fracture ; later 982
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early postmenopausal osteoporosis primarily involves cancellous bone, which is especially
important for maintaining the integrity of the vertebral column. Therefore, vertebral fractures are
the most common manifestation of osteoporosis. With advancing age, the cortical bone, the
cortical bone (compact bone) that makes up the shafts of long bones and outer envelopes of
all bones become more involved, leading to an increased risk of hip fracture ...... neck of femur is
50% trabecular and 50% cortical>>>>2nd most common site of osteoporosis
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at the epiphyseal growth plate(catilage). this growth is normally regulated by GH, IGF-1, insulin, sex steroid, thyroid
hormone and fibroblast growth factor.
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normally bone form middle to end. diaphysis, metaphysis, espiphyseal cartilage/growth plate, epiphysis
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risk factor:caucasion race ,menopause,steroid,inactivity,low body weight,alcohol use ........ two major type of bone
present in adult skeleton: trabecular>>>15% by weight, but metabolically more active because of large surface
area. cortical>>>mechanical support and site of muscle attachment.
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unfractioned heparin>>>decrease bone formation. thiazolidinedione also>>>decrease bone formation
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hperthyroidism or over thyroid replacement in case of hypothyroidism can increase bone turnover. hypothyroidism
does not cause this
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BMI <22 (or weight <57.6 kg/127 pound) is associated with increase risk of low bone density and fragility
fracture.
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histologically persistence of primary , unmineralized spongiosa in the medullary canal. in normal individual
spongiosa is replaced by bone marrow ........ the osteoblast in patients with this condition
function normally
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nbme,11,3,25 steroid induced osteoporosis is due to >>>>increased bone resorption due to decreased calcium
absorption. Mechanisms of SIOP include:[5] Direct inhibition of osteoblast function Direct enhancement of bone
resorption Inhibition of gastrointestinal calcium absorption Increased urine calcium loss Inhibition of sex steroids
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is not
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Renal tubular acidosis
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medoxyprogesterone and aromatase inhibitor>>>decreases estrogen. GnRH agonist>>>decreases testosterone
and estrogen. PPI>>>decreases Ca absorption( insoluble form: calcium carbonate)
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which stimulate P450 (eg phenytoin, carbamazepine, primidone, phenobarbital)>>>>increases Vit D metabolism
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increase osteoclast differentiation and activity, decreasing osteoblast activity and synthesis of bone matrix,
inhibiting the intestinal action of Vit D in promoting calcium absorption , and increasing parathyroid hormone
level. glucocorticoid>>>>decrease intestinal Ca absorption, decreases osteoblast collagen depostion, decrease
GnRH (hypogoadism) and increase urinary excretion of Ca............ osteoporosis can also occur due to systemic
absorption of topical glucucorticoids, such as inhaled one in asthma
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fibroblast growth factor regulates the growth of epiphyseal growth plate and acts on other cell type, including
osteoblast and endothelial cell, which lead to bone matrix formation and blood vessels respectively, In
achondroplasia , bone vascularity is preserved because endothalial cells are not mediated by fibroblast growth
factor receptor 3 ...... FGF resultae chondrogenesis and osteogenesis.FGF induces proliferation of osteoblastic
precursor cells and anabolic functions of mature osteoblast.
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other form is in which there is hypothalamic or pituitary lesions cause short stature by decreasing the growth
hormone/ IGF-1 is proportional
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nbme,7,2,10
deficiency of carbonic anhydrase in osteoclasts is noted. The absence of this enzyme causes
defective hydrogen ion pumping by osteoclasts and this in turn causes defective bone resorption
by osteoclasts, as an acidic environment is needed for dissociation of calcium hydroxyapatite from
bone matrix. Hence, bone resorption fails while its formation persists. Excessive bone is formed.
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achondroplasia occurs as a sporadic mutaiton (due to advances paternal age) in 85% of cases and as as
an inherited AD trait in the remaining 15%.Only 1 mutant copy of the FGFR3 gene is sufficient to cause
the disorder, 2 copies of the mutant gene (ie, homozygosity) usually result in death shortly after birth,
achondroplasia is a fully penetrate genetic disorder.
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vertebal fracture; earlier 982
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bone pain and elevated alkaline phosphate level in an elderly patient can occur with osteoblast
metastases and Paget disease of bone (PDB)
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generally in elderly .............. osteoprotegrin(OPG) loss of fucntion mutation causes juvenile paget disease
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AVN involving the femoral head ossification center boys 3 to 10 years of age
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in paget disease osteoclast has upto 100 nuclei. normally osteoclast has 2-4 nuclei. ................... the new bone
formation is disorgnaized , and pagetic bone lesions typically appear on imaging as thickened areas of mixed
sclerosis and lucency ............... a condition that results in accelerated bone remodeling with eventual
bony overgrowth. the disease is thought to be caused by environmental factor and gene mutation.
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in the early stages of PDB, the adjacent marrow spaces are replaced by highly vascular stromal
tissue as a result of increased endothelial cell and fibroblast proliferation due to cytokines secreted
by osteoclasts, the increased vascularity causes arteriovenous shunting that can result in high out-
put heart failure. patients with PBD are also at increase risk of developing sarcomas (eg,
osteosarcoma) due to increased activity and dysregulation of osteoblasts and fibroblast
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characterized by continued osteoblastic bone formation and remodeling that result in dense,
hypovascular, mosaic pattern of lamellar bone with irregular, haphazardly oriented sections separated by
prominent cement lines. the end result is a thickened, deformed bone that is weaker than normal and
prone to fracture, ..... irregular section of lamellar bone are linked by cement line(previous area of bone resrption)
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primarily involve cortical bones..
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very characteristic finding. also has cystic degeneration
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forum
1-osteoporosis and osteopetrosis -- all ca ;po4;alk po4 and PTH normal
condition-----------------------Ca---------PHO4---------alk pho4----------PTH level

primary hyperparathyrodissm ----I------------D---------------I----------------I
Sec hyperparathyrodism----------D-----------I---------------N---------------I
CRF-----------------------------D-----------I--------------- N---------------I
VIT D DEF-----------------------D-----------D---------------N---------------I
OSTEOMALACIA------------------D-----------D---------------N---------------I
OSTEOPOROSIS -----------------N-----------N---------------N---------------N
OSTEOPETROSIS-----------------N-----------N---------------N---------------N
PAGETS DISEASE----------------N------------N--------------I---------------N
I--INCREASE
D-DECREASE
N=NORMAL
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due to excess production of mineralized matrix
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clinically present as osteomyelitis ....... 428 ewing sarcoma is an undifferentiated neoplasm of neuroectodermal
cells that most commonly occurs in the long and flat bones of children and adolescents.
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children osteomyelitis
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adults osteomielitis
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joint instability and crepitus may be present
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RA may also involve the wrists, elbow, knees and ankles. The hips and lumbosacral joints
are usually spared. Cervical spine involvement is also common and may lead to severe
disability due to pain and spinal instability, and potentially to radiculopathy and cord
compression ................ Severe chronic rheumatoid arthritis can involve the cervical spine and cause
joint destruction with vertebral malaignment (subluxation). The atlantoaxial joint is often involved and
more prone to subluxation as the atlas (C1) has a high degree of mobility relative to the axis (C2
odontoid and body) with limited intrinsic bony stability. Laxity/destuction of the transverse ligaments or
progressive erosin or fracture of the odontoid process can increase anterior movement of the atlas
and cause spinal cord compression due to posterior displacement of the odontoid. symptoms of
atlantoaxial instability with subluxation include neck pain, stiffness or neurological findings(radicular
pain). Endotracheal intubation with extension of the neck can worsen the subluxation.
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Hand joint mobility testing is part of the assessment of RA severity
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in susceptible individual after viral or bacterial infection there is an autoreactive humoral immune response
directed against cartilage components, causing inflammatory synovitis. CDR+ T-helper cells become activated
by the cartilage protiens and release cytokines that mediate chronic inflammation. CD4 T helper cells also induce
B cells to become rheumatoid factor synthsizing plasma cells. Rh factor is an IgM antibody specific for the Fc
component of self IgG. Rh factor binds IgG and forms immune complex that circulate in the serum. depostion of IC
on the synovium and cartilage activates complement in those locaiton and contributes to chronic
inflammation.......................... cartilage component serve as autoantigen that activate CD4+ T-cells.
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osteo nbme>>>1,3,22>>>>60 year old women with osteoarthritis has recurrence of pain and stiffness in her joints,
she is afebrile, the most appropiate therapy is >>>>aspirin, not colchicine neither allopurinol
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spongy synovitis and joint deformities
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progressive arthritis in the distal hands and weight-bearing joints. synovial fluid analysis show
normal to minimal inflammatory findings
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RA can cause a variety of pulmonary manifestations:the most common is a form of interstitial lung disease similar to
idiopathic intersticial pneumonia. methotrexate is a drug frequently use for RH that can also cause interstitial
pneumonitis and fibrosis
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episcelritis and scleritis associated with rhematoid arthritis causes ocular discomfort but not blindness.
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in RA tissue inflammation causes arginine residues in proteins such as vimentin to be enzymetically converted
into citulline through a process called citrullination. this can significantly alter the shape and serve as an antigen.
anti citrullinated peptide measure by ELISA. Rh factor>>> found in 80% of patients but it also found in 10% of
normal individual, 30% of SLE and nearly in all patients of mixed cryoglubulinemia. ANA>>>>
characteristically occur in IgM form in RA, but they are found less frequently than rheumatoid factor ...........
rheumatoid factor also present in nonrheumatic disease (eg hepatitis C) and in up to 4% of younf, healthy
individuals...............
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morning stiffness, tenderness and edema predominate early in this disease. later osteopenia, erosions and joint
space narrowing lead to decreased range of motion and deformities. rheumatoid nodules are firm, non-tender,
subcutaneous nodules present in 25% of patietns with RA. these occur in areas subject to pressure such as the
elbows or lumbosacral areas.
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minocycline>>>is also a DMARD
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Rheumatoid arteritis is a hypersensitivity vasculitis affecting arterioles and arteries of any size.it
produces visceral infarctions after long-standing rheumatoid arthritis. The pathology is similar to
polyarteritis and hypersensitivity angiitis, but distinct from giant cell arteritides.
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nbme>>>5,1,25
if the thinned cartilage and extensive osteophyte formaiton present on X ray, earliest stage in the
development of this condition is>>>>cracking of the cartilaginous surface not seepage of articular
fluid into the bone, not subchondral bone cyst formation.
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nbme,11,1,3 Ninety percent of patients with gout develop excess urate stores due to an inability to excrete sufficient
amounts of normally produced uric acid in the urine (underexcretion). The remaining patients either overconsume
purines or produce excessive amounts of uric acid endogenously (overproduction). •In rare cases, overproduction of
uric acid is primary, due to a genetic disorder. These disorders include hypoxanthine-guanine
phosphoribosyltransferase deficiency (Lesch-Nyhan syndrome), glucose-6-phosphatase deficiency (von Gierke
disease), fructose 1-phosphate aldolase deficiency, and PP-ribose-P synthetase variants. •Overproduction of
uric acid may also occur in disorders that cause high cell turnover with release of purines, such as meat intake and
seafood intake. These disorders include myeloproliferative and lymphoproliferative disorders, psoriasis, chemotherapy
(tissue lysis), hemolytic anemias, pernicious anemia, ineffective erythropoiesis (as in B-12 deficiency), excessive
exercise, and obesity. •Overproduction of uric acid can occur from overconsumption of foods high in purines.
•Common causes of secondary gout due to underexcretion of uric acid include renal insufficiency, lead nephropathy
(saturnine gout), starvation or dehydration, hypothyroidism, hyperparathyroidism, drugs (including loop and thiazide
diuretics and cyclosporine A), low-dose aspirin, and chronic ethanol (especially beer and hard liquor) abuse. These
disorders should be identified and corrected, if possible. •Comorbidities, including hypertension, diabetes, renal
insufficiency, hypertriglyceridemia, hypercholesterolemia, diabetes, obesity, and early menopause, are associated
with a higher incidence of gout. •Consumption of fructose-rich foods and beverages are associated with an
increased risk of gout in both men and women Because of no clinical symptoms or history we should think about
risk factors that can cause Gout... ....gender...Men more than women .......................age.....elderly more than younger
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deposit in cartilage and synovium.(engulfed by neutrophil) neutrophil amplification phenomenon
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synovial fluid crystal analysis is the definite test for gout. serum uric acid levels are less useful for diagnosis
and may be normal during an acute gout attack.
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mono or oligoarticular(in synovial fluid) deposition. knee joint is involved in 50% of cases.
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calcific tendonitis: caused by deposition of calcium hydroxyapetite crystals in periarticular soft tissue (especially
tendons)>>most common in rotator cuff tendons
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chronic infection: uric acid crystals with fibrosis and giant cell reaction in the soft tissue and
joints. subcutaneous tissue accumulation
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Phagocytosis of urate crystals by neutrophlis causes the release of various cytokines and
inflammatory mediators that leads to further neutrophil activation and chemotaxis, resulting in
a positive feedback loop that amplifies the inflammatory response ....... neutrophil positive feed
back loop that amplifies the inflammatory response, is the central mechanism in acute gouty arthritis. synovial cell
and macrophage involve in initiating inflammatory response but targeting these cell in treatment would not
decrease neutrophil positive feedback loop
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acute undiagnosed synovitis, especially when accompanis by fever or leukocytosis, represents a true emergency
and warrants an expected evaluation(arthrocentesis)>>>gross inspection may assist in diagnoses, with purulent ir
cloudy fluid suggesting an infectious or inflammatory preocess.fluid should be send for crystal analysis,cell count,
gram stain and culture.blood culture should also be drawn if septic arthritis is suspected. synovitis causes
acute joint pain, swelling, and eryhthema with restricted range of motion (both passive and active) potential causes
include spetic arthtitis (gono and non gono), crystal arthropathy (eg gout), hemarthrosis or rheumatic disease.
delayed diagnoses of septic arthtiis may lead to loss of the joint and long-term disability, and may be fatal.
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radionunleotide bone scans are useful in evaluation of metastatic and infectious bone disorders.
these findings are sensitive but very non-specific.
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low back stiffness that resolve with excercise. sacroiliac and apophyseal joints of the spine are the most
commonly affected.leading to restricted spinal mobility. many patients also develop peripheral arthritis and
enthesitis, which is defined as pain, tenderness and swelling at the sites of tendon indertion into bones (eg achilles
tendon insertion) ........ besides sacroiliac joints arthritis of the hips, shoulders and
costochondral joints canalso results
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complication in extraskeletal system: respiratory>>>involvement of thoracic spine and enthesopathies of the
costovertebral and costosternal junctions can limit chest wall expansion, leading to hypoventilaiton. chest
expansion should be monitered regularly in AS patient. cariovascular>>>the most common complication is
ascending aortitis, which can lead to aortic ring dilation and aortic insufficeincy. eye>>>>anterior uveitis,
develop in some pateitns and resent with pain, blurred vision, photophobia and conjunctival erythema.
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also can have prostatitis or cervicitis
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sterile joint aspiration always. its asymmetric arthritis of large joint. commonly affects patient 20-40 years of age
............ after 1- 4 weeks of GI infection and are caused by an autoimmune reaction.
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asymmetric mono or oligo type. enthesitis and dactylitis.
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also have keratoderma blennorrhgicum (hyperkeratotic vesicles on palms and soles) and circinate balanitis
(serpiginous annular dermatitis of glans penis)
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also peripheral enthesopathies and apical pulmonary fibrosis
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butterfly rash,inflammatory arthritis and an ulcer at the hard palate>>>>this constellation of clinical
features is typical for new-onset SLE.
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young female with pleuritis is SLE untill proven otherwise
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discoid lupus erythematosus: is characterized by thick, scaly, discoid plaques that erupt on unesposed skin and
may result in scarring. systemic symtoms is not present in most patients with DLE
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small wart like fibrinous lesions and generalized thickening on any of the valves and lead to valular insuficiency
and embolism............ produces small(1-4mm in diamter), consisting of sterile , finely ganular, fibrinous
eosinophilc material.. these vegetation may result form immune complex deposition. the condition may progress
to valve fibrosis resulting in regurgitation or possible stenosis.
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immune complex deposits in blood vessels>>.complement activation and resulting inflammation an injury. in acute
phase there is fibrinoid necrosis chronic vasculitis leads to fibrosis and narrowing of the lumen
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pleuritis and fibrinous percarditis
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present only in 60% of patients so its absence cannot rule out disease
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C1 complement component deficiency associated with development of SLE. complement may still be activated
without C1 by the alternate pathway.
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cause irreversible retinal damage, follow up ophthalmologic examination
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last two are specific antiphospholidid antibodeis.
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by reacting with cardiolipin(the dominant agent used in non-treponemal test)
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renal involvement is virtually present in all patient although it may be asymptomatic initially
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SLE may cause acute coronary syndrome at a young age even with
angiographically normal coronary arteres..
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due to activation of phospholipid-dependent coagulation pathway by
antiphospholipid antibody(lupus anticoagulant).............. aPTT not reversed on
plasma mixing studies.
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although antiphospholipid antibodies are present in 10-30% of patients with SLE,
not all exhibit clinial syndorme
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drug discontinue only when symptoms appear. not due to presence of antihisotne or antinuclear Ab
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present only in 20-30% of patients>>>its absence cannot rule out disease
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Type 2 HSR>>>autoimmune hemolytic anemia>>warm IgG antibodies against erythrocytes>>>characterized by
spherocytes, direct comb test positive and extravacular hemolysis. thrombicytopenia just like ITP. leukopenia
can also occur but is less common
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migratory arthralgias
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immune complex deposition is mesangium, subendothelial and/or subepithelial spaces. IgE deposits are
sometimes seen, confined to capillary wall and are associated with poor prognosis
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clinically present with heart murmur and may be otherwise asymtomatic. occur in 25% of patients with SLE,
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when MI occurs in the setting of normal coronary arteries, crononary arteriritis,
hypercoagulability with acute thrombosis or coronary vasospasm may be the
cause. SLE affect coronary atreries via arteritis and/or thrombosis.
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Hepatic expression of N-acetyltransferase is genetically determined
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sarcoidosis can cause arthralgia and skin changes occur is 30-50%. A variety of skin lesions are possible,
including subcutaneous nodules (erythema nodosum), erythematous plaques, or macules that are
slightly reddened and scaling. Liver biopsy shows changes in up to 75% of cases. Scattered
granulomas are the most common liver pathology finding. Liver granulomas affect the portal
triads to a greater degree than the lobular parenchyma
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Many patients experience cognitive dysfunction (known as "brain fog" or "fibrofog"), which may be characterized
by impaired concentration, problems with short and long-term memory, short-term memory consolidation,
impaired speed of performance, inability to multi-task, cognitive overload, and diminished attention span
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Lung granulomas in sarcoidosis are the result of intra-alveolar and interstitial accumulationf of
CD4+ T cells due to oligoclonal expansion and increased levels of IL-2 and IFN-y .....................
CD8 cells elevated in alveolar lavage>>>>in hypersensitivity pneumonitis
eosinophilia in alveolar lavage>>>>eosinophilic pneumonias and tropical
pulmonary eosinophilia neutrophil in alveolar lavage>>>bacterial pneumonias or
idiopathic pulmonary fibrosis
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any organ can be affeected, but lungs are more frequetly involve, folloed by skin
and eyes
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skin manifestation varies from macule to plaques, to erythema nodosum (painful)........ are erythematous to
violaceous subcutaneaous nodules usually appearing on the legs, it is a non-sepecific finding. associated with
multiple bacterial infections, most commonly S pyogens pharyngitis, but also staphylococcus sureus, fungi (eg
coccidioidis, histoplasma, blastomycosis), chlamydia and other. also associated with crhon , sarcoidosis and
other inflammatory conditions.
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Laminated Calcifications, are collection of calcium and protien
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even patients with normal serum calcium levels may have increased urinary
excretion suggesting abnormal calcium metabolism................... bone turnover also
increases due to very high 1,25 dihydoxyvitamin D levels.but this is not a primary
mechanism for hypercalcemia.
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although transient increase in pain initially with exercise, but gradual incrimental aerobic exercises is proven to
reduce pain.
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chest X-ray is essential for diagnosis.
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in the absence of acute phase reactants and other inflammatory markers.
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Stellate(star shaped) Giant-cell cytoplasmic Inclusions, are collection of lipids
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Granulomas with foreign body giant cells(means giant cell with DISORGANIZED nuclei) TYPE 4
HS
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stage 1:
bilateral hilar adenopathy
stage 2:
bilateral hilar adenopathy along with pulmonary infiltrates commonly in upper lobe
stage 3:
progession to disease causes disappearance of hilar adenopahty and only show pulmonary
infiltrate
stage 4:
characterized by lung fibrosis
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young
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produce by sarcoid granulomas
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heightened pain in response to tactile pressure (allodynia)
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occur in the absence of hypercoagulable state ............... precipitated by beta-blocker and ergotamine
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increased expression of MHC 1 antigens on the sarcolemma has been demonstrated and likely
leads to presentation of autoantigens to CD8 cytotoxic cells. muscle biopsy in polymyositis
reveals inflammation, patchy necrosis, and regeneration and fibrosis of muscle fibers.
Infiltration of the endomysium by macrophages and CD8+lymphocytes is typically seen.
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besides increase CK also has increase aldolase
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specific for dermatomyositis, but also present in polymyositis also called anti-histidyl-tRNA synthatase
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bilateral. typically present around middle age with insidious onset difficulty climbing stairs,, getting up from
chair, carrying heavy objects ........... reflexes are normal, as polymyositis involve muscles ,rather than nerves
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if first appear after the age of 50>>>>GI ................................... Symptoms may precede the dignosis of
malignancy but often parallel the course of the cancer.
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synaptic concentration of acetylcholine are unaffeted unlike in botulism or
lambert-eaton syndrome
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blockage of receptors active site, receptor internalization and degredation and damage to motor end plate due
to complememnt fixation................. causes complement mediated destruction of these receptor ............. the
decreae in number of available cation channels reduces the end-plate potential
followong acetylcholine release. because the thrushhold potential is not reached,
the muscle cell do not depolzarize.
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adverse effect of this controlled by scopolamine or hyoscyamine
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muscsrinic symptoms>>>just like botulinum toxin..and imrpvement in muscle
weakness is also like botulinum 1399 ......... Additionally, LEMS often presents with
autonomic symptoms, such as dry mouth or impotence. patients with LEMS have
hyporeflexia or areflexia, autonomic symptoms, and a classic incremental response to
repetitive stimulation.
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also associated with Pure red cell aplasia,
so chest CT should be done in suspicion of thymoma.
thymoma may appear as an anterior mediastinal mas on chest imaging.
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most often involve extraocular(ptosis and diplopia) and bulbar(dysphagia, fatigable chewing) muscles
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the action potential amplitude and action potential propagation velocity are the
intrinsic properties of the muscle...... AP amblitude is different thing form
compound muscle AP amplitude ......... in MG there is decreased compound
muscle action potential amplitude( the summed AP of all the muscle fibers in a
motor unit) on electromyography with repeated excitation.
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in certain areas, the musclemicrovasculature is attacked by antibodies and
coplement, resulting in perivascular foci of ischemic necrosis. extramuscular
manifestations may include interstitial lung disease, vsculitis and myocarditis
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associated complications with polymyositis are interstitial lung disease and myocarditis,
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other causes of increase CK are hypothyroid myopathy, muscular dystrophies, HMG-CoA reductase statin
medication, on the other hand normal CK found in polymyalgia rheumatica, vit d defecient myopathy,
glucucorticoid excess myopathy,
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nbme,7,3,37 Lambert-Eaton myasthenic syndrome (LEMS) main causal cancer small-cell lung cancer In LEMS,
antibodies against VGCC, particularly the P/Q-type VGCC, decrease the amount of calcium that can enter the nerve
ending, hence less acetylcholine can be mobilized to the neuromuscular junction. Apart from skeletal muscle, the
autonomic nervous system also requires acetylcholine neurotransmission; this explains the occurrence of
autonomic symptoms in LEMS. P/Q voltage-gated calcium channels are also found in the cerebellum, explaining
why some experience problems with coordination. Antibodies may also bind other VGCCs. Many people with
LEMS, both with and without VGCC antibodies, have detectable antibodies against the M1 subtype of the
acetylcholine receptor; it is thought that their presence participates in a lack of compensation for the slow calcium
influx.
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also prostacyclin analog (iloprost)
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pathogenesis: 1, chronic autoimmune inflammation, 2, vascular endothelial injury leading to chronic ischemic tissue
damage. 3, excessive activation of fibroblast leading to progressive tissue fibrosis.
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pallor, cyanosis and erythema that can last minutes to hours.
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thickening of the skin of hands and feets. begins as non-opitting edema of the hands and fingers.later in the course
skin become thickened, tight and shiny.
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found in 40% of patients.
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CD 4 + lymphocytes secrete biological active substances that stimulate FIBROBLAST........... one of early visceral
manifestation is esophageal involvement. incompetence of LES with atrophy and fibrous replacement.
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where melanocytes present and produce melanin for about 20-30 keratinocytes.
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occurs on the skin of the face, hands and upper trunk and on mucosal surfaces.
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atonic and dilated LES causes heart burn which is resistant to ant-acid. ........... is the result of fibrosis of the
distal esophagus with associated esophageal hypomotality. it manifests with symptoms gastroesophageal reflux
(heart burn and regurgitation)
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subcutaneous calcium deposition which may be asymptomatic or painful
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nbme>>>6,3,34
CD4+ T lymphocytes or platelets (confusion),still controversies.>>>play an important part in the
pathogenesis(be releasing cytokines) of scleroderma (systemic sclerosis, SSc)...............
Scleroderma:correct answer is T lymphcoytes and the chemokines are TGF +PDGF.triggering
agent is unknown.check UW and Goljan.
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Fibronectin binds to integrins on the cell surface and to components of the extracellular
matrix such as collagen and fibrin. It functions as an adhesive protein involved in cellular
differentiation, phagocytosis, platelet adhesion, and thrombus formation. ............ fibronectin
is a high molecular weight glycoprotein that binds to component of extracellular matrix and to integrin receptors.it is
synthsized in the liver and play a role in wound healingHeparan sulfate is a proteoglycan component of the
extracellular matrix that is primarily associated with reticular fibers and basal laminae. It contributes to
vascular endothelial cell attachment to the basement membrane, but does not specifically bind to
integrins. Hyaluronic acid is a glucuronic acid-containing glycosaminoglycan in the extracellular matrix.
It contributes to water retention in the extracellular matrix, endowing the matrix with lubricant properties
and viscous, gel-like consistency. elastic fibers consist of a core of elastin protein surrounded by fibrillin
protein microfibrils. keratan sulfate is a galactose-containing glycosaminoglycan that may play a role in
maintaining type I collagen fibril organization in the cornea. ....... laminins are heterotrimeric
glycoproteins that bind to type IV collagen underlying epithelial cells. They contribute to the
organization and function of the basal lamina (basement membrane).
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nbme>>>4,1,4 rapid efflux of newely excreted bile from canaliculi into the hepatic interstitum can be caused by
structural or functional alteraltion>>>>>>>>in tight junction. explanation Tight junctions, or zonula occludens, are the
closely associated areas of two cells whose membranes join together forming a virtually impermeable barrier to fluid
They help to maintain the polarity of cells by preventing the lateral diffusion of integral membrane proteins between
the apical and lateral/basal surfaces, allowing the specialized functions of each surface (for example receptor-
mediated endocytosis at the apical surface and exocytosis at the basolateral surface) to be preserved. This aims to
preserve the transcellular transport. They prevent the passage of molecules and ions through the space between
cells. So materials must actually enter the cells (by diffusion or active transport) in order to pass through the
tissue. This pathway provides control over what substances are allowed through. (Tight junctions play this role
in maintaining the blood-brain barrier.)
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Adhesion molecules such as E-cadherin are also responsible for transduction of growth signals
important for normal tissue growth and regeneration; disruption of intercellular adhesion signaling can
promote unchecked cellular proliferation.
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composed primarily of laminin and collagens IV and VII
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so barrier can have only trans-cellular movements
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is a transmembrane glycoprotein. it is a predictor of disease progression in some cancers.
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Plakoglobin is a member of the catenin protein family and homologous to β-catenin. Plakoglobin is a
cytoplasmic component of desmosomes and adherens junctions structures located within intercalated
discs of cardiac muscle that function to anchor sarcomeres and join adjacent cells in cardiac muscle.
Mutations in plakoglobin are associated with arrhythmogenic right ventricular dysplasia and
Pemphigus vulgaris.
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Mutations in desmoplakin have been shown to play a role in dilated cardiomyopathy,arrhythmogenic
right ventricular cardiomyopathy
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most noticeable in skin( stratum spinosum) spot like junctions
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intermediate junction
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belt-like seal at apical side hallmark of BBB and other barriers(eg testes and placental).. the cytoxtoxin of
clostridiumperfringes binds to claudin and break tight junction, and cause leakage.
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keratin major protein component of hairs and nails, and the large amount of keratin in epidermal cells makes the
outermost layer of skin waterproof. A defect in keratins 5 and 14 results in epidermolysis bullosa
simplex.(non autoimmune).................... autoantibodies against basement membrane proteins are characteristic
of epidermolysis bullosa aquistica (forms tense acral bullae) and cicatricial pemphigoid (causing chronic
conjuntivitis and scarring) ........... no known cutaneous diseases result from conenexin autoimmunity, but connexin
defects do underlie some specific forms of palmoplantar keratoderma or deafness associated ichthyosis
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nbme>>>5,2,37
the backflow of glucose from basal side of intestinal epithelium into intestinal lumen is prevented
by>>.tight junction
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3 process involve invasive tumor: 1, detachment 2,detached tumor cells have the ability to adhere to basement
membrnaes. Neoplastic cells may acquire this ability due to increased expression of laminin and
other adhesion molecules. 3, invasion of basement membrane occurs due to secretion of
proteolytic enzymes (metalloproteinases), an other important enzyme is the cathepsin D
protease
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adhesion molecule classed include the integrins, cadherins, selectins and lg superfamily
members. The intergins area family of transmembrane protein receptors that interact with the
extracellular matrix by binding to collagen, fibronectin and laminin. Because integrins bind
ligands with relatively low affinity, cells are allowed some flexibility to explore the surrounding
environment without becoming affixed to one location or losing an attachment altogether.
Fibronectins are large glycoproteins produced by fibroblasts and some epithelial cells.
Fibronectin binds to integrins, matrix collagen, and glycosaminoglycans, serving as a
mediator of normal cell adhesion and migration
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Postinflammatory hypopigmentation is characterized by redistribution of existing melanin
within the skin. This finding may also be associated with reduced transfer of melanin to
keratinocytes.
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or in adnexal structures.
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melanocyte are neural crest derivative that migrate to the basal layer of epidermis during embryogenesis. they
posses dendritic processes that intercalate between the remianing cells of the epidermis and facilitate the delivery
of pigment-laden melanosomes form the melanocyte to the keratinocyte. darkening of the skin on exposure to UV
rays is not due to a proiferation of melanocytes, it is due to an increase in prodcution of melanin by a stable
number of melanocytes. darker skin and fairer skin peaople have roughly same number of melanocytes.
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there is loss of epidermal melanocytes. .... partial or complete loss of epidermal melanocytes. Ages of
onset varies, but most afflicted individuals will have developed lesions by the second or third
decade of life. histologic examination of the epidermis demonstrates a loss of melanocytes and a complete
absence of melanin pigment. Proposed mechanisms encompass autoimmune activity,
neurohumoral toxicity specific for melanocytes and melanocytic self-destruction secondary to
toxic intermediate exposure during melanin synthesis. Not only have circulating melanocyte
antibodies been identified in this population, but there is also significant, pernicious anemia.
Addison disease, autoimmune hepatitis, Graves’s disease autoimmune thyroiditis
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also with seborrheic dermatitis, atopic dermatitis and psoriasis
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normal number of melanocytes produce more melanin
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eczematous dermatitis also.
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dyskeratosis: is abnormal premature keratinization of individual kertinocytes below the stratum granulosum.
dyskeratosis can be due to genetic mutations (dyskeratosis congenita) or may be found in diseases such as
squamous cell carcinoma.
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Lentigo is benign linear (not nested) melanocytic hyperplasia
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nbme>>>4,3,43
supernumerary nipple (also known as a third nipple, triple nipple, accessory nipple, polythelia or
the related condition: polymastia) is an additional nipple occurring in mammals, including humans.
Often mistaken for moles, supernumerary nipples are diagnosed at a rate of 1 in 18 males and 1 in
approximately 50 female humans.
The nipples appear along the two vertical "milk lines", which start in the armpit on each side, run
down through the typical nipples and end at the groin. They are classified into eight levels of
completeness from a simple patch of hair to a milk-bearing breast in miniature.
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intense pruritis is a hallmark of this disease and diagnoses cannot be made with out it
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histological manifestation of active eczema such as intraepidermal vesicles, superficial epidermal hyperkeratosis
producing scales, epidermal hyperplasia(acanthosis), and/or chronic inflammatory infiltrate within the dermis
.............. most present symptoms with 5 years of age, with many developing symptoms in first year of life
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characterized histologically by spongiosis (abnormal accumulation od edema fluid in the intercellular spaces
between keratinocytes>>the intercellular bridges become more distinctive in an edematous background, and the
epidermis is often described as "spongy". eventually, the edema can become so marked as to form intraepidermal
vesicles ). a pervascular infiltrates of lymphocytes and eosinophils may also be seen ,this may involve only the
superficial dermis(if due to exposure to a surface antigen) or extend to include the deeper vessels(if due to a
systemic antigen exposure (eg drug). with persisitent antigen exposure lesion may become less edematous and
weepy. thickening of the stratum spinosum (acanthosis) and stratum corneum (hyperkeratosis) produces raised,
scaly plaques..... characterized by localized erythema, vesicles, edema, and severe pruritis.
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neoplasm composed of round, uniform melanocytes (nevus cells) that are mitotically quiescent, they are typically
less than or equall to 6mm. melaocytic nevi are progressive lesions that typically mature through the following
phases, junctional>>>compound>>intradermal
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aggregates of nevus cells along the dermoepidermal junction. flat black to brown pigmented macules with darker
coloration in the center than the periphery and preserved skin markings
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pathogenesis is complex involving CD4+, CD8+ T cells, dendritic cell, and surrounding keratinocytes, Interection
among these cell results Th1 and Th17 type cytokines (including TNF-alpha, IL-12, IFN-gamma, IL-23, and IL-17)
and keratinocyte growth factors, leading to keratinocyte proliferation , inflammation and angiogenesis ....
cyclosporine, etanercept (moderate to severe plaque type psoriasis) and methotrexate (target rapidly dividing
epithelial cell) also been used for psoriasis ......... Ustekinumab (stelara) is a human monoclonal antibody used in
psoriasis that targets IL-12 and IL-23, it inhibits differentiation and activation of CD4+ Th1 and Th17 cells ........
topical Vit D analogue (calcipotriol, calcitriol, and tacalcitol), these medication bind to and activate Vit D receptor,
a nuclear transcription factor that causes inhibition of keratinocyte proliferation and stimulation of keratinocyte
differentiation. Vit D analogue have also been shown to inhibit T-cell proliferation and other inflammatory
mediators
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sharply demarcated, salmon colored rounded covered with a loosely adherent ,silvery white plaque.
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most common complication is psychological ...... patient with psoriasis frequeltly develop additional complications
1, psoriatic arthritis 2, nail changes: yellow discoloration, pitting, thickening or crumbling 3, Inflammatory disorders
of the eye: conjunctivitis, blepharitis, or uveitis
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pilosebaceous units
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of small cells resembling basal cells.
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tan or brown epidermal tumor commonly identified on the skin of middle-aged to elderly individuals. can be found
almost anywhere on the body. may have variable appearence from nearly flat macules to raised wart-like lesions
ranging in size from a few millimeters to several centimeters. they typically have a valvety to greasy surface and
well demarcated border, and are often described as having a "stuck on" appearence.
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nbme>>>2,2,10>>>>thickened stratum corneum and epidermis with vacuolated squamous cell
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are two types IgE dependent and independent.>>>>increased postcapillary hyperpermeability. IgE independent
form occur after exposure to certain substances that directly stimulate mast cell degranulation (eg opiates, antibiotcs,
and radiocontrast media) ... also there is mast cell independent urticaria>>which is in aspirin use and angioedema
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atypical (dysplastic) nevi can resemble melanoma but typically have less extreme features>>>>>the melanocytes
commonly show cellular atypia and form coalescing nests that may fuse into a continuous layer at the
dermoepidermal border.
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pathogeneis >>>skin barrier abnormalities, defects in innate immunity, and Th2
skewed immuneresponse 740 .... caused mutation affecting proteins such as filaggrin or other
components of epidermis>>>>impairment of skin barrier function>>immunnological exposure to environmental
allergen>>>immune hypersensitivity>>have high serum level of IgE and peripheral eosinophilia with high levels
of cAMP phosphodiestrase in their leukocytes. .... atopic dermatitis is a chronic , pruritic, eczematous skin
condition that almost always begins in childhood. the pathogeneis is uncertain. it can but need not involve Type I
hypersensitivity to allergens.
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histologically>>mild superficial infiltrate composed of mononuclear cells and occasional eosinophils immediately
around dermal venules. superficially collagen are parted by dermal edema and lymphatic channel are dilated by
excess transudate. Epidermal changes are not identified.
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microscopic examination>>>composed of small cells resembling basal cells, with variable
pigmentation, hyperkeratosis (thickening of the stratum corneum), and keratin containing cysts.
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OR Intraepithelial basaloid cell proliferation with keratin-filled pseudocysts
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Sebaceous gland hyperplasia
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Psoriatic arthritis can range from mild to severe and may manifest as arthritis of the distal
interphalangeal joints, asymmetric or symmetric polyarthritis ( resembling rheumatoid
arthritis), seronegative spondyloarthropathy, or an aggressive and destructive arthritis
mutilans. The risk is increased in patients who are HLA-B27 positive.
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lumbosacara, scalp, glans penis and gluteal cleft
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munromicroabscesses>>>neutrophil may form spongiotic clusters in superficial dermis and parakeratotic
statum corneum.
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compound nevi are form as the aggregates of nevus cells extend into the dermis. compound nevi are raised
papules with uniform brown to tan pigmentation.
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are considered to be older lesions in which epidermal nests of nevus cells have been lost. the remaining nevus
cells lose tyrosinase activity and produce little to no pigment. intradermal nevi are skin to tan colored dome-
shaped, and sometimes pedunculated
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eczemaotus dematitis (eczema) is a group of conditions characterized by erythematous, papulovesicular,
weeping lesions.acute allergic contact dermatitis is a form of aczema caused by type IV hyerpsensitivty reactions
to an antigen on the skin surface, in ACD antigen are taken up by antigen-presenting langerhans cells and
presented to CD4+T cells in regional lymph nodes. the T cells are activated and migrate to the skin, where they incite
an inflammaltory response within 24 hours of antigen re-exposure. ........ depending on the type of antigen, it can be
CD8 eg poison ivy or CD4 eg nickel and neomycin
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treated with corticosteroids>>>which cure the disease but also causes atrophy of the dermis with loss of dermal
collagen, drying, cracking, and/or tightening of the skin. telangiectasias, ecchymoses from mild trauma, and
atrophic striae may also be found.
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red, weeping crusted lesions in infant involving the face, scalp and extensor surfaces. the diaper area is usually
spared. in older children it manifest as lichenification in flexural distribution
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seborrheic dermatitis>>>chronic inflammatory condition characterized by accumulation of scaly greasy skin on
the scalp,face, ears, eyelids and eyebrows
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overlying epidermis is normal
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missnomer>>>have only granulation tissue, not granuloma ........ often grows rapidly
as exophitic red nodules attached by a stalk to the gingival or oral mucosa, or skin. histologically>>>resemble
hypertrophic granulation tissues
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port wine stain (nevus flammeus) is a birthmark consisting of malformed, dilated blood vessels in
the superficial dermis>>>dark red or purple patches, typically involving the face or limbs..
port-wine stain are permanent lesions, present after bith.
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most common benign vascular tumor in adults
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in numbers
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nbme>>>1,2,44>>>>4*4 cm mass posterior to the right sternocleidomastoid muscle, mass is unilocular and filled with
watery fluid, no other abnormalities are present
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most commonly on the posterior neck and lateral chest wall (axilla) ............. lymphangioma tend to occur
subepidermally in the head, neck and axilla..... on physcial exam these tumors are lobulated , compressible and
usually transiluminate
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bluish neoplasm underneath the nail bed may be either glomus tumor or a subungual melanoma.. both are rare
diagnoses.
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tumor arises from primitive mesenchymal cells.................... biopsy will show spindle shaped cell proliferation,
neovascularization(endothelial proliferation), extravasated RBCs and inflammation........ it is a hyperplasia or
neoplasm of spindle shaped cells with markers of both smooth muscle and vascular endothelial lineage. .......
Kaposi sarcoma, the most common cancer in HIV-positive individuals, is caused by endothelial
transformation mediated by the Kaposi sarcoma herpes virus (KSHV)-encoded G-protein-
coupled receptor (vGPCR).
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also involve mucosal surfaces of face and genitals
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1/3
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unencapsulated aggregates of closely packed, thin walled capillaries. ........... these tumors are composed of
capillaries separated by connective tissue. ............ bright red when near the epidermis and more violacious,
when deeper. .......... they may be multiple and can found in skin, subcutaneous tissue, oral mucosa or lips. may
also occur in liver spleen and kidney
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intergluteal pilonidal disease is an acquired skin infection involving the upper natal celft of the
buttocks.
although pateint may present with draining sinus tracts in the intergluteal region, abdominal pain/
tenderness and diarrhea are not characteristic.
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grow in proportion to the growth of the child. capillary hemangioma are lined by endothelium that rapidly
proliferates during the growth phase of the tumor.
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in advanced stages .. endoscopically show raddish/violet ,flat maculopopular lasion or hemorrhagic nodules or
polypoid masses
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first appear on feet and leg before spreading proximally.
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numerous small, encapsulated neurovascular organs found in tge dermis of the nail bed, the pads of the fingers
and toes, and the ears. each glomus body is composed of an afferetn arteriole connected to a rsichly innervated,
muscular arteriovenous anastomosis, which is then connected to an efferent vein.. modified smooth muscle cells
are arranged in layers around these vascular channels. glomus body shunt blood away or toward skin surface to
regulate temperature.
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and down syndrome
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endothelium lined lymph spaces beneath the epidermis. differ from cavernous hemangioma only by the absence of
luminal blood cells
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are always superficial on the skin, not found on mucosa or deep tissue>>> histologicaly are sharply circumcised
areas of congested capillaries and and post capillary venules in the papillary dermis
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3-4 decades
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cutaneous angiosarcoma also known as Stewart-Treves syndrome. histopathology>>>>infiltration of the dermis with
slit-like abnormal vascular spaces.. this entitiy is arises from blood vessel rather than from lymphatic cessels
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achrocordons>>>skin tags
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just like HPV affect p-53 and Rb... knock down p53 and produces cyclin that
overpass rb ..... effects vascular and lymphatic endothelial cell,differentiate into mixed
phenotype>>increases oncogenetic potential. its genome carry several viral oncogene that inhibit both cell cycle
regulation and apoptosis, thus promoting tumorigenesis.
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strep pyogen causes this due to production of hyaluroniase and other hydrolytic enzymes. M protein is another
virulence factor, allows the bacteria to evade phagocytosis by preventing activation of the alternate pathway .also
secrete hemolysis O and S (cytotoxin that cause hemolysis) and pyrogenic exotoxins (superantigens that result in
tissue injury and septic shock) . agggressive surgical debridement and empiric broad spectrum antibiotics are
needed for treatment
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also from staph aureus , strep agalactaeie, and aeromonas hydrophilia.
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area of keratosis(white patches or plaques) that appear on mucous membrane. most often seen in smokerscannot
be easily scraped off. ....................................... ofthen suggestive of squamous cell dysplasia ...............
Erythroplakia (red plaque) represents vascularized leukoplakia and is highly suggestive of
squamous cell dysplasia,
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EBV-induced squamous cell hyperplasia; not pre-malignant
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pseudomembranous candidiasis. revealing an erythematous mucosal surface
underneath.
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clostridium
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type 3 reaction not a type 2
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nbme>>4,1,3
disease casuses>>>
disrupted assembly of keratin into intermediate filament.
explanation:
The severity of the disease, as well as the mucosal lesions, is believed to be directly proportional
to the levels of desmoglein 3
Transudative fluid accumulates in between the keratinocytes and basement membrane
(suprabasal split), forming a blister. This is a contrasting feature from bullous pemphigoid, where
the detachment occurs between the epidermis and dermis (subepidermal bullae).
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1 and 3 which disrupt cohesion of keratinocytes
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netlike intercellular IgG
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bullous pemphigoud antigen 1 and 2
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linear IgG and C3 at basement membrane
unlike pemphigous in which there is netlike intercullar IgG
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acute inflammaroty disorder, that can involve the skin of the extermities, face, trunk and neck. severe cases (EM
major) can also affect oral mucous membranes and the tongue. EM represent a cell mediated immune process,
with an inflmmatory infiltrate predominated by cytotoxic CD8 lymphocytes. EM is most frequently associated with
infections and may be due to an immune response against antigens deposited in the skin. HSV is the most
common trigger and mycopalsma is also frequently associated.
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not commonly associated with drugs.
SJS are more commonlu associtaed with drugs
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type IV HSR that primarily involves the skin and mucous membranes
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SJS is <10% of body surface involvement.
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necrotic keratinocytes in the findings. does not involve palm and soles. usually occured 1-3 weeks after and
infection (cytomegalovirus, mycolasma) or drug use ................ flue like illness followed by
extensive cutaneous and mucosal lesion. histopathologically, lesions are
characterized by epidermal necrosis and subepidermal bullae.
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unlike EM, SJS usually associated with medications (eg sulfonamides, allopuronil and phenytoin)
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necrosis
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dusky central area, a dark red inflammaorty zone, surrounded by a pale ring, and an erythematous laho in the
lesions peripherry.
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histologically, microabscesses cintaining fibrin and neutrophils at the dermal papillae tips. the overlying basal
cells become vacuolated, and blisters form at the tips of the involed papillae.
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have suepidermal cleavage. and no acantholysis............... remain intact as the entore spidermis seperates form
the dermis ( no intraepithelial cleavage). these bullae form on normal or erythematous skin. most common sites
are inner thigh, flexor aspects of the forearm, axilla, groin, and lower abdomen. elderly individuals are most
commonly involved
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biopsy of an active PV lesion will show intraepithelial cleavage with detached keratinocytes (acantholysis), retained
keratinocytes along the basement membrane, and an eosinophilic inflammatory infiltrate. direct immunoflourescence
of unaffected skin adjacent to PV lesions will show epidermal intercellular IgG and C3 deposits. circulating
autoantibodeis against desmpglein are present in many patients and can aid disgnoses.
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painful flaccid bullae and erosions of the skin and mucosal membranes. the bullae are stucturally weak and often
rupture prior to presentation, with only erosions remaining. the bullae spreads laterally when pressure is applied
on top (Asboe-Hansen sign), also have NIkolsky sign.
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also on upper back and buttocks.
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hypergranulosis is increased thickness of the stratum granulosum of the epidermis and is seen in conditons such as
lichen planus
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AK do not invade the dermis>>>premalignant>>>overtime>>>>SCC (refelcted by increase in lesion size, thickness,
dermal invasion and metastatic potential.
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has overlying whitish scale and sand paper like texture. they are often felt more than seen. hyperkerartosis in
these lesion may become prominent and from cutaneous horns.
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with destruciton of basal epidermal cells.
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Frequently misdiagnosed as tinea corporis (ringworm). begin as solitary pink or brown scaly plaque with central
clearing on the trunk, neck or extremities (herald patch)
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can be caused by OCPs and other drugs
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microscopically>>>>hyperkeratosis, parakertosis, and atypical keratinocyts(pleomorphic nuclei and multiple
mitosis). may also have pigment irregularities and dilated blood vessel in the surrounding skin, which are
consistent with the chronic sun exposure.
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dermatofibroma: (superficial benign fibrous histicytoma) result from the benign proliferation of of fibroblasts. they
commonly arise in lower extremities as solitary nodules.
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Measurement of the depth of invasion (Breslow thickness) is the mist important prognosticindicator
for patients with malignant melanoma. Dense lymphocytic infiltration of the melanoma is thought to
improve prognosis in this patient population.
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they can have varying degree of pigmentation due to functional melanocytes within the lesion. the tumor cell
resemble basal epidermal cells but extend into the dermis and form clusters with a palisade arrangement of
peripheral cells.
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dyskeratrosis>>abnormal premature keratinization of individual keratinocytes.
dyskeratotic cell is highly eosinophilic and may have small basophilic nuclear remnant.
dyskeratosis found in diseases such as SCC
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both solar and tanning-bed ultraviolet sources.
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elderly, Extension of lentigo maligna (intraepidermal lesion) into the dermis, Long radial growth phase ,face .......
multinucleated giant melanocytes are a characteristic findings in lentigo maligna melanoma. lentigo maligna are
common pigmented lesions in elderly patients and are considered by some experts to be a type of melenoma in situ.
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valine replaced by glutamate
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S-100 proteins are homodimeric calcium-binindg proteins, similar in structure to calmodulin and important in
intracellular funciotns such as protein phosphorylation and cell growth and differentiation. S-100 is a marker of
cells of neural crest deviation (melanocytes and schwann cells), as well as langerhans cells and other dendritic
cells
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melanoma typically expand superficially at first but may extend vertically into the dermis and subcutaneous
tossues, portending a poor prognosis.
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albinism and xeroderma pigmentosum
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melanoma cells are larger, contain larger nuclei with prominent nucleoli, and have greater mitotic activity
compared to nevus cell (melanocyte) atypical (dysplastic) nevi can resemble melamoma but typically have less
extreme features.
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has significant anti-tumor effects with improved survival and long term outcomes in stage 3 and stage 4 V600E
positive melanoma.
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Not related to sun exposure Located on the palm, sole, or beneath the nail, Often confused with a subungual
hematoma
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No radial phase, only a vertical phase,Can be found in any sun-exposed area
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Most common type
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marjolins ulceris an aggressive, ulcerating squamous cell carcinoma that present in an area of previously
traumatized , chronically indflammed or scarred skin. malignant transformation often occurs long after the initial
trauma, usually >10 years later
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SCC does not involve pigmented cells.BCC can involve pigemented cells, but its not a diagnoses in case of bluish
tumor in nail beds, cause it most commoly involve head and neck,and BCC rarely affect the dorsum of the hands.
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Both melanoma and squamous cell carcinoma can metastasize from the skin causing
lymphadenopathy.
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cycloxygenase also known as prostaglandin endoperoxide synthase, catalyzes the convirsion ot arachidonic acid
into prostanoids. it exists in 2 isoforms, COX 1 is constitutively expressed in various tissues an is involved in
platelet aggregation, gastric mucosal protection, vascular homeostasis. COX 2 is an inducible enzyme that is
undetectable in most tissues except in cases of inflammatory cells activation. COX 2 is induced by IL-1
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lipoxin A4 and lipoxin B4>>>dec leukocyte recruitment>>>antiinflammatory
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cysteinyl-containing leukotriens (eg LTC4, LTD4 LTE4) cause bronchospasm and increase bronchial mucus
secretion and are important in asthma pathogeenesis.
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and its precursor 5-HPETE
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centrilobular type>>can extend to include the entire lobule. death from fulminant liver failure several
days after the overdose
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enhancing glutathione production and conjugaion of the toxic NAPQI
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normally 90% metabolize in liver by sulfation and glucuronide conjugation. remainder via oxidation P450 and by
urinary excretion in unchanged form ....... in toxicity sulfation and glucuronide conjugation is saturated and
excess NAPQI is produced by P450 ....... single dose of 250mg/kg body weight or a cumulative 24 hour dose of
more than 12g/days
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also provide sulfhydral group to enhance no toxic sulfation elimination of drug
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metabolite of P450 N-acetyl-p-bezoquinoneimine, a toxic and highly reactive compound
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produced by PG H2 by prostaglandin synthase in vascular endothelium
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nbme>>>>2,4,18
regulaotr invoving inflammaotry or immediate (type 1) hypersensitivity reaction is capable of
causing increased vascular permeability and attraction of leukocytes are >>>>>> leukotrines not
PGs
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inhibit LT D4 receptor
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5-Hydroperoxyeicosatetraenoic acid
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Both COX1 and COX2 are expressed in renal tissues. Both traditional NSAIDs and selective COX2
inhibitors can cause fluid retention and aggravation of hypertension. The COX 2 enzyme is also
expressed in vascular endothelial cells and vascular smooth muscle cells, and may play a role in the
local production of prostacyclin (PGI2) a substance have been associated with an increased incidence
of cardiovascular events, aspirin Acetylating serine residues of the platelet cyclooxygenase enzyme.
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also causes apoptosis and inhibit development/recruitment of osteoclast
precursor cells 699
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at high doses. preferentially expressed at site of inflammation
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low dose aspirin is prscribed to certain pregnant pateirtns at risk of preeclampsia.
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at least two distinct COX-1 dependent mechanism contribute to GI bleeding: 1, inhibition of platelet aggregation 2,
impairment of PGs dependent GI mucosal protection. PPI can help reduce the risk of upper GI bleeding
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osteoclast take up the bisphophonate and are unable to adhere to more bony surfaces to continue resorption.
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can be caused with chronic glucucorticoid therapy. ....... osteonecrosis ( ie avascular necrosis) of jaw can occur as
an adverse reaction of bisphosphonates in the treatment of osteoporosis. chronic glucu can cause this but
primeraly involve femoral head (vertebral involvement is uncommon)
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excreted unchanged, avoid in renal failure
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and vascular smooth muscle>>where it play a role in local production of prostacyclin (PGI2)>>>that promote
anticoagulation and vascular dilation.
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very high doses of aspirin causes salicylism (vertigo, tinnitus, hearing loss) ...... acute overdose presents with
vertigo, tinnitus, vomiting and diarrhea, whereas severe intoxication can lead to coma, hyperpyrexia, pulmonary
edema and death.
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aspirin result in inhibition of platelet thomboxane A2 synthesis, but do not significantly impair endothelial PGI2
produciton, as endothelial cells continue synthsizing new Prostaglandin G/H synthase.
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at low doses predominantly inhibit COX-1.
constitutively expressed in platelets and GI track.
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SERM (eg raloxifene)>>>slow the rate of bone loss by inhibiting osteoclast differentiation.
denosumab>>>>monoclonal antibody against RANKL...
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sulfinpyrazone
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decreases tyrosine phosphorylation in response to monosodium urate crystal, resulting decreased neutrophil
activation
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disrupt cytoskeletal dependent function>>>chemotaxis,phagocytosis and degranulation
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while initiating urate-lowering therapy.
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risk of fungi and atypical mycobacteria also increases
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used to treat moderate to severe plaque type psoriasis
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34 amino acid sequence at the N-terminal portion of endogenous PTH. similar to PTH stimulates maturation of pre-
osteoblasts into bone forming osteoblasts that lay down collagen and eventually mineralize the matrix. also
increases GI calcium absorption and renal tubular calcium reabsorption.
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Severe osteoporosis may require the use of teriparatide
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added to methotrexate therapy,who have failed alone with metho
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many patient develop diarrhea and less commonly nausea, vomiting and abdominal pain
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initially at the first signs of a gout flare and can be repeated an hour later.
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should not be given in elderly and those with severe renal dysfunction.
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nbme 2,4,4>>> it filtered at the glomerulus, secreted in the proximal tubule and reabsorbed in the distal tubule.. it
works by interfering with the kidneys organic anion transporter (OAT),whihc reclaims uric acid from the urine and
returns it to the plasma. if probanacid (an arganic acid) is present, the OAT binds preferentially to it (instead of to
uric acid) preventing reabdsorpton of the uric acid.
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tumor lysis syndrome is an oncologic emergency that can develop during
chemotherpy for high grade lymphomas, leukemias and other cancer with rapid
turnover, substaintial tumor burden or high sensitivty to chemotherapy. when
large number of tumor cells are destroyed in short interval, intracellular ions such as
potassium and phophorus are released into the serum along with nucleic
acid.also causes hypocalcemia elevated potassium levels can result in
arrythmias that may be fatal, uric acid can precicipitate in kidney, causing
obstructive and acute renal failure................. RASBURICASE, can also be used
to reduce uric acid levels, rasburicase is a recombinant veriosn of urate oxidase,
an enzyme present in many mammals but not in humans. it catalyzes the
conversion of uric acid to allantoin, which is 5-10 times more soluble than uric
acid. rasburicase is effective in preventing and treating hyperurcemia and the
resulting renal manifestation of tumor lysis syndroem
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gasttulation is initiated by formation of the primitve streak, a thickening of the epiblast cell layer that appear at the
caudal end of the embryo and grows cranially. epiblast cell then undergo epithelial to mesenchymal transition,
causing them to lose their cell-cell adhesion properties. this allows them to migrate downward through the primitve
streak to form the mesoderm and endoderm layers.the remainder form ectoderm. about 2 days after gastrulation ,
some of epiblast cell migrate cranially thorugh the primitive node (the cephalic end of the primitive streak) to form a
midline cellular cord known as notochord.
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located dorsal to superior and inferior colliculi of midbrain.
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ligamenta flava>>>help hold the body errect>>>paired elastic ligament that connects the elastic laminae. form the
posterior wall of spinal canal.
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anterior pore close at 25th day
posterior pore close at 27th day
anterior defect>>>encephalocele
posterior defect>>>rachischisis
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lissencephaly (agyria) is a congenital absence of gyri. associated with severe mental retardation.
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risk factor is diabetic mothor
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developmental delay and progressive skull enlargement. cerebellar dysfunction can result in
unsteadiness and impaired muscles coordination. non-communicating hydrocephalus may
occur due to atresia of the foramina of Luschka and Magendie,resulting in symptoms of
elevated intracranial pressure (eg irratibilty,vomiting).often associated features can include
agenesis of the corpus callosum and malformations involving the face, heart, and limbs
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The ventral spinothalamic tract located in this area. it transmits light touch and pressure
sensation, although it plays a minor role. It should not be confused with the lateral spinothalamic
tract, which carries pain and temperature information
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congenital disease. more severe than type 1. it manifests in neonatal period.
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if left untreated can cause mental impairment
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in the legs
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upper extremity>>>lower motor neuron sign lower extremity>>>upper motor neuron sign. in the setting of scoliosis
......... associated with scoliosis also
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type 1
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symptoms of compression of medulla such as difficulty swallowing, dysphonia stridor and apnea.
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medulla also
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due to small space of posterior fossa. causes parts of cerebellum and medulla to herniate
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The ventral white commissure is located just anterior to the grey commissure. it is the area of
decussation for the fibers of the lateral spinothalamic tract, which transmits pain and temperature
sensation from peripheral receptors to the somatosensory cortex. Its first-order neurons are
located in the dorsal root ganglia, and its second-order neurons are found in the dorsal horn.
The axons of the second-order neurons decussate in the ventral white commissure and
ascend in the contralateral lateral funiculus. Third-order neurons are located in the ventral
posterolateral nucleus of the thalamus. Fourth-order neurons are found in the primary
somatosensory cortex in the parietal lobe. Destruction of the ventral white commissure leads to
loss of pain and temperature sensation bilaterally over the affected dermatomes (starting 1 to 2
levels below the lesion, as first-order axons briefly ascend in the zone of Lissauer before
synapsing).
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atresia of foramne lushka and megendie..... also absence of corpus callosum,
and facial malformation
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release cytotoxin and neurotoxin (NO and glutamine)>>>>inflammation
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Proliferation astrocytes are enlarges and contain a large number of fibrils and glycogen granules. Their
nuclei are large, vesicular and display prominent nucleoli.
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chorda tympani nerve,passes along the deep surface of tympanic membrane and through the pertrotympanic
fissure before merging with lingual nerve deliver taste sensation
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all intrinsic except palatoglossus
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degeneration of axon and myelin distal to the point of injury>>>>first swelling and irregularity are noted>>> with in
a week the axon is destroyed and and its fragments are digested by schwann cell and macrophages.
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at the moment of wallenrian degenration their is compensatory response also,called chromatolysis in which cell
body show sign of cellular edema. it becomes swollen and rounded, wiht the nucleus displaced to the periphery.
nissl substance become fine, granular and dispersed through out the cytoplasm (central chromatolysis) . axonal
reaction become visible in 24-48 hours after injury. maximal changes in neuronal body occur approximately 12
days after the injury. these changes reflect increased synthesis of protein by the cells in order to regenerate the
severed axon.
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terminal sulcus delineates the anterior 2/3 with posterior 1/3 and foramen cecum present along this sulcus at
midline.
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pharynx and epiglottis but not tongue
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lingual nerve
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the cell bodies of neurons contain basophilic granules called Nissl substance. It represents rough
endoplasmic reticulum and is responsible for protein synthesis.
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sustained pressure and stretching.
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The length constant, also known as the space constant, is a measure of how far along an
axon an electrical impulse can propagate. More specifically the length constant is the distance
at which the originating potential decreases to 37% of its original amplitude. ................. The
time constant represents the time it takes for a change in membrane potential to achieve 63%
of the new value. myelination decreases membrane capacitance, which reduces the time
constant; demyelination would increase the time constant and lead to slower impulse
conduction. ....... Summation can occur in the dendrites, cell body and axon hillock, but not in
the axon. Temporal summation refers to sequential impulses from the same neuron over time,
whereas spatial summation refers to simultaneous impulses from several different neurons.
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in diabetic neuropathy>>>intermittent tinglning and numbness of feet,sensation of joint position is decreases in toes
and ankels.and decreased vibration sense in feet, and decrease ankle jerk bilaterally >>>>>>>>>>are due to defect
in "larger diameter" axon of distal portion of peripheral nerve. and not due to dorsal column of spinal cord.
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golgi tendon organ Ib >>>>extrafusal muscle fiber, series>>>sensitive to muscle contraction. golgi respond to force.
muscle spindle Ia >>>intrafusal fiberm parallel>>sensitive to muscle length. muscle spindle respnd to stretch
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both pacinian and ruffini mediate touch, propioception and vibration, and are innervated by
myelinated A-beta fibers
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detect a steady stimulus;respond repetitively to a prolonged stimulus.tonic
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skin, subcutaneous tissue and joints
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both are thin fibers
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merket cells are neuroendocrine cells of the basal layer of the epidermis that are felt to play a role in perception of
touch.on histology they are often found in association with nerve projections. they are associated with a rare but
highly maliganant form of skin cancer known as merkel cell carcinoam
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subcutanoeus tissue of the skin as well as the mesentary, peritoneum and joint capsule
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withdrawl from noxcious stimuli>>>>afferent portion of reflex arc
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nbme>>>3,3,19>>>> case of congenital insensitivity to pain..... ---First we have to understand the pain
pathway.....The first order neurons for pain pathway are slow diameter neurons of dorsal root ganglia...and the second
Order neurons are in the spinothalamic TRACT ....and the third order neurons are found between THALAMUS AND
PRIMARY SOMATOSENSORY CORTEX.... --The receptors for pain pathway are called NOCICEPTORS...and these
are mainly free nerve endings and the cell bodies for these free nerve endings are found in the LATERAL part of the
DORSAL ROOT GANGLIA or the TRIGEMINAL GANGLIA ....called FIRST ORDER NEURONS There are two types
of nociceptors based on the TYPE of the AXONS 1-A delta fiber =are thin but myelinated and can allow an action
potential to travel at a rate of about 20 m/second towards the CNS.... 2-C fiber axons=thin and unmyelinated only
conduct at a speed of 2m/sec...slow compared to 1... --And in the CONGENITAL ABSCENCE OF PAIN
PERCEPTTION ...the problem is in the first order neurons Voltage Gated sodium Channel....Called Nav 1.7... --
these ION channel is usually expressed in NOCICEPTIVE FIRST ORDER NEURONS(small diameter neurons of
DRG(PAIN TRANSMISSION) and the Sympathetic Ganglion of ANS(choice C...but as there is no mention about
ANS dysregulation...C is out)..... hence the answer is EEEE Choice A- is for touch sensation ...DORSAL COLUMN
...PATHWAY-fast ,myelinated ,thick A beta fibers....
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also seen with HPV koilocytes and testicular tumor seminoma.
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vertical indentation
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dull, diffuse pain>>>C fiber
sharp, localized pain>>>Adelta fiber,
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The red nucleus is located in the anterior midbrain. Its neurons participate in motor coordination of the
upper extremities
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locus ceruleus participate in activation of the “fight or flight” response to physical and
emotional stressors. It is located in the dorsal pons. these neurons are implicated in some
anxiety symptoms ................. locus ceruleus (present in pons) play a role in the pathogeneis of panic attacks
and panic disorder. located in caudal pontine central gray matter
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medial part of brain stem reticular formation
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Nucleus accumbens and septal nucleus—reward center, pleasure, addiction, fear
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Mesolimbic pathway: Stimulus>>Cerebral Cortex>>> Ventral Tegmental Area>>Nucleus
Accumbens which produces dopamine (increase desire for stimulus) and serotonin (gives
body the impression of satisfaction so cravings are reduced). The addiction pathway in the
brain is a dopamine pathway
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this is pairedpigmented brianstem nucleus located in the posterior rostral pons
and the lateral floor of the forth ventricles, this is a principal site of NE
synthesis in the brain and projects to virtually all arts of the CNS,. INVOLVES IN
CONTROL OF MOOD, arousal( RAS), sleep wake states, cognition and
autonomic nervous systems functions( eg blood pesuure).. abnomral activation
causes anxiety ........... bilateral pontine hemorrhage presents with coma due to
disrutption of the RAS
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dynorphin is an opioid peptide that modulates pain response, it is produced
mostly in the periaquedactal gray, rostral ventral medulla, and dorsal horn of
spinal cord. ... histamine and orexin produced in posterior hypothalamus and
play a role in arousal and wakefulness
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Drugs working in ventral tegmental area Opiates Alcohol Barbiturates Benzodiazepines Drugs working in nucleus
accumbens Amphetamines Cocaine Opiates TCH PCP Nicotine Ketamine
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generally DA and 5HT goes side by side>>>>one increase other decrease and viceversa>>>DA is gas pedal and
5HT is a break
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participates in memory and cognition. located at the base of forebrain and widely projects to neocortex. ............
In the central nervous system, acetylcholine is involved primarily in arousal, memory and learning.
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CSF fluid cocnetration of homovenilic acid (primary dopamine metabolite) are aslo decrease in parkinson patients
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raphe nuclei are located in the midbrain, pons and medulla and axons from these cell bodies project widely
throughout the CNS to synapse on structures such as the cerebral cortex, thalamus, hypothalamus,
cerebellum, hippocampus and spinal cord. These neurons play a role in the sleep-wake cycle, anxiety,
mood psychosis, sexuality, eating behavior and impulsivity. .............. serotonin implicated in the
pathogeneis of anorexia, depression and sleep disorder. .......... low serotonin is related to suicide. serotonin
control impulsivity. ........ low CSF 5-HIAA concentration has been associated with impulse, destructive behaviors,
particularly aggression, suicide and violance.
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3
4
2
2
3
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via supraoptic nucleus
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adults have starvation
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VMN monitor blood glucose.
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via inhibition of adrenergic input, causing vasodilation and stimulaiton of cholinergic
input that results in sweating
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jet lag is due to dyssynchrony between the bodys circadian rhythms (the sleep/wake cycle in particular) and local
environmental rhythms. eastward travel takes longer to recover from than westward travel as it is easier to
lengthen the natural sleep/wake cycle than to shorten it. melatonin supplementation is recommended for the
traetment of insomnia associated with jet lag.
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Dorsomedial nucleus stimulation causes savage behaviour.
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neuropeptide Y>>>NT which play a role in pain perception and appetite>>>>its antagonist has been investigated
for use as antiobesity drugs
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located immediately above the optic chiasm,receives visual input from the retina via optic
track(retinohypothalamic) helps to regulate circadian rythm by relaying visual infromation to other hypothalamic
nuclei and pineal gland. thus modulate body temperature and the production of hormones such as cortisol and
melatonin. circulating melatonin levels are highest during the night and lowest during the day.incontrast, cortisol
peaks in the morning and reaches its lowest level at night.
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heat conversation and heat produciton via vasoconstriction and shivering.
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lesion is invasion of this tumor
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in children tumor of hypothlamus are commonly gliomas. in adults, they are more
likely to be metastatic
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located on dorsal surface of medulla at the caudal end of fourth ventricle. the nucleus tractus solitarius (NTS)
in the medulla receive information from the area postrema, GI track via vagus nerve, vestibular system and from
CNS (eg meninges, hypothalamus). neurona from the NTS project to other medullary nuclei and coordinate the
vomiting process. the five major receptor involved in stimulating the the vomiting reflux in the area postrema>>M1,
D2, H1, 5HT and NK1
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septal nucleaus...
...
and emotions via septate nucleus
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NON-REM sleep.(stage N3)
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diphenhydrmaine used at night time to reduce the time to sleep onset and to increase the depth of sleep .........
TCA>>>insomnia in depressed patient......... tryptophan( eg in milk before bed time) has hypnotic action, as
serotonin can be synthesized endogenously from tryptophan.
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night-mere occur in REM sleep.
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induces sleep.
used in age related insomnia.
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brodmann area 3 1 and 2
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brodmann area 41 and 42
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are interconnected by lateral lemniscus(present in midbrian)
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anterior nucleus: INFO>>>>>>Mamillary nucleus (via mamillothalamic tract) OUTPUT>>>>>>Cingulate gyrus (part of
Papez circuit
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thought to participate in new memory formation.
unique in that it freely diffuse across cell membranes and does not need to interect with other
neurons via a synapse.
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The hippocampus is important in learning and memory. The amygdala attaches an emotional significance to a stimulus
and helps imprint the emotional response in memory
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limbic system express through hypothamaus(headquarter of ANS)
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amygdala>play role in insular cortex. important for emothional anticipation and conditioned response>>>>eg
seeing heroin bag and needles>>>>>precipitates in conscious desire (craving) ....................... The amygdala is a
group of neurons in the medial temporal lobe located adjacent to the hippocampus that plays a role in
the limbic system. The amygdala can be identified on the image as the circular grey matter structures in
the medial temporal lobe immediately inferior to the globus pallidus and putamen. The amygdala
mediates fear and some sympathetic stimulation in humans.
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fornix>>is a bundle of axon originating from the hippocampal subiculum that projects to the mamillary body.
because fornix is part of papez circuit, damamge to the structure can lead to wernick encephalopathy...... the
anterior nucleus of the thalamus is a part of the papez circuit,damage to this structure can lead to wernicke
encephalopathy
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Hippocampal formation (hippocampus, dentate gyrus, the subiculum, and entorhinal cortex
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in temporal lobe
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Papez Circuit: hippocampal pyramidal cells>>>>>>>mammillary bodies in the hypothalamus(via fornix)>>>>>>anterior
nucleus of the thalamus (via mammillothalamic tract)>>>>>>cingulate gyrus>>>>>>entorhinal cortex (via the
cingulum)>>>>>hippocampus (via the perforant pathway) ......... The limbic system is interconnected with anterior and
dorsomedial nuclei of the thalamus and the mammillary bodies. • The cingulate gyrus is the main limbic cortical area. •
Limbic-related structures also project to wide areas of the prefrontal cortex. • Central projections of olfactory structures
reach parts of the temporal lobe and the amygdala ............... anterior nucleus of thalamus also involved in papez
circuit. septal nuclei also.
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mamillary body is a part of the papez circuit, which is a neural pathway of the limbic system that is involved in the
cortical control of the emotion and memory
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MD:(Dorsomedial nucleus). Involved in memory. Damaged in Wernicke-Korsakoff syndrome.. ...... Pulvinar nucleus: Helps
integrate somesthetic, visual, and auditory input Midline/intralaminar nucleus: Involved in arousal
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superior olive are present in lower pons. inferior olive are present lateral to pyramid in rostral 2/3 of
medulla,characteristic structure of upper medulla
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striate cortex
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The insula plays a role in the limbic system (emotion) as well as in the coordination of some autonomic
functions, particularly of the cardiac system.
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blood supply: 1, superior cerebellar artery,arise from basillar artery just before it bifurcates in 2 PCA. 2, AICA(arise
from basillar artery) and PICA(arise from vertebral artery)
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cerebellar infarction presents with vertigo, nystagmus, ipsilateral limb ataxia, and truncal lateropulsion
(falling toward the lesion). autopsy would show area of liquefactive necrosis (acute infarcts) and glial
scarring (chronic infarcts). .......... Cerebellar metastasis can cause progressively worsening subacute
cerebellar symptoms. Additional findings such as headaches or decreased consciousness are often
present due to significant mass effect from the tumor. However, autopsy would show metastatic cancer
cells with surrounding inflammation as opposed to purkinje cell degenration.
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nbme>>>4,3,25 anatomical studies have found that it actually consists of two parts with very different connections and
functions, the pars compacta and pars reticulata. The pars compacta serves mainly as an input to the basal ganglia
circuit, supplying the striatum with dopamine. The pars reticulata, on the other hand, serves mainly as an output,
conveying signals from the basal ganglia to numerous other brain structures.
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striatum after excitation form the motor cortex either has inhibitory signal to GPI or
GPE. in short striatum send inhibitory signal ........................ subthalamic
nucleus send excitatory signal to substancia negra(pars reticulata) whereas
substancia negra send inhibitory signal to subthalamic nucleus. ......... damage to external
globus pallidus>>decreased motion damage to internal globus pallidus>>increased motion.
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damage, associated with transient hamiparesis as well as frontal lobe symptoms such as inattentiveness, abulia,
and forgetfulness.there may be also psychosis, choreoathetosis(extrapyrmidal symptoms) and other dyskinesias.
............... damge causes behavior abnormalities,( eg agitationm pschosis, abulia,), speech/langiage
disturbances and movement disroder eg chorioathetosis....... caudate lie in inferolateral wall of anterior horn of
lateral ventricle.
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in parkinson disease: subtancia negra cant initiate movemement in the direct
pathway. also cant inhibitextra movement in the indirect pathway.
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in midbrain
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Thalamus is under the inhibitory control of GPI .If you knock out GPi then there is excessive
movement. Subthalamus is under the inhibitory control of GPE if you lesion GPE then
subthalamus is free to activate GpI that can inhibit thalamus >>decreased movement. (in resting
condotion thalamus inhibit motor cortex)The normal function of thalamus is to create
movement .It is through (dis)inhibition and release of thalamus(so that GPI does not any more
inhibit thalamus) that we achieve specific movement patterns .......... aim of the indirect
pathway is tighten(stop) the leash(extra movement) on the thalamus. which is done
when GPI inhibit thalamus. aim of the direct pathway>>>is take away of inhibition
from the thalamus, allow to become more active (thalamus is normally under
inhibition unless we desire to move)......... indirect pathway: normally GPE hold
down the activity in the STN. ................ when wo dont wanna movement , striatum
after excitation form the motor cortex inhibit GPE.so GPE does not hold down the
activity in the STN, so STN send excitatoty signal to GPI (which is our leash on
the thalamus) ............... through indirect pathway we control(adjust) leash on
thalamus. by activatng indirect pathway (D2 pathway)>>>GPE become more active
and thus GPI less active so leash from the thalamus is released>>>>and there is
excessive movement.
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nbme>>3,1,25>>>>1-direct / excitatory pathway
2-indirect /inhibitory pathway
Excitatory pathway -SNc's dopamine binds to D1 recepatar in xcitatory pathway ;stimulating the
excitatory pathway [motion] --so loss of dopamine in SN in parkinsons leads to decrease in motion
Inhibitory pathway- SNc's dopamine binds to D2 receptar in inhibitory pathway ,inhibiting the
inhibitory pathway ie disinhibition leading to increase in motion .therefore loss of dopamine in
parkinsons excites the the inhibitory pathway leading to decrease in motion.
net result decrese in motion ...

