REVALIDA MUST KNOW TOPICS

Integumentary Hematopoietic 8. Fecalysis normal values

1. Layers 1. CBC normal values 9. Bilirubin metabolism
2. Layers traversed by an 2. IVF 10. Muscles of mastication
injection 3. ECF vs ICF 11. GI metabolism
3. Layers of the scalp 4. Bacterial vs. viral infection 12. Alcoholic liver disease
4. Burns 5. RBC components
5. Layers of lumbar puncture 6. Blood component therapy- GUT
6. Layers- pericardiocentesis components and functions 1. Renal blood floz/ circulation
7. Layers- thoracentesis 7. Anemias 2. Urine formation
8. Peripheral blood smear 3. Urea cycle
Musculoskeletal 9. Reye’s syndrome 4. Kreb’s cycle
1. Physiology of muscle 5. Urinalysis normal values
contraction Cardiovascular 6. Renal syndromes
2. Carpal and tarsal bones 1. Heart blood supply 7. BUN
3. Trauma 2. Blood circulation – upper and 8. Renal functions – filtration,
4. Physiology of smile lower reabsorption, secretion
5. Muscles of mastication 3. Cardiac cycle
6. Rotator cuff muscles 4. ECG tracing Endocrine
7. Hamstring muscle 5. Murmurs- types and grading 1. Thyroid storm
8. Diagnostic criteria for 6. Fetal circulation 2. Thyroid hormone synthesis
rheumatoid arthritis 7. Shock – types and 3. Hypertensive vs. DM
parameters retinopathy
Nervous 8. Layers- pericardiocentesis 4. DM and GDM
1. CSF flow 9. DVT treatment 5. Insulin preparation
2. CNS infection – bacterial, 10. CHF criteria
viral, fungal, parasitic 11. Jones criteria Reproductive
3. Parts of brain and basic 12. Advantages of enoxaparin vs. 1. Menstrual cycle
function heparin 2. HPO axis
4. Spinal nerves 13. Warfarin/heparin overdose 3. Breast CA
5. Cranial nerves exits treatment 4. Lactation
6. Brachial plexus 5. Drugs safe in pregnancy
7. Sympathetic and Respiratory 6. Leopold’s maneuver
parasympathetic nervous 1. Physiology of breathing
system 2. Cough and sneeze reflex Pediatrics
8. Cavernous sinus thrombosis 3. Muscles of respiration 1. EPI vaccines
9. Lumbar puncture analysis 4. CART program for 2. Developmental milestones
10. Neurotransmitter pneumonia 3. SMR staging
11. Circle of Willis 5. Transudate vs. exudates
12. Pain pathway 6. PTB –clinical and radiologic Surgery
13. Benign febrile seizures classification, treatment 1. Trauma
14. Substance abuse disorder 7. Upper vs. lower respiratory 2. Burns
15. Schizophrenia tract infection 3. Inflammation and repair
16. OC disorder 8. Layers- thoracentesis 4. Surgical nutrition
9. Common mediastinal tumors 5. Wound classification
Special Senses 10. Endotracheal intubation
1. Principles of accommodation indications Pharmacology
2. Waldeyer’s ring 1. H1 and H2 histamines
3. Pathway of tearing GIT 2. Steroids
4. Visual pathway 1. Physiology of digestion – 3. Antibiotics
5. Auditory pathway CHO, CHON, fats
6. Sinuses 2. Vomiting reflex Infectious diseases
7. Papilledema vs. papillitis 3. Swallowing reflex 1. Malaria life cycle
8. Ocular hypertension 4. TCA (Kreb’s cycle) 2. Bacterial vs. viral infection
9. Layers of retina 5. Upper vs. lower bleeding
10. Layers of cornea 6. Diarrhea treatment Bioethics
7. Layers of abdominal wall 1. principles
 For any missing parts, pls see the reviewer from Blessings  Wla akong soft copy
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put this together. GOOD LUCK AND GOD BLESS SA REVALIDA!! – Batch 2014 
Respiratory
4. CART(?) program for pneumonia
Community-acquired pneumonia (CAP):
Lower respiratory infection involving the pulmonary
parenchyma, results from proliferation of microbial pathogens
at the alveolar level and subsequent immunologic response
mounted by the host
Most common: Streptococcus pneumoniae, Haemophilus
influenzae, and Moraxella catarrhalis
 Purulent sputum is characteristic
 Rales are heard over the involved lobe or segment
 Increased tactile fremitus, bronchial breathing, and E-to-A
change may be present if consolidation has occurred
 Decreased tactile fremitus and dullness on chest percussion
may result from pleural effusion (usually due to H
influenzae infection) or empyema
DX: Chest radiograph: predominantly focal segmental or lobar
distribution of infiltrates
Sputum gram stain, blood culture
DDX: Acute bronchitis, Acute exacerbation of chronic bronchitis,
Myocardial infarction, Congestive heart failure and pulmonary
edema, Pulmonary fibrosis
TX: Effective monotherapy antibiotics include doxycycline or
respiratory quinolones
Combination therapy usually consists of ceftriaxone plus
doxycycline, azithromycin, or a respiratory quinolone
CURB-65, also known as the CURB criteria, is a clinical prediction
rule that has been validated for predicting mortality
in community-acquired pneumonia. The risk of death at 30 days
increases as the score increases
0-1: Treat as an outpatient
2-3: Consider a short stay in hospital or watch very closely as an
outpatient
4-5: Requires hospitalization with consideration as to whether
they need to be in the intensive care unit
6. PTB -clinical and radiologic classification, treatment
-Caused by mycobacterium tuberculosis
-Most commonly transmitted from a person with infectious
pulmonary TB to others by droplet nuclei, which are aerosolized
by coughing, sneezing, or speaking
-The most infectious patients have cavitary pulmonary disease
and laryngeal TB
New- a patient who has never had treatment for TB or who has
taken ant-TB drugs for less than one month
Relapse- a patient previously treated for tuberculosis, who has
been declared ‘cured’ or ‘treatment completed,’ and is now
diagnosed with bacteriologically positive (smear or culture)
tuberculosis
Failure- a patient who, while on treatment, is sputum smear
positive at 5 months or later during the course of treatment
Return after Default- a patient who returns to treatment with
positive bacteriology (smear or culture), following interruption
of treatment for two months or more
Transfer-in-a patient who has been transferred from another
facility with proper referral slip to continue treatment
Clinical manifestations:
-Cough of 2 weeks or more
-Night sweats, weight loss, anorexia, unexplained fever and
chills, chest pain, fatigue, body malaise
DX: AFB Sputum microscopy, Sputum TB Culture, Chest
radiograph, TB-PCR
Radiologic: Chest and spine radiographs may show old or active
pulmonary tubercular (TB) lesions. However, in 50% of patients,
chest radiographic findings are negative.
Kidney, ureter, and bladder (KUB) radiographs reveal
calcifications in the kidney and ureter in approximately 50% of
patients. Calcifications are intraluminal, as opposed to
schistosomiasis cases, which produce intramural calcifications.
Calcifications in the bladder are uncommon.
Plain abdominal radiography is useful to search for evidence of
renal or ureteral tuberculosis (ie, renal or ureteral calcifications).
MX: Isoniazid (H) - 5mg/kg
Rifampicin (R) - 10mg/kg
Pyrazinamide (Z) - 25mg/kg
Ethambutol (E) - 15mg/kg
Streptomycin (S) - 15mg/kg
Treatment regimen:
WHO category I: New smear-positive PTB, or smear-negative
PTB with extended parenchymal involvement. New cases of
severe extrapulmonary TB.
Intensive phase: 2HRZE
Maintenance phase: 4HR
WHO category II: Sputum smear-positive, relapse; treatment
failure, treatment after interruption
Intensive phase: 2HRZES +1 HRZE
Maintenance phase: 5HRE
WHO category III: New smear-negative PTB (other than in cat I).
New less severe forms of extra-pulmonary TB.
Intensive phase: 2HRZE recurrent disease. It consists of transient inflammation of the
Maintenance phase: 4HR major bronchi and trachea. Most often it is caused by viral
infection and hence antibiotic therapy is not indicated in
7. Upper vs. lower respiratory tract infection immunocompetent individuals. There are no effective therapies
for viral bronchitis. Acute Exacerbations of Chronic Bronchitis
(AECB) are frequently due to non-infective causes along with
viral ones. 50% of patients are colonised with Haemophilus
influenzae, Streptococcus pneumoniae or Moraxella
catarrhalis. Antibiotics have only been shown to be effective if
all three of the following symptoms are present:-
increased dyspnea, increased sputum volume and purulence. In
these cases 500 mg of Amoxicillin orally, every 8 hours for 5
days or 100 mg doxycycline orally for 5 days should be used