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this patient on long-term levodopa treatment for Parkinson disease has likely developed motor
fluctuations and dyskinesia which often occur >5 years after starting therapy. Motor fluctuation ca
initially correlate with serum drug levels and are characterized by good mobility during “on” periods
and increased bradykinesia/rigidity during “off” periods when drugs wears off. Dyskinesia typically
occurs when the patients is “on” and is characterized by excessive involuntary movements. Nigrostriatal
degeneration is Parkinson disease results in excessive excitation of the globus pallidus internus by
the subthalamic nucleus, which in turn causes excessive inhibition of the thalamun, Reduced activity of
the thalamus and its projections to the cortex consequently result in rigidity and bradykinesia. Patients
with medically intractable symptoms of Parkinson disease may benefit from high-frequency deep brain
stimulation of the globus pallidus internus or subthalamic nucleus. High- frequency stimulation
inhibits firing of these nuclei. This causes increases activity in the downstream nuclei, resulting in
thalamo-cortical disinhibition with improved mobility. High frequency stimulation of the ventral
intermediate nucleus of the thalamus may reduce thalamic excitation and lessen excessive
movements in patients with medically intractable essential tremor.
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can be pyramidal according to uworld
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Associative auditory
cortex
nbme>>>1,4,36>>>dont be confuse with primary auditroy cortex.
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is in the caudal end of middle frontal gyrus immedatialy anterior to the precentral gyrus(brodmann areas 6 and 8)
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nbme>>>4,2,25
45 year old man has four episode of involuntart twitching of the right foot.
following a last episdoe he had a tonic-clonic seixure,structure involve on the left is>>>>>primary
motor cortex not supplementary motor cortex.
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an increase in PCO2 from 25 to 100 causes a linear increase in cerebral blood flow and decrease in PCO2 causes a
linear decrease in cerebral perfusion.
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the main factors influencing cerebral circulation are the systemic blood pressure and the arterial
blood gas levels. when it is between 60-140 the systemic blood pressure has little effect on
cerebral blood flow because autoregulation (via cerebral vasodilation and vasoconstriction) keeps
blood flow constant.
blood pressure above 150 increase cerebral flow and blood pressure below 50 will cause
hypoperfusiona and cerebral ischemia.
the arterial blood gas has a more powerful effect on cerebral blood flow, with the PCO2 as the
most important regulator
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the anterior choroidal artery is the last branch of internal carotid artery before the trifurcation. it supplies the
posterior limb of internal capsule, optic track, lateral geniculate body, choroid plexus, uncus, hippocampus and
amygdala
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INTERNAL drain brain and superficial face and neck. EXTERNAL drain scalp and portions of lateral face.
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the dynamic balance b/w production and absorption of CSF allows stable intracranial volume(120-
150ml)
and pressure(50-180mmhg_
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lateral and fourth ventricles...
in other U WORLD says.
by 4 chroid plexus found in each of the ventricles.
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the choroid plexus is made of ependymal cell-covered outgrowths of pia mater capillaries that are
fenesterated unlike other central nervous systme capillaries.
the ependymal layer is a simple ciliated columnar epithelium with tight junctions between the cells.
this selectively allows only certain material from the blood to enter the CSF.
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nbme>>5,1,36,>>>>>only lateral ventricle are dilated..>>>>its tuberous sclerosis but not
congenital stenosis of acquedact of sylvius
explanation:
tuberous sc;erosis in which there is subependymal giant cell astrocytoma, which itself obstructs
the foramen of Monro -ïƒ enlarged lateral ventricles. Also history supports this autosomal
dominant transmission characteristic.
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at the level of superior colliculus. red nucleus are present at this level only
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IV>>>at the level of inferior colliculus. red nucleus are not present here.lateral lamniscus fibers present here
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superior ollive also associated with it
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fracture tot he orbital floor commonly result from direct frontal trauma to the orbit. the infraorbital nerve runs along
the orbital floor in a groove in the maxilla before exiting the skull just inferior to the orbit. damage can result in
paresthesia of the upper cheek,upper lip and upper gingiva.in addiiton , the inferior rectus muscle can also
become entrapped, limiitng supeior gaze.
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nbme,7,4,18
during esophagectomy >>>>vagus nerve is served not phrenic.
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ansa cervicales.>>>>arises from the C1,C2 and C3 NERVE ROOTS AND INNERVATED THE STERNOHYOID,
STERNOTHYROID AND OMOHYOID mucsles of anterior neck. penetrating trauma to the neck above the cricoid
cartilage can injure this nerve
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also contain lesser petrosal nerve.the accessory meningeal artery and the emissary vein.
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branch of maxillary,which itself is branch of external carotid
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large aperture located in the base of the skull behind the carotid canal.it is formed by the petrous portion of
temporal bone and the occipital bone. its lesion produce vernet (jugular foramne) syndorme
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inferior petrosal and sigmoid sinuses.and the posterior meningeal artery.
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ciliary muscle contract,zonular fiber relax,lens become thick,accomodation for near vision. ciliary muscle
relax,zonular fiber stretch,lens become thin,accomodation for far vision
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exit the brian stem at the lateral aspect of mid-pons at the level of middle cerebral peduncle(a key neuroanatomic
landmark for locating the nerve)
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sensory nuclei (eg principal sensory, spinal, mesencephalic) run from the midbrain to the upper
cervical spine and receive afferet signals for facial sensation via all 3 nerve branches.
motor nucleus is located in the lateral mid-pons and sends efferent signals to the muscles of
mastication via mandibular branch
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mediated by parasympathetic fibers originating in the superior salivatory nucleus carried on the facial nerve via the
chorda tympani and lingual nerve, across the submandibular ganglion
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arise from postoolivary sulcus just rostral to vagus nerve
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parasympathetic: inferior salivatory nucleus>>>>>CN 9>>>>otic ganglion>>travels along auriculotemporal nerve(CN
5)>>>parotid gland secretion.
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vagus control cough reflex both afferent and efferent
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arise from lateral medulla and upper segments of cervical spinal cord.
injured during surgery involving posterior triangle.(a region bounded by sternocleidomastoid,
trapezius and clavicle).
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transmit the maxillary division of the trigeminal from within the skull to the pterygopalatine fossa. from there it
courses through the inferior orbital fissure to appear on the face at the infraorbital foramen as the infraorbital
nerve
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inferior orbital fissure>>>maxilary division of trigeminal nerve V3, the infraorbital vessels, and branches from
the spjenopalatine gangion pass thorught he inferior orbital fissure but do not enter the orbit
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nucleus is located medially on the floor of the fourth ventricle at the level of medulla and the nerve exits at the
rostral end of the preolivary sulcus
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arise from postoolivary sulcus just caudal to glossopharyngeal
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during swallowing
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also general sensation from inner surface of tympanic membrane,eustachian tube,tonsillar region
and upper pharynx(afferent portion of gag reflux)
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origin is from wall of tympanic cavity and inserts on the neck of stapes.
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nucleus is located in the dorsolateral aspect of caudal pons and the nerve exits at the ventrolateral
pontomedullary junction,which is located at the level of the facial colliculus(below the middle
cerebellar peduncle.
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mandibular (V3) division provides sensory innervation to face and motor innervation to the muscles of mastication.
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nucleus is located in the caudal midbrain and the nerve exits the dorsal midbrain just below the
inferior colliculus (below the red nucleuss).
only cranial nerve decussate before innervating its target (the superior oblique muscle)
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nucleus is located in the rostral midbrain(mesencephalon) at the level of the superior colliculus and red nucleus,
and the nerve exits at the interpeduncular fossa.
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courses on top of levator scapulae muscle.
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foramen lacerum contains the meningeal branch of ascending pharyngeal artery, emissary veins and the artery
and nerve of pterygoid canal. This foramen is otherwise occluded by cartilage and fibrous tissue. the internal carotid
artery courses just superior to the foramen lacerum in the lacerum portion of the carotid canal but does not
transverse it.
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also contain middle meningeal artery and vein, meningeal(recurrent) branch of CN V3 which supplies the dura
and contains sympathetic fibers.
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nasociliary branch.
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in the upper back and neck that serves to elevate, rotate and stabilize the scapula.frequently injured in rear-end
("whiplash") motor vehicle accidents. .... frequently injured in rear-end (whiplash) motor vehicle accidents. also
in cervical lymph node excision when at posterior triangle of neck. .... vulnerable to penetrating trauma
and iatrogenic injury (eg, from cervical lymup node dissection). Symptoms of trapezius including
drooping of the shoulder impaired abduction of the arm above horizontal (due to weakness in
rotating the glenoid upward), and winging of the scapula. if injury involves the proximal portions of
the nerve, weakness of the sternocleidomastoid may be seen as well. .......... composed of fibers from
carnial and cervical spinal nerve roots.it is a pure motor nerve that passes through the
posterior triangles of the neck trapezius has a large origin extending from the occipital bone
and the spinous processes and ligaments of the cervical and thoracic vertebrae down to T12. It
inserts on the lateral one-third of the clavicle, acromion, and spine of the scapula. The
trapezius acts to elevate the scapula, rotate it upward, and stabilize the shoulder.
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nbme,11,3,18 wrong number. pte unable to open her left eye since she awoke.has no history of trauma.vital signs
normal..when left eyelid is raised during examination,her eye is fixed in the out position.when pte is asked to move her
eye out,the intorts.an MRI of the brian shows as aneurysm of left posteriror communicating artery.the most likely
cause of pte condition is compression of>>>>oculomotor nerve.
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hematoma ove rthe mastoid process (battle sign), along with perorbital ecchymosis and clear otorrhea, are signs
of basilar skull fracture
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damage to the nucleus ambiguous of the medulla characteristically produce myoclonus
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nbme>>>2,1,27>>>blink reflex
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closes the eye lid
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cough reflex:>>>also has nbme q 1,3,25 internal branch superior laryngeal nerve (CN X) which courses superior to
piriformis recess. and carry sensory and autonomic fibers mainly from larynx and epiglottis, it makes afferent limb
of cough reflex. external and recurrant laryngeal nerves carry motor fibers to the muscles involved in vocal cord
function.
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involve in speaking and swallowing. receive input from both hemisphere, so
lesion of nucleus>>>uvula deviate away from the lesion. lesion above the
nucleus>>.no uvula deviation.
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L5 radiculopathy occurs due to compression of the L5 nerve root usually as a result of vertebral disc herniation or
spinal foraminal stenosis. .......... L5 radiculopathy causes back pain that radiates the leg in an L5 dermatomal
distribution.the pain is often exacerbated by prolonged walking or standing an may be reproduced when the leg is
extended at the knee and the hip is passively flexed by the examiner (straight leg raise test).additional findings
caninclude sensory loss over the buttocks, lateral thigh and calf, and dorsal foot. there may also be weakness
on foot dorsiflexion and inversion (due to denervation of the tinialis anterior), foot eversion (peroneus) and toe
extension (extensor digitorum brevis), lower limb reflexes are usually not affected
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arise from brodmann area 4 and 6(motor and premotor cortex) pass throughB
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fibers that do not decussate in anterior medulla
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cervical regions (C5/C6 or C6/C7) of individuals younger

than age 50. shelf
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Herniations may follow
degenerative changes in
the anulus fibrosus and be
caused by sudden
compression of the nucleus
pulposus.
shelf
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1st order in dorsal root ganglion
2nd order in dorsal horn(1st order neuron briefly ascend in the zone of lissauer before synapsing
with 2nd order neuron.2nd order neuron decussate in anterior white commisure and ascend in the
contralateral funiculus.
3rd order in VPL nucleus of thalamus
4th order in primary somatosensory cortex in parietal lobe.
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fibers that decussate in anterior medulla
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forming conus medullaris.
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progressive low back pain in likely due to spinal foraminal stenosis causing L5 radiculopathy. degenerative arthritis
of the spine can result in the formation of osteophytes that compress nerve roots as they exit their spinal
foramina.nerve root in the lumbosacral spine exit below their corresponding verebral body level.although vertebral
disk herniation is a common cause of radiculopathy. disk herniation at the L5-S1 level classically affects the S1
nerve root, resulting in S1 radiculopathy as opposed to L5 radiculopathy.
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L3 L4 anterior thigh
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contribute to femoral nerve and mediate quadriceps(knee jerk and paterllar reflex)
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elicited by stroking medial thigh, which causes contraction of the cremaster muscle to pull up the ipsilateral testis. this
reflux is mediated by the genitofemoral nerve, which originates from the L1-L2 spinal nerves. loss of cremasteric
reflux is most commonly seen with testicular torsion or L1-L2 spinal injury.
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check integrity of radial nerve
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levator ani innervated by pudendal(S 234) keep close shit of the floor(puborectalis) levator ani and coccygeus make
the pelvic diphragm levator ani consists of puporectalis,pupococcygeus and iliococcygeus. coccygeus muscle
which support pelvic structure innervated by S4-S5
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tapping a biceps brachi as it passes through the cubital fossa. muscle stretch receptor activates that communicate
via the musculocutaneous nerve with lower motor neurons in anterior horn(C5-C6). axon from these motor neurons
return along the musculonutaneous nerve and cause involuntary biceps muscle contraction.
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test for the integrity of the sciatic nerve.sensory loss and paresthesia over the posterior thigh and leg
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L2 lesions cause anesthesia or paresthesias posteriorly in the gluteal region inferior to the iliac crests
and anteriorly on the thigh inferior to the femoral triangle and inguinal ligament. The L3 and L4
spinal levels contribute to the femoral nerve and mediate the quadriceps (i.e, knee-jerk and patellar)
reflex. Lesions in these levels cause loss of this reflex as well as paresthesias and weakness over the
anterior thigh. L5 lesions cause sensory loss or paresthesias over the anterior leg. The S1 and S2 roots
mediate the Achilles (i.e, ankle-jerk)reflex, which test for the integrity of the sciatic nerve. Lesions in
these roots cause sensory loss or paresthesias over the posterior leg and thigh.
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Injury to the temporal lobes may cause patients to experience various disturbances such as language
problems, difficulty with sensory interpretation, and impaired memory. These patients can also
exhibit behavioral changes (eg, hyperorality and hypersexuality as seen in Kluver-Bucy syndrome).
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lesion to the angular gyrus>>>located posterior and superior to wernickes area
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nbme>>>>4,4,22, lesion pic given>>>
ipsilateral intestion tremor.
Lateral cerebellum hemispheres has efect on Ipsilateral voluntary movement, especially sequence
and precision .
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lcaunar stroke involving VPLN and VPMN of the thalamus typically result in
complete contralateral sensory loss. damage to the thalamus may also cause
thalamic syndorme, characterized by contralateral buruning or stabbing pain
over one side of the body.
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frontal release syndrome
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damage to inferior parietal lobe of nondominant hemisphere causes constructionalapraxia , anosgnosia (inability
of illness awareness) and contralateral hemineglect
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but lesion affecting pontocerebellar fibers in the basis pontis result in contralateral deficits(weakness and ataxia)
because these fibers enter the cerebellum through the contralateral cerebellar peduncle.in basis pontis location
we also affect descending motor fibers (corticospinal, corticobulbar) .................. disrutpion of
corticopontine fibers ( convey motor information from the cortex to the ipsilateral pontine grey) also result in
contralateraldysmetria and dysdiadochokineisa (ataxic hemiparesis)
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The anterior cerebellar vermis is involved in the control of posture in the axial skeleton that is,
control of neck-to-toe posture when standing. Chronic alcohol use can lead to degeneration of
the anterior vermis, resulting in the "drunken sailor"gait.' These patients place their feet farther
apart than normal in an attempt to control balance and posture ........... A patient with lower and
posterior vermis hematoma presented with truncal ataxia; paroxysmal, positional,
downbeating nystagmus; and saccade dysmetria. Drainage of the hematoma resulted in
complete resolution of all signs and symptoms ..... also has vertigo and nystagmus due to involvement of
inferior vermis and floculonodular lobe(vestibulocerebellum) which modulate balance and ocular movement via
connections with the vestibular nuclei and medial longitudinal fasciculus.
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lesion affect medial descending motor system ( eg anterior coticospinal track, reticuospinal track,
vestibulospinal track, tectospinal track)..
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face book. Left frontal eye field - neither eye can look right but slow drift to left which will show lesion side. And it
normally seen with right lower face weakness Right PPRF- Neither Eye can look to right. eye looks toward left Right
abducens neucleus- neither eye can look right. And may be slow drift to left (not toward lesion side) and there will
be complete right facial weakness. Yes facial weakness will tell and in case of frontal cortex lower limb weakness
too The left eye field lesion has two possible scinarios Irritating lesion makes it over-firing and the both eyes look
to the right Destructive lesion will cause under-firing and both eyes looks to the left
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also has problem in accomodation and light reflux
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located inside the medial temporal lobe and is part of limbic system.
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wide based, unsteady gate
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lesion affect lateral descending motor system( eg lateral corticospinal, rubrospinal track)
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nbme>>3,1,21 The reticular activating system (RAS) is an area of the brain (including the reticular formation and
its connections) responsible for regulating arousal and sleep-wake transitions.>>>>its lesion result in coma or
hypersomnolence The RAS is composed of several neuronal circuits connecting the brainstem to the cortex.
These pathways originate in the upper brainstem reticular core and project through synaptic relays in the rostral
intralaminar and thalamic nuclei to the cerebral cortex. Several areas traditionally included in the RAS are:
Midbrain Reticular Formation Mesencephalic Nucleus (mesencephalon) Thalamic Intralaminar nucleus Dorsal
Hypothalamus Tegmentum
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inferior parietal lobe
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spontaneous temporal lobe encephalitis. Amygdala present in temporal lobe
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lesion(demyelinating or ischemic)splenium of corpus callosum will clinically result in alexia without agraphia
............. damage to the corpus callosum can result in what is called the “split-brain” syndrome. While
these patients may appear normal in general social situations, further evaluation can illustrate that they
have a lack of inter-hemispheric transfer of information. For example, these patients are unable to
retrieve with one hand an object palpated with the other.
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The parietal lobes process and interpret visual, auditory and motors signals received from other areas
of the brain. Parietal lobe damage can result in difficulties with spatial and visual perception, writing and
calculating, left-right differentiation and object identification. ................... parietal cortex play an important
role in integrating sensory information.
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Injury to the frontal lobe often results in behavioral changes secondary to impairment of the
organizational, restraint, and motivational systems present within the prefrontal cortex. Typically,
symptoms span across all three behavioral systems, but impairment of one system usually dominated.
Thus, frontal lobe syndrome is often categorized into 3 different types, disorganized, disinhibited and
apathetic. The constellation of symptoms associated with frontal lobe syndrome appears contradictory(i.e,
social disinhibition vs, withdrawal), but that is because a patient’s presentation depends upon which of
the three systems is primarily affected. Most of the time, it is the family that informs the physician of the
change in behavior, often after the patient’s new behavior has caused personal or professional
problems. Neuropsychological testing and structural brain imaging are important steps in the
diagnostic workup. ........ control executive function and response inhibition. ........ incontinence and gait
disturbance may also be seen in prefrontal cortex lesion
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in global cerebral ischemia also called "hypoxic-ishchemic encephalopathy" due to systemic hypoperfusion
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purkinje cell
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shrinkage of cell body,
pyknosis of nucleus(darkly basophilic)
loss of nissl substance and nucleous
eosinophilic cytoplasm
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liquafactive, lysosomal enzyme damage.
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the abundance of lipid seen in cytoplasm of microglia results from extensive phagocytosis of myelin breakdown
product. microglia phagocytose myelin,neuronsand necrotic debris. .............. microglia replace necrotic area by
phagocytoses in to cystic space.
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infarction eventually replaced with cystic spaces(contaning CSF) surrounded by dense astroglial scar(gliosis)
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calcification of ischemic stroke is a rare phenomenon, it most commonly occur with tumor (eg oligodendroglioma),
with infection (neurocysticercosis) and with vascular malformation
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embolic ischemic stroke has a high risk of hemorrhagic transformation in the first 7 days after
ischemic stroke
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can develop amaurosis fugax( tansient monocular blindness) but its not due to optic neuritis
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CT image study will reveal ischemic area to be hypodense and poorly delineated from the surrounding tissue.
edema and loss of distinction of gray white matter junction are also seen.
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degenerative diseases characterized by progressive loss of neuron with reactive gliosis eg alzheimer,pick and
huntington
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decrease in size and number of neurons= compression atrophy................... liquafactive necrosis>>>>>acute
symptoms caseous necrosis(TB infection)>>>>> chronic symptoms
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large ischemic stroke may result in perivascular fibroblast infiltration with fibrotic scar formation within the core
of lesion>>>this region is seperated by reactive gliosis from normal region so that do not damage normal tissue due to
fibrotic inflammatory response.
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astrocyte enlarge and proliferate on the periphery of cystic space. dense network of their processes forms a wall
around the cystic cavity.
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unlike microglia>>>neutrophil do not phagocytose myelin remnants
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red neuron are not seen in normal aging neuronal loss and atrophy
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gray matter located b/w perfusion zone of major cerebral arteries. infarcts typically appear as ((((((((bilateral)))))))))
wedge shaped strips of necrosis over the cereberal convexity, parallel and adjacent to the longitudinal cerebral
fissures. unlike global hypoxia which result is watershed areas infarct, patient with severe carotid artery stenosis
may develop ((((((unilateral)))) infarcts, cardiac embolism result in multiple infarct within different major vascular
territories. ............ hypoxic-ischemic brain injury may occur with complicated deliveries (eg,
emergency cesarean section), but it typically presents with altered consciousness and
decreased spontaneous movements during the neonatal period. Neuroimaging classically
shows watershed necrosis of the gray matter between perfusion zones of the major cerebral
arteries.
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pyramidal cell of these>>>>>>3,5,,6 layers>>>caled cortical laminar necrosis
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often with fracture of Temporal bone.
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Berry aneurysms are particularly prone to rupture when associated with coarctation, because of
hypertension in branches of the aortic arch proximal to the coarct. Subarachnoid hemorrhage is
the result.
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cavernous hemangioma (sporadic or familial) that most commonly occur within the brain parenchyma above the
cerebellar tentorium. they consist of cluster of dilated, thin walled capillaries with little or no intervening nervous
tissue. patient often have seizure and may develop progressive neurologic deficits due to mass effect with
interruption of the cerebral microcirculation.. these lesion have tendency to bleed. which can contribute to neurologic
symptoms (eg due to subcortical, cortical tissue irritation) and appear as irregular hyperdense/bright mass on head
CT
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frontal branch of MMA. enter the skull at foramen spinosum and supplies the dura matter and periostium.
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can cause cushing reflex.
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carry blood from cortex to venous sinuses
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emissary veins pass through apertures b/w the intracranial sinuses and veins outside the cranial vaults.
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vessels surrounding the ruptures aneurysm.
most common complication (about more than half of patients)
new onset confusion and focal neurological sign most frequently 4-12 days following SAH,(no
earlier than 3 days)
mechanism of vasospasm is impaired autoregulation due to degradation products of blood clots
major cause of morbidity and mortality
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most dangerous complication but not most common(30%)
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arteriovenous malformation is the most common cause of intracranial hemorrhage in children and it tend to be a
single lesion. cerebral amyloid angiopathy is the most common cause of intracranial hemorrhage in elderly and it
tend to be a multiple lesions ............... brain arteriovenous malformations are developmental
vascular lesions that usually present at age 10-30 with intracranial hemorrhage, seizure,
headache, or focal neurologic deficits.
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manifest with progessive onset of focal neurological deficits( hemiplegia,hemianesthesia,cranial nerve deficits and
aphasia etc) and headache may follow.
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usually affect small areas of cerebral hemisphere and present as headache and focal neurological signs(ie
paresis,sensory loss) CEREBRAL AMYLOID ANGIOPATHY is the most common cause of lobar/cortical
parenchymal hemorrhage in older adults.. B-amyloid deposition is wall of small to medium sized cerebral arteries
resaulting in vessel wall weakening and predisposition to rupture, the disease is not associtaed with systemic
amyloidosis, rather the amyloidogenic proteins are usually the same as those seen in the alzhemer disease.most
commonly involve occipital and parietal lobes. occipital hemorrhage>>>homonymous hemianopsia parietal
hemorrhage>>>contralateral hemisensory loss frontal lobe hemorrhage is less common>>>contraleral hemiparesis
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hemorrhagic stroke present with acute focal neurologic symptoms but ischemic stroke symptoms appear gradually
over a few hours????????????? carotid artery atherosclerosis and cadiac emnolism may cause acute
ischemic stroke, which typically presents with sudden neurological deficits that are maxiaml at syptom onset
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and deep white matter
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cerebral amyloid angiopathy is the most common cause of lobar parenchymal hemorrahge,location where
hypertensive hemorrahge is less common. Charcot-Bouchard aneurysm is the most common cause of
hemorrahge in basal ganglia and thalami.
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hydrocephalus can occur if patient survive due to arachnoid granulation disruption
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small in size <1mm..
results from chronic hypertension which causes arteriolar hyalinization and fibrinoid necrosis
results in weakening of vessel wall.
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putamen
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embolic stroke can present with multiple infarcts involving the cerebral cortex and has a higher likelihood of
spontaneous hemorrhagic transformation. however hemorrhagic tranformation would be rare within hours of
symptom onset. so gradual worsening symtoms due to multiple spontabeous hemorrhagic stroke in most
likely due to amyloid angiopathy
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hypoxic encephalopathy presents with loss of consciousness, focal neurologic symptoms are absent..
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hypertensive encephalopathy is different thing, present as progressive headache and nausea/vomiting followed
by non-localizing neurological symptoms(eg confusion) it refers to global symptoms caused by cerebral edema in
patient with severe acute hypertension.
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CT>>non-contrast. should be done during the first 24 hours from the onset of symtoms. this is positive in upto
90% of cases. if not then spinal tap with presence of xanthocromia in the presence of clinical suspicion is the most
sensitive test
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not visible on CT, tanscranial color doppler is needed
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fever and nuchal rigidity commonly present. focal neurological sign usually not present.(unlike hypertensive
hemorrhage) pailledema and pupillary dilation may be noted.
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whitish
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"great imitator" due to its subtle and variable presentation.may present as gait
abnormalities,seizures,somnolence,confusion and memory loss,many patient go undiagnosed for weeks
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at suture outer and inner layer are continuous.
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one of the terminal branches of external carotid artery.
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b/w the inner and outer layer of Duramater. outer layer from inner periosteum of skull and remain adherent to
bone.
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The most common causes of SICH in young adults are arteriovenous malformations, ruptured
cerebral aneurysms, or abuse of sympathomimetic drugs such as cocaine.
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nbme>>5,1,2,
no symptom present after the fall. but she developed blurred vision and weakness of the left
extremities. 18 hours after the fall examination shows left hemiparesis, the right pupil is dilated and
unresponsive to light >>>>>>mechanism is laceration of a cerebral bridging vein, not rupture of
middle meningeal artery.
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nbme>>>3,2,23>>>
37 year man falling down the stairs>>>physical examination alcohol intoxication>>bruise over left
temple>>>over the next 30 min level of conscious deterioratesnd and the left pupil become
dilated>>>>>>is a "laceration of middle meningeal artery"
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Lateral medullar syndrome (Wallenberg) leads to contralateral loss of pain and temperature sensation
along with ipsilateral paralysis of CN V, IX, X and XI. Medial medullar syndrome causes contralateral
paralysis and ipsilateral flaccid paralysis of the tongue (CN XII).
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lesion in parietla association cortex
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supplies inferior frontal, medial frontal and superior medial parietal lobes; anterior 4/5 of corpus callosum,
olfactory bulb and track; anterior portion of basal ganglia and ; and internal capsule
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in case of bilateral ACA stroke present with unrinary incontinence (if frontal micturation center eg medial frontal
lobe/cingulate gyrus is affected)) and primitve reflexes(eg moro,grasp,tonic neck reflexes)may also present ...........
with bilateral ACA Stroke also present behavior and mood changes due to injury of frontal lobe structure (eg abulia)
.......... the ACA occlusion also causes transcortical motor aphasia .......... nbme>>5,1,1 3-
transcortical apraxia/uworld say transcortical motor aphasia--cant move left arm in response to commond -this is
becoz of lsion of corpus callosum--also called as disconnect syndrome-There is no motor weakness but becoz
lesion of corpus callosum, left wernikes cant communicate with rt motor area.But person can move rt arm becoz lts
werkines can communicate with lt motor so person can move rt hand.
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anterior 2/3 of posterior limb is mainly composed of motor fibers (eg corticospinal track) and the posterior 1/3
contains sensory fibers (eg thalamocortical track) . Although very small lesion to the posterior limb may cause
contralateral pure sensory deficit , but most lesion result in pure motor or sensorimotor deficits ...............
anterior limb has thalamocrotical and genu has corticobulbar... posterior limb also has auditory and visual
fibers
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cystic cavities of <15mm due to lipohyalinosis and microatheromas causing (hypertensive arteriolar sclerosis..
emboli can also cause(when no other pathological cause can be found) ............ lacunar infarcts are a form of
ischemic stroke involving the small penetrating vessels that supply the deep brain stuctures (eg basal ganglia,
pons) and subcortical white matter (eg internal capsule, corona radiata). they are primarily caused by chronic
hypertension, which predisposes arterioles to undergo ipohyalinosis, microatheroma formation and occlusion
(hypertensive arteriolar sclerosis). diabetes and smoking are additional risk factors. depending on portion of brain
characteristic clinical syndromes develop such as 1, pure motor hemiparesis>>>posterior limb of the internal capsule
or basal pons 2, pure sensory stroke>>>ventroposterolateral or ventroposteromedial thalamus 3, ataxia-hemiplegia
syndrome>>>>posterior limb of internal capsule or basal pons. 4, dysarthria-clumsy hand syndrome>>>>genu of the
internal capsule or basal pons
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lacunar infarct are not show on CT as hypodense area acutely. but show as cystic spaces lately cause necrotic
lesion turn into cavitary spaces. ................... charcot-bouchard aneurysm also occur in this territory but they
appear as hyperdense area on initial CT intaparenchymally
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due to spinal trigeminal nucleus of CN V
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infarct involving the anterior medial pons at the level of middle cerebral peduncles can afffect the corticospinal
track (contralteral hemiparesis, babinsky sign) and corticobulbar tract (contralateral lower facial palsy,dysarthria).
disruption of corticopontine fibers (convay motor information from the cortex to the ipsilateral pontine grey) may also
result in contralteral dysmetria and dysdiadochokinesia (ataxic hemiparesis).the cerebral deficits are
contralateral because the pontocerebellar fibers (relay information from the pontine gray to the cerebellum)
decussate and enter the cerebellum through the contralteral middle cerebellar peduncle .......... infarcts involving the
anterior portion of the medial pons can produce dysarthria(corticobulbar fibers) and contralateral ataxic
hemiparesis(dysdiadochokinesia and dysmetria) due to corticopontine fibers ........ anterior pons(medial
pons) infarct>>>>corticobulbar, corticspinal, corticopontine (causes cotralateral
dysmetria and dysdiadocokinesia)and pontocerebellar fibers (contralateral
cerebellar symtopms) 2125
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dont have corticobulbar>>>>
pons has this
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AICA aneurysm can compress facial and vestibulocochlear nerves.
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due to spinothalamic tract
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and diabetes mellitus
lacunar infarct are not show on CT as hypodense area acutely.
but show as cystic spaces lately cause necrotic lesion turn into cavitary spaces.
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internal capsule lesion typically results in contralateral motor/sensory deficits. cortical signs (eg aphasia, agnosia,,
neglect, apraixa, hemianospisa) are classically absent
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called lateral striate arteries, Arise form MCA, also called penetrating artery................. basal ganglia,posterior
limb of internal capsule, pons and cerebellum>>>>deep structures of brain>>supplied by this artery
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trunck and genitals
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supplies lateral convexity of the frontal, parietal and temporal lobes. it also supplies deep subcortical structures,
such as internal capsule and basal ganglia......... frontal eye field also supplied by this
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conjugate gaze deviation toward side of stroke. contralateral homonymous hemianopsia (due to damage to the
optic radiation in the subcortical temporoparietal lobes). anosognosia (in nondominant hemisphere)
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PCA branches off the basilar artery at the level of the pontomesencephalic junction and supplies CN 3 and 4 and
other structures in the midbrain.. it also supplies thalamus, medial temporal lobe, splenium of corpus callosum,
parahippocampal gyrus, fusifrom gyrus and and occipital lobe...... visual cortex>>>calcarine sulcus
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blinking>>>pretectal nuclei in upper midbrain
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damage above the red nucleus>>>decorticate rigidity.
damage at or below the red nucleus (midbrain tegmentum/pons)>>>>decerebrate rigidity.
not midbrain tectum
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contraletral hemianopia without macular sparing we have MCA occlusion
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suprior colliculs
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supplies a large portion of brain,including most of brainstem and bilateral cerebral hemispheres.
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bilateral pontine hemorrhage presents with coma due to disrutpion of RAS, ALSO
WITH TOTAL PARALYSIS WITH EXtensor posturing due to corticospinal anad
corticobulbart trac injury and pinpoint pupil secondary to decending
sympathetic track damage. ........... ischemic damage to pons causes coma,bilateral
paralysis,decereberate rigidity,pinpoint pupils and often death ............ pontine hemorrahge or tumors>>>locked in
syndrome,spastic quadriplegia and paralysis of most cranial nerves with preserved consciousnees and eye
movmeent.
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symptoms appear on one half of the body(contralateral to the lesion) .... lacunar strokes can occur in thalamus
causing thalamic pain syndrome. lacunar stroke in VPL and VPM nucleus results in complete contrlateral
hemisensory loss
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psudobulbar palsy
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the artery of percheron branches off either the right or left PCA and supplies the bilateral thalami and dorsal
midbrain.it is considered to be a rare normal variant and can be seen in patient with bilateral thalamic or dorsal
midbarin strokes ............ involvement of lateral thalamus presents with contralateral paresthesia and numbness
affecting the face, trunk and limbs. a variety of cortical symptoms can also occur, including dyslexia, visual
agnosia, (eg impaired visual recognition of objects) and prosopagnosia (inability to recognize faces)
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Thalamic syndrome (or thalamic pain syndrome)It is also known as "Dejerine-Roussy disease" is a condition
that can be associated with inadequate blood supply from the posterior cerebral artery. It is a rare neurological
disorder in which the body becomes hypersensitive to pain as a result of damage to the thalamus, a part of the brain
that affects sensation. The thalamus has been described as the brain’s sensory relay station. Primary symptoms
include pain and loss of sensation, usually in the face, arms, and/or legs. Pain or discomfort may be fel after
being mildly touched or even in the absence of a stimulus. The pain associated with thalamic syndrome may be
made worse by exposure to heat or cold and by emotional distress. Sometimes, this may include even such
emotions as those brought on by listening to music.
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Broca;s area is in the caudal part of the inferior frontal gyrus of the dominant (usually left)
hemisphere (Brodmann areas 44 and 45). The frontal eye field is found near the caudal end of the
middle frontal gyrus immediately anterior to the precentral sulcus (Brodmann areas 6 and 8).
Damage here would cause the eyes to deviate to the ipsilateral side. Lesions to the precental gyrus
(primary motor cortex) can cause dysarthria (eg, slurred or explosive speech) due to paresis/paralysis
of the skeletal muscles involved in movements of the mouth, tongue and larynx. Damage to Broca’s
areas is often associated with right-sided hemiparesis and oral apraxia due to extension of the
lesions into the ipsilateral motor regions.
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brodmann areas 44 and 45. is in the caudal part of the inferior frontal gyrus of the dominant hemisphere. supplied by
superior division of MCA
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visual cortex lesion causes cortical blindness that can make reading and writing difficult but spoken speach
would be unaffected
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2nd most is posterior communicating artery
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cardio> ██ Fluency██Comprehension██Repetition██Naming█████Localization Broca -----------Severe--------Mild--
-----------Severe----Phonemic------Frontal operculum/Broca area Wernicke--------Intact--------Severe-----------Severe----
Semantic------PST/Wernicke area Conduction----Intact/mild--Intact/mild---------Severe-----Varies--------Arcuate
fasciculus/or insula Global----------Severe-------- Severe-----------Severe-----Severe-------Entire MCA gang area TM-------
-------Severe----------Intact-----------Intact-----Phonemic-----Frontal/watershed area TS---------------Intact-------- Severe-----
------Intact------Semantic-----Parietal/watershed area Isolation speech-Severe-------Severe-----------Intact------Severe-----
--MCA/watershed area Anomic---------Intact----------Intact-----------Intact------Semantic----Anterior temporal/Inferior
parieta
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posterior portion of superior temporal gyrus(located in visual association cortex) (brodmann area 22) supplied by
inferior division of MCA
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forum ant comm artery aneurysm may cause bitemporal lower quadrantanopia>>>>>cause it located above the
optic chiasm; you know the lower fibers travel on top.. The damage happens from pressure from the dilated
aneurysm The opposite happens in early pituitary involvement ( which is located below the chiasm; early on its
bitemporal upper quadrantanopia before it becomes hemianopia
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nbme,7,4,32 Absence seizures or petit mal epilepsy There is a correlation between SLOW WAVE SLEEP (stage 3
and 4 aka delta sleep ) and abscence seizures ....one of the correlation is Slow-wave sleep as well as generalized
absence seizures are characterized by the occurrence of synchronized oscillations in thalamocortical systems
that spontaneously appear and disappear. What are this synchronized oscillations ? -Oscillations =Remember from
highschool physics ...if u put a load to a spring it oscillates ....the same thing neurons oscillate (another term is
repititive variation) ...which is called neural oscillation Neural oscillation is rhythmic or repetitive neural activity in the
central nervous system .And this can be due to rhythmic increases and decreases in action potential activity,which
then produce rhythmic activation of synapses in target neurons. This oscillations can be physiolgical or patholgical.
Pathological oscillations =Specific types of neural oscillations may also appear in pathological situations, such as
Parkinson's disease or epilepsy. Interestingly, these pathological oscillations often consist of an aberrant version of a
normal oscillation. For example, one of the best known types is the spike and wave oscillation(synchronized
oscillation ) , which is typical of generalized or absence epileptic seizures, and which resembles normal sleep
spindle oscillations.
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rythmic blinking and occasionally small clonic jerks of arms and hands. no recollection that seizure has
occured. most last less than 10 sec ................. sudden, momentary lapsed in awareness (the absence
attack), staring, rhythmic, blinking, and occasionally, small jerks of arms or hands. The
interictal EEG of patients with typical absence seizures reveals generalized 3.0 Hz spike-wave
complexes superimposed on normal background activity.
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myoclonic seizure due to juvenile myoclonic epilepsy (JME), a form of idiopathic generalized epilepsy that may be
familial. paietnt are typically otherwise healthy and present duriing adolescence with myoclonic seizure (brief,
involuntary jerking movements) involving both upper exteremities with preservation of consciousnes. symtopms
usually occur within first hour of waking and can be provoked by sleep deprivation. affected patietns can also
developgeneralized tonic-clonic and absence seizures. ........... myoclonic movements are neither suppressible
nor preceded by an urge to make a movement unlike tourretete syndorme... myoclonic seizures may be confised
with the motor tics of torrette syndrome, however, motor tics are usually temporarily suppressible and often
preceded by an urge to make the stereotyped movement.
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often symmetric ,muscle contraction with loss of body tone causing the patient to fall or slump forward. seizure
usually occur in the morning and usually precipitated by stress and sleep deprivation.. valproic is 1st line.
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nbme>>>2,3,36>>>Déjà vu , (meaning "already seen") is the experience of feeling sure that one
has already witnessed or experienced a current situation, even though the exact circumstances of
the previous encounter are uncertain and were perhaps imagined.
The strongest pathological association of déjà vu is with temporal lobe epilepsy
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tend to occur around the same time each day on consecutive days for a period of weeks. commonly episodes
occur at night few hours after going to sleep. patient may have a pain free interval for a year b/w attacks
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or temporal
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results in neurogenic inflammation due to vasodialiton, and plasma protein extravasation, neuronal
sensitization also occur, causing central nociceptive pathway to become more sensitive to both painful and non-
painful stimulation
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nonmalignant arterial hypertension: may cause occipital morning headache
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mainly mandibular V2 and maxillary distribution V3
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tto: carbamezapine,1st line(effective in 80% of cases) baclofen and valproic can be used but not 1st line.
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gradually worsen and involve the entire head. recumbent position causes the discomfort to worsen,may
accompanied by papilledema.vomiting and cognitive decline
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and venlafazine ........................ venlafazine also used for prophylaxis 8476
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localized in frontotemporal and ocular area,then progresses posteriorly and becomes diffuse.
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non-pulsatile, unilateral can present with ptosis along other symptoms
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Lesions above the midbrain produce decorticate rigidity(i.e., postural flexion of the arm and extension of the leg);
lesions below the mid brain produce decerebrate rigidity(i.e., postural extension of the arm and leg)
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involumntary muscle activity that flows form one muscle group to another
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may be the result of impaired function of the basal ganglia.
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autosomal dominent.
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it is located ventral(inferior) to the thalamus and dorsal (superior) to the substancia nigra and medial to the
internal capsule................. injury in or near the subthalamic nucleus.
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damage to nucleus ambiguous of the medulla characteristically produces myoclonus
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pathological myoclonus is seen in epilepsy and creuzfeldt-jakob disease.
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cervical dystonia (torticollis) is the most common focal dystonia.
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caudate nucleus
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globus pallidus
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examples of physiologic myoclonus.
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damage to the subthalamic nucleus can decrease excitation of the globus pallidus
internus, thereby reducing inhibition of the thalamus
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via its CNS effects
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most commonly diagnosed movement disorder.
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dystonia may occcur without any obvious cause (idiopathic). these movements may affect a single muscle, a
group of muscle or the entore body.
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RYTHMICAL TREMORS: postural: anxiety,beta agonist intention: cerebellum resting: basal ganglia flapping:
metabolic(liver failure,renal failure) NON RYTHMICAL:Jerky: 1,chorea(in hands due to caudate nucleus damage)
2,hemiballismus(in limbs due to contraleteral subthalamic nucleus) Non Jerky:athetosis(due to globus pallidus
damage)
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metabolized to phenobarbitone (barbiturate). anticonvulsant.
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presenilin 1 and 2 on chromosomes 14 and 1 respectively
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gain of function mutation due to expansion of protein polyglutamine region .
huntiginton gene play a role in embyonic development, and its loss result in
embyonic death. 840 ........ The defective huntingtin gene is a gain-of-function
mutation which causes the buildup of toxic protein aggregates (intranuclear) in neurons,
causing their death ................ expansion of the proteins polyglutamine region result in gain of function that
leads to pathologival interaction with ither proteins,including various transcription factor.. transcriptional
repression (silencing) is one mechanism for the disease to occur.. in huntington disease abnormal huntington
causes increased histone deacetylation, silencing the genes necessary for neural survival>>>less prpoduciton of
neurotropic factors .
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has 100% penetrance, meaning that if a child inherits the abnormal gene, that child will inevitable develop huntington
disease.most pateints develp symtoms in their 40 or 50s.an earlier age on onset is associated with a larger number of
trincleotide repeats.during sprematogenesis, CAG repeats in the abnormal HD gene rapidly increase.thus
patiens whi receive an abnormal gene from their fathers tend to develop the disease earlier in life. (the
number of trinucleotide repeats on HD gene remains the same during maternal transmission). the
tendency for clonical symtoms to worsen and/or occur earlier in subsequent generation is called
anticipation............. tricunleotide expansion occurs during paternal transmission , causing a genetic phenomen
called anticipation.
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about 30% of patients have a family history of the disease. the following three mutation have been
associated with early-onset familial alzheimer disease (onset<60 years old) 1 APP 2 presenilin 1 gene in
chromosme 14 3, presenilinn 2 gene o chromosme 1 Both APP and presenilin gene mutation are thought
to promote the production of A-B amyloid. late-onset familial Alzheimer disease is associated with
the e4 allele ofApolipoprotein E.exact mechanis is not known.it is thought that the ApoE4
protein may be involved in the formation of senile plaques........... mutation in the gene coding for
apolupoprotein E result in impaired synthesis of this protein and impaired clearance of AB from the brain
parenchyma consequently, apolipoprotein E mutation are associated with a higher risk for late-onset AD.
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Presynaptic acetlycholine synthesis is reduced in AD due to decreased cerebral content of choline
transferase. Consequently, acetylcholinesterase inhibitors (eg, donepezil) are often used to treat this
condition.
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Neurofibrillary tangles are composed of tau protein, a primary component of intracellular microtubules,
in AD, tau protein is hyperhosphorylated, causing microtubule structures to collapse into “tangles” that
contribute to global neuronal dysfunction. AB is an abnormal fragment of amyloid precursor protein
(APP), which is normally involved is synaptic formation and repair. the extra Copy of APP
present in Down syndrome is thought to accelerate amyloid accumulation and lead to early-onset AD.
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progressive supranuclear palsy is a form of parkinsonism resulting from neurodegenration of the midbrain and
frontal subcortical white matter>>>presents with progressive gait dysfunction and falls, executive function
loss and vertical gaze palsy.. brain biopsy usually shows deposits of abnormally phosphorylated tau proteins.
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of the extremities and less commonly bradykinesia
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most characteristic biochemical feature ...... also decrease in substance-P
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PET scan show decrease metabolic activity in the striatum (especially putamen) ........... avg survival after diagnosis
is 15-20 years
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in order to make diagnosis of dementia, the patient must demonstrate impairment
across several cognitive domains during tetsing(MMSE) as well as functional
impairment in activities of daily living ................................. before diagnoses of this,
potential medical causes of congnitive decline must ruled out.
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pick disease=behavior problem first then dementia
alzheimer disease=dementia first than behavior problem
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differentiate by vascular dementia(multiple lacunar infarct) by step wise rather than gradual decline in cognitive
ability. also multiple focal neurological sign present.
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more pronounced in temporoparietal lobe and hippocampus.
hippocampus(new memory formation impaired) atrophy evident in early stages in MRI
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also called amyloid plaque
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beta-amyloid protein loses its alpha-helical configuration and form beta-sheets, which are less soluble and prone
to aggregating
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20-40% has autosomal dominent inheritence.
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inctracellualr eosinophilic inclusions>>>alpha-synuclien
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round cytoplasmic inclusions containing aggregates of tau protein (pick bodies)
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damage the media and adventitia of cerebral vessels and cause thickening of the basal membrane, stenosis of
vessel lumen and fragmentation of the internal elastic lamina.
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decrease in hippocampus and nucleus basalis of meynart
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in alzhemir disease amyloid deposits are seen exclusively in brain tissue. these deposits contain beta-amyloid (Ab),
whihc is formed by cleavage of amyloid precursoe protein (a transmembrane glycoproetein).early in disease
neuritic (senile) palques can be found in the medial temporal lobe (eg hippocampus, amygdala,entorhinal
cortex) and are composed of a central Abeta core surrounded by dystrophic neurites. Abeta depostion alsi occurs
in media/adventitia of cerebral vessles (amyloid angiopathy) and may cause vessel wakening with intracranial
hemorrhage............ both senile plaque and amyloid angiopathy may also be seen in brain tissue of healthy elderly
individual. ...........
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level of melatonin is CSF has been shown to decrease with the progression of alzheimer disease.
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after 60. early in disease course language deficit(problem in finding words) and impaired visuospatial
ability(misplacement of itmes) later in disease course problem in executive functions and behavioral problem and
trouble performing every day functions
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bilaterally. caudate atrophy leads to the typical dilation of the frontal horns of the lateral ventricles, and
microscopy of the atropic areas reveals gliosis and neuronal loss. microscopically reveals intranuclear
inclusions containing aggregates of huntington protiens ....... bilateral atrophy of caudate nucleas and putamen
which together form striatum. NMDA receptors are depleted in the striatum of these patients ........................... The
head of the caudate can be identified in the inferolateral walls of the anterior horns of the lateral
ventricles.
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Common causes of death include suicide (most common)aspiration pneumonia, head trauma (resulting from loss of
motor control)
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or anxiety, decreased concentration and psychosis
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with 100% complete penetrance
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generally not jerking extremity movement type except in levodopa toxicity
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nbme>>>5,1,111
58 year old women with 2 year history of progressive memory loss, disorientation of time and
place, and increasingly frequent episodes of lethargy and confusion.there were no focal neurologic
deficit.most likely finding is>>>>>degenration of cortical and basal forebrain neurons, not
increased concentration of acetylcholinesterase in the cerebral cortex.
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nbme,11,4,32 treatment with a cholinesterase inhibitor is most likely to improve this patients memory because of its
ability to target synaptic connections between>>>>>>the basal forebrain (nucleus of meynert(which is located in
the basal forebrain and its function is to produce ach) and neurons in the cerebral cortex. The cerebral cortex is
an extremely convoluted and complicated structure associated with the "higher" functions of the mind—thought,
reasoning, sensation, and motion. The hippocampus plays a crucial role in learning and in processing various
forms of information as long-term memory. Damage to the hippocampus produces global amnesi
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nbme,,1,3,45 drug that prevent egress of Mg from the NMDA receptor>>>prevent Ca entry into the neuron and
reduction of excitotoxin mediated cell death. ...................... NMDA receptors channels have 2 componenet: 1-
Ligand-gated (that require co-activation by two ligands "Glutamate and Glysine")---Ca influx 2-Voltage-dependent
these receptors have Mg attached to them on the outside. upon action potential the Mg egress(expell) and the
channel opens and Ca WILL ENTER THE NEURON.so if a drug block the egress of Mg, it will prevent Ca entry.
(perhaps u wanna read about 'EXITOTOXICITY" and a drug called "Memantine" given in Alzheimer) just wanted to
clear that the NMDA-receptors is not that they are of two kinds rather wanted to say that they depend on both co-
activation by two ligands and action potential. so it's the neuronal membrane depolarization -----> expell the
attached Mg and now Glutamate and Glysine bind to these receptors and the channel opens---->Ca Entry. to add to
what sarim explained... Activation of NMDA receptors requires binding of glutamate or aspartate (aspartate does not
stimulate the receptors as strongly).[12] In addition, NMDARs also require the binding of the co-agonist glycine for
the efficient opening of the ion channel, which is a part of this receptor. In addition, a third requirement is
membrane depolarization. A positive change in transmembrane potential will make it more likely that the ion channel
in the NMDA receptor will open by expelling the Mg2+ ion that blocks the channel from the outside. This property
is fundamental to the role of the NMDA receptor in memory and learning, and it has been suggested that this
channel is a biochemical substrate of Hebbian learning, where it can act as a coincidence detector for membrane
depolarization and synaptic transmission. A unique property of the NMDA receptor is its voltage-dependent activation,
a result of ion channel block by extracellular Mg2+ ions. This allows voltage-dependent flow of Na+ and small
amounts of Ca2+ ions into the cell and K+ out of the cell.[3][4][5][6] Calcium flux through NMDARs is thought to play a
critical role in synaptic plasticity, a cellular mechanism for learning and memory. The NMDA receptor is distinct in
two ways: First, it is both ligand-gated and voltage-dependent; second, it requires co-activation by two
ligands - glutamate and glycine.
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nbme,11,1,21
genetic analysis shows two loss of function mutations in the perkin gene, which encodes a
ubiquitin protein ligase.
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also in progressive supranuclear palsy, which is a form of parkinsonism,present
in midbrain and frontal subcortical white matter
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TAR DNA binding protein 43 (TDP-43)
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HIV associated dementia Usually presents in patient with Cd4 counts <200 cells/mm3. but its
incidence has significantly declined since the introduction of antiretroviral therapy. Patients
typically have features of subcortical dementia (e.g, attention/working memory problems,
executive dysfunction, slow information processing) as HIV affects primarily the
subcortical/deep gray matter structures. The pathogenesis of HIV-associated dementia
involves inflammatory activation of microglial cells. HIV-infected monocytes initially cross
the blood-brain barrier to become perivascular macrophages. Activated macrophages and
microglial cells (resident macrophages of the central nervous system) form groups
(microglial nodules) around small areas of necrosis and may fuse to form multi nucleated
giant cells. Neuronal damage is believed to occur from inflammatory cytokine release by
macrophage/microglial cells and the direct toxic effects of HIV-derived proteins.
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possible sequelae include optic nerve atrophy and blindness.
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seen in patient that receive contaminated corneal transplant,implantable electrodes or preparation of growth
hormones. .................. kuru and fatal familial insomnia are other examples of prion disorders in humans.
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normally found in neurons in alpha-helix form
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the absence of glial scar formation on autopsy makes vascular dementia less likely.... ...................... large areas
of encephalomalacia can be seen in patients with vascular dementia due to ischemic stroke,
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accumulate in gray matter(intracellular accumulation).form vacuoles in neurons and neutrophil. form cyst.
.............. have no inflammatory changes.. ......... large intracytoplasmic vacoules sometimes described as
spongiform
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characteristic along with dementia.
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it is thought to be related to cerebral venous outflow abnormalities due to elevated intracranial
pressures.
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and have normal CSF content.
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hydrocephalus can cause impaired upward gaze due to dilation to the third ventricle with compression of the dorsal
midbrain (pretectal area)
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rarely can be due to increased production>>>papillomas of choroid plexus>>>>all ventricles are symmetrically
enlarged just like communicating hydrocephalus
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ataxic gait and urge incontinence(detrusor hyperactivity) occur due to stretch of the sacral motor fibers that
innervated the legs and bladder. incontinence is due to lack of inhibition of sacral micturation centers.>>>traction
disrupts the periventricular pathways that transmit impulses from the cortex to the sacral micturation center.
voluntary relaxation of urethral sphincter remains intact (pontine reticular formation)
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note that no permanent damage to the brian strcuture occurs, therefore symptoms of NPH, including dementia,
are sometomes reversed by lowering the CSF volume
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true hydrocephalus is a rise in volume and pressure of CSF caused by abnormal production, flow,
or reabsorption of the fluid.
in disease such as alzhemier, pick and HIV ventricular enlargement occurs secondary to atrophy
of the brain. such compnesatory exapnsion is called" hydrocephalus ex vacuo"
although distended ventricle produce a CT image similar to true hydrcephalus, CSF pressure is
not increased
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ventricular enlargement out of proportion to sulci enlargment>>>normal pressure hydrocephalus ventricular
enlargemnet in proportion to sulci enlargement>>>ex vacuo hydrocephalus
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in children hydrocephalus when head circumference is greater than two standard deviation. its due to Arnold-chiari
malformation,dandy-walker marlformation, aqueductal stenosis and prenatal toxoplasmosis. besides other
symptoms hyperreflexia due to stretching of periventricular pyramidal track. long term sequela besides
hyperreflexia are visual problems and learning disabilities.
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ventricles are not symmetrically enlarged.
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due to distention of the periventricular lymbic system. (mini-mental status examination socre </22) ................ if
left untreated progressivedementia and emotional blunting occur due to distention of periventrcular limbic
system. order of symptoms(first urinary incontenence and ataxic gait,then dementia) are important in
distinguishing NPH from alzheimer and other dementia
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in this hydrocephalus impaired absorption of CSF is compensated for by decreased CSF formation. although ICP
is normal, there is still a pressure gradient between ventricles and subarachnoid space which is responsible for
the ventricular enlargement.............. symmetrically enlarge ventricles ................ pathophysiliology and etiology
are debated, but most agree that a gradula decline in the rsorbtive capacity of the arachnoid villi, with slow
accumulation of CSF, is the root of the problem. pressure remain nomral due to gradual ventricualr distention
accomodates the CSF increase;
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all ventriculi are symmertically enlarged.
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the typical clinical features are quadriplegia due to demyelination of the corticospinal tracks and pseudobulbar
pasly due to demyelination of the corticobulbar tracks of CN 9, 10, 11. pseudobulbar palsy is characterized by head
and neck muscle weakness, dysphagia, and dysarthria
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CD-8 positive, type 4
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tizanidine is also effective and commonly used.
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acutely demylination occur butthere is relative preservation of axons in plaques besides lipid laden macrophages
which digest myelin,astrocytosis and infiltration of lymphocytes and mononuclear cells chronically there is
degeneration of axons in plaques ....... loss of axons, neurons and oligodendrocytes (the myelin-producing cells
of the CNS) occurs overtime in chronic MS plaques.
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temperate latitude.
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cerebellar dysfunction: tremor,ataxia,nystagmus
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mostly with urge incontinence due to loss of CNS inhibition of detrusor contraction in the bladder. As disease
progresses , the bladder can become atonic and dilated, leading to overflow incontinence ................ contrast to
flaccid bladder, spastic bladder patient has frequent episode of urinary incontinence through out the day. flaccid
bladder patient has urinary incontinence at the end of the day>>>when bladder pressure increases more than
uretheral sphincter pressure .............. overactive or spastic bladder>>>urodynamic studies>>>little or no residual
urine after emptying as bladder contactility is normal but distensibility is poor>>>>due to loss of discending
inhibitory control
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appear as pink patches in the white matter tracks due to oligodendrocytes apoptosis. predilection for
subcortical periventricular region. also present in transcortical,infratentorial and spinal cord.
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visual evoked potentials are used to assess conduction velocity.which slows in MS due to demylination.
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thiamine deficiency(dry beriberi) can cause peripheral demyelination but does not cause inflammation ...............
toxin penetration through the blood-nerve barrier, leading to peripheral neuropathy, occurs with diphtheria.
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segmental
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some infectious agents have ganglioside like substanse in their lipopolysaccharide layer.Ab form against these
substances cross-react with ganglioside component of myelin ............... this disease occur after infection(respiratory
and GI),immunization or allergic reaction
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paralysis may ascend to the cranial nerves especially 7(bells palsy)
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endoneural inflammatory infiltrate consisting of lymphocyte and macrophages.
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counteraction of inflammatory action of immune cell.
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following histologic changes are seen inside acute (active) plaques 1, demyelination with relative preservation of
axons. 2, accumulation of lipid laden macrophages containing the products of myelin breakdown. 3, astrocytosis
(proliferation in response to injury) 4, infiltration by lymphocytes and mononuclear cells. ................ acutely
demylination occur butthere is relative preservation of axons in plaques besides lipid laden macrophages which
digest myelin,astrocytosis and infiltration of lymphocytes and mononuclear cells chronically there is
degeneration of axons in plaques ....... loss of axons, neurons and oligodendrocytes (the myelin-producing cells
of the CNS) occurs overtime in chronic MS plaques. ............ helper T-cell abnormally react to antigens in myelin
causing a release of cytokines (es INF gamma) that promote the infiltration of destructive macrophages/microglia
and leukocytes. B-cells may also play a role as most MS patient has oligoclonal immunoglobulin bands in the
CSF.
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plaques which are detected on MRI are necessary for definitive diagnosis.
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cerebellar defect
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MS occur most commonly as a relapsing-remitting CNS disorder charaterized by recurrent episodes of
demyelination and subsequent partial remyelination. there is relative preservation of axons in acute MS
plaques,with axonal degeneration seen mostly in chronic plaques.
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afferent defect. accompanied by painful eye movementand decreased vision common initial presentation
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fatigue is the most common non-specific symptom.particularly after taking hot shower r strenous exercise in hot
environment.this is due to decreased axonal transmission due to hest.(heat sensitivity)
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spasticity is defined as an increase in resistance to passive muscle movement or a velocity-
dependent increase in tonic stretch reflexes.
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mutation of the genes responsible for myelin synthesis. abnormal myelin synthesis leads to decreased nerve
conduction velocity. common presentation is foot frop (weakness of foot dorsiflexion) due to involvement of
common peroneal nerve...... demyelination of peripheral nerves.typical findings include distal leg
weakness/atrophywith sensory deficits, pes cavus, and kyphoscoliosis,cardiomyopathy is not
characteristic ......... the mutation of a myelin protein gene is the pathogenesis of Charcot-Marie-Tooth
disease, a so-called “neural form” of muscular atrophy.
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cytoplasmic inclusions in oligodendrocytes
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bony abnormalities: 1,sphenoid dysplaia 2, pseudo arthrosis 3, scoliosis 1307
............................... bony deformities include long bone dysplasia (tibial bowing) and pseudoarthrosis that
typically present in toddlers
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these patients may also develop multiple meningiomas, gliomas, and ependymomas of the spinal cord.
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skin lacking pigment.
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melanin to keratinocytes. Café au lait spots demonstrates increased melanosome aggregates
within the melanocytes cytoplasm.. ... hyperpigmented macules develop soon after birth over the trunk
and have increased risk of CNS neoplasms (eg optic gliomas and pilocytic astrocytomas) which can cause
elevated intracranial pressure and headache. ... unlike Mccune albright syndrom they are usually smaller,
bilateral and have relatively smooth border ('coast of california')
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cortical and subependymal
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most common primary tumor of heart in pediatric population,but generally produce obstruction or stenosis of
valvular orifice
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visceral cysts are also present
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inherited peripheral nervous system tumor syndrome
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Mutated ras inhibits the activity of GTPase activating protein. This prolongs the activated
state of ras, resulting in increased growth signals
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cerebellar hemangioblastoma is often associated with polycythemia
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although von-HLD and tuberous sclerosis both may cause cysts in liver, kidney and pancreas but
CNS lesion are different.
In von-HLD there are hemangioblastomas but in tuberous sclerosis there are cortical and
subependymal hamartomas.
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flesh colored, raised, rough skin, due to subepidermal fibrosis
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TSC1 mutation on chromosome 9 or TSC2 mutation on chromosome 16."
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VHL>>tumor suppressor gene>>ch 3>regulating the transcription of hypoxia inducible factor 1 (HIF-1)>>>>causes
increased expression of VEGF and erythropoetin
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congenital cyst or neoplasm in the kidney liver and pancreas
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"button hole" sign (applying pressure to some neurofibromas may cause them to retract into the subcutaneous
tissue) is pathognomonic,. these are benign nerve sheeth neoplasm predominantly comprised of schwann cells,
also have neural fibroblast. usually manifest during early adolescent as multiple, raised, fleshy tumors (<2cm)
that often increase in size and number with age.............. Skin tumors of NF-1 are derived from neural
crest cells.
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nbme>>>1,3,47>>>we have to give them special education begining in the first grade.
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clinically seizures are a major complication
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adenoma sebaceum
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skull radioopacities,characteristic finding
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nbme>>>3,2,24
Cafe au lait coffee colored macules
dont mistake with Shagreen Patch in tuberous sclerosis....it is irregular WHITE SKIN
'''LEUKODERMA'''
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Angiomyolipomas are associated with tuberous sclerosis. Inpatients with bilateral renal
angiomyolipomas, the incidence of tuberous sclerosis is 80%-90%. characterized by cortical tubers
and subependymal hamartomas in the brain, consequent seizures and mental retardation.
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can also have schwanommaas of the dorsal roots in the spical cord.
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are asymptomatic unlike optic gliomas which causes blindness 1307
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Guanine nucleotide-binding protein G(q) subunit alpha
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primary brain neoplasm most often metastasize within the CNS, but they can rarely present with
metastasis outside of the nervous system.
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Light microscopy typically shows spindle cells with palisading nuclei arranged around Verocay
bodies composed of eosinophilic cores ( Antoni A pattern). ,.............. microsopically appear
biphasic, high cellular area(Antoni A pattern) intermixed with myxoid region of low cellularity ( Antoni B pattern).
Antoni A areas composed of spindle cell(elongated cell with regular oval nuclei) that form palisading patterns with
interspersing nuclear free zone called VEROCAY BODIES
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metastatic tumor are more common overall>>>> lung cancer, renal cancer and melanoma in decreasing order.
gross examination>>multiple well circuscribed masses at the junction of gray and white matter
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most common primary neuroglial tumor. on gross examination are soft and poorly defined with areas of necrois
and hemorrahge.
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reticulin deposits and chronic inflammatry infiltrates are seen in pleomorphic xanthoastrocytoma, an
astrocytoma found in children and young adults. pleomorphic xanthoastrocytoma can progress to GBM (very
rarely)
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2nd most
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compressing the medial surface of hemisphere present with spastic paresis of legs. tend to rise in dural reflection (
falx cerebri and tentorium cerebelli)
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in the region of sphenoid wing and olfactory bulb.
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meningothelial cells
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unilateral hearing loss is the setiing of facial numbness and weakness (eg CN 5 and CN 7) is highly suggestive of
an intracranial schwannoma. CN 5, 7 are in close proximity with CN 8 and acoustic neuromas at
pontomedulalry junciton can affect these nerves via extrinsic compression.symptoms can vary base on the
pattern of nerve involvement. 1, impairment of CN VIII coclear and vestibular portion affect. 2, compression of CN V
may cause loss of facial sensation(loss of afferetn limb of the corneal reflux) ana paralysis of the muscle of
mastication. 3, compression of CN VII in resutls in fascial muscle paralysis (lower and upper), loss of tase in anterior
2/3 of the tongue, decdreased lacrimation/salivation, and hyperacusis (paralysis of the stapedius)
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b/w cerebellum and lateral pons.
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and multiple meningiomas
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with finely granular chromatin.
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Synaptophysin is a transmembrane glycoprotein found in the presynaptic vesicles of
neurons, neuroectodermal and neuroendocrine cells. Immunoreactivity of a CNS tumor for
synaptophysin indicates a neuronal origin Such neoplasms are rare and compose less than
1% of CNS tumors. ........... astrocytes(glioblastoma/pilocytic), oligodendroglioma, ependymoma and peripheral
neural sheath tumor are stained by GFAP.
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astrocytes(glioblastoma/pilocytic), oligodendroglioma, ependymoma and peripheral neural sheath tumor are stained
by GFAP. synaptophysin. transmembrane gycoprotein found in presynaptic vesicles of neurons,neuroectoderm
and neuroendocrine cells.
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typically involve white matter of cerebral hemisphere. gross examination usually appear as well-circumscribed gray
masses with calcification.
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CN VIII arise from pontomedullary junction. schwannoma typically arise from vestibular portion. BUT commonly
presents with coclear defects>>>hearing loss, tiniitus. can cause vestibular defect>>> vertigo,dysequalibrium
and nystagmus.
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triad of vertigo,tinnitus and sensorineural hearing loss which also present in meniere disease but
its episodic with exacerbation and remission in this.
in schwannoma its progessive and constant
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characteristic. round eosinophilic.surrounded by collagen fibers.
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most are discovered incidently, but some may have seizure, headache or focal neurological deficits.
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are diagnosed by imaging (usually homogenous appearence) not stained by GFAP or synaptophysin
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classic clinical presentation is the new onset seizure in adults. ................. estrogen postive tumor and its
common tumor in fertile obese 40 women .............. meningioma located in olfactory grove present with
headache and anosmia.
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common in frontotemporoparietal white matter and grows along white matter tracks across corpus callosum and
affect other hemisphere.
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PDGFB Platelet-derived growth factor Overexpression,>>>>autocrine loop>>>>causes
Astrocytoma.. ............................ glioblastoma have been associated with overexpression of growth factors (eg
PDGF, EGFR, IGF, TGF)
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cyst formation and rare mitoses indicate a colloid cyst, a pathological benign tumor usually found in the third
ventricle.although colloid cysts are benign, they cause lethal obstructive hydrocephalus
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germ cell tumor above the diaphragma sellae are in pineal and suprasellar region.causes aquedactal
stenosis(with obstructive hydrocephalus) and perinaud syndrome (paralysis of vertical gaze)
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Encapsulation occurs when a tumor pushes against but does not invade fibrous as may occur
in a meningioma.
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brain tumor are common in children than in adults. They are the second most common type
of childhood neoplasm (leukemia is the most common).
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On macroscopic examination. the neoplasm is cystic with a tumor nodule protruding from the
wall. This nodule is the active part of the tumor. On imaging studies, a pilocytic astrocytoma
appears as a mass with both solid (red arrow) and cystic (white arrow) components. .........
microscopically, pilocytic astrocytomas are well differentiated neoplasm, comprised of spindle cells with hair like
glial processes that are associated with microcysts. these cells are mixed with rosenthal fibers and granular
eosinophilic bodies.
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intracraneal germinoma can also arise is the suprasellar region(less common site),due to their proximity to the
pituitary gland and hypothalamus, suprasellar germinomas do not lead to parinaud syndrome,but they are more
likely to present with endocrinopathies( eg central precosious puberty, diabetes inspidus)
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paralysis of upward gaze, ptosis and pupillary abnormalities>>>due to direct compression of the pretectal region of
the midbrain.
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also in brain stem, hypothallamic region or optic pathway.
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most common malignant brain tumor of children. 2nd most common brain tumor of posterior fossa
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this classic rosettes seen in 1/5 of patients.
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palisading.
histologically ependymal cells form gland like structure called rosettes
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macroscopically>>cyst or partially cyst with solid areas light microscopically>>>cyst are seen to be lined with
stratified squamous epithelium. keratin pearls may also be seen. cysts are usually filled with a yellow, viscous fluid
that is rich in cholesterol crystals ...... characteristically have 3 components: solid>>comprised of actual tumor
cells, cystic>>>filled with 'machinery oil liquid' b. any suprasellar mass with three component is highly suggestive of
craniopharyngoma
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gliomas>>>can occur in suprasellar region if they arise from the optic apparatus. they typically present with visual
impairment, hypothalamic dysfunction and hypopituitarism.
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Germinomas are the most common tumor of the pineal gland. these germ cell neoplasms have identical
counterparts that occur in the gonads and mediastinum. Germinoamas are found in children and
adolescents and show a strong male predominance. following combination of symptoms: precocious
puberty may occur in males and is caused by B-hCG production aqueductal compression by the tumor
may lead to obstructive hydrocephalus. parinaud syndrome included paralysis of upward gaze and of
convergence these symptoms occur due to compression of the tectal area of the midbrain
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prolactinoma>>>>uncommon in children, they typically present as homogenous mass when imaged.
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granular layer of cerebellum
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pseudorosettes
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between 5-10 years >>>>present as headache, visual field defect and hypopituitarism.
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spinal ependymoma present in adults unlike in children .................... 3rd most common brian neoplasm in children
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sheets of primitive cells with many mitotic figures. primitive cells are small, round blue cells. ..........................
characterized by small blue cells that may surround neuropil, forming Homer-Wright rosettes
under light microscopy.
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most common location is cerebellar vermis. symptoms are from increased intracranial pressure(morning
headache,vomiting,lethargy) cerebellar dysfunction(dizziness,,nystagmus. limb ataxia) occur as tumor compress
adjacent structure.
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the sis protooncogene is overexpressed which encodes PDGF.
also overexpressed in osteosarcoma.
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papilledema, headache and vomiting.
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growth of facial and pubic hair along with enlatged genitalia in a boy younger than 9 years old signifies precocious
puberty, for girls this syndrome is defined as an appearence of secondary sexual characteritics before age 7.
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Adamantinomatous craniopharnygiomas most often present as benign suprasellar tumors in
children and appear as cords/nests of palisading squamous epithelium with internal areas of
lamellar “wet” keratin under light microscopy.
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Pilocytic astrocytomas hve both cystic and solid components, while medulloblastomas are
always solid.
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also present in optic glioma
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nbme>>4,2,28
After a LMN, the muscles undergo atrophy due to lack of neurotrophic input. Even after surgical
rejoining the prognosis of nerve injury is poor & the denerved muscle fibers undergo atrophy.
after surgical correction>>.circulation resumes and their is no defect of circulation
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due to lack of inhibtion of UMNs on spinal stretch reflex
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gap b/w crus cerebri and tentorium. most common causes are brain tumor, subdural or epidural hematoma and
intracerebral hemorrhage
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in the midbrain and pons due to streching and rupturing of basilar artery>>>usually fatal
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compression of ipsilateral crus cerebri can also cause contralateral hemiparesis
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uncal herniation can compress the cerebral peduncles, resulting in corticospinal track injury with hemiplegia. however
patients initially have flaccid paralysis with hyporeflexia (ie spinal shock) and develop spasticity/hyperreflexia
days to weeks following acute upper motor neuron damage.
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first sign of uncal herniation. due to damage to the preganglionic parasympathetic fibers running on the outer
portion of the third cranial nerve. as the herniation progresses, damage to the midbrain results in mid-positioned
and fixed pupilsbilaterally. additional findings in advanced transtentorial herniation include loss of vestibular-
ocular reflexes and decorticate followed by decereberate posturing.
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space occupying lesions within the temporal lobe can cause elevated intracranial pressure with transtentorial
herniation of the uncus.
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abducens palsy can occur with downward displacement of the brianstem (central herniation) due to nerve traction
along the clivus.
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UMN lesion can affect any from PYRAMIDAL MOTOR SYSTEM including the coticospinal track of spinal
cord,medulla,pons,midbrian,internal capsule and precentral gyrus
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cauda equina is most sever form in comarison to conus medularis syndronme and
is due to massive rupture of intervertebral dick
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Clinical manifestations include lancinating pains, loss of vibratory and positions sensation,
areflexia and a neurogenic bladder with overflow incontinence. The sensory ataxia causes
patients to develop a wide-base gait and makes it impossible for them to maintain balance with
their eyes closed (positive Romberg sign). argyl robertson pupill are thought to be caused by
spirochetes invading and damaging the midbrain tectum.
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most common motor neuron disease.manifest in middle aged (40-60)people and has progressive course, die
within 5 year of diagnosis.
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demyalination of corticospinal track.
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(neuron destruction by superoxide free radicals) or misfolded copper-zinc SOD 1 leading to apoptosis of neurons
(most likely mechanism)
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5-20 years after primary infection..
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but not dorsal horn.
spirochete directly damage this.
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fall during night time. cause vision does not compensated his dorsal column defect
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have kyphoscoliosis also.
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neurological deficit look like vit-E deficiency
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conus medularis is just at L2 dont below
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saddle anesthesia and loss of anocutaneous reflex are symptoms of cauda equine syndrome.associated with S2
through S4 nerve.
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below the level of conus medularis.
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bowel and bladder dysfunction>>>>>s3-s5
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can have bilateral symptoms
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This collection of spinal nerves (now considered peripheral nerves) is referred to as the cauda equina
(i.e, horse’s tail). Conus medullaris syndrome refers to lesions at L2. It has symptoms of flaccid
paralysis of the bladder and rectum, impotence, and saddle, (S3-S5 roots) anesthesia. There is usually
mild weakness of the leg muscle if the lesion spares both the lumbar cord and the adjacent spinal
and lumbar nerve roots. Common causes include disk herniation, tumors and spinal fractures. In
contrast, cauda equina syndrome typically results from a massive rupture of an intervertebral disk that is
capable of causing compression of two or more of the 18 spinal nerve roots of the cauda equina.
However it can aslo occur due to any trauma or space-occupying lesion of the lower vertebral column. The
cauda equina nerve roots provide the sensory and motor innervation of most of the lower extremities,
the pelvic floor, and the sphincters. 1693' ....... cauda equina is most sever form in
comarison to conus medularis syndronme and is due to massive rupture of
intervertebral dick
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lumbosacral plexopathy>>> occurs during fetal descent as a result of direct
compresison of lumbisacral plexus, pte has foot drop and numbness of lateral
aspect of the leg and the dorsum of the foot, condiiton typically transient, most
women experience resolution with year 11952
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radiating to one or both leg
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anterior horn causing LMN signs at the level of syrinx and UMN lesions below the level cause of lateral corticospinal
track lesion
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pain,paresthesia,polyuria>>>>>tabes dorsalis
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thought to be caused by spirochete invading and damaging the midbrain tectum. light-near dissociation
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secondary degeneration.
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aspiration pneumonia MCC of death
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damage to anterior horn nuclei and motor neuron of CN 5, 9, 10, and 12
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denervation atrophy of muscle(amyotrophy)>>>>>muscles have small angular fibers ..................... Diagnosis •
Electromyography and nerve conduction studies
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loss of sensatio in the perianal area (saddle anesthesia) can indicate cauda equina syndrome, which is commonly
due to epidural cord compression from a malignancy. patienst usually develop urinary retenstion late in the course of
the disease, usually associated with fecal incontinence ............ bowel and bladder incontinence are
late manifestation of cauda equina syndrome.... in internal pudendal lesion they are
early manifestation 11952
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The spirochetes cause damage to sensory serves in the dorsal roots, which results in secondary
demyelination and loss of axons within the dorsal columns of the spinal cord. This leads to lancinating
pains, paresthesias, and loss of vibratory and position sensation. Loss of proprioception is usually
compensated for by visual clues, but sensory ataxia prevails in the dark (demonstrated by this
patient’s frequent stumbling at night). Areflexia and loss of bladder function can also occur. Argyll
Robertson pupils and a positive Romberg sign are found on physical examination.
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FXN gene codes for an essential mitochondrial protein involved in the assembly of iron-sulfur enzymes.
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amplification>>>in non-coding region(intron)>>>loss of function mutation>>no protein synthesis.
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caridac arrythmia and CHF.
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and pes cavus are characteristic skeletal deformities.
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cerebellar ataxia
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Sites of degeneration: (1) Dorsal root ganglia (2) Posterior columns/dorsal column( 1 and 2 cause impaired joint and
vibrairon sense) (3) Spinocerebellar tract(gait ataxia) (4) Lateral corticospinal tracts(spastic paralysis) (5) Large
sensory peripheral neurons .......... Most common neurodegenerative hereditary ataxic disorder ............
symptomalogy resembles with vit E and vit B12
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and adulthood with progressive gait ataxia
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Initially at the ankles
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is a spinicerebellar degenration with predominantly spinal ataxia. there is initial loss of sensory (including
propiocetion) neurons in the dorsal root ganglia, with accompanying gait ataxia.
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decrease mitochondrial energy production and increased oxidative stress, resulting in degeneration of neural
tracts and peripheral nerves... ...... cells become more prone to apoptosis
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due to weakness of the levator veli palatani.
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deviation of angle of mouth on the opposite side(normal).>>>mouth being drawn to the non-affected side.
drooping of angle of mouth on the same side.drooling of saliva on the same side.
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in unilateral lesion of mandibular divsion of CN-V. bilaterla lesion of this nerve result in mandibular drop and lack
of jaw movemement
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the cochlear cupula is the apex of the cochlea and is distant from the oval window. The distal cochlea
primarily registers low-frequency sound.
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tympanic membrane
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smallest bone of human body
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means negative
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nbme>>>2,1,4>>>a dysnfucntional eustachian tube that is always open is called a "patulous" eustachian
tube.patients with this rare condition are plagued by chronic ear infection. result in failure of regulation of air
pressure in middle ear. partial or complete blockage of tube can cause sensation of popping, clicking and ear
fullness and occasionaly moderate to severe ear pain. toung children may describe the poppinh sensation as "a tickle
in my ear". in this condition external canal and tympanic membrane appear normal but dytmpanic membrane
does not move when the pressure is increased in nasopharynx.
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vertigo due to vestibular dysfunction tend to be of sudden onset, interfere with walking and cause nausea and
vomiting, typical causes of vestibulopathy are perilymph fistulas,benign positional vertigo,labyrinthitis.acoustic
neuroma
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meniere disease>>>due to increased pressure and volume of endolymph>>>recurrent vertigo, ear fullness/
pain, unilateral hearing loss and tinitus .......................... BPPV>>>>deu to otoliths in semicircular
canals>>>>brief vertigo episodes brought on by head movement, no auditroy symtoms ...................
vestibular neuritis(labyrinthitis)>>>inflammation of vestibular nerve,(viral or postviral)>>>single episode that
can last days, severe vertigo but no hearing loss
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or exagerated sense of motion for a given motion.
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squamous cell debris form a round, pearly mass behind the tympanic membrane in the middle ear. can occur
congenitally or may develop in adults as either an acquired, primary lesion or secondary to infection, trauma or
surgery of the middle ear. primary cholesteatomas are a result of chronic negative pressure in the middle ear
causing retraction pockets in the tympanic membrane that besome cystic; as the squamous cell debris accumulate,
a cholesteatoma is formed. secondary cholesteatoma occur after squamous epithelium migrates to or is implanted
in the middle ear ("skin in the wrong place") ....... they most commonly cause painless otorrhea. they aslo can
produce lytic enzymes and are often discovered when they erode the auditory ossicles, causing conductive
hearing loss. if a mass grow sufficiently large, it can erode into the vestibular apparatus or facial nerve, causing
vertigo or facial paralysis
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cholesterol ganuloma can form in the middle ear after hemorrhage but are less common than
cholesteatoma.
they appear as bluish-black gelatinous metarial behind the tympanic membrane.
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otosclerosis: inherited condition with onset in middle age .pte present with conductive hearing loss and due to
bony overgrowth of footplate of stapes. vertigo does not occur ....... otosclerosis affects air
conduction across all frequencies 1633
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also contain two skeletal muscle. tensor tympani and stapedius (bodys smallest skeletal muscle).
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the acoustic reflex normally dampens the effects of loud noise by causing the stapedius and tensor
tympani muscles to contract High frequency hearing is lost first, regardless of the frequency of the
sound causing the damage
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positive rinne test
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Photoreceptor Rods: one kind • Achromatic • Low-light sensitive •Night vision, motionCones: 3 kinds • Red, green, blue •
Chromatic • Bright light Sensitive • Object recognition
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at iridocorneal angle
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The anterior chamber angles (iridocorneal angle) contains a trabecular meshwork through
which the aqeous humor diffuses into Schlemm’s canal (Scleral venous sinus) and subsequently
into episcleral and conjunctival veins.
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this canal drains into episcleral and conjunctival veins.
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Glaucoma is a type of optic neuropathy characterized by atrophy of the optic nerve head.
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have afferent pupillary defect also
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arcuate scotomas occur due to damage to a particular region of the optic nerve head.
the resulting visual field defect follows the arcuate shape of the nerve fiber pattern.
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scotomas occur due to pathological processes that involve part of retina or optic nerve.examples of such processes
include demyelinating diseases such as MS, diabettic retinopathy and retinitis pigmentosa. pathologic processes
that involve the entire optic nerve lead to monocular blindness.
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infectious causes of anterior uveitis are herpes, syphilis and lyme) .... other
inflammatory cause is sarcoidosis of anterior uveitis.
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ia a yellowish spot approximately 1.5 mm in diameter located near the center of the retina. it is characterized
histologically by the presence of densely packed cones, few overlying cells and no blood vessels. each macular
cone synapses to a single bopolar cell, which in turn synapses to a single ganglion cell. due to this rearrangement
visual acuity in the macular and particularly the fovea, is greater than in any other area of the retina. the neural fibers
that serve the macula transmit to an area of the occipital visual cortex that is seperate form the area of representation
of the peripheral fields (this area is also relativley large in size). due to this peculiar cortical representation,
macular sparing is common in lesions of the occipital cortex.
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smoking and hyperlipidemia>>>increase risk of ischemic retinal and optic vascular disease, but not associates
with hemorrahges
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nbme>>>4,1,25
Macular degeneration can make it difficult or impossible to read or recognize faces, although
enough peripheral vision remains to allow other activities of daily life.
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manifests with blurry vision, black spots,floaters and decreased peripheral vision. acute vision loss may occur in
the setting of a complication such as vitreous hemorrhage,
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is a branch of ophthalmic artery which is a branch of internal carotid artery................... the
retinal artery is
one of the first branches of the ophthalmic artery. the retinal artery then travels
within the retinal nerve to supply the innerretina and the surface of the optic
nerve ..... there are number of anastomoses between brnaches of ophthalmic
artery and branches of the external carotid, including the facial and temporal
artery
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due to diffuse rertinal ischemia...
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Hypertensive retinopathy>>>precapillary arteriolar endothelial damage due to severe hypertension>>>leakage of
plasma into arteriolar wall>>fibrinoid necrosis>>necrotic vessel can then bleed into nerve fiber layer>>dot and
flame hemorrahges. painless unilateral visual disturbances ranging from mild obscuration without loss of
visual acuity to permanent blindness. on fundoscopy also has thickening of arteriolar walls (copper and silver
wiring), compression of associated veins (arteriovenous nicking) and small,white foci of retinal ischemia (cotton
wool spots)
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its most often due to atherosclerosis, cardioembolic disease or vasculitis (eg giant cell arteritis)..... athero and
thromboembolism is the most common causes.
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amaurosis fugax is a painless, transient, monocular vision loss caused by a small embolus to the
ophthalmic artery. it usually does not last more than a few seconds.
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nbme,6,4,25 Papilledema may be asymptomatic or present with headache in the early stages. However it may
progress to enlargement of the blind spot, blurring of vision, visual obscurations (inability to see in a particular part
of the visual field for a period of time) and ultimately total loss of vision may occur. The signs of papilledema that
are seen using an ophthalmoscope include: venous engorgement (usually the first signs) loss of venous
pulsationhemorrhages over and / or adjacent to the optic disc blurring of optic margins elevation of optic disc
Paton's lines = radial retinal lines cascading from the optic disc Pathophysiology: As the optic nerve sheath is
continuous with the subarachnoid space of the brain (and is regarded as an extension of the central nervous
system), increased pressure is transmitted through to the optic nerve. The brain itself is relatively spared from
pathological consequences of high pressure. However, the anterior end of the optic nerve stops abruptly at the
eye. Hence the pressure is asymmetrical and this causes a pinching and protrusion of the optic nerve at its
head. The fibers of the retinal ganglion cells of the optic disc become engorged and bulge anteriorly. Persistent
and extensive optic nerve head swelling, or optic disc edema, can lead to loss of these fibers and permanent
visual impairment
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chroidal nevus (eye freckle) is a non-hereditary, usually benign pigmented areaunderneath the retina.
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has preganglionic parasympathetic neurons
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in superior colliculus.
at the level of superior colliculus
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affected by optic nerve lesion (MS) or in optic track lesion(relatiely) lesion in lateral geniculate nucleus and optic
radiation do no affect this
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along Ophthalmic division of trigeminal nerve
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along external carotid artery
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superior tarsal muscle
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optic neuritis in MS
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partial is key
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also compression of brachial plexus. tumors are squamous cell carcinoma , adnocarcinoma.
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2nd order neuron-intermediolateral cell column of C8-T2 segments of spinal cord(ciliospinal center of budge). 2nd
order axon exit the spinal cord through thr anterior nerve roots and white communicating rami to reach third order
neurons located in the superiro cervical ganglion.
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both brain stem and spinal cord lesion(above T2) can cause horners syndrome.
but brain stem lesion would have other cranial nerve sign.
spinal cord lesion would have ipsilateral spastic paresis and sensory loss below the level of spinal
involvement.
si if patient with horner syndorme have unilateral arm pain and weakness are more suggestive of
lesion affecting the brachial plexus/sympathetic ganglia.
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horner syndrome is associated with lesions affecting the lateral hypothalamus or sympathetic
tracts in the brianstem (eg lateral medulla)
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stellate ganglion affect in>>pancoast tumor... internal carotid artery level>>>>by
carotid dissection
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nbme>>2,4,35 right pupill is constricted and does not react to light, left pupill normal>>>>lesion is in cervical
spinal cord not in optic track or lateral geniculate nucleus
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Superior tarsal/mullers SM glue to inferior surface of LPS muscle(skeletal muscle) & both work
together keep the curtain UP.
“Partial” >>>>superior tarsal

"complete" >>>Levator palpebrae superioris
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pinpoint pupil are usually associated with large bilateral pontine lesions caused by damage to the descending
sympathetic tracts.
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3rd order neuron.
from here postganglionic fiebrs travel along the carotid arteries to reach the target
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1st order neuron-posterolateral hypothalamus(paraventricular nucleus)
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pupil asymmetry is more prominent when examined in dim light due to increased sympathetic activity
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synonym of muller muscle of upper eyelid.
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also by the lesion of optic track which causes relative afferent pupillary defect in pupil contralateral to the
tracklesion, as the nasal portion of retina contributes more input to the pretectal nucleus than temporal portion
of the retina. optic track lesion also has contralateral homonymous hemianopia
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along internal carotid artery
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along internal carotid artery
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afferent limb of this reflux are retina,optic nerve,optic chiasm and optic track.
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with the decussating fibers traversing within the posterior commissure. .....
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has postganglionic parasympathetic neurons.
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lacunar midbrain stroke can involve CN III nuclei. many neurologic pathway is densely packed in this area, CN III
nuclei impairment is almost always associated with other neurologic deficits (eg cerebellar ataxia, hemiparesis, or
contralateral extrapyramidal symptoms) . in addition contralateral superior rectus is affected because the
subnucleus fibers decussate to the contralateral side. midbrain lseions also causes bilateral ptosis because both
levator palpebrae are innervated by single subnucleus
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due to unopposed superior oblique and lateral rectus
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aneurysm and tumor
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due to efferent limb damage
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fixed dilated pupil,loss of accomodation(due to ciliary muscle paralysis) and unilateral headache
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vertical and torsional diplopia
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binasal hemianopsia>>caused by pressure to the lateral areas of the optic chaism. this may result from calcified
carotid arteries.
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MCA stroke is characterized by contalateral motor and sensory deficits(more pronounced in upper than lower limb)
and homonymous hemianopia with macular involvemnt
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temporal lobe lesion can also produce other neurologic manifestations, including aphasia (dominent hermisphere
lesions) memory deficits, seizures (complex partial and tonic-clonic) and hallucinations (auditory, olfactory and
visual)
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primary visual cortex also called striate cortex.
receive information from the contralateral visual field and ipsilateral geniculate nucleus
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to lingual gyrus
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retinal artery or vein occlusion
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RIGHT NASAL HEMIANOPISa>>>>calcificaiton of aneurysm of internal carotid
artery (eg cavernous or opthalmic segement)
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lesion of optic track causes pupillary liht reflux problem along with
homonymous hemianopsia. but lesion of lateral geniculate body and optic
radiation cause homonymous hemisnopsia but not pupillary light reflux problem.
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left homonymous hemianopia at: optictrack>>>>> occlusion of anterior choroidal
artery optic radiation>>> MCA, interanl capsule posterior limb
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aneurysm of ACA
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optic neuritis,
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optiac radiation to cuneus gyrus
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cause central visual rediation fibers occipital lobe region is supplied by collateral MCA.
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optic radiation also called geniocalcarine track cuase connect LGB and calcarine gyrus(striate cortex)
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Most fibers from the optic tract project to the lateral geniculate body (LGB); some also project to the pretectal area (light reflex),
the superior colliculi (reflex gaze), and the suprachiasmatic nuclei (circadian rhythm) . The LGB projects to the primary visual
cortex (striate cortex, Brodmann area 1 7) of the occipital lobe via the optic radiations
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horizontal diplopia and esotropia (inward deviation)
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CN 3 lesion also have diagonal diplopia (means vertical and horizontal both)
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due to unopposed pupillary dilator
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as CN 3 come out of midbrian passes b/w posterior cerebral and superior cerebellar arteries.aneurysm of either
artery can effect this GVE fiber. Anterior communicating artery aneurysm cause compression at optic
chaism(bitemporal hemianopsia)
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subserve the pupillary light and near reflex pathway.
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due to paralysis of levator palpebrae superiores
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in which adduction is not possible.
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nystagmus is generally seen with lesions to the pons, medulla or cerebellum due to disruption of vestibular
pathways.
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the enzyme responsible for catabolism of GABA in CNS.
it is a one of several drug use in treatment resistant epilepsy
353
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epileptic women who want to be pregnant, her valproic acid is replaced by
levetiracetam pre conception 507 .. dont induce P450 like other antiepileptic
10930
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binding of glutamate to the postsynaptic neuron causes opening of ligand gated Na channel>>>>leading to sodium
influx and membrane depolarization.>>>>which is transmitted from the dendrites through the cell body to the axon
hillock, which contains a large number of voltage gated sodium channel. once the axon hillock is sufficiently
depolarized an action potential is triggered and propagates along the axon via a steady influx of Na ion>>>at
axon terminal voltage gated calcium channels open and allow the influx of Ca>>>which is essential for the fusion
and release of neurotransmitter. voltage gated sodium channel are important for the generation (at axon hillock)
and propagation (at axon proper) of action potentials.
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treat with benzo.for prophylaxis>>phenytoin
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valproate is the drug of choice for patients with absence and associated tonic-clonic seizure.
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by reducing the recovery of Na channel from inactivated state. increase refractory period.
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phenytoin blocks presynaptic voltage gated Na channels and can be used to prevent recurrence of status epilepticus
due to its long duration of action. however it has slow onset of actionand patients in status epilepticus should be given
a rapid acting benzo first.
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gingival hyperplasia occur in 50% who have 3-4 months of therapy and is due to increase expression of PDGF.
when gingival macrophages are exposed to increased amounts of PDGF, they stimulate proliferation of gingival
cells and alveolar bone. may regress after discontinuation of drug
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good one in partial seizure.
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also used in diabetic neuropathy and bipolar disorder.
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reduce abnormal electrical activity in the brain by blocking NMDA receptors and affecting potassium current.
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1st line.
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precipitate acute intermittent porphyria.
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generally has fewer side effects than other, but this SE is particularly important in children and requires
discontinuation of treatment immediately. ........... upto 10% of patients will dvelop benign
rash,
1% will develop SJS or TEN particularly in children .................... GI symptoms are
relatively common but not life threatening ............ other anticonvulsanr with SJS are
carbamazepine, phenobarbital and phenytoin
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bone marrow suppression
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acts by disrupting vesicle fusion
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psuedotumor cerebri
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mainly for the treatment of refractory partial seizure.
also effective for the management of generalized tonic-clonic seizures.and in the treatment of
bipolar disorder(especially in depressive phase)
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primidone is an antiepileptic that is metabolized to phenobarbital and phenylethylmalonamide(PEMA) also active
anticonvulsant. primidone has its own antiseizure effects but less often causes lethargy.
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in acute mania and maintenance treatment, especialy in paients with rapid cycling (>4 episodes a year) and
episodes with mixed manic-depressive features.
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1-3% risk it inhibit folic acid absorption.
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enhances its synthesis and release.
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has both spina bifida and cleft lip and palate
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phenytoin and carbamazepine disrupts the generation and propagation of action potentials ( in the axon hillock and
axon proper, respectively) by blocking voltage-gated sodium channel.
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cause disrupt absorption of folic acid.
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hydroxylation of phenytoin is no dose dependent.
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also seizure prophylaxis after trauma and before neurosurgery
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that trigger and sustain rhythmic pulsed discharges..
block this channel cause hyperpolarization.
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broad spectrum anticonvulsant>>> valproic acid,lamitrigine,levetiracetam and topiramate.>>>>suucessfully
treated most seizure tyep( eg focal or generalized at onset) in contrast nrrow specttrum anticonvulsatn (eg
carbamazepine, gabapentin, phenobarbotal, phenytoin) are favored for focal onset seizures and should be
avoided in generalized epilepsy syndromes as they may aggravate seizures/
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also with allopurinol, sulfonamides, minocycline and vancomycin due to
activation of herpes virus and clonal expansion of T cell that cross react with
drug 508 .... type 4 HSR ................ drug reaction with eosinophilia and systemic syndrome DRESS:
typically occur 2-8 weeks after drug initiation causes fever, generalized lymphadenopathy, facial
edema.>>>>associated with anticonvulsant (eg phenytoin and carbamazapine), allupurinol, sulfonamides (eg
sulfasalazine) and antibiotics (eg minocycline and vanco). clinical findings improve after several weeks following
drug discontinuation....... generalized type(pseudolymphoma) without a serum sickness like syndrome.
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felbamate>>anticovulsant, block NMDA receptor 1199
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behavioral treatment of insomnia: 1,stimulus control. 2, sleep hygiene, many patients use alcohol at
bedtime to help them fall asleep but are aware that alcohol is disruptive to sleep in the second half of
the night. Patients should be educated that blood alcohol concentrations fall by the middle of the
night and cause shallow sleep and multiple awakenings. Initial non-pharmacological treatment of
chronic insomnia typically combines sleep hygiene education and stimulus control therapy. 3,
relaxation addressing maladaptive thoughts and expectations about sleep (eg, I must have 8 hours of
sleep in order to function) is a cognitive therapy technique that is commonly combined with behavioral
modification. 4, sleep restriction therapy aims to consolidate and improve sleep efficiency
(percentage of time in bed that the patient is asleep) by restriction sleep time. for example if a
patient is in bed for 8 hours but sleeps for only 4, sleep is restricted to 4 hours and then gradually
increased in 15 to 30 minutes intervals once sleep efficiency is over 90% ............. Non-
pharmacologic treatments for insomnia include sleep hygiene, stimulus control ,relaxation, sleep
restriction and cognitive behavioral therapy.
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Polypharmacy (>_5 prescription and over-the-counter medications) The Beers criteria were developed
to identify drugs requiring caution in geriatric patients. First-generations antihistamines (e.g,
diphenhydramine) and other anticholinergic drugs can increase the risk of confusion , hallucinations, dry
mouth and constipation. Other common drugs to avoid include alpha blockers (orthostatic hypotension),
tricycle antidepressants (sedation), sulfonylureas (hypoglycemia), and muscle relaxants (sedation).
amlodipine is a calcium channel blocker that is generally safe to use in older adults, however,
immediate-release nifedipine should be avoided asit can cause hypotension and possibly precipitate
myocardial ischmeia.
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BCDflurazepam=1-3 days
TLEstazolam=10-20 hours
MAOTr=3-8 hours
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rapid and short acting(half life of 1.5-5 hours)>>> used for insomnia treatment.
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generalized anxiety and panic attacks
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and seizure associated with alcohol withdrawal..1st line along with chlordiazepoxide
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also with barbiturates, neuroleptics and 1st generation anti-histamine.
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long acting such as diazepam avoided in elderly due to fear of falls
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structurally unrelated to benzo. also chemically different but same receptor of BZs
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Type: StrikeOut Author: LENOVO Subject: Cross-Out Date: 6/17/2017, 2:25:28 AM
“Oxazepam, Temazepam, and Lorazepam undergo firstpass metabolism Outside The Liver (ie, do not undergo P450
oxidation).
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rapid onset(15 min), metabolized by liver P450 microsomal oxidases. elimination half-life is normally about 3
hours, but may be prolonged in patient with liver disease.
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milk before bedtime has a hypnotic action, as serotonin can be synthesized endogenously from
tryptophan(present in milk)
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its a characteristic feature of toxicity.
the most common side effects of diazepam is sedation
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short term treatment of insomnia
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caused by UMN defects(MS, Stroke, spinal cord trauma) and tetanus.
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but best for insomnia treatment cause do not cause day time somnolence.
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GABAc found in retina which is also ion channel like GABAa but unlike GABAb whihc is G-protein coupled
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zolpidem it has adverse effects in older adults, including increased risk of falls and confusion. Non-
pharmacological strategies (eg, cognitive behavioral therapy) are preferred for initial management of
primary insomnia in older adults.
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long-acting benzodiazepines such as chlordiazepoxide, diazepam and flurazepam. The
benzodiazepines lorazepam, oxazepam and temazepam (mnemonic LOT) are preferred in patients with
impaired hepatic metabolism. They undergo glucuronidation directly and are not dependent on
hepatic enzymes for their metabolism. In clinical practice, lorazepam is commonly used to low doses 2
or 3 times a day as needed for short-term anxiety, Alprazolam and colanzepam have an intermediate
half-life and triazolam has a short half-life.
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Psychotropic drugs, including antipsychotics, antidepressants and benzodiazepines, are the class most
commonly associated with increased fall risk.amlodipine (a calcium channel blocker) and ibuprofen (a
non-steroidal anti-inflammatory drug) both of which are associated with increase risk of falls.
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also decreases neuronal inlflammation and neuronal sensitization
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abortive treatment
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substance-p and CGRP(calcitonin gene related peptide)
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oftentimes, these fluctuations appear to correlate with serum drug levels (eg, reduced mobility 4
hours after the last dose). As PD progresses, the therapeutic window for levodopa narrows, possibly
due to natural or levodopa-induced nigrostriatal degeneration. As a result small changes in serum
drug levels can result in motor fluctuation (eg, mild elevations may result in dyskinesia, whereas slight
reduction may result in bradykinesia/rigidity). In advanced PD, motor fluctuations can occur
independently of medication dosing and may become unpredictable. stopping levodopa abruptly is
not recommended as it could cause a condition similar to neuroleptic malignant syndrome. ........
many neurologists favors the use of combinations of selegline, amantadine and anticholinergic untill they no
longer provide control of symptoms. try to delay the introduction of levodopa and their related side effects.
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also pergolide. these two used for hyperprolactinemia also.
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as an indirect and direct dopaminergic agent
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thought to have some anticholinergic properties, which reduce tremors. should be used cautiously in elderly
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anxiety.agitation, insomnia, confusion, delusions hallunication are central effects of dopamine and are caused by L-
dopa, regardless of whether carbidopa is added to levodopa treatment. tto: reducing the dose, if not possible
give atypical antipsychotic such as clozapine.
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such as nausea vomiting, hypotension, hot flashes, tachyarythmias are all due to peripheral conversion of L-dopa
to dopamine. anxiety and agitation are not reduced by this.
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delay the clinical progression of PD
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also trihexyphenidryl>>>>they are centrally acting anticholinergic. both are mainly used for drug induced-and
idiopathic parkinson in which tremor is a dominant symptom ................. we give these drug mainly in
drug induced parkinson 265
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MAO converts epi and nor-epi to dihydoxymandelic acid.
COMT convert epi to metanehrine and nor-epi to normetanehrin,
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besides peripheral has central effect also. unlike entacapone, tolcapone has been associated with hepatotoxicity.
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Vit-B6 increases the peripheral metabolism of levodopa and decreases its effectiveness.
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dopamine has low lipid solubility and also do not have specific dopamine transporter protein in endothelial cells
of BBB. L-DOPA also has low solubility but has high affinity for large neutral amino acid transporter ............ l-
dopa absorbed in small intestine by large neutral amino-acid transporter
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also synthesis.
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also used in restless leg syndrome
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preferentially D2. provide only modest improvement in disease symptoms when used as mono therapy. they have
long half life and can delay the introduction of L-dopa to treatment by months or years, thus delaying levodopa
related side effects and the development of motor fluctuaitons until later in the disease course..........
pergolide>>> d2 agonist>>delay the introduciton of levodpa 259
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COMT found in brain and liver.
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3,4 dihydroxyphenylacetic acid
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just depend on body temperature and patient age(decreases MAC) so we give
less drug in elderly patient 851.. ................... MAC is the intrinsic property of the anesthetic that
does not depend on the type of surgery; duration of anesthesia; or the sex, height and weight of the patient. it
does however change with the body temperature and also decreases with increasing patient age
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potent anesthetic require lower partial pressure to be effective.
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this is doseindependent and unpredictable. if dose is kept constant on-off phenomenon is minimal.
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neuroprotective and used cilinically to delay the progression of disease.
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NMDA receptor activation is important for neurotransmission involved with learning and memory
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it is thought that NMDA receptor overstimulaiton by glutamate may contribute to AD symptoms.
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also has anticholinergic and antihistamine actions.
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in general BZs should be avoided given their depressive effects on cognition. in some
cicumstances however, they may be prescribed to AD patients to treat assoiated anziety and
insomnia
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Vit-E (alpha tocopherol) also used,which is neuropotective(antioxident). may slow functional losses in AD.
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prevent MPTP-induced damage of dopaminergic neuron
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"wearing off" phenomenon(destruction of nigrostiatal neuron) is dose dependent and more predictable
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blood-gas partition>>>>by increasing its value>>drug would be more soluble in blood>>>take longer time to be
saturated>>>prolong duration of onset of anesthesia.......................... if anethetic has high arterio-venous
difference>>>>means it has high solubility in peripheral tissue>>>so rate of induction is slow>>>cause large
amount of anesthetic is required first to concentrate blood and then to go to brain to have effect.
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in prefrontal cortex 265 ............................ improve cognition, behaviour and funcitoning in
activities of daily living in AD patients. although they donot appear to prevent ultimate neurodegenration but may
delayinstitutionalization and mortality
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hypersensitivity, autoimmune mediated, 369 ... 2 days to 4 weeks after surgery. liver
tendernes, shrunken/atrophied liver, increased PT(due to short half life of factor 7) and increased LFTs,
eosilphilia and leukocytosis... widespread centrilobular necrosis and inflammation of portal track and
parenchyma>>>histologically indistinguishable from acute viral hepatitis causes fulminant hepatitis>>50%
mortality rate. It is due to hypersensitivity reaction and thus immune-mediated damage to hepatocytes.
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nbme>>>6,1,42
As halothane is respiratory depressant ;it leads to retention of co2
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nbme>>>5,3,7 recovery time from anesthesia is longer in thiopental as compare to propofol cause of>>>>zero order
metabolic elemination not by distribution of thiopental into adipose tissue. explanation That only applies if the x and
y axis are time and concentration of the drug - in this case its not. It is duration of anasthesia vs. recovery time.
Thiopental follows zero order kinetics - this is why thiopental is not used for maintance because it takes so
long for pt to gain consciesness again. This isin't true for propofol b/c it doesn't follow zero order kinetics.
Thiopental is not used to maintain anesthesia in surgical procedures because, in infusion, it displays zero-order
elimination kinetics, leading to a long period before consciousness is regained. Instead, anesthesia is usually
maintained with an inhaled anesthetic (gas) agent. Inhaled anesthetics are eliminated relatively quickly, so that
stopping the inhaled anesthetic will allow rapid return of consciousness. Thiopental would have to be given in large
amounts to maintain an anesthetic plane, and because of its 11.5–26 hour half-life, consciousness would take a
long time to return.
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nbme>>>4,3,49 in elderly individuals risk of respiratory depression due to midazolam increases due to>>>>>increase
in sensitivty to sedatives and not by increase metabolites(rather in them there is decrease in metabolism) or
plasma protein binding.
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inhaled anesthetic used for maintaining general anesthesia
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autosomal dominant. abnormal ryanodine receptor release large amount of Ca.which stimulate ATP-dependent
reuptake by sarcoplasmic reticulum.excessive consumption of ATP generates heat. loss of ATP along with high
temperature damage muscle. rhamdomyolysis leads to potassium, myoglobin and creatine kinase into
circulation. ............. hyperkalemia, myoglobinema and increase CK are characteristic,
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equilibrates with in 1 min
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with in 5-10 min after administration.
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is less efective in ischemic and acidotic tissues.
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adverse effect>>>>acute pancreatitis>>>because it increases TGs content
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can lead to euforia.
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beacuse it is short acting, used intravenlously
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acts on ryanodine receptor and prevent hurther release of calcium>>muscle relaxant.
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inhaled anesthetic effect almost all organ system. 1, CV>>decrease CO. 2, respiratory>>>all inhalaltaiton except
nitrous oxide aer respiratory depressants. they decrease tdal volume and minute ventilation and cause
hypercapnia. also causes decrease mucociliary clearence (atelactasis). halothane and sevoflurane have
bronchodilaiton properties ans are preffered in patients with asthma. 3, in the brian, fluorinated anetheltic
increase cerebral blood flow. 4, in kidneys, decrease GFR, increase renal vascular resistance and decrease renal
plasma flow. 5, decrease hepatic blood flow.
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can also lead to euphoria ................. act via NMDA receptro antogonism,prolonged exposure can reduce
methinine synthase activity, causing megaloblastic anemia
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rapid plasma decay of thiopental was not metabolism of the drug but rather redistribution of
the drug to other tissues throughout the body (lean tissue).
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nbme>>>3,4,8
Genoype susceptibility related to ryanodine receptars and/or protein component of L -type calcium
channel in skeletal muscle.
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GABA, potassium(hyperpolarization), nicotine and glycine receptor 854 .. affect
potassium channel in neural membrane and lock them in state of hyperpolarization. they may also affect
nicotinic and glycine receptor
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analgesia and amnesia with preserved consciousness.
853
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presynaptic (primary afferent neuron)>>>decreases release of NT 776
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can produce histamine,
metabolized to laudanosine which causes seizure
848
.........................
also eliminated by hoffman eliminaiton>>>spontaneously degrade in plasma and tissues
856.
.............
it releases histamine>>>>flushing, hypotension and bronchoconstriciton>>>also metabolized to
laudanosine, which can provoke seizure
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also has NMDA receptor antagonist effect so has been shown to reverse opioid tolerance.
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N/OFQ (nociceptin/orphanin) is another type of opioid receptor which has effect of anxiolysis and increassed
appetite
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Smooth muscle 0 Longitudinal relaxes ° Circular constricts GI: decrease peristalsis, constipation, cramping
GU: urinary retention, urgency to void Biliary: increase pressurePupils: miosis. Cardiovascular: minimal
effects on heart, but vasodilation (avoid in head trauma)
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Contraindications and Cautions for Opioids• Head injuries (possible increased intracranial pressure) • Pulmonary
dysfunction (except pulmonary edema) • Hepatic/renal dysfunction (possible accumulation) • Adrenal or thyroid deficiencies
(exaggerated responses) • Pregnancy (possible neonatal depression or dependence), except meperidine
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central sensitization (increased pain sensitivity due to long term use caused by: 1, Increased turnover of inhibitory
opioid receptor (receptor downregulation) and decoupling of receptor form their secondary messenger system
(receptor decoupling) 2, upregulation of excitatory NMD receptor These changes manifests as increased dose
requirement (tolerance) and and increased pain sensation triggered by benign stimuli (opioid induced
hyperalgesia)
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delta has antidepressant effects
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activation include inhibition of adenylyl cyclase, and inhibtion of transmittor release.
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Cough suppression: antitussive action, independent of analgesia and respiratory depression. Affect cough
center of the medulla. Achieved with lower dose than required for analgesia
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Mu receptor agonist.combined with atropine(LOMOTIL) to reduce the abuse of this drug,cause in higher doses
have morphine like euphoria and physical dependence. struturaly similar to meperidine. common SE are
bloating and mild sedation
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most severe yet rare SE. reducing responsiveness of respiratory center in brain stem to cabon dioxide. tolerance
to this develop very rapidly and is unlikely to occur in patient with active pain or who have been taking opioid
regularly. (do not give 02; give naloxone)
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binds with all receptor but with mu-receptorwith greater affinity. must be given parenterally due to complete
metabolic inactivation by the liver when given orally. reversal effects can occur within minutes, and the duration is
dose dependent (1-4 hours)
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this condition is similar to non-depolarizing blocker
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some individual are homozygous for an atypical plasma cholinesterase>>which break down succinylcholine more
slowly
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poisoning due to nicotinic receptor antagonists (eg pancuronium, tubocuranium) is uncommon as these agents have
poor oral absorption
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is a G-protein couples receptor. increase K efflux and decrease Ca enteri into the cells. inhibit adenylyl cyclase
also
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succinylcholine have 4 adverse effects 1, hyperthermia 2, hyperkalemia in
susceptible patient(in burns, myopathy,crush injury and denervation, quadriplegia
and guillain barre) 3, bradycardia 4, tachycardia 8481
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codeine (produrg) metabolized to active form by cyp450
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inhalation anesthetic(halothane) and skeletal muscle relaxant(succinylcholine)
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selective muscarinic ,tertiary amine
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patients with burn/crush injuries, denervating injuries or diseases (es quadriplejia and gullain-barre) and
myopathies>>>>>uprergulates nAchR and/or rhabdomyolis, which can result in release of large amount of
potassium>>>>in these patients non-depolzarizing agnets are preferrable
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of the motor end plate>>>>flaccid paralysis due to surrounding Na channels inactivation.
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is the most common and persistent side effect. opioid stimulate mu receptro in the GI tract, causing decreased
secretion and gastric motility.patiets who require prolonged opiod therapy should receive prphylactic bowel
regirmen (increased fluid intake, dietery fibers, and laxatives)
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euphoria, mood alteration and rewarding properties. it may be due to dopaminergic pathway in nucleus
accumbens. tolerance to these affect develop rapidly and lead to addiction and abuse.
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commonly used for travelers diarrhea but can worsen nausea and vomiting due to colonic extension
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substance p is 11-amino acid polypeptide which act as pain NT in both peripheral and central nervous system. n
CNS thought to regulate mood, anxiety and stress behavior. capsaicin reduces pain by decreasing the level of
substance P in peripheral nervous system. substance-P receptor (neurokinin receptor 1 NK1) antagonist is used
as an antiemetic>>>>>> aprepitant and fosaprepitant
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kappa causes miosis, dysphoria and sedation
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is a G-protein coupled receptor.
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sedation typically occur during initiation of therapy and usually disappear after several days. .....................................
nausea with or without vomiting is th common and unpleasant side effect during the initiation of opiod therapy,
but tolerance develop within days and persistent nausea is uncommon.. it stimulate CTZ leading to emesis. .......
opioid block urinary voiding reflexes and also increaes sphinter tone and bladder volume. this results in an
antidiuretic effecr and urinary retention. toleracne to this effects develop rapidly
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morphine acts as a vasodilator, increasing venous capacitance, reducing systemic vascular resistance and
potentially causing CNS sympahtolyticeffects on the cardiovascular system.it is used to treat ischemic chest
pain, especially during acute MI.
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other possible secondary messenger pathway besides G-protien coupled K channel opening are: inhibition of
adenelyl cyclase. inhibition of calcium conductance. inhibition of transmittor release.
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partial agonist activity and weak antagonist activity at mu-receptor. it was originally design to give anelgesic effect
with little or no abuse potential. because of its weak antagonist activity at mu-receptor can cause withdrawl
symptoms in patient who are dependent or tolerant to morphine or other opioids.
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but increase release of hisatmin and somatostatin. decrease release of gastric
acid from parietal cells. 1258
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in postsynaptic neuron(2nd order neuron) 776
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dorzolamide
11841
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also due to miosis which causes the iris to move futher apart from the cornea.this widens the
anterior chamber angle.
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non addictive analgesic
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agonist
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travoprost
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uroprostone, travoprost
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Transference is the unconscious shifting of emotions or desires associated with a person from the past to
another person n the present.
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immature defenses are maladaptive and generally seen in children and in psychopathologic states.
mature defenses are more often used by adults and allow for a “health”, adaptive response to emotional
distress.
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Undoing involves symbolically nullifying an unacceptable or guilt-provoking thought, idea or
feeling by confession or atonement (commonly seen in obsessive-compulsive disorder
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misattributing one's own unconscious, undesired or feelings to another person who does not actually have
them projection commonly occurs in patients who lack insight into their own motivations and feelings,
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Splitting is a defense mechanism that involves experiencing the self or others as all bad or all
good.
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Other examples of passive resistance behaviors include procrastination, forgetfulness and purposeful
inefficiency. Backhand compliments, sarcasm and denial of being angry are also characteristic of
passive-aggressive behavior.
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Pica is the compulsive consumption of a nonfood and/or non-staple food source for>1 month. it is most
commonly seen in pregnant women and schoolchildren. Although the cause of pica us unclear, it is often
(but not always) associated with nutritional deficiencies, including iron and zinc deficiencies and anemia
of any etiology. ............. In cravings of normal pregnancy, the patient desires nutritive food items.
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ADHD is more common in boys, girls are more likely to have the inattentive subtype.
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Selective mutism involves failure to speak in specific situations (eg, school despite speaking in other
settings. This boy’s language impairment in all settings. deficits in social reciprocity, repetitive behaviors
are more characteristic.
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Rett syndrome is a neurodevelopmental disorder that occur mainly in girls. It is characterized by normal
development until age 5-18 months, followed by a loss of motor and language skills and the
development of stereotypic hand movements. Deceleration of head growth is a classic features of
Rett syndrome and can be early sign. Other features include development of seizures, intellectual
disability, autistic features, and breathing abnormalities. ............... There is no specific therapy for
Rett syndrome, and management focuses on treating associated conditions. Most cases are due to de
novo mutations in the X-linked MECP2 gene.
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Children with separation anxiety disorder will commonly experience physical symptoms (eg, headaches,
stomach aches, nausea) when separation occurs or is anticipated and repeated nightmares involving
the theme of separation. According the DSM-5 symptoms must be present for >_4 weeks in children
and >_6 months in adults. .......... Physical symptoms and nightmares may accompany anxiety.
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intermittent explosive disorder:
agression is not premeditated or commited to achieve some tangible objectives (eg money, power,
intimidation)
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pyromania: intentional and repeated fire setting with no obvious motive; it does not involve other behaviors seen
in conduct disorder (eg lying, theft, cruelty to others) a seperate diagnosis of pyromania is not given when fire setting
occurs as part of conduct disorder. .......... kleptomania: inability to resist the impulse to steal onjects that are of low
monetary value or not needed dor personal use. overwhelming feelings of tension or anxiety precede impulses and
are releived with the act of theft.
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This patients pattern of deliberately annoying behavior and defiance of rules and authority figures that
causes problems at home and at school suggests a diagnosis of oppositional defiant disorder (ODD).
her angry outbursts and blaming failures on others are also characteristic of the disorder. For
diagnosis, the oppositional behaviors must be excessive compared to normative age-appropriate behaviors
and observed during interactions with individuals other than siblings. ODD should be differentiated
from conduct disorder, in which the problem behaviors are more severe and aggressive this patient does
not exhibit physical aggressive or cruelty toward people or animals. destruction of property, or the
typical pattern of stealing or deceit seen in conduct disorder. ODD may precede the development of
conduct disorder and increases the risk of adult antisocial behavior, impulse-control problems, substance
abuse, anxiety, and depression.
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This child;s lack of social engagement, speech delay, repetitive play, and insistence on sameness
are consistent with autism spectrum disorder (ASD). ASD is more common in boys and
symptoms are typically recognized by age 2................... . It can occur with or without language and
intellectual impairment.......
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Typically presenting by age 3. Autistic features can be seen in a number of other neurodevelopmental
disorder. including Rett and fragile X syndromes, but must be specified as such (eg, ASD associated
with Rett syndrome).
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Norepinephrine and dopamine are the keys neurotransmitters involved in the pathophysiology of ADHS
symptoms. Symptoms of hyperactivity, impulsivity and inattention have been linked to reduced levels of
norepinephrine and dopamine in the prefrontal cortex
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can be confused with myoclonic epilepsy
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X-linked methyl-CpG-binding protein 2
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Depersonalization/derealization disorder is not diagnosed as a separate illness when it occurs as an
associated symptoms in borderline personality disorder and post-traumatic stress disorder.
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Delirium is a reversible, acute-onset confusional state characterized by a fluctuating level of
consciousness with deficits in attention, memory, and executive function.
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It is most common seen in elderly patients with medical illness and is often associated with anxiety,
agitation, delusion and/or hallucinations. Patients of advanced age and with neurologic conditions such as
Parkinson disease, dementia and prior stroke are more likely to develop delirium due to reduced
cognitive reserve, The pathophysiology of delirium is multifactorial and thought to be related to increased
oxidative stress, neuroinflammatory mediators and impaired neurotransmitter functioning.
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Episodes of depersonalization are characterized by a feeling of detachment or estrangement from the self
or sense of being an outside observer of the self. Derealization is a subjective sense of detachment or
unreality regarding surroundings. In contrast to psychotic disorders, reality testing is intact during
these unusual experiences (ie, an individual may feel detached from his or her body but knows thus is
not true).
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Primary psychotic disorders are diagnoses of exclusion that requires ruling out substance
use and medical etiologies. Brief psychotic disorder is characterized by acute onset of >_ 1
psychotic symptoms (delusions, hallucinations, disorganized speech or behavior) lasting >_1
day but <1 month, with eventual complete resolution
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remote memory is spared initially, and there is no impairment of consciousness until late in
the disease
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delusion non-bizarre (theoratically possible but highly implausible)
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The total illness duration must be >_6 months (including prodromal and residual periods) with >_ month
of active symptoms. .................. mesolombic-mesocotical pathway is hyperactive(frontal cortex). this pathway
regulates behavior
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symptoms of mania (eg, elevated mood, decreased need for sleep, hyper-sexuality, grandiose
delusions) but also has a history of delusions or hallucinations occurring in the absence of a major
mood episode. (manic or depressive). A lifetime history of at least 2 weeks of psychotic symptoms
without significant mood disturbance is a key requirement for the schizoaffective diagnosis.
Differentiating schizoaffective disorder from the bipolar disorder or major depression with psychotic features
requires determining the temporal relationship between psychotic symptoms and mood symptoms.
In bipolar disorder and major depression with psychotic features, the psychotic symptoms occur
exclusively during manic or depressive episodes. when the patient’s mood is euthymic, there are no
psychotic symptoms. ...............
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Substance-induced mood disorder is diagnosed when depressive symptoms develop during or
within a month of substance intoxication or withdrawal.
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anhedonia: lack of interest
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sudden onset with full return to premorbid level of functioning
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other postive psychotic symptoms such as hallucinations and disorganization are absent.
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poverty of speech
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"( males > females )."
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the diagnoses is further classidfied based on the tyoe of belief; erotomanic (believing that someone isin love with
them), grandiose (believing that have great talent, insights or achieemnt) jealous(believing hat partner is unfaithful)
persecutory(belieivng that they are bieng sheated, spied or poisonded or harassed) and somatic (believing bodily
functions and sensation are abnomrla)
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1st and 2nd generation antipsychotic>>>> for positive symptoms. psychosocial therapy (congnitive behavioral
therapy and social skill training)>>> for negative symptoms
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Disruptive mood dysregulation disorder is a new diagnosis in DSM-5 characterized by persistent
irritability and frequent, developmentally inappropriate temper outburst.
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The essential feature delusions disorders is >_1 delusion lasting >_1 month without other
psychotic symptoms. Schizophreniform disorder involves >_2 psychotic symptoms lasting >_1
month but <6 months
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nbme,7,3,23
Legally, a patient is incompetent if unable to do the following:
-- (1) respond knowingly and intelligently to questions about recommended treatment;
--(2) participate in treatment decisions by means of rational thought processes; and
-- (3) understand the items of minimum basic medical treatment information with respect to that
treatment
--hence the paranoid schizophrenic patient is legally competent and able to decide and refuse
treatment....
---here is more explanation
it could be said that even a patient whose 'delusions are plainly irrational 'may be competent to
make a treatment decision if he or she fulfills the following criteria
1-comprehending and retaining information relating to the decision
2-believing the information provided by the treating physician
3-weighing it in the balance when making a choice....

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does not require functional impairment to diagnose like schizepherina, but
functional impairment most of the time present 2063 ... Functional decline, although
often present, is not required for diagnosis. Approximately two-third of patients with
schizophreniform disorder will eventually be diagnosed with schizophrenia or schizoaffective
disorder
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CORTICAL ATROPHY, small frontal lobe temporal lobe atriphy
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quetiapine is also a first line mood stabilizer
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Major depressive episodes are common but not required for diagnosis..
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Bipolar disorder is a highly recurrent illness requiring maintenance treatment with mood stabilizers to
decrease the risk of recurrent mood episodes. First-line medications for bipolar maintenance treatment
include lithium, the anticonvulsant valproate, and the second-generation antipsychotic
quetiapine.Lamotrigine, another anticonvulsant used in maintenance treatment, has been found to be
more effective in preventing depression than mania. Antidepressant mono therapy should be avoided in
bipolar maintenance treatment due to the risk of mood destabilization.
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Appetite, sleep and motor activity can be increased or decreased
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Some women with mood disorders report that heir symptoms worsen before their menstrual periods.
However, in premenstrual dysphoric disorder, depressive symptoms must remit with the onset of
menses and the diagnosis must be confirmed by daily prospective ratings over several cycles.
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most bipolar 1 patients will experience both major depressive and manic episodes, but depressive episodes are
not required for diagnoses
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in acute mania and maintenance treatment, especially in patient with rapid cyling ( >4 episodes in year) and
episodes with mixed manic-depressive features
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patient with one or more life time manic episode are diagnosed with bipolar 1 disorder
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is a chronic depression that persists for at least 2 years. it inculdes pure dysthymia and chronic major depression
...................... In DSM-5 persistent depressive disorder includes both “pure dysthymic syndrome” and
chronic major depression or dysthymia with concurrent or intermittent major depressive episodes.
This patient would be diagnosed with “pure dysthymic syndrome” as she has never met the criteria for a
major depressive episodes. Persistent depressive disorder is treated with antidepressants, psychotherapy,
a combination of these.
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this is main differentiation between mania and hypomania, mania have psychosis
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this does not occur in typical/major depression
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manic episode can occur with or with our psychotic features (eg delusions, hallucinations). delusions, if present,
are often mood congruent (eg grandiose theme involving special talen and powers) but can also be mood
incongruent
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and do not have psychotic symptoms
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manic episode treated with lithium, carbamazapine, valproate and olanzapine. depressed episode treated with
lamotrigine.
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major depressive disorder with psychotic features.>>> Delusions and hallucinations are commonly mood
congruent and have depressive themes (eg, deserved punishment, worthlessness, nihilism ) although
mood incongruent psychotic symptoms (unrelated to depressive themes) can also occur. effective
treatment requires the combination of an antidepressant and antipsychotic or electroconvulsive therapy.
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Untreated hypothyroidism is a known medical cause of depression. ... when anxiety symptoms occur
coincident with depression,patients are likely to be less responsive to any antidepressant treatment. ... MAO
inhibitors used in treatment-resistant depression.
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Cyclothymic disorder is a chronic, fluctuating mood disturbance involving numerous periods of hypomanic
and depressive symptoms that are insufficient to meet the criteria for manic or major depressive episodes.
Symptoms must be present for at least a year in children and adolescents and cause significant
distress and impairment
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Hypomania is differentiated from mania by a lesser degree of severity and functional impairment
and the absence of psychosis. Patients experiencing hypomania exhibit a noticeable change in
behavior but are often very productive despite requiring less sleep. In contrast to manic patients,
those who are hypomanic are often able to work and see rarely hospitalized.
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more effective for depressive symptoms of bipolar disorder
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nbme>>>6,1,29
the risk of depression is greatest after delivery , and depression during pregnancy can often be
safely treated.
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hallucination of recently deceasedrelatives in children are part of a normal grief reaction and may not be
indicative of major psychiatric illness. Children under age 6 usually do not understand the finality of death and
may believe that it is temporary or reversible.
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Age, male sex, and being separated or divorced are static risk factors for suicide. Elderly (age>75) white
men have the highest suicide rate. Suicide risk is highest in those who have never married, followed by
those who are widowed separated or divorced. ..... Other potentially modifiable factors associated with
suicidal behavior include physical illness, alcohol and drug abuse, impulsivity and untreated
psychiatric illness. Static risk factor include age, gender and history of previous attempts. The highest
risk age group fro suicide is age 45-64, the second highest risk group is age >_ 85.... Among
American age <40, it is the second leading cause of death behind motor vehicle accidents, with the
majority of these deaths occurring by firearm.
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also in patient who cannot tolerate medication, and catatonic patient who require rapid treatment response.
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normal bereavement>>>>>has sadness , insomnia , decreased appetite and weight loss. which may resembel a
major depression. bu in normal grief , the asadness revolves around feelings of loss and typically occurs in waves
intermixed with postitive memories of the deceased. the intensity of normal grief decreases over time. in normal
grief pervasive anhedonia, worthlessness and suicidality are not present.
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Suicide rates in military veterans are significant higher than in the general population.Ninety percent of
patients who die by suicide have diagnosable psychiatric disorder at the time of death. increased
severity of illness and recent discharge fro psychiatric inpatient care are additional risk factor
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Although previously thought to occur in sequence, patients may experience stages of grief in a different
order or only some of the stages. The best approach to a patient in denial is to first determine whether
the denial is interfering with medical care (eg, patient refusing a curative treatment) or significant
relationships. This patient’s denial is not interfering with his receiving treatment or his relationships
therefore, his denial should not be confronted.
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Escitalopram is a selective serotonin reuptake inhibitor used in the treatment of panic disorder, and social
anxiety disorder. It is not a first-line treatment for specific phobia.
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GAD is treated with cognitive behavioral psychotherapy and/or antidepressant medication. Selective
serotonin reuptake inibitors (SSRIs) such as citalopram or serotonin-norepinephrine reuptake inhibitors
(SNRIs) are first-line treatment. SSRIs and SNRIs can also treat depression, a common co-morbid
condition. ........... Benzodiazepines can be used on a limited basis to manage acute anxiety while
waiting for SSRIs or SNRIs to take effect. Benzodiazepines should be avoided in patients with a history of
substance use disorder.
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For diagnosis, obsessions or compulsions must be time-consuming (>! hr/day) or cause
significant distress or functional impairment. OCD is typically a chronic disorder starting in
childhood or adolescence
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Patients with body dysmorphic disorder can have delusional beliefs about their appearance, with a firm
conviction that their perception is accurate. This is diagnosed as body dysmorphic disorder with absent
insight, rather than delusion disorder. ....... body dysmorphic disorder It is diagnosed when weight gain is
the preoccupation of an individual who meets the criteria for an eating disorder.
?????????????????????????
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diagnoses of panic disorder require first ruling out medical and substance-induced causes. ..... Substance-
induced caused of panic attacks include intoxication with central nervous system stimulants (eg,
amphetamines, cocaine caffeine) and alcohol or sedative hypnotic withdrawal.
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exposure is typically performed in a gradual, step-wise manner, resulting in decreased anxiety
over time as habituation and extinction occur. Confrontation with the phobic stimulus in a safe
and controlled manner can be accomplished through in vivo (most effective) imaginal and
virtual exposure techniques
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“If symptoms last > 6 months and cause continual impairment.
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diagnoses require recurrent, unexpected panic attacks, typically reaching a peak within minutes and followed by
persistent concern about additional attacks. ................... key feature is that at least some of the attcks are
spontaneous with no obvious trigger (eg when an individual is relaxing or emerging from sleep ie nocturnal panic
attack)
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Patient insight ranges from good to absent (complete conviction that beliefs about their appearance are
true). In DSM-5, body dysmorphic disorder is classified under obsessive-compulsive and related
disorders, recognizing the similarities of preoccupations and repetitive behaviors.
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shoulf not be confused with OC personality disorder.This disorder involved a lifelong pattern of insistence on
control, orderliness and perfection and does not involve performed in response to intrusive obsessions.
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social anxiety disorder (social phobia).It is common psychiatric disorder with typical onset in adolescence
that can result in significant impairment in functioning and quality of life. anticipatory anxiety weeks
before a social event and avoidance (not going to parties, school refusal) are common. The specifier
“performance-only” is given to patients who have symptoms in performance situations (eg, speaking or
performing in public). .... social anxiety disorder is considered when anxiety and avoidance of social setting
are due to worry about being viewed negatively by others.
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Somatic presentations are common and include cardiac, neurologic and gastrointestinal symptoms.
administration of benzodiazepine in the emergency setting results in rapid relief of symptoms. Selective
serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are first-line pharmacologic
treatments for panic disorder but would not be initiated in the emergency department as they weeks to
begin working and require ongoing monitoring.
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intense self-consciousness concerns about appearance and social acceptance, moodiness, increasing
need for privacy and transient emotional outbursts are characteristic of normal adolescence. although
differentiating normal adolescent behavior from early signs of psychiatric disorders can be difficult, this
child’s engagement with school and friends is reassuring. In contrast, adolescent exhibiting persistent
anger, sadness, impulsivity, sleep or appetite disturbance, declining academic performance, and social
isolation from peers warrant further evaluation.
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Psychodynamic psychotherapy focuses on developing insight into unresolved conflicts that began in
childhood. Supportive psychotherapy is aimed at bolstering adaptive psychological defenses to help
individuals cope with acute crises or chronic psychiatric illness.
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exposure to a traumatic event followed by development of characteristic symptoms (re-experiencing, avoidance,
arousal) lasting from 3 days to 1 month
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Factors associated with better treatment adherence rates include close peers with complementary
behavioral practices, positively family functioning, physician empathy and immediate benefits of
treatment.the most effective approach to imroving adherence in this pateitns would be finding support
and role models within his peer group. Another factor affecting adolescent treatment adherence is that
the prefrontal cortex (center of executive function) does not fully develop until the third decade of
life. compare to adults, adolescents are less to weigh the risks and benefits of their decisions or
anticipate that negative consequences may occur.......................... Adolescents have low treatment
adherence rates related to issue with autonomy rebellion against authority figures, and lack of
understanding of potential risks, peer behavior has strong influence on adherence at this age due to
adolescents’ desire to fit in with their social groups.
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patients with this disorder exhibit a pattern of pervasive distrust of others beginning in early adulthood. It
can be differentiated from psychotic disorder by the lack of specific, well-developed delusions.
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borderline personality disorder is characterized by transient mood shift that occurs in response to
interpersonal stressors. Patients with borderline personality disorder may experience transient,
stress-related paranoid ideation, but they do not exhibit a pervasive pattern of distrust and
suspiciousness characteristic of paranoid personality disorder
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avoidance of social situations in multiple settings avoidant personality disorder manifests in early
adulthood.
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can be treated with omega 3 FA, 2nd generation antipsychotic and mood stabilizes.
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treated with mood stabilizer, antipsychotic and antidepressant.
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They struggle with feelings of inadequacy and pursue relationships only when they feel
assured of uncritical acceptance
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This patient’s depression, suicidal ideation and impulsivity in the setting of feeling rejected are
characteristic of borderline personality disorder. Patients with borderline personality disorder exhibit a
persistent pattern and intense relationships beginning in adolescenece or early adulthood. patient with
borderline personality disorder frequently come to clonical attention due to suicidal behavior ir threats during an
interpersonal criris and comprise approximately 20% of psychiatric inpatietns.
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nbme>>>3,3,25 somatization>>>variety of complains in multiple organ systems over a period of years Criteria: a
history of somatic symptoms prior to the age of 30 pain in at least four different sites on the body two
gastrointestinal problems other than pain such as vomiting or diarrhea one sexual symptom such as lack of
interest or erectile dysfunction one pseudoneurological symptom similar to those seen in Conversion disorder
such as fainting or blindness.
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The best approach is to schedule (to treat) regular visits with her primary care provider, who can monitor
her condition. and avoid unnecessary diagnostic testing and specialist referrals. In contrast to
symptoms-driven visits, regular visits provide patients with an opportunity to discuss their concerns and
may decrease the use of emergency services. Office visits should focus on functional improvement
rather than symptoms eliminations by promoting stress reduction and healthy behaviors (diet, exercise,
return to productive activities). Once a physician-patient relationship is established, she may be more
receptive to a referral. Psychiatric consultation can assist in identifying and treating comorbid
depressive and anxiety disorder. Both cognitive behavioral therapy and antidepressants have a role
in the treatment of this disorder.
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Conversion disorder is a somatic symptoms disorder characterized by symptoms or deficits of
voluntary motor and/or sensory function that are incompatible with any recognized neurological
condition and cannot be explained by another medical or mental disorder. Symptoms must
be neurological and include weakness, paralysis, gait disturbance, blindness, diplopia, aphonia,
anesthesia, and seizures (and also called psychogenic or non-epileptic seizures). Internal
consistency at examination can demonstrate incompatibility (eg, “paralyzed” limb moves when
patient performs movement with unaffected limb, eyes closed with resistance to opening during a
“seizure”). The phenomenon of la belle indifference (ie, incongruous lack of concern about
symptoms) has been associated with conversion disorders, but it is not pathognomonic and
should not be used to make the diagnosis
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their anxiety is primarily related to their physical symptoms and physical health.
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Olanzapine, an antipsychotic associated with weight gain, has been used as an adjunctive treatment to
psychotherapy for anorexia nervosa. It has no role in the treatment of bulimia nervosa.
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Although self-induced vomiting is the most common compensatory behavior, patients may also fast and
exercise excessively or misuse laxatives, enemas, diuretics, or diet pills. In DSM-5, both binges and
inappropriate compensatory behaviors must occur to least once a week for 3 months for diagnosis. Both
bulimia nervosa and anorexia nervosa may be characterized by preoccupation with weight, binge eating
and compensatory behavior (thee is a binge-eating/purging subtype pf anorexia).
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its a functional hypothalamic amenorrhea (FHA)>>is due to reduced circulaitng leptin levels as a result of
diminished adipose tissue stores. decrease in leptin levels inhibits pulsatile GnRH
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SSRIs for comorbid anxiety and/or depression .”
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antidepressants (ie, SSRIs). "
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due to low caloric intake.
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SSRI is used for treatment, fluoxetine has the best evidence and is considrered the drug of choice. it is most
effective when combined with nutritional rehabilitation (establishing a strutured and consistent meal pattern) and
cognitive behavioral therapy.
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Multiple studies support the efficacy of pharmacotherapy in bulimia nervosa. In contrast, there is little
evidence to support the use of pharmacotherapy as a primary treatment in anorexia nervosa.
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the amphetamine lisdexamfetamine has been used to treat binge eating disorder, but not bulimia
nervosa.
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Hypersomnolence disorder is diagnosed when excessive and impairing daytime sleepiness cannot be
explained by another sleep disorder. patients with ypersomnolence disorder have persistent daytime
sleepiness rather than “sleep attack” unlike patients with narcolepsy, they typically do not fell
refreshed after naps.
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Amphetamines are second line agent due to their sympathomimetic side effects (HTN< arrythmia,
psychosis) and risk for dependency.
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narcolepsy with cataplexy is most often caused by the lack of 2 related neuropeptides, hypocretin-1 (orexin A) AND
HYPOCRETIN 2 (OREXIN b), which are produced only in neurons located in the lateral hypothalamus. these
neuropeptides funciton to promote wakefulness and inhibit REM sleep related phenomenon. hypocretin 1 levels
are measureable in the CSF but are not detectable in the blood or any ther peripheral tissues.so these patients
dont have hypocretin 1 in their CSF
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cataplexy also defined as>>>spontaneous, abnormal facial movements without emotional triggers.
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also have inability to move on awakening (sleep paralysis) ........ sleep paralysis (inability to move immediately
after awakening)
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1st line
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DSM 5 criteria for narcolepsy: recurrent lapses into sleep or nagging mutliple times within the same day, occuring at
least 3times weekly for 3 months. at least one of the following symptoms 1, cataplexy 2, hypocretin 1 def by CSF
analysis 3, REM sleep latency </15min.......... episoded of irresistible, refreshing sleep during the daytime
and usually one or more REM sleep-related phenomena such as cataplexy, hypnogogic hallucinations
and sleep paralysis.
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sleep deprivation may result in excessive daytime sleepiness, napping and quicker REM onset,
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nbme..5,1,10
10-D (Malingering)
these are all subjective symptoms which can be facticiously told to the doctor for the secondary
gain e.g. escape the charges as the pt was also recently involved in an auto accident.
Now why it is not Narcolepsy?
*pt says he "Lose Conciousness when he laugh"-------But in cataplxy u Never lose conciousness
rather "Transient Lose of Muscle Tone".
*he says he is "Sleeping for 14 hrs at "NIGHT-Time"-----But in narcolepsy u get sleep attacks
during the DAY-Time
first i had picked Narcolepsy but above thing i learned it from the forum discussion.
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muscarininc antagonist have been used to treat cataplexy 10362
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In the preparations stage, the physician should encourage and facilitate the patient’s plan to change,
In the contemplation stage, the patient realizes and acknowledges the problem but is not ready to do
anything about it. (eg, patient thinks about quitting but takes no step to do so.
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in the United States, the majority of overdose deaths are caused by prescription drugs, particularly
opioid analgesics.
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withdrawal symptoms can occur within 5-10 hours after the patient’s last drink typically reach maximal
intensity in 2-3 days and subside in 4-5 days if the withdrawal is not severe. Tremor, or the “shakes” is
the most common initial finding. ...... Alcohol withdrawal is one of the few potentially fatal drug
withdrawal syndromes. ... hypersomnolence can occur in acute ethanol intoxicaiton but is not common during
ethnaol withdrawal.Most patients have insomnia attributable to increased CNS excitability.
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Bradycardia can occur with GHB (gamma hydroxybutyric acid), opiate, or benzodiazepine intoxication.
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Violent behavior may also be seen with its abuse, but nystagmus is less common. Methamphetamine
intoxication typically lasts for up to 20 hours, longer than intoxication with PCP.
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The patient’s depression, fatigue, hypersomnia, hyperphagia, and vivid dreams are characteristic of
cocaine withdrawal. Symptoms occur within hours to days of cessation or reduction of heavy or
prolonged use . Following a binge, patients may experience a periods of acute, intense symptoms
including severe depression with suicidal ideation, pronounced lassitude, and drug craving (the
“crash”). ......... cocaine withdrawl>>>severe depression, hypersomnia, hyperphagia,
fatigue vivd dreams 11746........ severe form>>>>depression and suicidality
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neonate abstinence syndrome:tremors, irritability diarrhea and poor feeding are classic finding. opiate
replacement therapy (methadone or morphine), the dose is titrated to the patients symptoms and the patient is than
slowely weaned................................ ............... drugs with shorter half life (eg heroin) present with withdrawal
symptoms in 1-2 days; those esposed to drugs with longer half life (eg methadone) may present later..... .......... at risk
newborn include those born to mothers with poor mental health, no prenatal care and and hepatitis C infection.
...... neonate treat with tincture of opium or paregoric
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naltrexone has longer halflife (24 hours)
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QRS prolongaiton and severe hypotentsion are not common side effects of isolated opioid overdose.
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nbme>>>1,2,37>>>>2 year old girl brought 90min after ingesting drug form her mother purse>>>on arrival the child is
sedated, repsirations and blood pressure are normal.>>>>benzointoxication>>>fulmazenil
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mimic acute form of schizophrenia (paranoia type). so for this reason treatment is antipsychotic
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partial nicotinic agonist.
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propranolol can be tried after benzo if symptoms are still present. it treat both tremor and hypertension.
........................... role of phenytoin is controversial but carbamezapine should never be used for alcohol
withdrawal.
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for barbiturate withdrawal is life threatening mostly.
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visual hallucination can develop within 12-24 hours after the last drink and typically resolves within 24-48 hours
(alcoholic hallucinosis). these early haluucinations are distinct from delirium tremens
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antidepressants are given to treat underlying depression so that patient can quit smoking easily
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very useful sign
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grand mal
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opiate intoxication is life threatening but withdrawal not but it very agonizing so patient prefer to be addicted
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now a days more people are addicted of methadone than opioid...
withdrawal symptoms are less severe but prolonged (6-8 weeks)
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Nicotine withdrawal is commonly seen in the inpatient setting in chronic tobacco users. Besides cravings
for cigarettes, symptoms are generally mild and include dysphoria, irritability, anxiety, and increased
appetite/weight gain.
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signs and symptoms of cocaine intoxication typically lasting fir <_ 1hour. ........ cocaine overdose is potetially
life-threatening and ........... can effect every organ system. altered mental status,new onset
seizure.hypertension.intracranial hemorrhage, epistaxis ............ cocaine intoxication is marked by euphoria,
increased vigilance and psychomotor agitation. Physical signs of intoxication include increased heart rate,
blood pressure, hyperthermia, and occasional focal neurologic deficits. As in opioid withdrawal, pupils
are dilated in cocaine intoxication. ......... nbme>>>also called cracker>>> have hypertension along with sinus
tachycardia on ECG
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also have perceptual disturbances (depersonalizaiton), dysuria and psychosis.
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Although withdrawal is uncomfortable, it is generally not life-threatening. ............ Opioid withdrawal can
start as soon as 6-12 hours after cessation of a short-acting opioid such as heroin and usually peaks by
24-48 hours. People who have been taking chronic prescription narcotics, such as cancer patients can
also develop opioid withdrawal upon abrupt discontinuation or markedly reduced usage.
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Chronic ethanol use causes downregulation of GABA receptors. Alcohol also weekly inhibits excitatory
NMDA receptors in the brain, and chronic exposure leads to up-regulation of these receptors. Both
tolerance and withdrawal are signs of substance dependence
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amphetamine effect lasts hours, cocaine effect lasts minutes.
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give to reduce craving, and give when patient is still using alcohol
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PCP is a hallucinogen that works primarily as an N0methyl-D-aspartate (NMDA) receptor antagonist; it
can work secondarily to inhibit the reuptake of norepinephrine, dopamine, and serotonin, PCP can also
have effects on sigma-opioid receptors. PCP was originally develop as an anesthetic but was
discontinued due to its adverse effects in humans..... PCP is an NMDA receptor antagonist, not an
agonist. Examples of NMDA agonists are glutamate, aspartate, and D-cycloserine............ Moderate
amounts of PCP cause anesthetic and dissociative symptoms including detachment and withdrawal.
Agitation, hallucinations, and violent behavior can occur with higher doses. Fatalities are often associated
not with direct PCP intoxication but with related trauma due to combative behavior. Hospital urine
toxicology screen usually tests for PCP. ...... give patient non stimulating environment and gradually
restrain the patient. vit C, acidify the urine to pee out drug
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The most characteristic physiological signs of marijuana intoxication are conjunctival injection(red eyes),
tachycardia, increased appetite, and dry mouth. Marijuana is metabolized in the liver, distributed and
stored in lipophilic tissues and slowly released. It remains in the body for a long time; depending on
the amount and frequency of use, it can be detected in the urine up to 30 days after daily use has
ceased. ..... active ingredient tetrahydrocannabinol (THC). smoking is the preferred route of delivery,
and once inhaled, marijuana produces effects that last from 1-4 hours. THC stimulates cannabinoid
receptors (CB1 and CB2 receptors) to produce effects on mood, perception and cognition........
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nbme,7,1,40
patient present 45 minutes after collapsing at a party, he is agitated and disoreintated .his
temperature is 39 pulse 138, respiration 28 and BP 160/102.physical examination shows hot,
flashed skin, the pupils are dilated and responsive to light, its due to>>>>>MDMA and not by LSD
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nbme>>>6,1,4
major disadvantage of naloxone as a treatment of opioid overdose>>>>it has shorter duration of
action than most opioids. not tolerance development.not low TI,
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Disulfiram does not reduce craving and can be used only in abstinent patients with strong
motivation to maintain abstinence. Acamprostate, another abstinent-promoting drugs,
modulated glutamate neurotransmission at the N-methyl-D aspartate receptor and is
recommended once abstinence has been achieved.
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inhalants (in young poor male)are very much like PCP but has nose or mouth crusting and uncoordination is due to
cerebellar dysfuntion, unlike in LCD where it is due to perceptual problem
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low intrinsic activity and high potency(affinity), so in the presence of full agonist work as an antagonist.
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nalmefene is also antagonist
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and apathy,inattentiveness,disorientation indicate the development of encephalopathy
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cerebellar damage(degenration of all layers of the cortex) can be irreversible
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mild euphoria with inappropriate laughter.
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damage to anterior and dorsomedial thalamic nuclei
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horizontal nystagmus,bilateral abducens palsy. first to respond to thiamine supplimentation
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naloxone is used for acute opioid intoxication or overdose and for diagnosing opioid dependence
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rapidly acting antagonist(but has shorter duration of action), incontrast with long acting naltrexone
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is a very potent, long acting opiate with good oral bioavailability. it can cause respiratory depression like all other
opiates. it binds to protein in many tissues, after chronic dosing, it accumulates significantly is tissues. when
methadone is discontinued , it slowely released from tissue to maintain low level in blood. this allow for very mild but
extended withdrawal symptoms ..... its long half life and sustained effects after chronic dosing allows for
continuous suppression of withdrawal symptoms in heroin dependent patients.
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here with intoxication and in cocaine and amphetamine its a withdrawal issue
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angel dust, dust
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Medication used to treat alcohol dependence include oral and intramuscular depot naltrexone,
disulfiram, and acamprosate, Naltrexone blocks the mu-opioid receptor and can be initiated
while the individual is still drinking. it block the rewarding and reinforcing effects of alcohol
and has been shown to reduce the craving for it. acamprosate,modulates glutamate
neurotransmission at the NMDR receptor and is recommended one abstinenece have beec
achieved ......... SSRI>>Although they have been shown some efficacy in reducing alcohol use in
depressed alcoholic patients, they have not been effective fro treating alcohol dependence in
those without comorbid depression
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nbme>>>5,3,34
patient come with confusion, abdominal pain and diarrhea for 4 hours.the symptoms begun during
a party.most likely has MDMA and LSD.temperature is 30'c, physical examination show
myoclonus and hyperreflexia. an excess of NT in the synaptic cleft is>>>>serotonin.
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Patients who cease heavy and prolonged cannabis use may present with irritability, anxiety, depressed
mood, insomnia and decreased appetite.
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most patients are orientated and perceive that the effects are due to the drug ingestion.
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modulate glutamate at NMDA receptor,
give to pte in the abstinence phase
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in rave parties. these people are hyperthermic and sweat
more>>dehydrated>>>replaced with water, also has SIADH>>>so got
hyponatremia>>>>>treatment is normal saline and cooling
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The most common adverse effects include decreased appetite, weight loss, and insomnia. Most
affected children will experience a mild decrease in appetite that can typically be managed by
administering the medication after meals and encouraging the child to eat nutrient-dense foods.
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atomaxatine is an alternative in selected patients
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for treating seizure associated with withdrawal.
its a first line drug along with diazepam
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high potency type, not generally atypical type
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short acting: lorazepam and oxazepam are used in patients with liver dysfunction
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clonidine is an alpha-2 agonist that may be effective in children in ADHD who have failed treatment with
stimulants (eg methylphenidate)
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along with oxazepam are short acting and indicated for patient with advanced liver disease. other two have long half
life(up to few days) and are metabolized by liver into active metabolites
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The second-generation antipsychotic clozapine has a 1% risk of agranulocytosis and requires regular
monitoring of the absolute neutrophil count. Among the second-generation antipsychotics, ziprasidone is
most often associated with prolongation of the QT interval. Among the second-generation
antipsychotics, risperidone has been associated with greater of prolactin elevation.
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due to D2 receptor blocker in nigrostriatal pathway
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that resembles retinitis pigmentosa.
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tto is with benztropine/trhexiphenidyl (centrally acting)
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its an idiosyncratic reaction. generally with in 7-10 days od neuroleptic drug use but can occur with chronic use of
drug. Its due to disordered thermoregulation and skeletal muscle metabolism mediated via central
mechanisms...... Central dopaminergic systems are involved in thermoregulation as well as muscle tone and
movement
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lip smacking,bitting, grimacing, tongue protusions and choreoathetoid movements of head neck and limbs
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it is a low potency with superior efficacy than other 1st and 2nd generation drug. but due to agranulocytosis, not a
1st line agent. unlike other which act on D2 receptor clozapine act on D4 receptor. .... The second-generations
antipsychotic clozapine is the only medication that has consistently shown superior efficacy in treatment -
resistance schizophrenia.
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olanzapine aldo increase risk of metabolic syndrome(dyslipidemia, hypertension and hyeprglycemia)
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partial agonist/antagonist at the D2 receptor.it causes less weight gain than other but in efficacy is not superior
to other.
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irreversible and can worsen or persist following medication discontinuation. ....................... Possible
mechanisms of TD include development of supersenitivity of b D2 receptors following prolonged D2
blockade and an imbalanced between D1 and D2 receptors-mediated effects. Management strategies
include discontinuing the offending agent if feasible or switching to a second-generation antipsychotic,
preferable clozapine.
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NMS is differentiated from serotonin syndrome by the presence of muscle rigidity and the absence
of myoclonus
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restless leg syndrome>>>is due to iron deficiency, chronic renal failure and diabetes (especially with
neuropathy) more common in middle age and older patients DA agonist (pramipexole) is the preferred medication
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range from subjuctive restlessness to marked physical restlessness. frequently misdiagnosed with increasing
psychotic agitation. tto: decrease drug dose(if feasible) or use beta-blocker or benzodiazepine
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should be avoided in elderly patient, especially those who have BPH and acute-closure glaucoma. they cause dry
mouth and may cause acute suppurative parotitis............ Acute dystonia can develop abruptly any time
between 4 hours and 4 days after receiving an antipsychotic medication. The condition is characterized by
a sudden involuntary contradiction of a major muscle group. Other examples of acute dystonia include
oculogyric crisis (a forced ,sustained elevation of the eyes in an upward position), opisthotonus (Arching
of the back and head thrown backward), and rarely, laryngospasm, Risk factors include young age, male
sex, and treatment with high-potency first-generation antipsychotics. acute dystonia are result from
the antipsychotic property of D2 antagonism in the nigrostriatal pathway. In the striatum, the inhibitory
effects of dopaminergic neurons (D2) are normally balanced by the excitatory actions of muscarinic
cholinergic neurons (M1). Medications with M1 receptors antagonist properties, such as
benztropine or the antihistamine diphenhydramine, help re-establish the dopaminergic-
cholinergic balance and effectively treat acute dystonia
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thiothexine
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ziprasidone most commonly prolong QT interval
11848
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modify second messenger signal transduction( eg adenyl cyclase and phosphoinositol) at several levels, resulting
in decreased excitatory neurotransmission.
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due to antagonizing ADH on principal cell in collecting tubules. reversible after drug discontinuation, but can be
permanent due to chronic use
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and also renal fucntion tests (BUN and creatinine). accumulate in blood in renal insufficiency. also measure
serum thyroid stimulating hormone level
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1st line treatment
not effective for panic disorder, social phobia or specific phobia.
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so not effective on an as-needed bases.
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does not lead to euphoria
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acute toxicity>>>GI problems.
chronic toxicity>>>neurologic problem (ataxia, tremors/fasciculations)
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lithium toxicity beside thiazide, are ACE inhibitor and NSAIDs(not aspirin) and nondihydropyridine
CCB.
also with volume depletion from GI losses,decompensated CHF and cirrhosis.
hemodialysis for toxicity
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long term treatment may reduce the suicide attempts and deaths in bipolar disorder patient. in bipolar disorder
used to treat acute mania, hypomania, and bipolar and unipolar depression.
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thiazide make patient sodium depleted, so Na is reabsorbed with lithium in PCT.
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not usually use for anxiety spectrum
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first generation antihisamine with serotonin blocker effects 2089 is a 1st generationanti-
histamine with non-specific 5-HT1 and 5-HT2 receptor antagonist properties. ..................... benzo for agitation and
short acting anti-hypertensive(esmolol and nitroprusside) for hypertension also used. dnt give long acting
antihypertensive(propanolol) due to risk of developing hypotension and shock.............. genrally treatment include
supportive care>>airway maintenance, hydration, and temperature maintenance.
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SSRI may cause initial worsening of anxiety and therefore treatment often started at lower dose
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neuromuscular excitation: hyperreflexia, clonus, myoclonus, rigidity and tremor autonomic stimulation:
(hyperthermia,tachycardia,diaphoresis and vomiting/diarrhea) altered mental status: (agitation and confusion) ..........
it is important to maintian high index of suspicion of serotonin poisoning in case of depressant pateitns who are
taking antidepressants
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by conjunction of two drugs and by overdose of single drug.
also with tramadol, ondansetron, linezolid, triptans
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amoxapine can cause mild parkinsonian symptoms.
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and QRS like quinidine.>>>torsades de point
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all antidepressant has potential to induce mania in susceptible(bipolar) patients.
TCA and venlafazine has relatively greater potential of inducing mood switches.
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mainly with clomipramine.
proconvulsant effect of many antidepressanr is due to antihistaminic, anticholinergic and
anesthetic properties of drug and not due to neurotransmitor level alteration.
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MCC of death in toxicity.
its due to inhibition of fast Na channel
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meperidine also has this along with tramadol
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blockage of cardiac fast sodium channels. blockage of fast sodium channel has causes QRS and QT prolongaiton.
a widened QRS interval or ventricular aeeythmias are indication for sodium biicarbonate. NaHCO3 increases
serum pH, which favors the non-inonized (neytral) form of the drug, making it less accessible to bind to sodium
channels, also increases extracellular sodium concentration, which help overcome the competitive, rapid sodium
channel blockage induced by TCAs
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TCS inhibit fast sodium channel conduction.resulting in arrythmias- the most common cause of death in patients
with antidepressant intixication. phase 0 myocardial depolrization is prolonged when sodium conductance is inhibited,
which results in decreased conduction with a prolonged QRS complex (>100 msec) and negative inotropic effect.
impaired excitation-contraction coupling within myocardial cells and dimished release of calcium from sarcoplasmic
calcium stores decreases cardiac contractitlity, and can promote arrythmia and death. refractory hypotension
resulting from decreasd cardiac contractility and direct perpheral vasodilation (from peripheral alpha-1 adrenergic
erceptor antagonism) oa also a major cause of martality. death due to TCA toxicity is usuallu the result of
ventricular fibrillation and/or cardiogenic shock. fluid resuscitation with normal saline (for refrectory
hypotension) and hypertonic sodium bicarobonate (for ventricular fibrillation) are crucial in these patients
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mainly with imipramine
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and also for painful diabetic neuropathy and are thought to be more effective for short term pain relief than
many newer generation anticonvulsant (gabapentin, capsaicin cream and carbamezapine)
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it has also been used to treat stress urinary incontinence in women because it enhances urethral
closure.
generally rarely causes obstructive voiding symptoms.
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St. John's wort resultes in an up-regulation of 5-HT receptors. So along with Fluoxetine may lead
to 'serotonin syndrome'
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serotonin receptor blocker not stimulator >>>> causes appetite stimulation and weight gain
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Serotonin syndrome typically does not cause diffuse muscle rigidity, which os instead more
commonly seen with NMS
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develops within minutes after giving drugs. NMS develops hours to days after
giving drugs
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postsynaptic serotoin recpetor and also inhibit serotonin reuptake 707
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responsible for sedation
707
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5HTreuptake>>>>trazodone, vilazodone and vortioxetine 5HT1 A
agonist>>>>vortiozetine and partial agonist>>>vilazodone 5ht2
antagonist>>>mirtazapine, trazodone 5ht3 mirtazapine and vortiozetine. sleep
disturbance>>varenicline and vortiozetine
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Tyramine is a an indirect sympathomimetic that is usually metabolized in the gastrointestinal tract by
monoamine (MAO).
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Due to its stimulating effects, bupropion is useful in treating depression associated with hypersomnia
and low energy. Bupropion is also preferred as it causes less weight gain compared to other
antidepressants Bupropion is contraindicated in patients with bulimia nervosa, anorexia nervosa, and
seizures disorders due to its lowering of the seizure threshold,......... useful for treatment of depression
associated with psychomotor retardation or hypersomnia , because it has stimulatory effects
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binds irreversibly
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atypical depression: 1, mood reactivity (major characteristic)>>improvement in mood on response to something
positive unlike typical depression. 2, leaden fatigue 3, rejection sensitivity 4, increased sleep and apatite.
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besides major depression and hypoactive sexual disorder
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when given at high doses.
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has no anticholinergic or cardiac effects. but due to priapism it is relative CI in adolescent boys
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can be used with fluoxetine in patient who has depression associated with insomnia.
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structurally related to amphetamine and inhibits presynaptic reuptake of dopamine and
norepinephrine but with a greater effect on dopamine.
some says its a selective norepinephrine reuptake blocker without significantly influencing
serotonin, Ach and histamine,
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olanzapine are associated with weight gain but bupropion associated with weight loss or neutrality.
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mitochondrial enzyme that deaminates primary and secondary aromatic amines
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Varenicline acts as a partial neuronal nicotinic receptor agonist and prevents nicotine
stimulation of the mesolimbic dopamine system associated with nicotine addiction. However, it
is not effective in reducing the craving for alcohol.
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The pathophysiologic basis of depression involves the dysregulation of monoamine (e.g,
serotonin, norepinephrine, dopamine) neurotransimission because phenelzine irreversibly
inhibits MAFO, it may take up to 2 weeks following discontinuation of the drug before the
enzyme is resynthesized to levels adequate for normal monoamine degradation.
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and also treatment resistant depression
573
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this is responsible for postural hypotension and priapism
707
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in mesolimbic dopamine pathway
11577
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in females it form vestigial gartner's ducts
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also called metanephric mesoderom/blastema
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the kidney migrate in cephalad direction during fetal development, forming new vascular connections with the aorta
as they travel. some of these vestigial blood vessels may persist in the adult as accessory renal arteries.
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potter syndrome rsults form bilateral renal aplaia.
potter sequence results form other etiologies
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depressed nasal tip, and suborbital creases.
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vesicoureteral junction maldevelopment>>>causes reflux and fetal hydronehrosis>>>conservative management as
children may outgorw it, prophilactic antibiotic to prevent UTI
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interercts with sacral intermediate mesoderm
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also called metanephric diverticulum
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T12-L3>>>location. ..... in development we have a role of WT-1, c-ret(tyorosine
kinase receptor) and GDNF
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prostatic
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nbme>>>2,3,48
due to fusion metanephric mass; horseshoe kidney.
development of kidney =
during 5th week permant kidneys are formed from two sources
1- metanephric mass [mesoderm]- which gives rise to-

GLOMERULOUS
BOWMENS CAPSULE
PCT
LOOP OF HENLE
DCT
COLLECTING TUBULES
2-ureteric bud- which gives rise to collecting system

COLLECTING DUCT
MINOR CALYCES
MAJOR CALYES
RENAL PELVIS
URETERS
Horseshoe kidney -- due to fusion of lower pole of kidneys due to fusion of metanephric mass
It leads to failure of ascend of kidney due to inf mesentric artery.
Kidney function will be NORMA
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eg cartilage
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most cases of horseshoe kidneys are asymptomatic and discovered upon autopsy
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L1 level
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pass in front of renal artery and aorta
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hyperosmotic volume contraction>>> diabetes inspidus and profuse sweating isoosmotic volume contraction>>>acute
blood loss hypoosmotic volume contraction>>adrenal insufficiency hyposomotic volume expansion>>SIADHA
and primary polydipsia
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depending on the ratio of low to high molecular weight proteins in the urine determine proteinuria
is a highly or poorly selective
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negative
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endothelium
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1, selective proteinuria>>>albumin loss with minimal loss of alpha-2 macroglobulin and IgG. 2, tubular
proteinuria>>presence of low molecular weight protein (such as beta-2 microglobulin, immunoglobulin light chain,
amino acids and retinol binding protein), these are normally filtered by glomerulus and are almost completely
reabsorbed by proximal tubules. they appear in urine when proximal tubular function is impaired, for instance in
tubulointerstitial nephritis. 3, overload proteinuria>>>low molecular weight proteins are produced in greater
amount eg in MM immunoglobulin light chain are produced in large amount. 4, functional proteinuria>>>due to
change in blood flow through the glomerulus (eg in exercise, fever, emothional stress or cold exposure) 5,
orthostatic proteinuria>>>occur in older, tall thin adolescents, increased protein excretion in upright position but
normal in supine position.albuminuria is usually less that 1.0 g/day, renal fucniton is normal, and overnight
collection of urine reveals normal albumin excretion (less than 50mg during 8 hours period) 6, isolated
proteinuria>>incidental finding in an asymptomatic individual with normal renal function
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endothelial cells have fenestration with radius of 40nm GBM have pores with radius of 4nm slit diaphragm (b/w foot
processes of epithelial cells which are covered by thin membrane) have size of 4nm>>>>so GBM and slit
diaphragm are size barriers ........ charge barrier>>provided by negatively charged anion ( eg heparan sulfate and
other proteoglycan) located on endothelial cells and GBM>>>>they repel negatively charged molecules .......
albumin has 70,000 delton weight and 3.6 nm radius. so barrier to its excreton is provided mostly by charge
barrier
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mnemonic is MISS
M-Mannitol I-Inulin S-Sodium S-SucroseThey distributed only in extracellular(intravascular +
interstitial) space not with in cell.
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the relation ship between serum creatinine and GFR is nonlinear. GFR is essentially normal even after a 50% loss
of kidney funciton (ie kidney donation.creatinine levels begin to rise only as the GFR declines to <60 mL/min
(assuming no change in muscle mass). serum creatitne is therefore as insensitive indicator of decreasing GFR
when creatinine levels are normal......... when GFR is normal, relatively large decrease in GFR result in only small
increases in serum creatinine. conversely, when the GFR is significantly decreased, small decrements in GFR
produce relatively large changes in serum creatinine. a good rule of thumb is that every time GFR halves, serum
creatinine doubles ......... for the most part creatinine synthesis in muscle and tubular secretion remains relatively
constant. as a result, serum creatinine levels depend primarily in the GFR.
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FF always increases with increasing efferent arteriolar constriction..but GFR may increase or decrease depending
on the condition
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with acute ureteral obstrucitn( first 12 hours) the RPF may transiently increase, however with time, efferent
arteriolar constriction( in response to reduced GFR) will decrease RPF. even at later stages, though, the GFR
remains depressed to a greater extent than the RPF, resulting in reduced FF
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Renal perfusion drives glomerular filtration; for this reason, renal blood flow in normally 3-5
times greater than that of blood flow in other organs
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A ngiotensin II
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the early distal is impermeable to both water and urea ........ cortical collecting duct is impermeable to
urea, vasopressin activates urea transporter in the medullary collecting duct
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the degree of K filtration by the kidneys depends on the GFR, which is relatively constant in healthy individuals.
100% filtered in bowmans space(cause it is freely filtered) 65% filtered load is reabsorbed in proximal tubule. the thick
ascending limb reabsorbs 25-30% of the filtered load.these processes occur at relatively fixed rate and do not
play a significant role in the regulation of K excretion in the urine.even in hyperkalemic state, the pateint will
absorb the majority of filtered K in the proximal tubuel and loop of henle. the principal and alpha-interclated
cells of the late distal and cortical collecting tubules are primary regulaotr of K. hypokalemia stimulates reabsorption
of K via apically located H/K-ATPase on. conversely normal or increased k load stimulates principal cells to secrete
K through apical K channels. increased K excretion may be caused by the following 1, high extracellualr K levels
directly stimulate basolateral Na/K pumps on bcells. 2, increase aldosterone enhances activity of prinicpal cells
Na/K pumps and also increases their apical permeability to Na and K. 3, alkalosis>>>K entery into cells in
exchange of H 4, volume expansion, high sodium intake or diuretic causes increase fliod flow through distal
tubule,quickly flushing away secreted k. this helps to maintain a high concentration gradient, allowing more
intracellular K to shift into tht tubular fluid...................... high dietery intake of K can cause the amount of K in the
collecitng tubules to actually exceed that of the filtered load.
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due to glutamine metabolism. NH3 is more important than H2PO4 for excreting H ion>>>cause kidney increases
NH3 production in chronic acidosis
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proxiaml convulated tubule absorb 60% of isotonic water (passively with the reabsorption of solutes) regarless of
patient hydration statedescending loop of henle absorb 20% of water. late distal and collecting duct absorb 20% of
water depending on presence of ADH
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aldosterone not increases H/K atpase on alpha-intercalated cells
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in thin ascending limb NaCl is passively reabsorbed.
in thick ascending limb NaK2Cl absorbed actively
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lactoferin bind to free iron in the urine and possibly recover it for metabolism. this mechanism play a limited role in
iron homeostasis
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cuboidal epithelial cell in PCT ..... squamous epithelial cell in ascending limb loop of henle
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adh also increases number of passive urea tramsporters in the medullary collecting duct, allowing a substaincial
fraction of highly concentrated urea to diffuse down its concentration gradient into the medullary
interstitium.when ADH levels are high this urea resorptioncontributes up to 50% of total
osmolarity of the medulla further increasing the water-absorbing capacity of the nephron. .........
the thin ascending limb of the loop of henle is permeable to urea,which passivley diffuses down its concentration
gradient into the tubular luman.secretoin of urea into the thin part of loop of henle allows to recirculate and
concentrate in the tubular syste, further increasing its concentration to the medullary osmotic gradient. ................
ADH also increase water absorption in the cortical segment of the collecting duct, reducing the
amount of free water delivered to the medullary collecting duct. this prevents excess water from
being absorbed into the medullary interstitium, which would otherwise dilute the osmotic
gradient and reduce the maximum achievable urine concentration. ......... the proximal tubule is
permeable to urea and resorbs abput half of the filtered load. however it does not respond to ADH. 40-50% of
filtered urea is reabsorbed by the proximal tubules. with variable further net secretion or absorption occuring in
remainder of nephron depending on systemic hydration and final urinary osmolality. ........ when ADH levels are
low, aquaporin 2 accumulates within pits along the luminal membrane and is returned to the cell cytoplasm through
endocytosis,
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increasing + charge due to Na channel inhibition, thus preventing K secretion
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Mutations in gama or beta (more B)
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----------Plasma renin conc---- BP------ Na excretion conc ----Plasma aldosterone
c)-----------------↓---------------↑--------------↔--------------------------↓
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Pseudoaldosteronism
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20% of amount of creatinine present with in post glomerular capillary are secreted in proximal tubule.
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urea is freely filtered but poorly reabsorbed, less so than PAH and inulin. renal handling of urea varies through out
the different tubular system. but it is ultimately secreted in very high concentration because it is a waste product
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unlike PAH and creatinine inulin does not secrete
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at low plasma concentration the secretion amount of PAH is 90%.
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afferent arteriole(modified>>>renin containing zymogen granules). chronic renal artery stenosis result in
hypertropht and hyperplasia of these cells (in affected kidney/kidneys) due to increase RAA synthesis
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it acts locally to constrict veins and dilate arterioles to increase renal perfusion
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is arginine vasopressin >>>the set point for ADH release is lowered in response to low effective intravascular
volume (eg low Co in CHF)
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renin-secreting tumor (reninomas) are rare, small, solitaroy benign juxtaglomerular cell neoplasms. should be strogly
considrerd in pateitns with marked hyperreninemia and hypertension wwoho clearly do not have renovascular
disease.
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core regulation of Ag II. sustained production of aldosterone requires persistent calcium entry
through low-voltage-activated Ca2+ channels. Innate electrical excitability of zona
glomerulosa cells provides a platform for the production of a recurrent Ca2+ channels signal
that can be controlled by angiotensin II and extracellular potassium, the 2 major regulators of
aldosterone production. Voltage-gated Ca2+ channels have been detected in the zona
glomerulosa of the human adrenal, which suggests that Ca2+ channel blockers may directly
influence the adrenocortical biosynthesis of aldosterone in vivo.
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tall, narrow cell>>>>also detect urine flow rate
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regulation of the RAAS involves 3 major components; macula densa (distal tubule sodium sensor)
intrarenal baroreceptors, and beta-adrenergic receptors.
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in fetus it is released by the liver
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sodium polystyrene sulfonate>>>exchange excess potassium with sodium(in
the body) and excrete it in stool>>>used is hyperkalemia 8542 ............... give
calcium gluconate IV
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as in diabetic ketoacidosis>>loss of intracellular free water>>>extracellular movement of K secondary to increased
intracellular K concentration.
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phophate binder (eg calcium acetate) or sevelamer lower serum phosphate in patients with end stage renal disease.
.............................. sevelamer is a non-absorbable phosphate binding polymer that decreases absorption of
phosphate in GI track>>>>used to treat hyperphosphotemia in dialysis patient
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hyperkalemia is rare with selective beta-1 blocker eg metoprolol. as beta-blockers associated hyperkalemia occurs
primarily through beta-2 antagonism.. nonselective beta blocker causes hyperkalemia
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premature ventricular and atrial beats, AV block and in severe cases ventricular
fibrillation or tahcycardia 275
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when the PaCo2 and HCO3 are outside the normal range, a norma; pH suggests a mixed
acidosis/alkalosis disorder, as compensatory responses do not correct the pH completely.
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generally less than 18
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in this renal compensation requires atleast 3-5 days to have maximum effect.
In acute form (less than 8 hours) there is no renal compensation and HCO3 levels less than 30.
In chronic form (greater than 24 hours) renal compensation can start and HCO3 level greater than
30
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Anion gap metabolic acidosis begin to develop shortly afterwards, as high concentration of
salicylates increase lipolysis, uncouple oxidative phosphorylation, and inhibit the citric acid
cycle. This results in the accumulation of organic acids in the blood )eg, ketoacids, lactate, and
pyruvate). Because this patient is presenting approximately 4-5 hours after salicylate ingestion, it
is likely that the initial primary respiratory alkalosis has progressed to mixed respiratory
alkalosis/metabolism acidosis.the ABG in salicylate toxicity often shows a a pH in the normal
range as the 2 primary acid-base disturbances shift the pH in opposite directions.in addition, the
ABG will show a low PaCO2 (due to respiratory alkalosis and compensation for metabolic
acidosis, both ) and low HCO3 (due to metabolic acidosis). Note that the PaCO2 will be lower
than the predicted respiratory compensation as estimated by Winter’s formula (in this case,
expected PaCO2 + [ 1.5* 12] + 8 +- 2 + 26 +- 2 + 24-28 mm Hg). These ABG values are indicative
of primary respiratory alkalosis, which can be seen in early salicylate intoxication (<3 hours)
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due to decrease HCO3, so kidney increase CL absorption>>>>>so normal anoin is hyperchloremic
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due to increase organic acid , excess H ion is balanced by HCO3, but anion component is still present in blood,
so increase acid anion component relative to HCO3
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suppresses respiratory centers
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first look in question Ph then CO2 if both in are in same direction either increase or decrease than its metabolic
definitely
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generally greater than 30
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causes of lactic acidosis: 1,enahnced metabolic rate seizure, exercise 2, reduced
oxygen delivery 3, diminished lactate metablism, hepatic failure or hypoperfusion,
4, decreased oxygen utilization, cyanide poisoning 5, enzymatic defects, von-
gierke, mitchondrial myopathies 2101 ........ hepatic failure or hypoperfusion also causes
this>>>>liver is the main site of lactate catabolism. enzymatic defects in glycogenolysis and gluconeogenesis also
causes this. impaired hepatic gluconeogenesis as seen in congenital pyruvate carboxylase deficiency>>>>lactic
acidosis
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nbme>>>6,2,1 45 year old man become hypotensive for several hours after sever burn, urine output decrease to
150ml/day fro 3 day, microscopic examination of urine on third day show >>>>epithelial cast and not uric acid
crystals Epithelial/granularcell casts:This cast is formed by inclusion or adhesion of desquamated
epithelial cells of the tubule lining. Cells can adhere in random order or in sheets and are
distinguished by large, round nuclei and a lower amount of cytoplasm. These can be seen in
acute tubular necrosis and toxic ingestion, such as from mercury, diethylene glycol, or
salicylate. In each case, clumps or sheets of cells may slough off simultaneously, depending of
the focality of injury. Cytomegalovirus and viral hepatitis are organisms that can cause
epithelial cell death as well.
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chronic renal vascular disease (eg renal artery stenosis) usually develop diffuse ischemic changes,including
intersticial fibrosis, crowding of glomeruli and tubular atrophy
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frothy urine>>>due to proteinuria or bile salts in urine
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H/K atpase. and mutation at CL/HCO3 at basal side
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due to defect in Na/H antiport and Na/HCO3 cotransoport at the basolateral side ... tto is low sodium
diet>>>>so it make PCT to absorb more Na and try to compensate HCO3 absortion
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WBC are precipitated by tamm-horsfall protein secreted by tubular epithelial cell.
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poor bicarbonate reabsorption also seen in multiple myeloma and azetazolamide toxicity
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TYPE 1 RPGN is characterized by anti-glomerular basement membrane antibodies.linear GBM deposits of
IgG and C3 are found on immunofluoresence.goodpasteur syndrome is type 1 RPGN. Type 2 RPGN is
immune-complex mediated. There is a “lumpy bumpy” granular pattern of staining on
immunofluorescence microscopy. Type 2 RPGN can be a complication of poststreptococcal
glomerulonephritis, SLE, IgA nephropathy, or Henoch-Schonlein purpura. Type 3 RPGN is called
“pauci immune” because there are no immunoglobulin or complement deposits on the basement
membrane.most patient have ANCA. This condition is often associated with granulomatosis with
polyangiitis (Wenger’s), but can also be idiopathic............ in type 3 although crescent formation is
obvious on light microscopy but . there are no immunoglobulin or complement deposits found by
immunoflourescent studies as in other types of RPGN.
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combination of leukocytes infiltration (neutrophil and monocytes) and mesangial and endothelial cell proliferation.
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pyrogenic exotoxin B is one of the antigens implicated in the pathogenesis of PSGN
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6-10 years of age
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age is the most important prognostic factor. 95% recover completely 1-2% develop chronic glomerulonephritis
1% progress to RPGN. prognosis is not good in adults. only 60% recover completely ................... therapy includes
loop diuretics and vasodilators
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C3 and total decreases>>>>but C4 is generally normal. slightly decrease in C4 results due to classical pathway
activation as well. ...................... antistreptolysin O often not elevated with streptococcal skin infection .................
Decreased serum C3 level is seen with poststerptococcal glomerulonephritis and with dense-deposit
disease (type II MPGN). The cause is activation of the alternative complement pathway, so C1 and C4
levels are normal.
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GBM disruptions and fibrin deposition on EM are findings in goodpasture syndrome. the GBM breaks are due to
fibrinoid necrosis of the glomeruli. crescent may not be detectable in early disease. an important contributor to
crescent formation is fibrin escape into bowmans space.
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RPGN including the idiopathic variety, may occur in the absence of a systemic vasculitic syndrome.
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deposition of IgA IC in small vessels and renal mesenagiam leads to recrutitment of
neutrophyl and lymphocytes as wll as actation of complememnt via the alternate/
lectin pathway.
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painless hamturia within 5-7 days of upper respiratory infection (synpharyngitis hematuria)>>>>it lasts for severla
days, subsides temporarily, returning every few months or with another respiratory track infection.
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widespread intraalveolar hemorrahge may occur in pulmonary hemorrahge syndromes,including goodpasture
syndrome, granulomatosis with polyangitis (wegeners) and lupus erythrematosus.
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nbme>>>2,1,43>>>>student present with hematuria>>>>denays any histroy of renal problem or recent
illness(contradictory to FA), vital signs are normal, in microscopic analysis just present RBCs cast.no
preoteninuria.>>>>diagnoses is IgA nephropahty
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this type found in infective endocarditis.
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alpha-3 chain of type 4 collagen.
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deposition of fibrin within bowman space is an essential pathologic step in crescent formation.
it consist of proliferated parietal cells. monocytes and macrophages that have migrated into
bowmans space, as well as abundant fibrin between the cellular layers of the crescents.
as disease progresses crescents become sclerotic and obliterate bowmans space, thus impeding
glomerular fucntion.
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anti DNAase B along with anti-streptolysin and anti-cationic proteninase.cryglobulins may also be present in
serum
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particular strains (1, 4, and 12)
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damage is due to both IC deposition on the basement membrane and complement activation (causing massive
inflammatory response and glomerular basement membrane structural damage. 725 .............. all glomeruli are
involved. the kidneys are enlarged and swollen, with multiple surface punctuate hemorrhages
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and in glomerular capillaries
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On light microscopy, there is proliferation of cells (eg, lymphocytesm endothelial cells) within the
capillary loops. Diffuse wire loop deposits may also be seen,
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splitting also seen with MPGN type 1
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lamellated basement membrane with irregular thinning and thickening.
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increase susceptibility to recurrent pyogenic sinus and respiratory track infection. and also risk of type 3 HS
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C1q deposits may be seen in MPGN type 1. ..... PSCG have alternative/leptin complement pathway>>>so have
deposition of C3, Type 2 MPGN also has c3 deposits
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it frequently progresses to renal failure by the age of 40.
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and thickening (lamellated BM) 10
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serum antibodies to the PLA2R indicative of glomerulonephritis. the M-type PLA2R is a transmembrane receptor
found in high concentrations in glomerular podocytes and thought to be a major antigen in the pathogenesis if
idiopathic membranous nephropathy. these antibodies are present in idiopathic form but not in secondary
membranous nephropathy. these antibodies were mainly IgG4 and lead to immune deposition in the glomerulus,
possible contributing to the development of the disease.
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possibly due to abnormal T cell production of a glomerular permeability factor that affects the glomerular capillary
wall, leading to fusion of the foot processes and marked proteinuria. ..... caused by primary defect in
immunological function. this immune dysfunction leads to overproduction of specific cytokine (possibly IL-13)
that cause direct damage to podocytes leading to retraction and fusion of foot processes with reduced number of
slit processes>>>>which causes selective albuminuria
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class V lupus nephritis.
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KW nodules have the following characteristics: ・ located in the peripheral mesangium ・ ovoid or
sperical in shape ・ lamellated appearance ・ eosinophilic on hematoxylin and eosin stain ・ periodic
acid-Schiff (+) over time progressive expansion of the mesangium leads to the formation of nodules
that compress the glomerular capillaries and cause loss of glomerular function. The urinary sediment is
typically bland (no red or white cells or casts) in diabetic nephropathy. ........... The presence of kImmelstiel-
Wilson nodules indicates irreversible glomerular damage and predicts a rapid decline in kidney function.
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caused by liver general increase in all synthetic function in its effort to make more albumin.
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alpha-2 globulin are normal serum protein produced by liver and kidney. they include heptoglobin,
cerulloplasmin and alpha-2 macroglobulin.
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on silver methenamine stain
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also malaria and syphilis
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lipiduria is common>>>>leading to loss of free fat and oval fat bodies(with characteristic Maltese cross
appearance under polarized light)
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Nephrotoc syndrome is a hypercoagulable state. Sudden onset abdominal or flank pain hematuria and
right sided varicocele suggest renal vein thrombosis, a well-known complication of nephrotic syndrome.
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or insect bite
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The loss of immunoglobulins and low-molecular-weight components of complement (such as
factor B) makes patients with nephrotic syndrome vulnerable to infections, especially
pneumococcal infections
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lung and colon.
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b/w basement membrane and epithelial cells.
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and hepatitis
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pathogeneis of nephrotic syndrome: 1, increased permability of glomerular capillary
wall.>>>massive urine proetin loss (mainly albumin but in some diseases globulin
also) 2, drop in oncotic pressure. 3, intravascular compartment of fluid
decreases>>>activation of RAAS>>>secondary hyperaldosteronims, also have
increased ADH>>>result in retenstion of Na and water 4, to compensate albumin
loss increased lipoprotien produciton. this increased in lipoprotien produciton
along with the decrease in lipid catabolism due to low plasma levels of
lipoprotein lipase and abnormal transport of circulating lipid particles,
contributes to the increased cholesterol, TGs, VLDL, LDL,Lp(a) liporotein and
apoprotien concentration seen. 5, increase in serum lipoprotein is followed by
lipiduria ..... patient with nephrotic syndrome have elevated RAAS>>> due to decrease in intravascular
volume.a
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nbme>>6,2,10 Nodules of pink hyaline material form in regions of glomerular capillary loops in the
glomerulus. This is due to a marked increase in mesangial matrix from damage as a result of
non-enzymatic glycosylation of proteins.
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membranous nephropathy, flank pain, hematuria and right-sided varicocele likely has renal vein
thrombosis (RVT) as a result of nephrotic syndrome. loss of anticoagulant factors, especially
antithrombin III, leads to a hypercoagulable state of which RVT can be a manifestation. patietns with RVT
can develop sudden-onset abdominal of flank pain and gross hematurai with elevated lactate
dehyrogenase as a result of renal infarction.
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nbme>>>6,2,12
in minimal change disease , most likely cause is a disorder in>>>glomerular capillary loops
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and pamidronate
694
anabolic steroid and pamidronate
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excreted in the form of oxalate
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Urine output and serum creatinine remain within norma limits is most individual with unilateral
obstruction because the contralateral kidney functions normally and compensates for decreased
functioning of the affected kidney.
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Increased urine uric acid concentration promotes the formation of calcium and uric acid stones.
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elongated wedge shaped>>>forms rosettes.
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rapidly absorb from the GI tract and metabolized to glycolic acid( toxic to renal tubules) and oxalic acid, which
precipitates as calcium oxalate crystals. ATN synptoms develop after 24-72 hours after ingestion. a high anion gap
metabolic acidosis and osmolar gap are also typically seen. urinalysis show tubular cast and oxalate crystals.
morphologically normal glomeruli with proximal tubular necrosis are seen on light mucroscopy.
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acetazolamide associated with calcium stone formation. metabolic acidosis produced by this is compensated by
release of calcium phosphate from the bone. other medications that alkalinize the urine, such as potassium
citrate, are better for reducing the risk of calcium oxalate and uric acid nephrolithiasis.unlike triamterene
amiloride has been shown to increase Ca reabsorption.............. citrtae binds to free (ionized) calcium,
preventing its precipitation and facilitating its excretion. Potassium citrates is often prescribed to prevent
recurrent calcium stones in adults when dietary modifications are unsuccessful.
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"natural inhibitor" of Ca oxalate/phosphate stones>>>citrate.
question:
You are about to collect blood sample in tube from pat, in order to inhibit coagulation your tube
need to contain what?
citrate>>>Stop aggregation of molecules of calcium , and by acidify the urine.
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also formed of calcium carbonate apatite
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is a (homodimer of cysteine)
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affecting the high affinity, sodium independent dibasic amino acid transporter found on the apical membrane of
intestinal and proximal renal tubular epithelial cells. this prevents dibasic amino acids ( eg cysteine,
ornithine,lysine and arginine ) from being reabsorbed.
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patient with suspected cystinuria without cystine crystals on urinalysis can be diagnosed by detecting elevated
urinary cysteine levels.
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and hydration
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" Faintly radiopaque ."
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we give pyridoxine is hyperoxaluria>>>> b6 decreases endogenous produciton of oxalate
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octahedron (square with an X in the center)
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uworld says>>>>radiopaque slightly
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qualitative screeing test,detects presence of excess urinary cystine. cyanide initially convert cystine to cysteine.
afterward nitroprusside is added and reacts with the sulfhydral group on free cysteine, causing a red-purple
discoloration (positive test)
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recurrent nephrolithiasis in a young patient should raise suspicion for cystinuria, which is confirmed by
pathognomonic hexagonal-shaped crystals.
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flat, yellow hexagonal.
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yellow or red brown diamond or rhombus.
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idiopathic hypercalciuria,
normocalcemic due to intact regulation of serum calciums by vit D and parathyroid hormone.
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through 2 major mechanism:
1, inhibition of the Na/Cl cotransporter>>which decreases intracellular Na
concentraiton>>activates basolaterlateral Na/Ca antiporter>>>decreases intracellular Ca
concentration.
2, Hypovolemia induced by thiazides, increases Na and water reabsorption in the proximal
tubules, leading to passive increase in paracellular Ca reabsorption.
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hypercalciurua with hypercalcemia>>>>primary hyperparathyroidism, sarcoidosis,
malignancy, and chronic acidemia...................... ..... hyperuricosuria with
hyperuricemia>>>myeloproliferative disorder, tumor lysis syndrome, gout, lesch-
nehan syndroem. hyperuricuria with normouricemia>>>>high protein diet, can
cause uric acid stone formation and also predisposes to calcium nephrolithiasis
(uric acid preciptation acts as a nidus for calcium deposition)........... .........
hyperoxaluria result form diet high in oxalate( chocolate, nuts and spinach), low-
calcium diest and crohn disease cause less calcium to be avaible to bind and trap
oxalate in the gut.
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Ca oxalate MC, Ca oxalate stone most prevalent Southeast according to hospital discharge rates
highest among veterans
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hypercalciuria (eg sarcoidosis) hyperoxaluria (eg crohn disease) , hyperuricosuria (eg gout) and hypocitraturia (eg
distal renal tubular acidosis) are risk factor for recurrent calcium stones.
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Increased protein intake raises acid production from the metabolism of sulfur-containing amino acid. The
acids are buffered with bone salts, leading to increased calcium excretion (hypercalciuria). Increased acid
load also increases citrate reabsorption in the proximal tubule, causing hypocitruria. Calcium passively
follows the reabsorption of sodium and water. Increased dietary sodium intake leads to reduced sodium
reabsorption in the proximal tubule and lowers calcium reabsorption (leading to hypercalciuria). Dietary
calcium helps bind oxalate in the gut to form unabsorbable calcium oxalate. Low-calcium diets allow
increased amount of free oxalate to be absorbed and then excreted in the kidney, thereby causing
hyperoxaluria. Pyridoxine (vitamin B6) is recommended for calcium stones in patients who have been
diagnosed with hyperoxaluria as the cause of renal stone formation. Vitamin b6 decreases endogenous
oxalate production and therefore decreases the rate of stone formation in these patients.
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also in chronic diarrhea and G6PDH deficiency (metabolic syndrome)
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common in type 1 renal tubular acidosis
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Nuclei can be either eccentric or central in clear cell carcinoma. Patients with renal cell carcinoma
develop clinical symptoms late in the course of the disease. The classic triad of hematuria, flank pain, and
palpable abdominal mass occurs in less than 10% of cases. Non-specific symptoms such as fever,
malaise, anorexia, and weight loss are more common. Hypercalcemia due to synthesis of parathyroid
hormone-related peptide is also common. Renal cell carcinoma is often detected incidentally since
localizing symptoms only develop in advanced disease. Therefore. it is not uncommon for metastases
to be discovered earlier than the primary neoplasm. renal cell carcinoma can widely metastasize and
the lung are the most common site, with pulmonary metastases found in about half of ll cases of
disseminated disease. bone metastases are the next most common.
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RCC originate in the renal cortex and account for 80-85% of primary renal tumors.
tumors are identified incidently on radiographic imaging, and many individuals remain
asymptomatic untill the disease is relatively advanced.
however majority of symptomatic pateitns present with combinaiton of hemauria, flank pain and
an abdominal mass.
hemauria is most common symtom indicates that the colloecting system has been invaded by the
tumor.
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cause staining technique typically dissolve glycogen and lipids.
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can cause both anemia of chronic disease and iron deficiency anemia due to chronic hematuria..
so anemia, polycythemia or normal hemoglobin may be present in the setting of RCC.
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During nephrectomy using posterolateral approach transversalis fascia is cut in RCC confined
within the fascia of kidney.
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claer cell carcinoma is often golden-yellow on macroscopic examination due to high glycogen and lipid content.
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lead to increase IGF-1 and HIF transcription factor which increases PDGF and VEGF
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renal oncocytoma is a very rare tumor of the collecting ducts. oncocytes are large, well digfferentiated neoplastic
cells that contain numerous mitichondria.
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accounts for 70% of all renal tumors.
clear cell carcinoma is the most common variant.
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due to this have eccentric nuclei
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tubular epithelial cell.
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lead to hypertension, deteriorating renal function, and sepsis.
signs and symptoms may include pain, lower extremity edema and palpable kidneys or bladder if
the obstruction is low enough.
the most common cause is lower UT obstruction.
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The majority of renal cell neoplasms are spordic. A small number of cases are hereditary such as those
associated with Von hippel-Lindau disease. characterized by cerebellar hemangioblastomas, clear cell
renal carcinomas and pheochromocytomas. Renal cell carcinoma develops in nearly 40% of these
patients and is a major cause of death. Although Von Hippel-Lindau disease is rare, deletion or
mutations of the VHL gene are relatively common. In fact, defects of the VHL gene are found in the
majority of patients (40%-50%) with sporadic renal cell carcinoma. VHL is a tumor suppressor gene..
RCC is the only abnormality associated with deletions or mutation of this gene
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nbme,11,1,7 2-Naphthylamine is an aromatic amine. It is used to make azo dyes. It is a known human carcinogen.
Anilin e dyes...aromatic amin 2-Naphthylamine is found in cigarette smoke and suspected to contribute to the
development of transitional cell carcinoma of urinary tract system (It is activated in the liver but quickly deactivated by
conjugation to glucuronic acid. In the bladder, glucuronidase re-activates it by deconjugation, which leads to the
development of bladder cancer.
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The pelvic floor is composed of the levator ani muscles and forms a U-shaped sling around the pelvic
viscera. The levator ani muscles (i.e, iliococcygeus, pubococcygeus, puborectalis) hold the bladder and
the urethra in the appropriate anatomic position. Urethral hypermobility results in incomplete closure of the
urethra and bladder neck against the anterior vaginal wall. The bulbospongiosus muscle is part of the
superficial urogential triangle of the perineum. It compresses the vestibular bulb and constricts the
vaginal orifice. The external urethral sphincter is a skeletal muscle located at the distal end of the
urethra and innervated by the pudendal nerve. the uterosacral ligaments run along the lateral
pelvic wall and anchor the uterus apex by attaching to the sacrum. Weakening of these
ligaments contributes to uterine and vaginal apical prolapse
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triggers of urge incontinence can include running water, hand washing or exposure to cold weather.. loss of
inhibitory central nerovuse system input ot bladder due to the frontal lobe and internal capsule infarcs
commonly cause detrusor hyperreflexia and urgeincontinence. .............. cognitive impairment (mini-mental status
examination score </22) is often seen in normal pressure hydrocephalus, lower extremitiy hyperreflexia would
suggest spinal cord disease. both of these conditions can cause loss of central nervous system inhibition of
detrusor contractio, leading to urge incontinence.
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in overflow incontinence patietn usually develop involuntary and cintinuous urinary leakage when the bladder is full
and often have incomplete emptying. overflow incontinence due to diabetic autonomic neuropathy affecting
detrusor muscle innervation, which is common in type 1 diabetics. patient initially have infrequent urination due to
loss of autonomic afferetn innervation and inability to sense a full bladder. involement of efferent fibers to the bladder
subsequwntly causes incomplete emptying. patients can develop recurrent urinary tact infections and overflow
incontinence woth poor urinary stream and driblling. pelvic floor relaxation at night combined with a full bladder can
lead to nocturnal enuresis. PVR testing with US or catheterizaiton can confirm inadequate bladder emptying.
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primitive metanephric tissue
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transitional cell carcinoma is responsible fot the 90% of the tumors involving the renal pelvis. it arises from the renal
pelivslining , tends to be multifocal in nature, and often forms papillary tumors composed of urothelium and
supported by a thin fibrovascular stalk....... cystoscopy which show multifocal sessile or papillary tumor. ........
malignant epithelial cell are pleomorphic and have hyperchromatic nuclei, an increased nucleus to cytoplasmic ratio,
and disrupted orientation and polarity ( in relation to basal membrane)
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duloxetine has also been used to treat stress urinary incontinence in women because it enhances urethral
closure.
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related to IGF-2
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Arises via two distinct pathways (Fig. 12.21) 1. Flat—develops as a high-grade flat tumor and then
invades; associated with early p53 mutations 2, Papillary—develops as a low-grade papillary
tumor that progresses to a highgrade papillary tumor and then invades; not associated with early
p53 mutations E. Tumors are often multifocal and recur ("field detect"
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occupational exposure ( eg rubber, leather, textiles aromatic-amine containing dye)
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discover while bathing a baby. unilateral and smooth unlike neuroblastoma which are irregular and can cross
midline.
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enlarged prostate due to prostate hyperreflexia or prostate cancer, which causes urge incontinence (bladder
irritation from the enlarged prostate) or overflow incontinence (urethral obstruction)
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detrusor muscle is controlled by parasympathetic fibers from the pelvic slpanhnic nerves and inferior hypogastric
plexus.>>>>activation causes contraciton of detrusor. sympathetic fibers causes its relaxation.
IUS>>>>>parasympathetic causes relaxation and sympathetic causes contraction...... EUS is controlled by pudendal
nerve.>>>volunatrily controlled. post menopausal women has estrogen deficicnecy >>>>causes laxicity and pelvic
floor muscle weakness.
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tumor penetration of the bladder wall is the major determinant of prognosis
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COPD mneumonic
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WBC are present but no bacteria
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massive infiltration of interstitium by polymorphonuclear leukocytes(neutrophils) as well as a large number of
neutrophil in the tubular lumina>>>this is a microscopic presentation of acute pyelonephritis.immune complex
diseases of kidney>>>>>> microscopically show hypercellular glomeruli with infiltrating leukocytes. the tubules
may contain RBCs cast but tubular infiltration with inflammatory cells is not characteristic of immune complex
disease, although interstitium may show patchy lymphocytic infiltrates.
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nbme>>>>2,2,27>>>>renal infarct produces gross hematuira.
renal infarct is due to embolus poroudces wedge shaped infarct.
embolus later lodged in her brain and became cause of her death...............
in contrast RCC is located more on the poles
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neutrophil also fill the tubular lumina.
tubulorrhexis and microabscesses may also be present.
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ureaplasma also.
mostly sterile pyuria is with non-gonococcal urethritis
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the most common renal vascular injury>>>hypertensive nephrosclerosis causes arterial intimal fibroplasia and
arteriolar hyalinization, along with interstitial fibrosis.
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uremia has been shown to decrease perpheral conversion of T4 to T3. this could cause functional hypothyroidism
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this is in acute only chrinic has waxy casts
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DM is the leading cause of of end stage renal disease, followed by HT. however appriximatedly 50% of pateitns with
ESRD die due to cardiovascular diseases, with infections being the next most common cause.
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acute kidney injury (oliguria and azotemia) is the most common presenting symptoms of postprocedure
atheroembolism and is frequently seen in elderly pateints with preexisting renal atherosclerosis. Frank
infractio
with flank pain and hematuria does not occur as cholesterol emboli are usually small.
Cholesterol is dissolving during tissue preparation for microscopic evaluation, leaving needle-
shaped clefts that partially or completely obstruct the arcuate or intralobular renal arteries.
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Aminoglycoside antibodies accumulate within the renal cortex, causing acute tubular necrosis.
Proximal tubular vacuolar degeneration is usually seen . hypersenstivity interstitial nephritis causes
sterile pyuria. there is often ongoing exposure to an offending drug, Peripheral eosinophilia and
eosinophiluria may help confirm the diagnosis. Ischemia tubular necrosis classically presents with muddy
brown, granular, and epithelial cell casts and free tubular epithelial cells in the urine. chronic lead
intoxication produces chronic tubulointerstitial nephritis (interstital fibrosis and tubular atrophy seen on
light microscopy) that lead to renal failure.
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maculopapular
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symptoms almost always resolves completely after cessation of offending medications
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renal intersiticial infiltrate can be acute, reversible and chronic, irreversible. Acute is fairly common and many
drug are involves>>most common is methicilin others are cephalosporins, azetazolamide, allopurinol,
sulfonamide and NSAIDs. Lithium and cyclosporine causes chronic intersticial nephritis.
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Drug induced tubular obstruction:
due to intratubular precipitation of tissue degradation products, drugs and drugs metabolites,
sulfonamides, methotrexate (and its metabolite), IV acyclovir and triamterene are agents that can
precipitate in renal tubules and cause renal failure
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1,increased extracellular fluid volume>>weight gain, edema and pulmonary vascular congestion. 2, hyperkalemia is
usually asymptomatic at level <6 mEq/L.above this peaked T waves are apparent and potentially fatal ventricular
arrythmias are possible. 3, retention of body hydrogen and anions ( eg sulfate, phosphate and urate) will lead to high
anion gap metabolic acidosis. 4, other electroclytes changes include a decdreased concentration of sodium and
calcium, and an increased level of phosphate and magnesium 5, urinalysis reveals pathognomonic muddy brwon
cast, low urinary osmolarity (<350), high urinary sodium (>30) and high urinary fractional sodium excretion
(FeNa>>1) ........... if the pateint survive recovery phase follow in 1-2 weeks........... hypercalcemia does not occur in
ATN, instead hypocalcemia occurs, due to both the deposition of calcium phosphate and reduced levels of vit D
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characterized by re-epithelization of tubules.
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cause GFR recover faster than tubular function, as tubules clear of casts and debris
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foscarnet also
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hypercalcemia does not occur in ATN, instead hypocalcemia occurs, due to both the deposition of
calcium phosphate and reduced levels of vit D
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also can have acute, colicky flank pain(due to ureteral obstruction)
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decreases PGs>>>afferent arteriolar constriction
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chronic RPN>>>present as subtle recurrent hematuria .................. cortical scar formation due to fibrous
replacement of imflammation.
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gray-white or yellow necrosis in distal 2/3 of renal pyramid seen macroscopically and corresond microscopically
with coagulation necrosis and preserved tubule outline.
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which causes hypoperfusion due to diabetic vasculopathy.
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which causes intersticial edema that compresses medullary vasculature>>>ischemia. same mechanism is for
urinary track obstruction
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biopsy also show tubular space enlargement and tubular vacuolization.
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focal intersticial fibrosis causing medullary scarring and atrophy may be seen in small number of patient ,
especially when ATN is associated with multiple organ failure and disruption of tubular basement membrane.
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focal tubular epithelial necrosis and cell shedding often accompanied by rupture of tubule
basement membrane (tubulorrhexis)
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cause tubular function recover relatively slower than GFR... sometime >3 litters. electrolyte
imbalance>>>>decreased concentration of K, Mg, PO4 and Ca....................... polyuria and loss of electrolytes due
to impaired tubular resorption and decreased renal concentrating ability
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decrease in GFR>>>>creatinine level rises.
at this stage light microscopy show>>tubular epithelial necrosis, denudation of tubular basement
membrane, and casts containing degenrating cells and debris.
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last about 24-36 hours>>>during this phase there is only slight decrease in tubular function. this stage is usually
unnoticed by clinicians as the symptoms of main disorder prevail.
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glomeruli are intact. intersticial edema and infiltration with mononuclear cells (lymphocytes and macrophages)
are typical. plasma cell and eosinophils are also commonly seen. sometime the inflammatory cells may infiltrate
the tubular epithelium, which may cause tubulorrhexis(rupture of membrane) and spillage of tubular content into
the interstitium. if the later occurs, foreign body granulomas may be formed in the interstitium
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therefore IgE mediated HS and cell mediated reactions are thought to be involved in the pathogenesis of AIN
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eosinophilia and eosinophiluria (detected by hansel and wright stain) are the most important clues
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analgesic nephropathy:affected patients typically have a modest elevation in serum creatinine, mild
proteinuria, and evidence of tubular dysfunction (polyuria, nocturia). microscopic hematuria and sterile
pyuria may also be seen on urinalysis. NSAIDs concentrate in the renal medulla along the medullary
osmotic gradient with higher levels in the papillae. these drugs uncouple oxidative phosphorylation
and are thought to cause glutathione depletion with subsequent lipid preoxidation, resulting in damage
to tubular and vascular endothelial cells. prolonged use results in chronic interstitial nephritis, seen
as pathcy interstitial inflammation with subsequent fibrosis, tubular atrophy, papillary necrosis,
scarring and caliceal architecture distortion. Calcium may deposit in areas of chronic inflammation
and this calcification is visible on renal imaging, NSAIDs also decrease prostaglandin synthesis, causing
constriction of medullary vasa recta and ischemic papillary necrosis,
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acute crystal nephropathy presents with acute renal failure and is frequently symptomatic (nausea, vomiting and
flank pain). chronic nephropathy is most commonly seen in patients with gout or hyperuricemia secondary
to urate deposition in the medullary interstitium.
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also causes mild persistant proteinuria(hypoalbuminemia)that can result in dyslipidemia(due to generalized
increased synthesis in liver to compensate loss of albumin)
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microscopic cysts are present at birth but are too small to be detected by the abdominal US........
cyst are
usually seen on imaging by the 3rd or 4th decade of life. the contrast enhanced CT
scan above shows multiple renal cysts and hepatic cysts. the cysts are
homogenous with a smooth, regular outline.they do not enhance, differentiating
them form solid metastasis or malignancies ...... most common hereditary
cause of renal failure in adults.. asymptomatic untill their 4th or 5th decades. liver
cysts usually do not causes loss of liver funciton, but may cause pain if they are
large.
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cystic dilation of the collecting ducts is diagnostic of medullary sponge kindey. Medullary
cysts, lined by cuboidal or urothelial epithelium, are seen
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large cysts are present at birth or in first year of life as bilateral flank masses. cysts are formed by dilated distal
tubules and collecting ducts. abdominal US show cysts if they are >1 cm in diameter. ................ mutation in
PKHD1 >>>which codes for fibrocystin>>>>>present on epithelial of renal tubules and bile ducts ............
die during the first decade of life due to complications such as renal failure,
hepatic fibrosis and pulmonary hypoplaisa
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it is a systemic disease
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multicystic dysplastic kidney>>>>is non-inherited 833....... Multicystic kidney dysplasia:
presence of multiple cysts of varying size and the absence of the normal pelvocaliceal system. associated with
ureteral or ureteropelvic atresia.abdominal US of the fetus or newborn is diagnostic
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in the loop of henle Ca reabsorption occur through both the transcellular and paracellular pathways
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increases water redistribution from the tissues into the plasma helps to reduce cerebral edema and increased
intracranial pressure
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over aggressive treatment can lead to excessive volume depletion and eventual hypernatremia in certain patients
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increased GFR and enhanced drug delivery
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loop diuretics and spironolactone>>>excellent treatment for refractory ascitis ..... Furosemide is used in
patients with renal failure or severe heart failure and is best given by continuous intravenous
infusion
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inibiiton of similar symporters in the inner ear is beleieved to cause ototoxicity (tinnitus, vertigo, heairng impaiment
or deafness). it usually occur with hogher dosages, preexisting CKD, rapid intraveous adminitration, or whrn used in
combinaiton with other ototoxic agents (eg aminoglyco, salicylates and cisplatin). symptoms are usually reversible but
hearing imapirment may be permanent in some cases.
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causes hypokalemia and increase in serum bicarbonate level. they would also cause decrease in serum sodium
concentration and increase in serum osmolarity due to increased free water excretion.
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increases free water excretion
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due to initial increase intravsacular volume result in rapid rise in overall hydrostatic pressure in vasculature>>>the
continued rise in plasma osmolality causes more water and potassium to move out of the cell and brain>>>this
leads to further volume expansion, dilutional hyponatremia and metabolic acidosis and hyperkalemia>>>>therefore
osmotic diuretic should be cautiously used in CHF and preexisting pulmonary edema patients
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Mannitol will cause a massive osmotic diuresis. It will get filtered in the kidney, and will osmotically
pull a TON of water out with it. That will cause a massive decrease in intravascular volume, and
ADH will then respond.
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also causes hyotension>>>primary clinical use of thiazide is to reduce blood pressure. They accomplish this by
decreasing both blood volume and peripheral vascular resistance.
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Indapamide.>>>just this dont cuases hyperlipidemia ................ chlorothiazide excrete unchanged
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this hypercalcemia can also be contributed by increased Ca reabsorption in proximal tubule secondary to volume
depletion.
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it has less side effects
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reverse myocardial fibrosis and improvement in ventricular remodeling.
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unlike triamterene amiloride has also been shown to increase Ca reabsorption
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contraindicated in hyperkalemia and renal failure
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these two also block apical epithelial Na channel (eNaC)
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have normal corticomedullary concentration gradient and are better able to retain free water in response to
increased vasopressin levels.thus patients taking thizaide are more likely to retain free water and develop
hyponatremia. in contrast cortocomedullary gradient is lost in loop diuretics and are unable to maximally
concentrate their urine and thus lose substaintial amounts of both salt and water in the urine.
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becasue it also causes peripheral vasodilation, resulting in reduced peripheral vascular resistance.......................
one of the initial treatment in the absence CHF and diabetes
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Diuretics can cause an increase in serum creatinine by decreasing renal blood flow (a prerenal cause
of renal insufficiency). This is more common with loop diuretics, rarely do thiazide diuretics alone cause a
diuresis so brisk as to elevate the serum creatinine.
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is thought to increase prostaglandin produciton, which induces coughing due to bronchial irritation.
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predictable is 30% rise in serum creatinine with in 2-5 days, stabilizes in 2-3 weeks and reversible with drug
descontinuaiton.
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patient dependent on efferent arteriole constriction to maintain renal perfusion (those with renal artery stenosis,
decompensated HF, chronic kidney disease and volume depletion), ACE inhibitor can be detrimental causing
acute renal failure. ........... patient with a history of coronary artery disease should be started on ACEI with
caustion as the likelihood of concomitant renovascular disease is high in such patients
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first dose hypotension can be a potential limiitng factor when use in patients with high plasma renin activity such as
in volume depleted patient (eg from diuretic use) or heart failure.
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best agent in the presence of CHF and diabetes
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Angiotensin II is involved in atherogenesis. Hypertensive patients with iliofemoral
atherosclerosis would therefore benefit from ACEI/ARBs that reduce the effects of angiotensin
II. ..... angiotensin converting enzyme (ACE) inhibitors (e.g, lisinopril) have been shown to inhibit
the chronic angiotensin II-mediated left ventricular hypertrophy and remodeling that occurs in
associated with myocardial failure...... These drugs also show the progression of left
ventricular hypertrophy (in aortic regurgitation) and myocardial scar formation and expansion
( eg, aneurysm formation after infraction).
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highly conserved 180 base pair DNA sequence..
3' end cranial and 5' end caudal region of embryo
2015
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syndactly or failure of digits to seperate, is the most common upper limb
congenital deformity. the second most common deformity is a constrction band
syndorme which interrupt the fetal blood supply to the distal limbs and causes
amputation of fingers (or toes).. most upper limb deformities are the result of
developmental accidents of unknown etiology and are non-syndromic i-e not
associated with congenital abnormalities in other orgasn
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important role in morphogenesis, ........ retinoic acid alter HOX gene,
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PCSK9 play role in normal cerebral dev & neuronal apoptosis
Proprotein convertase subtilisin/kexin type 9 (PCSK9
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craneocaudal
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2015
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modified sweat gland
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preganglionic autonomic fibers
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mesothelium and endothelium
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vertebrae are derived form the paraxial mesoderm
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dura mater
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will form all of the urethra of the female and the prostatic, membranous, and proximal spongy urethra in the male. - The prostate
gland in the male is formed by an endodermal outgrowth of the prostatic urethra.
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rupture of amnion during fetal development may produce amniotic band which can compress or even amputate fetal
limbs
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pierre-robbin sequence: micrognathia characterized by hypoplasia of mandibular prominence>>>results in posterior
displacement of tongue (glossoptosis) and prevents fusion of the secondary palate (cleft palate)
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VACTREL is an exapmle of association, its define as multiple anomalies without a known common etiology
..... osteogenesis imperfacta is an example of dysplasia,
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distal part of male urethra
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cornea
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ectopia which result in embryologic life (congenital malformation). metaplasia
occurs during adult life and is initially a compensatory process.
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holoprosecephaly is an expample of developmental field defects>>>>initial embyonic disturnace leads to multiple
malformation by disrupting yhe development of adjacent tossies and structures within a particular region
.................. The term “malformation” describes a primary defect in the cells or tissues that form organ (an
intrinsic developmental abnormality). Normally the division of the prosencephalon happens during the 5th
week of embryonic development. Thus, holoprosencephaly is a malformation that originates very early in
fetal life. congenital heart disease, anencephaly polydactyly and syndactyly. ....... eg
holoprosencephaly(normal development occur in 5th week) found in patau 13,edward 18 sonic hedgehog and
fetal alcohol syndrome
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eg congenital hip dislocation,clubbed feet. and flat facies(potter syndrome)
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epithelial lining of outer and middle ear.
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mesoderm does not give rise to any epithelial surfaces.
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upper 2/3 by paramesonehric duct
lower 1/3 by urogenital sinus
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pneumonic MOTEL PASS.
tracheal carilage, enterochromafin cell, laryngeal cartilage.
A>>adrenal medulla and all ganglia.
S>>Schwann cell
S>>>spiral membrane.
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chroidal plexus
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cyclophosphamide>>>>limb hypoplasia
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Patients are born with agenesis of the sacrum and occasionally lumbar spine and experience
resultant flaccid paralysis of the legs, dorsiflexed contractures of the feet, and urinary
incontinence. Caudal regression syndrome can range in severity from isolated anal atresia to
sirenomelia.
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in female offspring it causes vaginal adenosis>>>>replacement of vaginal squamous epithelium with glandular
columnar epthelium.
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maternal HT>>>>asymmetric IUGR>>>normal or almost normal head size with a reduced abdominal
circumference.
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Vitamin A overdose in pregnancy can cause craniofacial abnormalities, posterior fossa CNS
defects, auditory defects, and abnormalities of the great vessels. (These defects are similar to
those in DiGeorge syndrome).
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diabetic mother most likely has>>>>macrsomia not sirenomelia, but sirenomelia can also present.
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Supplementation is particularly important in the second half of the pregnancy, when the maternal
blood volume expands considerably
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they are of same sex,are genetically identical, and are similar in aapearence
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have high fetal fatality rate , due primarily to the increased risk of umbilical cord enlargement.
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if cleavage occur before day 4 it is difficult to distinguish between monozygotci and dizogotic if the
sexes are same untill other chaarcteristics develop (or if blood groups are disscordant)
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the sex of twins may differ.
chorions and placenta may be fused depending on the proximity of the implantation.
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differential diagnosis of neck mass:
1 midline-thyroid
2 anterior to the sternocleidomastoid - branchial cleft cysts
3 posterior to the sternocleidomastoid- cystic hygrom
4 within the sternocleidomastoid- hematoma and torticollis
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at the angle of mandible can form draining sinus track.Rx is surgical removel
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ansa cervicales>>>C1-C3 cervical plexus contribution>>courses deep to sternocleidomastoid muscle and loops
around internal jugular vein>>>innervate sternohyoid, sternothyroid and omohyoid
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arises from cartilaginous portion of the auditory tube and the adjoining part of the sphenoid bone and inserts in to
the malleus>>>it function to contract the tympanic membrane medially , thereby increasing its tension and
dampening sound transmission... innervated by mandibular branch of CN V
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and epiglottis are unpaired other three are paired
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have 2 branches external(motor) run along superior thyroid artery(branch of external carotid)>>>cricothyroid muscle.
internal(sensory)>>>>above the vocal cords (supraglotic)
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tensor veli palatini is also innervated by CN V3
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run along inferior thyroid artery(branch of thyrocervical trunk)>>>>
all other laryngeal muscle and sensory innervation below the vocal cords
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exceptions:tensor veli palatini(CN 5) 1st arch AND stylopharyngeus( CN 9) 3rd arch
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together make the cartilaginous structure of larynx
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bones: maxilla,zygoma,mandible,vomer,palatine,incus,malleus,temporal
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orbits normally arise from the side of the face and rotate medially. however hyperplasia of frontonasal
prominence could result in orbital hypertelorism (wide-set eyes) in addition to broad forehead and wife nasal bridge.
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failure of medial nasal prominence to fuse and from the intermaxillary segment is associated with severe midline
defect, such as holoprosencephaly
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during the 7-8th week of embryonic development the maxillary prominence give rise to palatine shelves. the thin
sheets of tissue that comprise the palatine shelves grow medially and fuse into the secondary palate. fusion of
secondary palate with posterior aspect of primary palate forms the complete palate. failure of any of these
processes can lead to cleft palate.
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the lip and palate form during 5-6th week of embryonic development: 1, the 1st pharyngeal arch split into upper
maxillary and lower mandibular prominence. 2, fusion of 2 medial nasal prominence forms the midline
intermaxillary segment. the intermaxillary segment will become the philtrum of the upper lip, the 4 medial
maxillary teeth, and the primary palate. 3, the left and right maxillary prominences then fuse with the midline
intermaxillary segment to form the upper lip and primary palate. failure of maxillary prominence with the
intermaxillary segment result in cleft palate. if one side failure occur>>unilateral cleft palate. if both side failure
occur>>bilateral cleft.
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readily diagnosed by FISH 22q11 ......... DiGeorge syndrome is associated with at least 15% of cases of
interrupted aortic arch, a more extreme anomaly than aortic coarctation in which the aortic arch is
atretic or a segment of the arch is absent. Affected patients have poor lower-extremity pulses, but
respiratory distress, variable cyanosis, and signs of congestive heart failure will also develop during the
first days of life. ...... cleft palate, mandibular deformity, low set ears, aortic arch abnormalities are also associated
with the disease.
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in the presence of normal secondary sexual charactericits (means HPO axis is nomral and their is nomral
porduction of estrogen and gonadotrophin hormones) primary amenorrhea would called eugonadotrophic
amenorrhea. thier are two main causes of this. 1, mullerian ageneis (also called MRKH syndorme or upper vaginal
agenesis) 2, incomplete canalization of vaginal canal (it range from complete lower vaginal agenesis to
imperforate hymen)
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early in gestation (weeks 1-6) the embryo has a pair of primitive (indifferent) gonads.this primitive gonads develop
from the genital ridges (located near the adrenal glands) and can differentiate into either testes or females ovaries.
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complete agenesis of the paramesonephric ducts leads to mayer-rokitansky-
kuster-hauser syndrome.lower vagina originates form the urogenital sinus, and
affected patients would experience infertility due to a blind vaginal pouch and lack of
mullerian struture ................. this patient is most likely a 46XX female with mullerian aplasia,also
known as vaginal agenesis or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Aplasia is defined as
defective development or congenital absence of an organ or tissue a patients with MRKH have
variable uterine development and no upper vaginal (eg, short vagina). As the uterus is hypoplastic or
absent, the patient cannot menstruate (eg, primary amenorrhea). Patients with MRKH have normal
ovaries which secrete estrogen normally and enable regular development of secondary sexual
characteristics (eg breast, pubic hair). other mullerain defects may result from inapproapiate fusion of the
Mullerian ducts (eg, unicornuate bicornuate and septate uterus). All females with Mullerian defects
should undergo renal ultrasound as up to 50%
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cause DHT involve in fusion of labial folds during male fetal development.
normal secondary sexual features ( eg increased muscle mass and phallus enlargement) at
puberty cause these features are dependent on testosterone
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from urogenital sinus
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variable development of uterues and upper vaginal agenesis
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lateral fusion
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in HSG bicornuate uterus and longitudinal uterine septum represent similar>>2
unfused uterine horns with a central filling defect. MRI can distinguish these 2
anomalies as a septate uterus has a normal outer uterine contour
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imperforate hymen>>>most common obstructive anatomical anomaly>>>eugonadotrophic amenorrhea>>>at
birth mucocolpos>>>if undiagnosed>>>at puberty hemocolpos>>>bulging vagina or mass pulpated anterior to
rectum.
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innervatd by genital branch of genitofemoral nerve which is drive from(L1-L2 and courses on the anterior surface of
psoas major muscle)...same way labia majora is innervated
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bifid scrotum:
two seperate scrotum result from malunion of the labioscrotal folds.
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urogenital sinus in males give rise to bladder, urethra, prostate and bulbourethral glands. urogenotal sinus in females
give rise to bladder, urethra, lower vagina and bartholin glands.
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differentiation and development of external genitalia occurs during weeks 8-15 of gestation
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transverse vaginal septum is an example of failed vertical fusion of the
paramesonephic ducts with the urogenital sinus. the obstructive septum causes
primary amenorrhea with cyclic pelvic pain from hematometra (menses retained
in the uterus) and an HSG cannot be performed on these patients
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longitudinal uterine septum
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development of the paramesonephrin and mesonephric ducts is closely linked;
therefore, uterine anomalies often coexist with renal anomalies.(eg unilateral renal
agenesis)
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Scrotum.....superficial inguinal
Thigh...........superficial inguinal
Testes.....superficial and deep plexus......>para-aortic

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in the 5th week of gestation
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deep inguinal lymph node=glans penis/clitoris and superficial node. Located under the fascia lata on the medial
side of femoral vein
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vaginal artery=inferior vesical artery in men
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middle vagina>>>>internal iliac .............................. cervix is to internal iliac
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also called retroperitoneal
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As the aorta and SMA compress the left renal vein (“nutcracker effect”) there is generally increased
intravascular pressure in the left gonadal vein with retrograde blood flow and varicocele formation. isolated
right sided varicoceles, which are rare and can indicate IVC occlusion by a malignant tumor or
thrombus. Right RVT with clot expansion into the IVC (impeding venous flow from the right gonadal
vein) likely explains this patient’s right-sided varicocele.
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the pectineal (coopers) ligament is a thickend part of the pectineal fascia. it overlies the pectineal
ridge of the pubic bone and is located posteriorly to the femoral canal.
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ureter located medial (to suspensory ligament) at the level of the bifurcation of the common iliac artery.
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round ligament in women is homologous to the spermatic cord in men.
it leaves the pelvis through the deep inguinal ring and passes through the inguinal canal.
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an opening is made within nonvascular portion of the mesosalpinx below the isthmic portion of the fallopian tube
during a tubal ligation to ligate a segment of the tube
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is a band of connective tissue and smooth muscle
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it is continous with the simple squamous epithelium of of the peritoneum (mesothelium). ovarian epithelium is
involved in surface repair of defects from ovulation.
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The perineal body is essential to the integrity of the pelvic floor. This tendinous center point of the
perineum separates the urogenital and anal triangles. It blends anteriorly with the perineal
membrane and superiorly with the rectovesical or rectovaginal septum. The following
structures are anchored to the perineal body: ・ blubospongiosus muscle ・ external anal
sphincter muscle ・ superficial and deep transverse perineal muscles. ・ fibers from the external
urethral sphincter, levator ani, and muscular coat of the rectum. episiotomies are used to enlarge
the vaginal outlet to facilitate delivery and reduce the risk of severe (third-or-fourth-degree)
perineal laceration. Perineal lacerations are classifies according to the depth of the tear. A midline
episiotomy is a vertical incision from the posterior vaginal opening to the perineal body. It transects
the vaginal lining and the submucosal tissue (similar to a second-degree laceration) but not
the external anal sphincter or the rectal mucosa. Improper repair of a midline episiotomy or a
second-degree laceration may result in pelvic organ prolapse or dyspareunia. the external anal
sphincter is part of the anal triangle. It arises from the coccyx and anococcygeal ligament and
inserts into the perineal body. Women with third or fourth degree perineal laceration are at
risk for fecal incontinence due to anal sphincter damage. The ischicavernosus muscle is pat
of the urogential triangle. It arises from the inner surface of the ischial tuberosities and the
ischipubic rani and inserts into the corpus cavernosum. When the clitoris is stimulated, the
ischiocaernosus muscle forces blood into the clitoris. The levator ani muscle (part of the anal
triangle) suuports the pelvic floor and can be strengthened by Kegel exercises. This muscle is
often stretched, pushed aside, and torn by fetal crowing and delivery. It is not usually incised
during an episiotomy. The transverse perineal muscle is part of the superficial perineal space
(urogenital triangle). It arises from the ischial rami and tuberosities and inserts into the perineal
body. this muscle is cut during a mediolateral episiotomy.
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straight
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the round ligament are clamped and divided to enter the peritoneum of the broad ligament during a
hysterectomy.
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which rarely is a source of major bleeding. (dont have major significance)
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also called transverse ligament
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ovaries located posterolaterally to the uterus, suspended superiorly by mesoovarium,
medially by the ovarian ligament
laterally by the suspensory ligament
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nbme,11,4,19 The ureter passes under the uterine artery in females and the ductus deferens in the males in the
pelvis. The gonadal arteries cross the ureter in its middle 1/3 in the abdominal cavity where it overlies posas major
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due to cycling, penile erection defect is due to>>>>damaged blood and nerve supply to the
erectile tissue not by compromised blood flow from the pempiniform plexus, onot by lumbosacral
strain.
A study in 2002 found that ED can also be associated with bicycling. The number of hours on a
bike and/or the pressure on the penis from the saddle of an upright bicycle is directly related to
erectile dysfunction.
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additional sign are unable to urinate and a high-riding, boggy prostate ( caused by hematoma formation below the
gland)....>>>>>these signs are particularly important with pelvic fracture
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posterior urethra is located above the bulb of the penis, and the anterior urethra lies within the bulb and
remainder of the corpus spongiosum. posterior urethra divided into the prostatic and membranous segments.
anterior urethra divided into bulbous and penile urethra.. in contrast to prostatic and bulbous segements, the
membranous segemtn is relatively unsupported by the adjacent tissue and is the weakest point of the posterior
urethra. trauma to the pelvis severe enough to cause fracture results in disruption of posterior urethra ar the
bulbomembranous junction.
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prostatitic plexus lies within the fascia of the prostate and originates from the inferior hypogastric plexus (which
itself is a continuation of the hypogastric nerve with additional input from the pelvic and sacral splanchnic
nerves). the lesser and greater cavernous nerves arise from the protatic plexus and pass beneath the pubic arch to
innervate the corpora cavernosa of the penis and urethra. the cavernous nerves carry post-ganglionic
parasympathetic fibers that facilitate penile erection. prostatectomy or injury to the prostatic plexus can cause
erectile dysfunction; as a result, surgeons attempt to preserve the integrity of the prostatic fascial shell during
surgery.... ......... branches of pudendal nerve innervate the external urethral and anal sphincters.they also provide
sensory innervation of the external genitalia. pudendal nerve injury can lead to fecal incontinence, decreased
penile sensation or external urethral sphincter paralysis. although urethral muscle injury can occur during
prostate surgery. injury to the main pudendal nerve is less common with prostatectomy
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inferior hypogastric plexus has both sympathetic and parasympathetic components, innervates the internal
pelvic viscera but not the external perirectal area
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ilioinguinal nerve>>>>upper part of scrutm amd root of penis in female>>>mons pubis and labia majora
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bulbar and penile. although bulbous urethral segment is reinforced by the surrounding corpus spongiosum, it is
susceptible to crushing injuries when the perineum is stuck forcefully (ie straddle injury)... penile urethral segment
is most commonly injured due to penetrating trauma or instrumentation
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injury to anterior bladder wall os common with pelvic fracture>>>causes extraperitoneal leakage of
urine..
superior bladder wall ruptures often occur with abdominal trauma when the bladder is full and
result in leakage of urine into the intraperitoneal cavity
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testicular torsion is a rotation of testes around the apermatic cord. trauma or a congenitally-horizontal positioning
of the testes ("bell clapper defromity") facilitates torsion.
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Penila erection is initiated by release of acetylcholine and nitric oxide (NO) from
parasympathetic fibers
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testosterone inhibit both GnRH and LH but inhibin inhibit only FSH.
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this is different from sex hormone-binding globulin, which is found in the blood
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testes also
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low estrogen level lead to increased VEGF production locally with in the bone>>>augments new blood vessel
formation with in bone and increase blood flow.................. hypoestrogenic states results increased production of
inflamamotry cytokines eg IL-1 and TNF-alpha and also result in over expression fo RNAK ligand and also
increasees RNAK expression in osteoclast precurosrs>>>>increases bone resorption by increasing ostoaclast
actiity.......... in premenopausal women estrogen casues production of OPG by osteoblast and stromal
cells, also decrease expression of RANK on osteoclast prescurors.
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estrogen increases hepatic cholesterol uptake, also increase hmg-co-a reductase, whihc increases
cholesterol formation>>>>so both causes increase cholesterol gallstones
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nbme>>>>2,4,29 progesteron in pregnancy cause relaxation of "lower esophageal spinctor" leading to heart
burn and reflux. During the pregnancy, the progesterone is needed in the following ways, (mostly in conjunction with
estrogen): Makes the endometrium develop and secrete fluids after being primed by estrogen Maintains the functions
of the placenta and fights off unwanted cells near the womb that could cause damage to the placenta or foetus. Keeps
the endometrium in a thickened condition Stops the uterus making spontaneous movements Stimulates the growth of
breast tissue Prevents lactation until after the birth (with estrogen) Strengthens the mucus plug covering the cervix to
prevent infection. Strengthens the pelvic walls in preparation for labour. Stops the uterus from contracting (thus
keeping the baby where it is) At the end of the pregnancy, the levels of progesterone secreted by the placenta drop
off. It is this action that stimulates the beginning of the contractions that will lead to birth. The effects on a woman due
to raised levels of progesterone can include any or all of the following: Constipation Heartburn Runny and irritable
nose Eyesight problems (blurring or headaches) Increased kidney infection risk
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aromatase belongs to P450 superfamily and is highly expressed in ovarian tissue (ovarian expression of
aromatase in gonadotrophin dependent) Aromatase is also present in subcutaboeous fat, normal breast tissue
and cancerous breast tissue, In postmenopausal women extraovarian tissue maintain the low level of estrogen in
the peripheral circulation.
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in diplotene phase
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endometrial cell that are in early stages of decidualization appear most vulnerable to apoptosis
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causes endometrial cell growth and differentiate into decidual cells that can accomodate pregnancy
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the blood pressure falls early in gestation, secondary to a reduction in a systemic vascular
resistance. there is also expansion of plasma volume and an increase in red cell
mass........,................ Supine hypotension syndrome (or aortocaval compression syndrome)
>>>>>>>>>>>>when pregnant women lies supine (on her back)
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an ovulation predictor kit measures urinary LH and becomes positive 24 hours before ovulaiton.
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cytotrophoblast secretes HCG-H, where H means hyperglycosylated.
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urine is less sensitive, level is detectable when reaches 20IU/L
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highest level at week 9
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may appear at 6th day in serum but require 2 day more after implantation to rise to a detectable amount <5IU/L
(typically at 8th day)>>>>>>>>>>>>serum test is the most sensitiv test of preganacy
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steadily increases during pregnancy, and has secondary role in breast development and primary role in
lactogenesis.
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The triple test is used to determine alpha-fetoprotein (AFP), hCG and estriol levels. it shouls be
performed between weeks 16 and 18 of gestation. An abnormal triple test is an indication for
fetal ultrasonography (USG). f fetal USG reveals level of development consistent with the
mother’s reported dates and no anatomic abnormalities are seen, amniocentesis is performed.
Estriol levels reflect both placental and fetal function, as both are necessary for its
synthesis. Decreased estriol levels are suggestive of placental insufficiency. Placental
abnormalities and intrauterine growth retardation are associated with decreased levels of
estriol
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due to germinal matrix hemorrhage.
most common before 32 weeks, weight less than 1500 and almost always present with in first 5
days.
.............
the germinal matrix starts involuting around 28 weeks gestation and disappeares by the time an
infant is full term.
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OCs may mask vasomotor symptoms that are typical of menopausal transition, and the patient was likely having
iatrogenic withdrawal bleeding.
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effect of androgen abuse: 1, CV>>>increase hematocrit, increase LDL and decrease HDL. 2, derma>>>>acne,(
hirsutism and male-pattern hair loss (f)) 3, genitourinary>>>>clitromegaly, oligomenorrhea (f)...testicular atrophy ,
dec spermatogenesis (m) 4, psychiatric>>>>depression, hypomania (f).....aggressivemess, mossd disorders (m) 5,
breast>>>>atrophy (f)...gynecomastia (m) 6 other>>>>deepening of voice (f)..premature epiphyseal closure
(adolescents)
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IGF-1 causws the differentiation and proliferation of chondrocytes in the epiphyseal growth plate, causing an
increase in linear growth. however unlike estrogen,IGF-1 does not accelerates epiphyseal closure. so in
giagantism excessive pituitary production of GH and subsequent IGF-1,these patietns achieve enormous height,
cause unlike estrogen IGF-1 does not lead to premature colsure of the epiphysis.
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Decreased thickness of vaginal epithelium and decreased amount of glycogen in epithelial
cells are characteristic in postmenopausal and lactating women. These changes are caused by
low estrogen levels and lead to atrophic vaginitis.
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During meiosi 1I of male spermatogenesis, the X and Y chromosomes pair in the pseudoautosomal regions, allowing the
chromosomes to segregate into different cells.
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due to missing SHOX gene
1810
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The karyotype of an isochromosome for the long arm of the X chromosome would be 46,X,i(Xq); this karyotype results in an
individual with Turner syndrome, indicating that most of the critical genes responsible for the Turner phenotype are on Xp.
.................................... loss of a ring X chromosome would produce Turner syndrome
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Psychosocial abnormalities (eg, lack of insight, poor judgement) are also common. .... may be
associated with mild mental retardation or normal intelligence.
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Primary amenorrhea is defined as the absence of menses by age 15 in someone who has normal
growth and secondary sexual characteristic (eg, body hair growth, breast development) or absences of
menses by age 13 in girls without secondary sex characteristics.
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barrr body in leucocyte
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but their is an increase risk of aortic dissection or rupture in these pregnant womens.
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and gynecomastia is due to the increase activity of aromatase (stimulated by gonadotrohphin excess) ....... the
ratio of estrogen:testosterone determines the extent of feminization.
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patients with TS have normal ovarian development during fetal life. However, lack of the paternal X
chromosome causes loss of ovarian follicles by age 2, as well as a karyotype of 45, X. At puberty,
patients with TS usually have normal pubic hair but no breasts or menses due to ovarian failure.
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Variants include 46,XY/ 47,XXY mosaicism and 48,XXXY. In general, patients with higher numbers of X
chromosomes are more likely to have more severe manifestations. The disorder is usually not
diagnosed until puberty when the characteristic physical signs begins to develop. ........ classic
form>>>>azospermia mosaic form>>>variable degree of spermatogenesis.
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The 47, XXX karyotype is typically clinically silent. Some affected women may have slightly
decreased IQ scores. Female newborns with this karyotype phenotypically normal with no obvious
dysmorphism.
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1, mostly by meiotic nondisjunction during gametogenesis (all cell are
affected),majorly paternal 2, mitotic nondisjunction during early embryogenesis
(some cell are affected) 3, have both X but one is structurally abnormal and
missing some genetic material (isochromosome, X fragments) 1810 .... Girls with
a mixed chromosome pattern may have fewer symptoms if they have some normal (XX) cells. the loss of
X chromosome results in a missing SHOX gene, which is responsible for long bone growth. ..........
Patiens with Turner syndrome may have karyotype 45,X (complete monosomy) 45,X/ 46,XX (mosaicism) or
46,XX (with partial deletion of one X chromosome).
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Aromatase deficiency is an autosomal recessive disorder that manifests early in embryonal life with
high androgen and lowestrogen levels in the female fetus. Maternal virilization (eg, hirutism)
commonly occurs during pregnancy due to the transfer of excess androgens into the maternal
circulation. Affected newborn girls will have normal internal genitalia and ambiguous or male-type
external genitalia (eg, clitoromegaly, female pseudohermaphrodism). At puberty, impaired ovarian
estrogen synthesis causes primary amenorrhea, osteoporosis, and tall stature (low estrogen delays
fusion of the epiphyses). Men with aromatase deficiency have tall stature and osteoporosis but no
genital abnormalities.
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but sperm count is low as local concentration of testosterone is suboptimal for spermatogenesis.
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normal hormonal profile but lacking sperm>>>>>obstruction>>>congenital absence of vas
deference
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of GnRH neurons from olfactory lobe to the hypothalamus
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these patient are deficient in 5 alpha reductase type 2, which are present in genitals predominantly. at puberty
there is 5 alpha reductase type 1 become active which are present in postpubertal skin>>>>which result in
masculinization with male-pattern muscle mass, voice deepening, penile and scrotal growth, and testicular
descent.
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adrenarche is normal
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less likely to cause gynecomastia as the decrease in gondaotrophin reduces aromatasae activity.
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normal LH and testosterone, elevated FSH and a low sperm count >>>>cryptorchidism>>>>seminiferous tubules
are damaged and intersticial cells are preserved.
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most often the cause is a mutation in the KAL-1 gene or the fibroblast growth factor receptor-1 gene,
which code for proteins required in this migration. although there may be other midline defects as well,
(eg, cleft lip or cleft palate).most often these pateitns present with delayed puberty. on physical
examination the testes are often just 1-2 mL in volume.there is usually some pubic hair because
adrenarche occurs normally. in the United States, delayed puberty s defined as the absence or
incomplete development of secondary sexual characteristic by age 14 in boys and by age 12 in girls.
Testicular enlargement is the first sign of puberty in boys, and breast enlargement is the first sign in
girls.
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and have decreased villous blood.
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due to very high bHCG which stimulate ovarian growth.
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can have invasive mole (which is just like complete mole) except it penetrates the uterine
wall>>>>consists of diffusley hydropic villi and diffusely proliferated trophoblast
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abnormal vagial beeling., also with uterine enlargement.
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macroscopically>>>>bullky uterine mass that is usually sofr and yellow-white, with extensive areas
of necrosis and hemorrahge..
histologically, it is composed of abnormal proliferation of monolunlear cytotrphoblasts and
multinuclear syncytotrphoblas.
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most commonly preceded by a normal preganancy, but can occur following any pregnancy (molar, ectopoc,
aborted)
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complete mole has only edematous (eg hydropic) villi and diffuse proliferation of trophoblast.
in partial moles>>some edematous villi with focal traophoblastic proliferation and normal
appearing villi
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which make lining of villi
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immunochemistery staining is P57-negative in complete mole due to absence of a maternal
genome
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absence of decidua basalis
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also vaginal bleeding and orthostatic hypetension.
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MTX is the drug of choice before 6 week of gestation. its efficacy increases when used in combination with
misoprostol. ........ MTX used with misoprostol when mifepristone is not available
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amniotic fluid total protein and albumin concentrations normally decrease by about 50% from early gestation to
term.
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due to increase CO. also seen in twin-twin transfusion syndrome, alloimmunization, parvo-virus infection,
fetomaternal hemorrhage. these all related to increase urine production
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after 16 weeks of gestation when majority of amniotic fluid is fetal urine
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complication are preterm labor, placental abruption and uterine atony (due to uterine overdistention.
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maternal diabetes and multiple gestation cause relatively milder polyhydramnio
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immature chorionic villi would be seen at the site of ectopic implantation.
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neisseria and chlemydia.
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they have intrahepatic thrombotic angiopathy
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fibrinoid necrosis
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E6 binds protein p53 and increases its degradation, whereas E7 binds to the retinoblastoma (RB1) gene
and displaces transcription factors normally bound by pRB, the tumor suppressor protein product of RB.
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parabasal cells: are round cell with basophlic cytoplasm, finely granular chromatin in their nuclei, no visible
nucleoli and a high N/C ratio. fried egg with large central yolk these cells are found in pap smear of post-
menopausal and post-partum women >>>>these cell are normal finding in pap smear.
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treated with menotropin (human menopausal gonadotrophin) acts like FSH and triggers the formation of dominant
ovarian follicle. HCG administration after using menotropin which mimic LH surge(alpha subunit of HCG is similar to
LH) and causes ovulation.
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PCOS is the most common cause of hirsutism.
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by suppressing LH production>>>>>decreases ovarian androgen production...
also increases synthesis of SHBG by liver>>>decreases amount of free testosterone in circulation.
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patient with PCOS who develop diabetes is treated with metformin. it also help to normalize menses. ...........
ketoconazole and spironolactone are used when hirsutism are not controlled well with OCP.
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histologic changes include enlarged, scelrotic follicles.
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and finasteride(less efective) are only used in the setting of reliable contraception (due to teratogenicity) .
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tendency toward lipid profile abnormality is also present
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ratio >3
FSH is normal..
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are immature squamous cells>>> with dense irregularly stained cytoplasm and perinuclear
clearing result in halo formation. have pyknotic nuclei>>as part of process of apoptosis.
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the presence of normal glandular cell indicates adequate sampling.
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letrozole also used
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myoglobin positive also, also have cytoplamic cross striations
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nulliparity, misscariage, use of clomiphine citrate
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most common subtype of germ cell tumor.
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most common benign is teratoma in females, and most common maliognant in females are dysgerminoa
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multiparity.
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from ovarian surface (celomic, germinal epithelium)
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and pregnancy
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due to large estrogen secretion,older women may develop fibrocystic change pf
the breast, endometrail hyperplasia or carcinoma.
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histologic findings include sheets of tumor cells (with enlarged irregular nuclei, prominent nucleoli, and eosinophilic
cytoplasm) forming pseudoglandular spaces and papillae.
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grnulosa-theca cell tmors comprise approximately 5% of all ovarian tumors. these
tumors are unilateral and variable in size, with the lipid content (and therefor the
hormonal activity) indicated by the yellow cut surface. granulosa-theca cell tumors
yend to contain a predominacne of granulosa cells and a scattering of theca
cells .............. histologically, granulosa cells are small , cubidal cells that grow in
cords or sheets. small, gland-like structures that contain an acidophilic materoal
may be present, these are termed call-exner bodies, and are suggestive of
immature follicles. themcoma cells are presnt as clusters or sheets of cuboidal
cells. tumor that primarily consist of thecoma cells are almost always benign
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small follicle like structure filled with eosinophilic secretions. they have coffee been nuclei
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nbme,11,1,41
experimental trearmentr the involves instillation of embolizing agent directly into the vessels that
feed the leiomyomata.>>>>following is the most direct course of the catheter after entering the
femoral artery>>>>external iliac artery>>>>internal iliac artery>>>uterine artery.
explanation
The uterine artery usually arises from the anterior division of the internal iliac artery
Uterine artery embolization (UAE) is a procedure where an interventional radiologist uses a
catheter to deliver small particles that block the blood supply to the uterine body. If the procedure
is done for the treatment of uterine fibroids it is also called uterine fibroid embolization (UFE).
Under local anesthesia a catheter is introduced into the femoral artery at the groin and advanced
under radiographic control into the uterine arterty
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uterine fibroids can also produce erythropoietin and cause polycythemia.
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typically affect middle aged parous women. uterine enlargement is due to uterine smooth muscle cell
hypertrophy and hyperplasia in response to ectopic endometrial glandular tissues.
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chronic endometritis>>>>presence of plasma cells, which normally not present there, ,, lymphocytes can present
there normally
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atrophic type ndometrial carcinoma>>>>sporadic and related to P53 mutation and age grretar than 70
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unlike leiomyomas which are irregularly enlarged, benign pseudoencapsulated tumor of
monoclonal uterine smooth muscle cells
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retroveriosn is the most common type of uterine malposition and it is usually asymptomatic.
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posterior cul-de-sac, broad ligament and uterosacral ligament.
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as opposed to adenomyosis in which uterine size is enlarged(unifromly)
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implants through out the pelvis and abdomen can also appear as flesh-colored nodules,powder burn patterns or
adhesive disease. ........ histopathologic findings include hemosiderin deposits and endometrail glands and
stroma.
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ectopic endometrial tissue also secretes prostaglandins that interfere with ovulation and tubal function.
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during menstrual period bleeding and shedding outside the uterus lead to the formation of blood
collection. with time, the blood undergo hemolysis and induces an inflammatory response around
the ectopic endometrium.local inflammation is followed by the formation of adhesions and
distortion of organ structures.
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many patients are diagnosed with endometriosis while being evaluated for infertility.
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painful intercourse is related to retroversion of the uterus and endometrial implants on the uterosacral
ligaments. painful defecation can also occur due to pelvic adhesions. ........ nodularity of the uterosacral
ligaments and fixed retroversion of the uterus are commonly found in patients with endometriosis on vaginal
examination.
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nbme,11,3,16 supernumerary nipples (polythelia) more than the normal number of nipples, may be on the breast or
other parts of the body-found along the "milk line" from axilla to groin. These accessory nipples resemble raised nevi
(commonly called "moles"). It is derived from epithelial tissue . Usually, the supernumerary nipple remains
undetected or asymptomatic. Occasionally, the supernumerary nipple is noticed only when hormonal changes
during adolescence, menstruation, or pregnancy cause increased pigmentation, fluctuating swelling, tenderness, or
even lactation.
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nbme>>>4,2,44 A breast lump... in upper outer quadrant -----> Most common site of Ca Breast. Non-motile & ill
defined borders-----> rules out Fibroadenoma Painless ------>rules out painful breast disorder Mastitis,
fibrocystic changes etc. Plus inc, age points towards, Malignancy. Lymph node involvement would be in the axilla as
lymph from breast goes to the pectoral group of the axillary lymph nodes. Metastatic tumors of the breast are rare &
would present as a well-circumscribed tumor with multiple satellite foci, the absence of an intraductal component, and
the presence of many lymphatic emboli. In adults, the most frequent types of tumors metastasizing in the breast are
malignant melanoma and neuroendocrine-like tumors, especially small cell carcinoma and carcinoid. In
children, rhabdomyosarcoma is the most common.
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can also occur as multiple and/or bilateral lesion.
in younger women discovered as palpable mass by the patient or physicians.
in older patients more often found incidentally on mammography
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mammary duct ectasia:
characterized by ductal dilation , inspissated breast secretion, and chronic granulomatous
infamamtion in the periductal and intersticial area.
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androgen inhibit breast growth, where as estrogen induce breast growth.
hitopathologiclaly it is characterized by ductal epithelial hyperplasia surrounded by dense stromal
fibrosis.
Acinar development is driven primarily by progesterone and is not usually seen.
Page: 636
common pahtologic causes are 1, obesity (increased aromatase conversion of testosterone to estrogen) 2,
hyperthyroidism (increased LH secretion and estrogen production) 3, cirrhosis (increased aromatase activity,
decreased clearence of estrogens) 4, chronic kidney disease (decreasd testosterone production
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selctive estrogen receptro blocker tamoxifin is effective for prevention and treatment of
gynecomastia in patients on androgen-deprivation therapy
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central acinar proliferation and compression with surrounding fibrotic tissue and peripheral ductal dilation.
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also with lactation????????
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histologically charcterized by benign appearing cellular or myxoid stroma that encricles epithelium lined
glandular and cystic spaces. lesion have well defined border but may compress and distort the surrounding
glandular epithelium, as women age, epithelium atrophied and the stroma become more hyalinized.
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divided into 5 subtypes:
1, comedocarcinoma,
2, solid
3, papillary
4, micropapillary
5, cribriform
Most cases have mixture of patterns
Page: 637
Identified as solid sheets of pleomorphic, high grade cells with central necrosis.
chronic inflammation and periductal concentric fibrosis is additional finding..
As malignant cell become necrotic they calcify , allowing memographic detection of
microcalcification clusters.
if comedocarcinoma is extensive, the lesion may be palpable as poorly defined nodule
Page: 637
coopers ligament infiltration>>>retraction of overlying skin.. pectoral fascia infiltration>>>increases the likelihood of
mass adherent to the chest wall.
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solid sheets of vesicular, pleomorphic, mitotically active cells with a significant lymphoplasmacytic infiltrate
around and within tumor and a pushing noninfiltrating border....
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myoepthelial layer>>>basal membrane
Page: 637
leads to activation of tyrosine kinase.
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testes that is palpable in inguinal canal typically descends spontaneously by age 6 months. testes that have not
descended typically require surgical intervention. undescended testes which are paplpable in inguinal canal must be
mobilized through the superficial inguinal ring and stiched into place in the scrotum. .......... testes develop in the
fetal abdomen during organogenesis between 8 weeks and full term.they crosses deep inguinal ring(bounded by
tranaversus abdominis muscle laterally and the inferior epigastric vessels medially) and superficial inguinal
ring(above and medial to pubic tubercle) to enter in scrotum.
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play a role in venous drainage from testis, spididymis and ductus deferense into the testicular
veins
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is a part of dorsal midbrain. usually cause onstructive hydocephalus with symptoms in increased ICP (eg headache,
vomiting, altered mental status) and parinaud syndrome (eg upward gaze palsy)
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suprasellar location>>usually present with pituitary symtoms>>>diabtetes inspidus, precociouspuberty
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derived from seminiferous tubule
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nutcracker effect>>>>compression of vein when crosses between the aorta and SMA>>>>persistently elevated
pressure causes left renal vein entrapment syndrome>>>left flank or abdominal pain with gross or microsopic
hematuria
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work on fixed component of baldder outlet obstruction>>decreases protate volume
Page: 640
eg tadalafil produces symptomatic improvement.
Page: 640
the prostate gland may be nodular or boggy and tender to palpation.
Page: 640
after regional lymph nodes, liver and lungs the skelatal system is the fourth most common site of metastases.
which usually disseminate hematogenously. cancers of the pelvis imcluding prostate spread to the lumbosacral
spine via the vertebral venous plexus(VVP). the VVP communicates woth a number of venous networks, including
the protatic venous plexus.which receives the venous supply from the prostate, penis and bladder.it runs up the
entire spinal column and connects with the venos supply of the brain via a valveless system.,which allows for
bidirectional flow and regulaiton of intracranial pressure.this venous connection explains the tumor metastasis to
brian. the VVP also communicates with the azygous vein in the chest, which explains in part why breast and lung
cancers frequently metastasize to the thoracis spine.similarly due to pulmonary venous drainage into the left side of
the heart, lung tumors often spread systemically via the arterial system.
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Eosinophilic cytoplasmic inclusion in liver cell Mallory body (alcoholic liver disease) 374 Eosinophilic cytoplasmic
inclusion in neuron Lewy body (Parkinson disease and Lewy body dementia) 490 Eosinophilic globule in liver
Councilman body (viral hepatitis, yellow fever), represents hepatocyte undergoing apoptosis 168 Eosinophilic
inclusion bodies in cytoplasm of hippocampal and cerebellar neurons Negri bodies of rabies Intranuclear
eosinophilic droplet-like bodies Cowdry type A bodies (HSV or VZV)
Page: 640
acid phosphatase is a secondary prostate tumor marker antigen that is also elevated in patients
undergoing active osteoclast-initiated bone resorption.
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osteolytic bone metastasis>>>>represent aggressive cancer>>>MM, non-hodkin
lymphoma, non-small cell cancer of lung, melanoma, renal cell carcinoma.
osteoblastic metatasis>>>more indolent course>>prostate cancer, small cell lung
cancer, hodgkin-lymphoma.. mixed metatasis>>>>GI and breast cancer
Page: 640
phenazopyridine is a urinary analgesic.
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work on dynamic component of bladder outlet obstruction.
causes relaxation of smooth muscle in bladder neck, prostate capsule and prostatic urethra.
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danazol
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amino acid substitution that allow longer half-life and increased activity.
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androgen dependent. continuous use following androgen receptor blockade with flutamide),
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estrogen receptor modulator
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CVS and bloood lipoprotein
Page: 642
premenopausaly we use tamoxifen for ER/PR + cancer but postmenopausaly we add anastrolozole as adjuvant
therapy with tomoxifen for ER/PR + cancer. In postmenopausal women great source of estrogen is the conversion
of androstenedione , produced in adrenal gland, to estrone, through aromatization in liver, muscle and fat.
Page: 642
Clinical data demonstrate that these aromatase inhibitors are superior to tamoxifen as
adjuvant therapy for breast cancer and have now replaced tamoxifen as first line therapy in a
number of treatment regimens for postmenopausal breast cancer patients
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clomiphene increases risk of ovarian cancers
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equivalent or superior to tamoxifen in breast cancer.
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aminoglutethimide and fadrozole were the initial aromatase inhibitor.
Page: 642
even in the contralateral breast.
also increases disease free survival..
Page: 642
in caucasian females is defined as the development of secondary sexual characters at an age less
than seven years.
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goserlein, nafarelin, and histrelin
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premenopausal estrogen receptor positive breast cancer
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therapeutic abortion upto 49 days post conception.
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side effects>>>abdominal pain, GI effects(cause of drug affect of stimulate the release of
endogenous PGs and sensitization of prostagalndin receptor.)
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OCP can induce insulin resistance and cause glucose intolerance. however the risk of glucose intolerance was
most significant with the first generation of high-dose estroegen OCP. with the reduced quantities of estrogen
in the newer 2nd and 3rd generation OCP, glucose intolerance has become much less common...... 3rd gen OCP
have very little estrogen so is not contraindicated in controlled diabetics which have no other CV risk factor.
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medoxypregesterone acetate...also used parenterally as long-acting contraceptive>>>>prolonged use decrease
bone mineral density in women of all ages
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has been linked to an increased risk of neonatal intraventricular hemorrhage, hypoglycemia, hypocalcemia and
ilius.
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other contraindication are: hypertriglyceridemia, decompensated or acute liver disease(impair steroid
metablolism)
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has a number of androgenic and antiestrogenic effects. high doses can suppress gonadotrophin and
endogenous androgen production but are associated with a risk of rapid prostate cancer growth
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OCP use is not related to HDL but with LDL and its safe with level below 160mg/dl without any other CV risk
factor
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side effects of OCPs>>>>breakthrough menstrual bleeding, breast tenderness and weight gain.
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causes decidual necrosis and expulsion of product
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to have even more success rate.
generally have 80%
also used for NSAIDs induced GI ulcers
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have 5 times more affinity for receptor than progesterone
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nbme>>>6,1,47 Methandrostenolone is an orally-effective anabolic steroid. The 17α-
methylation of the steroid does allow it to pass through the liver with only a small portion of it
broken down (hence causing the damage to the liver) allowing it to be effective when taken
orally.In high doses (30 mg or more per day) , side effects such as gynecomastia, high blood
pressure, acne and male pattern baldness may begin to occur.
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anabolic steroid use is a known cause of acne especially in a competitive atheletes. four elements underlie the
pathophysiology of acne: 1, follicular epidermal hyperproliferation 2, excessive sebum production 3, inflammation 4,
propionibacterium acnes. after conversion to DHT, androgen promote both follicular spidermal hyperproliferation
and excessive sebum production.
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also bicalutamide
Page: 644
on the primary tumor and metastasis>>leads to reduction in their size (improving symptoms such
as bone pain and urinary obstruction.
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is a weak antiandrogen, inhibit synthesis of testosterone in leydig cells along with steroid synthesis inhibition in
adrenal glands
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nbme>>>4,4,45.
patient with orchitis, gynecomastia and testicular atrophy is treated with>>>>
Testosterone not danazol nor gonadotrophin releasing hormone.
explanation.
is used to treat hypogonadism and promote development of 2º sex characteristics, stimulation of
anabolism to promote.
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decreases testosterone production and inhibits the testosterone receptors
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but not for BPH>>cause of its significant antiandrogenic side effects
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cyproterone acetate and spironolactone also block androgen receptor
Page: 644
relationship of finasteride with carbamezapine(P450 inducer)
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acneiform eruption>>>>also have with lithium and EGFR inhibitor
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8 in left 10 in right
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also called flourescence polarization assay,
P value is inversely related to surfactant level.
Page: 648
found in terminal and respiratory bronchioles, the domed profile of membrane on
the luminal surface and lack of cilia make in distinguish
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The fetal adrenal gland consists of an inner active fetal zone and an outer dormant adult
zone. The fetal zone produces mainly androgens in concert with the placenta because it lacks
the enzyme 3-B hydroxysteroid dehydrogenase that converts pregnenolone to progesterone.
The outer zone is dormant during early early fetal life and produces only small amounts of
cortisol. The secretion of cortisol from the adult zone of the adrenal cortex is controlled by
ACTH and CRH from both the fetal pituitary and the placenta. Interestingly, CRH secretion
from the placental is up-regulated by cortisol. In late gestation, cortisol secretion from the
adult zone of the fetal adrenal cortex is augmented by high placental CRH secretion. is
summary both maternal and fetal cortisol helps accelerate fetal lung maturation by stimulating
surfactant production.
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make up 60% of alveolar cell type
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phosphatidylcholine (lecithin) and phosphatidylglycerol are major components of surfactant. fetal lung lecithin
production increases after 30th week of gestation, and phophatidylglycerol production increases at 36 weeks
gestation. the amniotic fluid sphingomyelin level should remain approximately constant during the third trimester.
................ The outward flow of pulmonary secretions from the fetal lungs into the amniotic fluid
maintains the level of lecithin and sphingomyelin equally until 32-33 weeks gestation, when the
lecithin concentration begins to increase significantly while the sphingomyelin remains nearly the
same.
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is a common membrane phospholipid and only a minor component of pulmonary surfactant.
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lamellar bodies are membrane bound intracellular inclusions>>>>store and release surfactant>>>released by
exocytosis>>>by calcium dependent fusion of lamellar body membrane with the type 2 pneumocyte cell membrane
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secretory constituent of terminal respiratory epithelium. secretory protein protects against airway inflammation
and oxidative stress.
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surfactant treatment can result in transient hypoxia and hypotension, blockage of endotracheal tube and
pulmonary hemorrhage.
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to regenerate alveoli.
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make up 40% of alveolar cell type
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via cytochrome p450 pathway
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for ciliated and (goblet cells ???)>>>not gtoblet regenerative source of ciliated cell in bronchioles
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normal when value is >/0.47
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nose,paranasal sinuses, nasopharynx, most of larynx, lower half of posterior epiglottis and
vestibular folds (false vocal cord)>>>pseudostratified columnar.
oropharynx, laryngopharynx, upper half of posterior epiglottis, anterior epiglottis and vocal folds
(true vocal cord)>>>>stratified squamous
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mucous secreting (goblet cells and submucosal mucus and mucoserous glands) present to the level of larger
bronchioles (or may be upto the bronchi) after which club cell (which secrete surfactant component) become the
prominent secretory cell type. ........................ bronchioles generally lack goblet cell, submucosal seromucus
glands and cartilage.
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respiratory control center in brain stem control the frequency and/or amplitude of involuntary respirations (ondines
curse, is defect in these centers)
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without cilia
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proximal portion
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5 things:
2>>goblet and cartilage>>bronchi
2>>columnar to cuboidal and SM>>> proximal and distal terminal bonchioles respectively..
1>>cilia>>proximal respiratory bronchioles
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10-15 micron>>>cleared by upper respiratory track.
2.5-10 micron>>cleared by mucociliary mechanism
<2 micron cleared by phagocytosis.
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enter superior portion of right inferior lobe
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Located to the right of the midline, within the central tendon. uworld says>>passed through the right side of the central tendon.
a penetratinf wounf to the back immediate right of the vertebral bodies could strike IVC.
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Located in the midline, behind the 2 crura.
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phrenic nerve pass between the lung and heart to provide motor function tot he diaphragm. it also provide sensory
fibers to the pericardium, mediatinal pleura and diaphragmatic peritnoneu,. the supraclavicular nerves originate
from C3-C4 and their branches innervate the sternoclavicular joint, local muscles (eg sternocleidomastoid) and
the skin of iupper and psterior shoulder. any abdominal process (eg ruptures spleen, perotonitis and
hemoperitoneum) produces referred pain. phrenic nerve irritation can cause huiccups due to spasmodic
diapharagmatic contraction pulling air against a closed larynx. phrenic nerve palsy is associated with
respsiratory distress and diminshed breath sound on the affected side, with elevation of the affected
hemidiaphargm on chest X-ray. upward movement of the affected diaphragm with inspiration is seen on
fluoroscopy
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IVC splits into common iliac at L4/L5>>>>and common iliac bifurcates into external and internal
iliac veins at the pelvic inlet
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kehr sign
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Located to the left of the midline, within the muscle of the right crus
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thoracocentesis done in 5-7th intercostal space midclavicular, 7-9th mid axillary ,9-10th
paravertebral.
insertion of needle below the 9th rib on the right side can injure liver
Page: 650
chest tube through the skin and subcutaneous fat into the 4th or 5th intercostal space in the anterior
axillary or midaxillary line. The tube traverses through the serratus anterior muscle, intercostal
(external, internal, innermost) muscles and parietal pleura to reach the pleural cavity. the serratus
anterior originates as multiple branches from the side of the chest along the 1st-8th ribs and inserts along
the entire length of the medial scapular border. The muscles is divided into 3 parts (superior, intermediate,
inferior) depending on the insertion site at the scapula. The inferior part of the muscle facilitates arm
elevation by pulling the lower end of the scapular forward (scapular rotation). All 3 muscle parts can help
with respiration by lifting the ribs when the should girdle is fixed. ................... the external oblique
muscle is usually inferior to the chest tube insertion site.
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nbme>>>2,1,37>>>expiratory flow rate and its pletuaing is increased to high level by increases in
lung volume not by increase in expiratory effort.
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arterial PaCO2 is the direct indicator of alveolar ventilation status.hypocapnia emplies ongoing alveolar
hyperventilation..... upper airway obstruction, reduced ventilatory drive, respiratory muscle fatigue and decreased
chest wall compliance are possible causes of alveolar hypoventilation and hypercapnia.
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in order to reduce energy consumption and fetigue, the tidal volume and repspiratoy rate are
optimized by respiratory control center to minimize the work of breathing while maintianing
adequate minute ventilation.
for nomral adult work of breathing is minimized at RR of 15.
in OPD>>>work of breathing is minimzed at low RR and high tidal volume
in RPD>>>>work of breathing is minimized at high RR and low tidal volume
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nbme,7,3,44 good explanation Air flow (ALVEOLAR SPACE) is maximal at the midpoint of either inspiration or
expiration. Because of the maximal difference (gradient) btwn Patmosphere = O and Palveoli = -1 (inspiration) or
+1 (expiration). But changes in airway compression (P alveloi) due to increases (inspiration) or decreases
(expiration) of lung volume (Pressure is inversely equal to Volume ( P = 1/V ) will cause Pressure of Alveoli to go
towards 0, and result in a slowing of airflow... towards zero...... in otherwords lessen the pressure gradient between
the alveoli and the atmosphere. Patm = 0 Remember that at the end of inspiration or expiration aveolar pressure
= 0 & there is also 0 flow during these times. Elastic Recoil (collapsing force) works opposing IPP (Expanding
force) - created by the diaphragm during inspiration. - this is the force required to get air into Conducting Zone of
the lung (not into the respiratory zone (alveoli). Airflow into ALVEOLI is dependant on pressure gradient created
by Alveolar pressure VS Atmospheric pressure (=0) But Airflow (INTO alveolar respiratory zone) is controlled
by the ability to create a NEGATIVE alveolar pressure (like a vacume pulling air into alveoli). In RESTRICTIVE
lung diseases (FIBROSIS) the problem is that the alveoli can not create this negative pressure (stretch) to get air into
lungs. Airflow (OUT of alveolar respiratory zone) is controlled by the ability to create a POSITIVE alveolar
pressure to push the air out during expiration). This is the problem in OBSTRUCTIVE lung diseases -
EMPHYSEMA (loss of elastic recoil) - alveoli can not create the POSITIVE pressure required to recoil (collapse) the
expanded alveoli during expiration
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1. progressive weakening diaphragmatic contraction>>>>>MS, or abnormally rapid diaphragmatic muscle fatigue( eg
restrictive lung or chest wall disease and inspiratory airflow obstruction) 2. uniformly decrease diaphragmatic
contraction>>>peripheral neuropathy3. damage to respiratory center in brain stem>>>>decrease frequency and/
or amplitude of involuntary respirations(ondines curse). voluntary breathing would be unaffected
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for any given volume the pressure will be significantly increased.
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at FRC their is negative intrapleural pressure approximately -5cm H2O. during inspiration intrapleural pressure
decreases to an average of -7.5 cm H20, which then induces a slightly negative alveolar pressure that draws air
into the lungs .................. when intrapleural pressure become positive lung colapses.stab wound ............... airflow is
maximal at midpoint of insipration and expiration, cause of pressure gradient between stmosphere and
alveoli. minumum airflow is at maximal inspiration and expiration
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the conversion of 1,3 to 2,3 is increased in hypoxia and chronic anemia 2;3 BPG present only in beta chains and it
dissciates O2 from Hb binding site and fetal has no beta chains so no 2;3 BPG so O2 attached strongly to fetal Hb
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asthma does not decrease pulmonary compliance. idiopathic pulmonary arterial hypertension does not effect
pulmonary compliance significantly.
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out ward recoil of chest wall limit the volume of air that can be expired during maz=ximal expiration. ............
due to elasticity of the lungs, the alveolar transmural pressure is always positive. the chest wall have a negative
transmural pressure except during maximal inspiration.
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nbme,1,3,23
1-Work of breathing---refers mainly to the work that is done during INSPIRATION ...recall
expiration is a PASSIVE PROCESS...
2-And there are three TYPES OF WORK to accompolish this WORK....
a-LUNG COMPLIANCE WORK =work that required to expand the lungs against its elastic forces
b-TISSUE RESISTANCE WORK= that required to overcome the viscosity of the lung and chest
wall structures
c-AIRWAY RESISTANCE WORK=that required to overcome airway resistance during the

movement of air into the lungs
d-total work is the sum of the above THREE.....TOTAL WORK OF BRATHING=LUNG

COMPLIANCE WORK + TISSUE RESISTANCE WORK + AIRWAY RESISTANCE WORK
e-hence any person who wants to minimize the WORK OF BRATHING should DECREASE one or
more of the works...
f-Restrictive disease patients have A DECREASED COMPLIANCE. Hence these patients has to
increase THE LUNG COMPLIANCE WORK in order to breath ( Inspire mainly as it is an active
process)...this in turn increases the TOTAL WORK....Then to decrease the INCREASE in WORK
OF BREATHING the patient decreases the TIDAL VOLUME as smaller TIDAL VOLUMES (from
the original 500 ml) require smaller distention of the lungs (hence decreasing LUNG
COMPLIANCE WORK and inturn the TOTAL WORK)....
g-But to maintain adequate ALVEOLAR VENTILATION the patient breaths FAST......

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nbme>>>3,4,17
At altitude and exercise 2;3 BPG will increase causing dissociation of O2 from Hb and rt shift of
curve.
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gray or blue colored skin,
also have shortness of breath
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mixed venous blood oxygen content is increased in condotions where abnormal hemoglobin binds with greater
affinity to oxygen preventing unloading of oxygen in the tissues or in condotions where oxidative metabolism is
inhibted such as in cyanide toxicity. .............. in cyanide poisoning>>>>laboratory shows lactic acidosis in
conjuction with a lessened defference in the arterial and venous O2 content ............. cyanide toxicity along with other
manifestation present with lactic acidosis and bright red venous blood (seen on arterial blood gas and fundoscopy)
........ cyanide poisoning presents with confusion, flushing or a "cherry-red" skin color, abdominal pain, and vomiitng.
......... the SaO2 of venous blood increases in cyanide intoxication due to failure of oxygen unloading in the tissues
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just like anemia,
in severity it is more than anemia cause of left ward shift.
..........................
decrease in oxygen content.
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heme is an iron containing protoporphyrin IX, where ferrous iron is held in the center of heme molecule by four
nitrogens in the porphyrin ring. CO binds to iron in metalloproteins, but it does not alter porphyrin oxidation in
cytochrome oxidase or covalent linkage in cytochrome C.
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hypothermia stabilizes the bond between oxygen and hemoglobin, and shift to
the left ...................... hemoglobin mutation which increases oxygen affinity are hemoglobin chesapeake and
kempsey
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P50 shifts from 26mmhg to 20mmhg show increase oxygen affinity and left ward shift in the graph. .......... normally
P50 for oxygen is 26mmhg
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myoglobin has P50 of 1mmHg>>>>it has very high affinity for O2. hemoglobin has P50>>26 mmHG................ if
hemoglobin dissociates than individual subunits will show hyperbolic curve just like myoglobin.
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anemia>>>lactic acidosis>>lower pH>>right shift.
hypoventilation and strenous exercise>>>>increased CO2>>>right shift.
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PaO2 is typically normal.
PaO2=dissolved oxygen
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this is a competitive binding
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as cannot carry oxygen
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also dapsone
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increase in>>> high altitude, COPD, CHF..
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congenital form>>>autosomal recessive>>>defective cytochrome b5 reductase..
............... HbM disease is a congenital cause of methmoglobinemia due to a mutation in the heme-binding
pocket,
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maximal amount of O2 bound to Hb
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hypoxia that results from CO poisoning is similar to hypoxia that results from anemia both are due to decrease
oxygen carrying capacity. CO poisoning is worse cause it causes left ward shift. ................... the SaO2 of venous
blood increases in cyanide intoxication due to failure of oxygen unloading in the tissues
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DlCO>>>depends on thickness, surface area, hamotocrit and total volume of pulmonary capillary blood.
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the diffuison capacity of CO2 across the respiratory membrane is approximately 20 times greater
than that of O2.
thus alveolar CO2 concentration are not nearly affected to the extent that O2 concentration are in
diffusion-limited states.
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due to too much increase in pulmonary blood flow... physiologically in exercise O2 equilibration become
diffusion limited due to very high pulmonary blood flow.
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in normal physiologic resting state>>blood equilibrates with the alveolar gas by the time blood transverses 1/3 of
total pulmonary capillary length.
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ratio of oxygen bound to hb compared to total amount that can be bound to Hb
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O2 saturation on pulse oximetrydecreases in methmoglobinemia(85-90) but
normal in CO poisoning ( doesnot differentiate between oxy and carboxy Hb
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normal is 40 at sea level
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A ventilation defects anatomically matched by a perfusion defect (i.e, matched defect) usually
indicates lung collapse or consolidation. .................... myocardial infarction if causes pulmonary edema,
there would be a matched defect on V/Q scan. ....... A pleural effusion can cause atelectasis,
which would produce a matched defect on V/Q scan,
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PIO2= FiO2"(Pb-Ph2O)
PIO2=21"(760-47)
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<80 mmhg
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arterial PaCO2 is inversely related to and considrerd to be the main indicator of
total alveolar ventilation. alveolar hyperventilation can result from V/Q mismatch
that causes decreased O2 and CO2 exhange(eg pneumonia or pulmonary
embolism)>>>>>it causes hypocapnea but hypoxemia persists since the blood
flowing through the highly oxygenated lung cannot absob extra O2 to compensate
for the hypoxmic blood returning from poorly oxygenated regions. this causes an
increased alveolar-arterial oxygen gradient, which can be treated with oxygen
and by correcting the underlying disease process. without treatment, persistent
tachypnea will ead to eventual respiratory muscle fatigue, hypoventilation and
hypercapnia.
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blood oxygenation is impaired by V/Q mismatch but PaCO2 is more dependent on total lung ventilation. blood
does not become saturated with CO2>>>highly ventilated region can compensate for the less ventilated regions.
blood quickly become saturated with O2 >>>>highly ventilated regions cannot compensate for less ventilated
regions
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ratio of CO2 to O2 across alveolar membrane.used to estimate metabolic rate.
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PVR is the sum of alveolar and extra alveolar resistances as these vessels lie in series with each other.. PVR is
lowest at functional residual capacity. increased lung volumes increase PVR due to longitudinal stretching of
alveolar capillaries by expanding alveoli. decreased lung volume also increases PVR due to decreased radial
traction from adjacent tissues on the large extra-alveolar vessels
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normal is 100 at sea level in healthy individual
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rapid increase in altitude>>>high altitude pulmonary and cerebral edema>>>due to
increase in arterial and capillary pressure and increase vascular permeability
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equal to response during stress and after surgery
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at tissue level CO2 which is produced are converted by erythrocyte carbonic anhydrase into HCO3 and H+ ion. HCO3
is exchanged by Cl, but H+ remains in the erythrocyte and are buffered by histidine residues present on histidie side
chain on alpha and beta chains of hemoglobin and in the process help stabilize deoxygenated form of
Hb............... erythrocytes in venous blood has higher chloride content due to chloride exchange by bicarbonate, that
are produced at tissue level due to Hb oxygen dissociation.
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compensatory physiologic changes that contribute to long-term high altitude acclimatization include: ・
increased, 2-3 diphosphoglycerate (2-3, DPG) ・ increased hemoglobin production (hypoxia increases
erythropoietin production) ・ increased pulmonary diffusing capacity ・ vascular endothelial growth
factor-induced angiogenesis ・ increased in cellular mitochondria counts ・ hemoconcentration (due to
HCO3 diuresis and fluid shift).
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right shift curve
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without hypoxic vasoconstriction pulmonary shunt is 20%>>>PaO2=50%.with
hypoxic vasoconstriction pulmonary shunt is 5%>>>PaO2=85%
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anterior nosebleeds are by far the most common. occur on (anteriorinferior part of the nasal septal mucosa) whihc is
a watershed area of the nasal septum known as kiesselbach plexus. its an anastomoses of the following vessels 1
septal branch of the anterior ethmoidal artery. 2, lateral nasal branch of the sphenopalatine artery 3, septal
branch of the superior labial artery (branch of facial artery)
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managment.
anterior>>>compression, or cautery (silver nitrate) of the area surrounding the bleeding in case of
persistent bleeding.
posteriro>>>cannot be treated with cautery
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phlegmasia alba dolens (painful white leg "milk leg") is a consequence of iliofemoral venous thrombosis
occuring in peripartum women. pregnancy predisposes to deep venous thromboses due to the pressure of the
gravid uterus on deep pelvic veins (producing venous stasis) as well as increased hypercoagulability.
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in posterolateral wall and posterior choanae.
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3 concchas on lateral nasal wall are covered with mucoss,they warm, humidify and filter inspired air and expand and
contract in response to enviromenta changes (eg temperature, humidity and allergens). ............. superiro
meatus>>>drian sphenoidal and posterior ethmoidal sinuses. middle meatus>>>drian the frontal, maxillary and
anteriro ethmoidal sinuses and is the most common site of nasal polyps. inferior meatus>>>drain nasolacrmal
duct.
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fat globules have been stained with osmium tetroxide, which imparts a black color to fat. the fat
embolism syndrome is a condition affecting less than 10%of patients with severe skeletal injuries, and is
characterized by pulmonary insufficiency, diffuse neurological impairment, thrombocytopenia, and
anemia. Fat globules dilodges from bone marrow enter the marrow vascular sinusoids and then occlude
pulmonary microvessels, impairing gas exchange. Microvascular occlusion in the cerebral white
matter, brain stem, and spinal cord causes the neurologic manifestations. The pulmonary and CNS
microvascular and parenchymal dysfunction may be promoted by: 1-release of mediators from platelets
which adhere to and coat the fat emboli (a phenomenon also resulting in thrombocytopenia), and 2-
systemic activation of lipoprotein lipase and intravascular release of toxic levels of oleic acid. The
anemia is thought to be due to increase RBA aggregation and destruction as well as possible pulmonary
hemorrhage. ........ The presence of black stain in spherical or elliptical compartments, with diameters
smaller the alveolar sacs, indicating that the stained material is intravascular. Surfactant is produced by
Type II alveolar lining cells (pneumocytes) and would be found within alveolar sacs. ........ there may be
numerous platelets adherent to fat emboli. however the commonly used platelet stains (eg wright's stain), color
platelets purple, not black.
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recombinant TPA may be used to treat PE in patients who are hemodinamically unstable. however endothelial-
derived TPA is limited primarily to the bronchial circulaiton, and spontaneous recanalization of the pulmonary
artery is a slow process.
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Inferior vena cava filter is used to prevent pulmonary embolism in patients who have
contraindications of anticoagulation.
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sequele pf PE>>> 1, asymtomatic, (due to double blood supply) 2, infarction. 3,sudden death, 4, CHRONIC>
causes PH
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in pulmonary embolism >>>Chest radiographs are often normal. Although they can be negative
despite the presence of a PE, V/Q scan can be helpful in evaluating these patients when
computed tomography (CT) angiography is contraindicated (e.g, contrast allergy). The first
test is usually CT angiography. Pulmonary angiography remains the gold standard in establishing
the diagnosis of a PE but is often not performed because of cost and treatment delay.
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due to thrombocytopenia caused by platelets adhesion to to fat droplet
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distal PEs in small arteries (3mm) are more likely to cause infarction as the clot may also occlude areas distal to
the pulmonary and bronchial anatomoses.
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although the distribution of alveolar ventilation remains the same,the amount of blood passing
through the alveoli is reduced in the affected areas and increased in the remainder of the lung.the
resulting V/Q mismatch often leads to hypoxemia due to increased perfusion of poorly ventilated
lung regions
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VLC in decreased in emphysema
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nbme,,6,4,22
Chronic bronchitis
Airway clearance indications associated with chronic bronchitis include:
Mucus hypersecretion: In the normal lung, ciliated cells line the epithelium from the bronchioles to
the trachea. A thin mucus blanket covers the cilia, which beat in a coordinated fashion, propelling
mucus toward the pharynx. This mucociliary escalator serves as the primary defense mechanism
for the lung, trapping inhaled particles, transporting them out of the lung, and maintaining a sterile
environment. Mucus hypersecretion overwhelms the mucociliary apparatus and results in
secretion retention.
Impaired mucociliary apparatus: If the mucociliary escalator is impaired, inhaled particles and
bacteria are not adequately cleared from the lung. The resulting irritation can lead to additional
secretion production initiating a vicious cycle of mucus obstruction, recurrent pulmonary infection,
bacterial colonization, and progressive pulmonary compromise.
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An example of a protein folding defect is that caused by the Z mutation in the gene coding for
alpha-1 antitrypsin.
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alveoloar hypocapnia also causes bronchoconstriction
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smokers have both chronic bronchitis and centrilobular emphysema.>>>> hypoxia in bronchitis is due to decreasing
diameter of conducting airways, preventing adequate airflow, and emphysema causes hypoxia by dilating the
alveolar air spaces so that there is insufficent contact between the airspaces and deoxygenated blood in the
alveolar capillaries. smoking can also independently cause hypoxia by increasing the concentration of
carboxyhemoglobin in the blood.
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PCO2 is a most potent vasodilator>>>it decreases cerebral vascular resistance leading to increased cerebral
perfusion and increased intracranial pressure.. patients with COPD usually have low PO2 (hypoxia) and high PCO2.
supplemental O2 must be used judiciously in patients with COPD because hypoxia derive their respiratory
function (whereas in nomral individual , the PCO2 mediate the respiratory derive) in patients with longstanding
COPD, O2 supplementation can lead to respiratory suppression and coma.
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uworld say: bronchioles also
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decrease in DlCO even when there is little evidence of expiratory flow obstruction on spirometry
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and causing irreversible airspace dilation distal to terminal bronchioles
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decrease radial traction>>>expiratory obstruction
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decreased breath sound are also common due to overall decrease in airflow
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most cases of asthma occur due to combination of environmental and genetic factors. increased quantities of Th2
cells predispose the child to developing asthma under certain environmental conditions. genetic predisposition to
asthma is due to imbalance between Th1 and Th2 lymphocytes.
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intermittet respiratory symtoms in a patient with normal CXR, occasional sputum eosniphil and reduced FEV1
suggests a diagnoses of asthma ................ mast cells help to initiate the acute response to allergen and other
nonimmune stimuli, such as exercise cold exposure, chemical irritants, environmental pollutants,
and viral infections. ........... Even in asymptomatic asthmatics, airway inflammation occurs. Important
chemical mediators liberated from mast cells include histamine, leukotrienes, prostaglandins, platelet
activating factor, interleukin-4, interleukin-5, tumor necrosis factor alpha, and transforming growth factor
beta.
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allergic asthma accounts for 1/3 of cases, that inlcude animal dander, deathers, dust mites, mold and pollens.
cold air induce athma attack is patients with exercise-induced asthma. cold air and exercise incie asthama by a non-
immune mechanism. aspirin and other NSAIDs inhibit cyclogeanse 1, can precopitate asthma attck by
overproduciton of leukotriene. food is rarely an inciting factor for asthma, most commonly is the result of added
preservatives such as sulfites
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methacoline challenge test: test in positive when there is greater than 20% decrease in FEV-1.... there are very few if
any test that can confirm the a diagnoses( rule in) but methacholine is s highly sensitive but non-specific
measures that can help to exclude the diagnosis. ................. BHR can be quantified as the concentration of an
inhaled aerosolized bronchoconstrictive substance required to produce a 20% decline in FEV1.
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submucosal mucus secrertng gland
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intrinsic asthma (non-immine) precipitated by pulmonary infection (especially viral) , aspirin ingestion, cold air,
inhaled irritant, stress, and/or exercise. .................... in asthma exacerbation deu to viral infection,
adenovirus is most common 665
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asthmatics can predispiose to pneumococcal infections>>>but generally results in resolution with preservation of
lung lobular architecture. potential complicaiton of bronchopneumonia or lobas pneumonia include lung abscesses
empyema or lung fibrosis. asthamatic also predispose to aspergillus>>>potential complication is proximal
bronchiectasis. chronic asthamtics can have adonovirus colonization of lung.
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nbme>>2,1,41>>>the major mediator of asthma are leukotrienes not eosinophliic chemotactic factor. and MBP is
mot likely to be responsible for damage to the epithelium. leukotriene D4) is to trigger contractions in the smooth
muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis.
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unlke emphysema asthma has increased DLCO due to increased pulmonay blood volumes. other
measure>>>>FEV1/FEV and total lung volume are same in both.?????????????
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decrease lung elasticity promotes dynamic compression of the airways during expiraiton, contributing to expiratory
airflow obstruciton
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compensatory breathing at higher lung volume that keeps the lung airway open
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proteinases>>>elastase, cathepsin, matrix metalloproteinase antiproteinases>>>alpha-antitypsin, alpha-2
microglobulin and TIMPs elastase is a neutral protease found in macrophage lysosomes and in azurophilic
granules of neutrophil. neutrophil elastase is inhibited by antitrpsin and macrophage eslastase is inhibited by
tissue inhibitor of metalloproteinase TIMP. destructive capacity increases when both proteases are present ........
smoking>>>oxidative damage>>activation of resident alveolar macrophages by component of
smoke>>>inflammation and recruitment of neutrophil>>activated macrophages produces proteases, cathepsin, and
metalooproteinases>>>oxygen free radical impair function of protease inhibitor (alpha 1 antitrypsin) .................
oxidant products of smoke (including free radicals) can inactivate endogenous a1-AT, producing a
“functional” a1-AT deficiency as well. Smoking also enhances elastase activity in macrophages and
macrophage elastase (unlikely neutrophil elastase) is not inhibited by a1-antitrypsin.
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normal is 40% sensitive indicator of both duration and severity.
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acute bronchitis is almost always are viral caused by Influenza type A and B,corona,,RSV,human
metapneumovirus.
bacterial causes are rare and are mycoplasma and bordetella
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FVC decreases less than FEV1 and can sometime be normal.>>>so ratio always decreases.
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COPD patients have compensatory lung hyperinflation, which helps to widen the airways and improve airflow.
however hyperinflation also reduces the inspiratory reserve volume, limiting the maximal tidal volume.this is
especially true during exercise, when expiration time is limited. since patients with COPD require extra time for
exhalation, increasing amounts of air can become trapped in the lungs duiring rapid breathing, leading to further
reduction in tidal volume.this is known as dynamic hyperinflation and is beleived to be a major cause of
dyspnea and excersie limitations in COPD.
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chronic asthmatics with extrinsci allergic asthma can develop bronchial wall pathology (remodeling) which includes
thickening of the bronchial epithelium basement membrane and bronchial walls as well as edema,
inflammatory infiltrates, submucosal mucous gland enlargement, and bronchial smooth muscle
hypertrophy. However the infiltrate will consist predominantly of eosinophils and mast cells. futhermore,
while asthma can cause chronic bronchitis 9eg chronic asthmatic bronchitis, chronic eosinophilic bronchitis),
cigarette smoking is a much more common cause of chronic bronchitis
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panacinar affects the the lower lung lobes most severely, and anterior margins of the lung. lower lung
fields may be affected most severely because they receive relatively greater perfusion, allowing a
greater rate of neutrophil infiltration ....... centriacinar predominantly have upper lung lobe distribution.
the predilection of this type of emphysema for upper lung segments may reflect the relatively low
perfusion and therefore low presence of serum a1- antitrypsin
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bronchiole(airway)>>>>mucoid exudate, goblet metaplasia, epithelial basement
and membrane thickening.
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1,V/Q unmatched in bronchitis and matched in emphysema, 2,obese,peripheral
edema due to cor-pulmonlae(RHf)>>bronchitis....cachectic due to anorexia and use
of acccesssory muscle for respiration>>emphysema 3, dyspnea mild inititally in
bronchitis,contrast to emphysema. 4, strong hypercarbic drive>>>struggle in
emphysema......in bronchitis>>lost hypercarbic drive>>>no struggle ..................
bronchitis>>>TLC normal, RV increased, partial bronchodilator response, DlCo normal emphysema>>>TLC
increased, RV too much increased, nonreversible broncho dilator response, DlCo decreased ..................
expiratory obstruction>>>>in bronchitis it is due to inflammation and fibrotic narrowing, in emphysema it is due
loss of elastic recoil (radial traction)............ Thickened bronchial walls, neutrophil infiltration, mucous gland
enlargement, and patchy squamous metaplasia of the bronchial mucosa are features of chronic
bronchitis.
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AVN protein in dried aerosolized bird droppings, different from psittacosis(true
pneumonia)
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1919
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in differential diagnoses of combined restrictive and obstructive pattern are bronchiectasis and cystic fibrosis>>>
FEV1/FEV decrease, total lung capacity decrease, and diffusing capacity decrease
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UWORLD>>
work of breathing is minimized in patietns with increased elastic resistance (eg pulmonary fibrosis)
when thier repsiraotry rate is high and tidal volume is low,(fast, shallow breaths) , in contrast
patitnes with diseases that increase airflow resostance (eg asthma and COPD) breath at a lower
rate and higher tidal volume (slow, deep breaths) in order to minimize the work of breathing.
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both decreases but FEV1 decreases less (due to airway traction ) relative to lung volume (FVC).................
................... FEV1 increase is the combined result of reduced FVC, decreased lung compliance and increased elastic
recoil.
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X-ray show diffusenodular intersticial densities
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nbme>>2,3,15>>>alveolitis with intersticial edema, inflammatory cell accumulation, and the type II epithelial cell
hypertrophy and hyperplasia>>>>this is pathogenesis of pulmonary fibrosis ** Pathogenesis Repeated cycles of
alveolitis triggered by an unknown agent Release of cytokines produces interstitial fibrosis Alveolar fibrosis leads to
proximal dilation of the small airways. Lung has a honeycomb appearance
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Insidious-onset exertional dyspnea and dry cough, together with a restrictive profile on
pulmonary function setting and interstitial fibrosis and subpleural cystic airspaceenlargement
are characteristic of progressive usual interstitial pneumonia (UIP). pulmonary interstitial
fibrosis causes alveolar wall collapse and formation of cystic spaces lined by hyperplastic type
II pneumocytes or bronchiolar epithelium (honeycomb fibrosis). most common causes are 1,
environmental exposure 25% 2, sarcoidosis 20% 3, collagen vascular disease (10%) 4, idiopathic 15%
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most intersticial lung diseases causes progressive pulmonary fibrosis>>>increases lung elastic recoil>>>outward
traction of vessel wall by the surrounding fibrotic tissue increases.
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in pulmonary fibrosis diffuse and bilateral pattern of small irregular(reticulonodular) opacities that are more
pronounced in lower lobes.>>>>manifest as gradual onset of dyspnea first with exertion then at rest. physical
examination may show end-inspiratory crackles at the lung base. have restirictive pattern. in advanced disease
cystically-dilated bronchioles coalesce to form the honeycomb. rheumatoid arthritis can cause this.
methotrexate therpy in RA can also cause this ............... lung biospy shows patchy interstitial lymphocytic
inflammation and fibrosis of the alveolar walls............... surgical biopsy showing extensive interstitial
fibrosis together with paraseptal and subpleural cystic airspace enlargement (honeycomb
lung) are ccharacteristic of idiopathic pulmonary fibrosis
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nbme>>>>1,3,23>>>work of breathing in pulmonary fibrosis is minimized by increasing respiratory
rate and decreasing tidal volume............
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chest CT is the test of choice
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actinomyces and aspergillus
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problem is in alveoli as opposed to asthma(airway)
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Ferruginous bodies are generally elongated, not rounded as in the slide above, and stain brown on
hematoxylin and eosin stain or dark blue with the Prussia blue stain. These accumulations would be
found within macrophages within alveolar sacs, not in the pulmonary microvasculature.
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posterolateral mid lung zone
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berylliosis and hypersensitivity pneumonitis may produce non-caseating granuloma
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multiple discrete nodules (1-4 mm)
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also have birefringent silica particles surrounded by fibrous tissue
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small pleural effusion which are exudative and possibly blood stained may occasionally be noted.
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nodular or smooth pleural thickening is the main finding on radiographic studies and macroscopic examinaiton. the
lung parenchyma is typically intact. histopathology will show tumor cells with numerous, long slender microvilli
and abundant tonofilaments.immunohistochemical markers ( eg pancytokeratin) are useful in diagnoses
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nodular densities
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histological examination of perilymphatic fluid and nodal tissue show characteristic accumulation of coal dust laden
macrophages called "coal macules"
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closely resemble sarcoidosis
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Berylliosis, or chronic beryllium disease (CBD), is a chronic allergic-type lung response and chronic lung disease
caused by exposure to beryllium and its compounds. With single or prolonged exposure by inhalation, the lungs
become hypersensitive to beryllium causing the development of small inflammatory nodules, called granulomas.
Granulomas are seen in other chronic diseases, such as tuberculosis, sarcoidosis, and it can occasionally be
hard to distinguish berylliosis from these disorders
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Byssinosis, also called "brown lung disease" or "Monday fever", is an occupational lung disease caused by
exposure to cotton dust in inadequately ventilated working environments.
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nbme,7,4,10 Survivors of ARDS frequently have significant functional impairment even 1 year after discharge .
-At 6 months Spirometry and Lung Volumes and Capacities became normal-Hence Choice A is out -Diffusing
Capacity of CO remained mildly diminished at 1 year=as in this case -Radiographic abnormalities alco
completely resolve within a year... -Choices B and E-About surfactant Protein D... --Surfactant Protein D is one of
the largest molecules found in the innate immune system.It is not the SURFACTANT that is responsible to decrease
SURFACE TENSION ...Completely Different (I thought first IT IS A SURFACTANT)...... --But ARDS and Surfactant
Protein D have some relationship ...Surfatant Proten D is a SERUM marker for the severity and occurence of
ARDS ...in the acute stage ...after ARDS resolved it turns to the NORMAL level... here is alink for further READING....
http://www.biomedcentral.com/1471-2466/10/6 hence decrease in diffusion capacity is the legitimate ANSWER
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Neuromuscular weakness as a pathogenic mechanism in OSA is supported by the fact that
apneas occur only during sleep, a time of muscle relaxation
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and shock>>2 major risk factor. 75% of cases arise within 24 hours. 95% of cases arise within 72 hours. injury
results from endotoxin induced release of injurious products from adherent leukocytes and/or ischemia induced
release of cytokines
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one of minor diagnostic criteria for ARDS is absence of carduigenic pulmonary edema, which
mans PCWP is normal.
ARDS is charazterized by diffuse injury to pulmonary mis=crovascular endothelium and/or alveolar
epithelium, resulting in increased pulmonary capillary permeability ad a leaky alveolocapillary
membrane.
the intersiticial and intraalveolar edema, inflammation and hyaline membrane formation cause lung
comlaince to decrease, the work of breathing to increase, and oxygen diffusion capacity of the
lung to decrease. more sever involvememnt and/or atelactasis of regional alveoli can cause V/Q
mismatch (decreased ventilaiton with maintained perfusion)
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transudate of cardiogenic pulmonary edema tends to resolve.
exudate of progressive respiratory insufficiency (ARDS) suggests a less reversible exudative
process.
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each nocturnal episode of of reduced ventilation causes transient hypercapnia and hypoxemia. these blood gas
dearrangement result in reflexive sysyemic and pulnonary vascoconstriction, endothelial dysfunction and
abnormal venous return and cardiac output and sympathrtic cardiac stimulation. prolonged untreated OSA can
cause pulmonary hypertension and right HF. most pateint also develop systemic hypertension due to chronic
sympathetic stimulation and elevated plasma norepinephrin levels. patinets also loss normal diurnal variation in
blood pressure.
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associated with significant underlysing chronic illness (eg congestive heart failure, cerebrovascular disease, renal
insufficiency) and is not more common in obesity.
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restless leg syndrome>>>
characterized by vague discomfort in the limbs that is brought on when trying to sleep and relieved
with movement.
symptoms may recur through the night and lead to nonrestorative sleep, but patients are usually
aware of the symptoms.
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X-rays finiding of all lung disease: 1, HF>>>kerly b lines, loss of costophrenic angle,
cephalization of pulomnary vessels,perihilar pulmonary edea(batwing distrbution) 2,
ARDS>>>all these 3 feature are absent, has bilateral airspace opacitites, intact
costophrenic angle, 3, intersticail lung disease>>>lung with decreasd volume,
diffuse retucular opacities, 4, pulomany HT>>>> enlargement of pulomanry arteries,
and right ventricle, 5, COPD>>>>hyperinflated lung and flattend diaphragm, 6,
pneumothorax>>>whte visceral pleural line, no visivble pulomanary vessel beyond
visceral line, mediastinum shifted asthma>>normal chest X-ray 8610
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pickwickian syndrome>>>caused by restricted expansion of the chest wall due to severe obesity, this leads to
hypoventilation with a chronically elevated PCO2 and reduced PO2.
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typical symtoms are excessive daytime sleepliness, morning headace, cognitive impairememtn
and deorssion.
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apnea is due to relaxation of pharyngeal muscle tone during sleep.
additional contributing factors include obesity, tonsillar hypertrophy adn hypothyroidism.
when the airway is occluded, PO2 declines and PCO2 rises untill chemoreceptors in the carotid
body and brianstem trigger arousal and pharyngeal tone resturns.
sleep is repeatedly disturbed throughout the night, even in the absence of cortical awareness.
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ARSD is characterized by progressive hypoxemia refractory to oxygen therapy, decdreasing lung
comliance, interstitial edema progressing to diffuse alveolar infiltrates, and absence of cardiogenic
pulomany edema in most cases.
ARDS is due to diffuse injury to the pulonary microvascular endothelium and/or the alveolar
epithelium results in a leaky alveolocapillary membrane. in the acute stage, the lungs are very
heavy, red and boggy.
the interstitial and intra-alveolar edema, inflammation and fibrin deposition cause the alveoli to
become lined with waxy hyaline mebranes.
these membranes consist of fibrin exudate and plasma protein-rich edema fluid mixed with the
cytoplasmic and lipid remnanats of necrotic epithelial cells.
morphologically similar to hyaline membrane disease of newborn
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nbme>>>2,2,47>>women with acute diverticultits>>>develops cyanosis and hypoxemia
unresponsive to oxygen therapy>>X RAY film shows diffuse alveolar infiltrate. blood culture grows
E.coli>>a major for pathogenesis of this syndorme>>>>release of oxygen free radiclas from
sequestered neutrophil.
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Stimulation of the hypoglossal nerve using an implantable nerve stimulation causes the tongue
to move forward slightly, increasing the anteroposterior diameter of the airway.
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nbme>>3,3,31
sleep apnea.......stop breathing for at least 10 secounds repeatedly during sleep
two types:
1.central....no respiratory effort
2.obsstructive......respiratory effort against airway obstruction
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nbme>>>6,2,50
patient with PAH undergoes right lung transplant.one month later her FEV1 is normal.and exercise
stress test show no abnormalities.most likely to increased due to lung transplant compared to left
lung.>>>>increase blood flow, not lung compliance.
explanation.
The ratio of blood flow in the transplanted and the native lungs in all patients studied was 2.8 +/-
0.83:
These differences in the volume and pattern of flow in the transplanted lung are most likely related
to the relative resistance in the native and the transplanted lung and could constitute an additional
index for monitoring the condition of patients with lung transplantation and help in the
understanding of the physiology of the denervated pulmonary vascular bed
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results from disease of pulmonary vasculature or pulmonary parenchyma
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in severe hypertension besides medial hypertropy and intimal fibrosis, lesions can progress to form intercalating
tufts of small vascular channels called plexiform lesions. these changes can occur in both PH due to underlying
lung, vascular or cardiac disease and in idiopathic or familial pulmonary arterial hypertension.
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concentric laminar
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pro-apoptotic gene>>>>the resulting increase in endothelial and smooth muscle cell proliferation. ................ PAH
defined as mean pulmonary arterial pressure of >_25mm Hg at rest (normal: <_ 20 mmHg). Pulmonary
arterial hypertension follows a 2-hit hypothesis. An abnormal BMPR2 gene acts as the first and
predisposes to excessive endothelial and smooth muscle cell proliferation. A second insult
(e.g, infection, drugs, ion channel defects) is then thought to activate the disease process, which involves
increased endothelin (vascoconstrictor) and decreased nitric oxide (vasodilator) and prostacyclin
(vasodilator and platelet inhibitor) levels.A second insult is then thought to activate the disease
process, resulting in vascular remodeling, elevated pulmonary vascular resistance, and
progressive pulmonary hypertension
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left heart failure also cause pulmonary hypertension secondary to reactive vasoconstriction and structural
remodeling of pulmonary vasculature due to impaired NO availability and increased endothelin expression.
passive increase in arterial and capillary pressure (due to venous congestion) causes endothelial damage and
cappilary leakage into intterstitium>>>this lead to decreased NO (vasodilator) production and increased endothelin
production (vasoconstrictor) by the dysfucntional epithelium resulting in increased vasculor tone. over time this
lead to remodeling>>SM cell proliferation (medial hypertrophy) and collagen and elastase depostion (intimal
thickening and fibrosis)
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hypertension is the most common cause
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chest X-rays in pulmonary embolism is normal. characteristic findings such as westermark sign (area of lucency
due to reduced perfusion) or Hampton's hump (wedge-shaped opacity adjacent to the pleura) occur less
frequently
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vascular resistance due to atelectasis are rarely sufficient to cause pulmonary hypertension
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nbme>>>1,2,9>>>in lobar consolidation patient spoken 'ee' sounds more like 'ay'
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the most common cause of PH is segmental obliteration of pulmonary vasculature by COPD
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The mechanism underlying hypoxic pulmonary vasoconstriction is thought to involve a direct
hypoxemia-induced increase in pulmonary artery smooth muscle cytosolic Ca2+, combined
with an unidentified endothelium-derived Ca2+ sensitization factor.
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cause lung are collapsed so no airflow, no fremitus
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fluid in alveolar spaces in pulmonary edema manifests as bilateral fluffy-appearing infiltrates, not unilateral lung
opacification.
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complete collapse of lung usually occurs following obstruction of a mainstem bronchus (eg central lung tumors in
chronic smokers). as the air trapped in the lung gradually gets absorbed into the blood, there us loss of lung
volume due to alveolar collapse, and trachea deviate toward the affected side. it is a obstructive atelactasis
........................ diffuse intraalveolar hemorrhage would tend to dilute alveolar surfactant, increasing alveolar
surface tension and promoting alveolar atelactasis
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mostly from rheumatic heart disease
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remodeling is less severe in PH due to LHF than Idiopathic PH>>>>so it is partially reversible by correcting LH
failure.
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Anorexigens (e.g., aminorex, fenfluramine),
Page: 664
leading to SUDDEN cardiac death ...... cor pulmonale defined as RVH (with or without CHF) due to pulmonary
hypertension.
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of arterioles or small arteries
Page: 664
primary pulmonary hypertension result in elevation of pulmonary arterial
pressure due to proliferative vasculopahty of small pulmonary muscular arterioles.
pulmonary capillares and venous pressure (whihc primary responsible for
pulmonary edema and congestion) remains normal
Page: 664
pulmonary alveolar proteinosis (PAP) presents with very gradual worsening of dyspnea and
productive cough. On histologic examination, there is bilateral patchy pulmonary opacification
due to intraalveolar accumulation of amorphous protein and phospholipid material
(constituents of surfactant)
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A lesion that is the histopathologic hallmark of pulmonary arterial
hypertension, which consists of obliterative endothelial cell
proliferation and vascular smooth muscle cell hypertrophy in small
precapillary pulmonary arterioles.
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tall, thin males around the age of 20 are the most commonly affected. (It is thought that individuals of this
stature have more negative intrapleural pressures in the apical lung). there is also an associated with
smoking
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obliteative lower airway inflammation can occur as a feature of bronchiolitis obliterans organizing pneumonia. in
this condition inflammation causes granulation tissue proliferation that proceeds to obstruct small bronchioles
and airways and consolidate the alveoli. this is an idiopathic condition that typically resolves with corticosteroid
treatment. ............. inflammation causes granulation tissue proliferation that proceeds to obstruct small bronchies
and airwyas and consolidate the alveoli, resolve with corticosteroid ....... Loose aggregates of fibroblasts in
ground substance (Masson bodies); Variable dense chronic inflammation; NO fibrosis
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Pulmonary abscesses are local collections within lung parenchyma that result in necrosis of the
surrounding lung tissues. Historically, suppurative destruction of the lung parenchyma within the
abscess cavity is seen. This destruction occurs to a large extent secondary to the release of
lysosomal enzymes by neutrophils and macrophages. The lysosomal enzymes serve to digest
the offending pathogens and tissue debris, as well as to chemotactically summon additional
neutrophils or macrophages to the area. Occasionally, however, the enzymes will also damage
the surrounding parenchyma, setting the stage for abscess formation.
Page: 667
pancoast tumor are non-small cell lung cancers (eg squamous cell carcinoma and adenocarcinoma)
........................... SVC syndrome occur in centrally located and mediastinal spread of more distant tumor.
commonly associated with small cell lung carcinoma
Page: 667
compression of lower brachial plexus causes ipsilateralshoulder pain (in the distribution of C8, T1 and T2) atrophy
of hand muscle and absent reflex. shoulder pain toward axilla and scapula is most common presenting
symptom)
Page: 667
have similar symptoms to BRACHIOCEPHALIC VEIN OBSTRUCTION(unilateral) except in this symptoms are
bilateral
Page: 667
external jugular vein drain into subclavian vein.
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followed by non-hodgkin lymphoma
Page: 667
formed behind 1st cartilage on the right, extends inferiorly for 6-8 cm and drians directly in the right
atrium.
it is surroinded by the sternum, trachea, right bronchus, aorta and pulmonary artery.
the vein also lie in close proximity to the perihelillar and paratracheal lymph node. it has thin walls
and is easily compressed by meediastinal mass.
Page: 667
upper extremity edema may be due to compression of subclavian vessels. also have spinal cord compression and
paraplegia, due to tumor extension into the intervertebral foramina...
Page: 667
groove formed by the subclavian vessels
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lung abscess may be caused by the following mechanisms: 1, Oropharyngeal aspiration is the most common
cause of lung abscess. 2, Lung abscess may also occur as a complication of bacterial
pneumonia.necrotizing pneumonias are usually nosocomial and caused by Staphylococcus aureus,
Escherichia coli, Klebsiella pneumoniae and pseudomonas aeruginosa. In patients with septicemia
or infectious endocarditis, there may be hematogenous spread of infection to the lung. Lung abscesses
that develop in this manner are often multiple and monomicrobial. The most common causative agents
areStaphylococcus and Streptococcus species.
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echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-
ALK) fusion oncogene on chromosome 2.its inhibitor is crizotinib
Page: 668
This paraneoplastic syndrome is most commonly associated with small cell lung cancer as well as
breast, ovarian, and uterine malignancies. Patients exhibit progressively worsening dizziness, limb
and truncal ataxia, dysartria and visual disturbances (eg, diplopoa, oscillopsia). Paranoplastic
cerebellar degenrations is due to an immune response against tumor cells that cross-reacts with
Purkinje neuron antigens, leading to acute-onset rapid degeneration of the cerebellum. anti-yo, antip/q
and anti hu are the most common antibodies detected in the serum. Antibodies are not always
detecable; thus paraneoplastc cerebellar degeneration is diagnosed clinically after excluding other
conditions.
Page: 668
nbme 11,2,42 biposy specimen shows a proliferation of irregularly shapedglands containing cells with
hyperchromic and pleomorphicnuclei invading the pulmonary parenchyma and lymphovascular spaces.
Adenocarcinoma is a type of cancer that develops in cells lining glandular types of internal organs,The World
Health Organization (WHO) defines adenocarcinoma as "a malignant epithelial tumor with tubular, acinar, or
papillary growth patterns, and/or mucus production by the tumor cells."Currently the WHO recognizes four
categories of adenocarcinoma: acinar papillary bronchioloalveolar solid carcinoma with mucus formation The
majority of adenocarcinomas occur at the periphery of the lung, and, as a resultare often asymptomatic until late in
their course. They frequently lie just below the pleura, and cause pleural retraction and thickening on x-ray.
Often adenocarcinomas are discovered on routine chest x-rays or in a primary search for distant metastases.
Adenocarcinomas grossly present with the "three P's" - peripheral, pigmented and puckered. Commonly lesions
are found near the pleural surface (peripheral) which is retracted (puckered) over the neoplasm.The cut surface is
often white .
Page: 668
Microsopic examination reveals well-differentiated, dysplactis columnar cells with or without
intracellular mucin (compare to normal lung). The tumor has tendency to undergo aerogenous
spread (along the airways) and can progress to invasive disease if not resected. Mucinous
forms can result in the production of copious amounts of watery sputum (bronchorrhea). Imaging
shows a discrete mass or pneumonia- like consolidation.
Page: 668
Strongly associated with smoking>>occur in major bronchi>>>arises from primitive cells of the basal layer of
bronchial epithelium and display endocrine feature. comprises 10-20% of all malignant lung tumors. ......... SVC
syndrome is commonly associated with this
Page: 668
flat, oval shaped cells with scant cytoplasm and hyperchromic nuclei. these cells may resemble lymphocytes but
are typically larger. tumor cells can form sheets or clusters. abundant mitoses are usually seen ............... on
electron microscopy some of the cells are found to have secretotry granules in the cytoplasm,
Page: 668
and females
Page: 668
adenocarcinoma which can show glandular or papillary elements, have short and plump micrivilli that distinguish
adenocarcinoma from mesothelioma (which has long slender microvilli and abundant tonofilaments)
Page: 668
characteristic feature, distribution along alveolar septae without vascular or stromal invasion.
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larger bronchi>>>>arises from squamous bronchial metaplasia
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keratin pearls are seen in well-differentiated squamous cell carcinoma.
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display feature of adeno or squamous cell carcinoma on electron miscroscopy
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causes galactorrhea and gynecomastia
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tend to involve large bronchi and can appear histologically as sheets of uniform cells with a 'salt and pepper'
pattern (chromatin with fine and coarse clumps)
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that form solid sheets or nests
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present with symptoms of hypercalcemia>>>>confusion, abdominal pain, bony
pain)
Page: 668
composed of polygonal cells with eosinophilic cytoplasm and distinct borders.
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almost always at periphery..
composed of tall, columnar cells that spread along the alveolar seplate and may form papillary
projections into the alveolar spaces.
the underlying lung architecture is preserved.
on chest X-ray appears as peripheral mass and or as a pneumonia like consolidation
Page: 668
tumor cells also form tubules or papillae. and some tumor may produce mucin
Page: 668
neuroendocrine markers , such as neural cell adhesion molecule(NCAM also known as CD56),neuron specific
enolase and synaptophisin (other neuroendocrine marker) is also positive
Page: 668
has euvolumic hyponatermia, dont have features of volume overload (eg peripheral edema, pulmonary crackles
and increase jugular pressure)
Page: 668
most common benign tumor is hamartoma of the lung>>>incedental finding in patients with 50-60 years of age as
peripherally located coin lesion. composed of mature hyaline cartilage, fat, smooth muscle and clefts lined by
respiratory epithelium
Page: 668
mutations of the genes that codes for the epidermal growth factor receptors are associated with non-
small cell lung carcinoma (erbB1), breast cancer (erbB2 aka HER2/neu), and some ovarian and gastric
tumor.
Page: 668
approximately four percent of patients with non-small cell lung carcinoma (NSCLC) have an inversion of
the short arm of chromosome 2 that creates a fusion gene between EMLA4 (echinoderm microtubule-
associated protein like 4) and ALK (anaplastic lymphoma kinase). This results in a constitutively
active tyrosine kinase that causes malignancy. Interestingly, patients who harbor this gene fusion are
usually young non-smokers, often with adenocarcinoma, who lack mutation in either the epidermal
growth factor receptor gene or the K-ras gene. The kinase activity of this fusion protein is a target of the
protein kinase inhibitor, crizotinib.
Page: 668
of clara and type 2 pneumocytes cells
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decrease the activity of this receptor by increasing the proportion of inactive H1 receptors, a process known as
reverse blockage
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promethazine and hydroxyzine
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postural dizziness
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central and peripheral acting cause are lipophilic.
Page: 669
beside phenylephrine, xylometazoline and oxymetazoline are used for the treatment of allergic rhinitis and
common cold associated congestion and rhinitis. these med show tachyphylaxis due to decreased production of
endogenous NE from the nerve terminal due to negative feedback mechanism, resulting in relative vasodilaiton. (
ie removal of normal vasoconstrictive tone) and subsequent edema and congestion...... rebound rhenorrhea (ie
rhinits medicamentosa) is describes as nasal congestion without cough, sneezing or postnasal drip. rhinorrhea
may or may not be present (note the paradox in naming). rebound rhinorrhea is associated with the use of topical
decongestant for >/3 days. if person excessively used decongestant and discontinues it and experiences
excessive withdrawal symptoms, a short term course of topical corticosteroid can be used for symptom control
but oral cortico is not used.
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blocks the effect of endothelin ( a potent vasoconstrictor that also stimulates endothelial
proliferation)
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midodrine is alpha agonist
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dry mouth, blurry vision, urinary retention
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antiserotonergic( appetite stimulation) and causes weight gain
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reduce the time to sleep and to increase the depth of sleep.
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interect with phenytoin and cimetidine
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nbme>>>3,1,33
the incidence and severity of asthma episodes is most likely be decreased by selective inhibition
of >>>>>5-lipoxygenase and not by phospholypase A1
Page: 670
low dose inhaled steroid>>> oral candidiasis, dysphonia, unrelated to candidiasis,its due to myopathy of
laryngeal muscle high dose inhaled steroid>>systemic effect may be seen>>>increase intraocular pressure,
cataract, growth retardation in children, bone loss, and suppression of hypothalamic-pituitary-adrenal axis. but does
not cause fluid retention as seen with systemic use. ......... calcium and Vit D supplements are used along with
systemic not with inhaled steroids.
Page: 670
inhaled glucucorticoid have role in prevention of acute asthma exacerbation, inhaled glucuroticoid are the most
preferred drugs for the prophylactic treatment of bronchial asthma. they do not have role in treatment of acute
exacerbation, systemic steroid does
Page: 670
in airway smooth muscle and submucosla glands. ..... only reverse vagally mediated bronchoconstriction.
Page: 670
are less effective than beta-2 adrenergic agonists. their effect starts 60-90 minutes after initiating treatment..
ipratropium enhances the bronchodilatory effects of beta-2 agonists.. inhaled ipratropium is poorly absorbed from
the respiratory mucosa and therefore has virtually no systemic anticholinergic side effects.
Page: 670
many asthamatics frequently have allergies as a trigger due to a high IgE response in the body. omalizumab effective
in patient with moderate to severe asthma. is a recombinant humanized IgG1 monoclonal antibody that binds with
IgE. studies have shown patietns receing omalizumab have fewer exacerbations of asthma and are able to
discontinue the use of oral steroid and decrease the dose of inhaled steroid. ..... FDA approved omalizumab with
moderate to severe persistent asthma, sensitivty to a perennial allergen and incomplete response with steroid. ....
has been shown to be effective in reducing dependency on both oral and inhaled steroids.
Page: 670
hypotension, tachycarida and cardiac arrrythmia.
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beside phosphodiesterase inhibitor also block adenosine receptors, augmenting their bronchodilatory effect........
theophiline also have mild antiinflammatory effect.
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nbme>>>>1,3,33>>>half life of theophiline in children is less cause of faster hepatic metabolism.
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low to moderate doses>>>low cortical arousal, insomnia much like caffeine. acute toxicity>>nausea, vomiting
abdominal pain, seizures and cardiac arrhythmias. seizures most common cause of morbidity and mortality,
followed by tachyarrhythmia but does not cause QT-prolongation. beta-blocker are drug of choice for theophyline
induced tachyarrhythmias. seizures are difficult to treat but use benzo and barbiturates
Page: 670
nbme>>1,4,50>>>>for maintenance therapy in poatient with moderate to severe asthma also has positive cardiac
inotropic effects, produces vasodilation, has diuretic action and stimulates diaphragmatic contraction.
Page: 670
excessive cnetral nervous system stimulation>>>tremors, insomina and seizure.
Page: 670
has 3 effects: bronchodilator, antiinflammatory, bronchoprotective
Page: 670
leukotrienes are potent activator of inflammation and bronchoconstrcition.
also promote mucosal edema and mucus hypersecretion.
Page: 670
this new drug is promising for COPD
Page: 670
inhaled
Page: 670
they also induce apoptosis of inflammatory cells eg macrophages, lymphocytes and eosinophil. additionaly reduced
the amount of mucus production by goblet cells
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in chidren we use monte to inhibit leukotriens , not other ones
Page: 670
use alone in COPD
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Summary of comments on 3662

Variable expressivity occurs when a phenotype is expressed to a different degree among

conditions. In these instances, a large percentage of the disease-producing allele

in autosomal dominant disease q is not hidden in 2pq,the largest number of

pedigree given is of "Li Fraumeni syndrome" , an Autosomal Dominant pattern.

Multiple mutations "WITHIN a GENE" (Tp53) i.e G.heterogeneity----->giving rise to Multiple

G.heterogeneity: can be either

*Multiple mutations(within a single locus or multiple loci-------->"SAME" Phenotype

• All X chromosomes are inactivated except one. In cases where a

phosphorylated by glycerol kinase to glycerol phosphate which is

Compound 5 -----> regulate Enzyme B

It can cause cytolysis of certain tumor cell lines;

Other adverse effects include hyperkalemia, hypomagnesemia, nausea, vomiting, diarrhea,

answer...on the cell membrane of the megakaryocytes

Seizures have been reported in patients with kidney failure

Symptoms of disseminated tuberculosis include:

•General discomfort, uneasiness, or ill feeling (malaise)

• Leptospiremic phase—severe headache, fever, myalgia.

• Ocular manifestations occur in the majority of patients.

• Conjunctivitis, uveitis, subconjunctival hemorrhages.

Coxsackieviruses are also the leading causes of aseptic meningitis

mnay bacterial speciesdsynthsizing multiple different penicillin-binding protein.

Fibrinous exudate is composed mainly of fibrinogen and fibrin. It is characteristic of rheumatic

This is the case on the concept of "Spare Receptors"

and now consider, if Emax is achieved with result

*Efficacy of Drug X decreases

---------------------------------Graph on the Right--------------------------

*Efficacy(Emax) of Drug X decreases

· Amino acid conjugation

physician burnout refers to a state of emotional exhaustion , cynicism, depersonalization, and

Registration---- Repeat the names of these three objects.

these are are mini mental scale and scoring is done-

Proportionate mortality rate (PMR)>>>Deaths from cause/

Meaning of the p-value

-Practical Importance means CLINICAL SIGNIFICANCE not Statistical....and clinical significance

as u know NNT= 1/49%-45 %=1/4%=25.....Taking Program A as a control (as u know control

---NNT=25 is not clinical significant.....hence choice B......

about the other choices....

maleficence - doing or causing evil.

beneficence - the quality of being kind or helpful or generous.

A sentinel event is an unexpected occurrence involving death or serious physical or psychological

β-endorphin is believed to have a number of other benefits, including:

Boosting the immune system[citation needed]

diffusion capacity and lung volume decreases

condition-----------------------Ca---------PHO4---------alk pho4----------PTH level

net result decrese in motion ...

cervical regions (C5/C6 or C6/C7) of individuals younger

The strongest pathological association of déjà vu is with temporal lobe epilepsy

“Partial” >>>>superior tarsal

-- (1) respond knowingly and intelligently to questions about recommended treatment;

--(2) participate in treatment decisions by means of rational thought processes; and

---here is more explanation

1-comprehending and retaining information relating to the decision

2-believing the information provided by the treating physician

3-weighing it in the balance when making a choice....

Now why it is not Narcolepsy?

1- metanephric mass [mesoderm]- which gives rise to-

2-ureteric bud- which gives rise to collecting system

Testes.....superficial and deep plexus......>para-aortic

2-And there are three TYPES OF WORK to accompolish this WORK....

c-AIRWAY RESISTANCE WORK=that required to overcome airway resistance during the

d-total work is the sum of the above THREE.....TOTAL WORK OF BRATHING=LUNG

g-But to maintain adequate ALVEOLAR VENTILATION the patient breaths FAST......