Pneumonia occurs in a variety of situations and treatment must

vary according to the situation. It is classified as either
community or hospital acquired depending on where the
patient contracted the infection. The most common treatment
is antibiotics and these vary in their adverse effects and their
effectiveness. The most common cause of pneumonia is
pneumococcal bacteria, Streptococcus pneumoniae accounts for
2/3 of bacteremic pneumonias. For optimal management of a
pneumonia patient the following must be assessed;- pneumonia
severity (including where to treat e.g. Home, hospital or
intensive care), identification of causative organism, analgesia of
Upper respiratory tract infections (URI or URTI) are the illnesses chest pain, the need for supplemental oxygen, physiotherapy,
caused by an acute infection which involves the Hydration, bronchodilators and possible complications of
upper respiratory tract: nose, sinuses,pharynx or larynx. This emphysema or lung abscess.
commonly includes:
tonsillitis, pharyngitis, laryngitis,sinusitis, otitis media, and 9. Common mediastinal tumors
the common cold.

Common URI terms are defined as follows:

 Rhinitis - Inflammation of the nasal mucosa
 Rhinosinusitis or sinusitis - Inflammation of the nares and
paranasal sinuses, including frontal, ethmoid, maxillary, and
sphenoid
 Nasopharyngitis (rhinopharyngitis or the common cold) -
Inflammation of the nares, pharynx, hypopharynx, uvula,
and tonsils
 Pharyngitis - Inflammation of the pharynx, hypopharynx,
uvula, and tonsils
 Epiglottitis (supraglottitis) - Inflammation of the superior
portion of the larynx and supraglottic area
 Laryngitis - Inflammation of the larynx
 Laryngotracheitis - Inflammation of the larynx, trachea, and
subglottic area
 Tracheitis - Inflammation of the trachea and subglottic area

Lower respiratory tract infection, while often used as a

synonym for pneumonia, can also be applied to other types of
infection including lung abscess and acute bronchitis. Symptoms
include shortness of breath, weakness, high fever, coughing and
fatigue.

Bronchitis can be classified as either acute or chronic. Acute The mediastinum is the cavity that separates the lungs from the
bronchitis can be defined as acute bacterial or viral infection of rest of the chest. It contains
the larger airways in healthy patients with no history of the heart, esophagus, trachea, thymus, and aorta. The
mediastinum has three main parts: the anterior
mediastinum (front), the middle mediastinum, and the posterior
mediastinum (back)
The most common mediastinal masses are neurogenic tumors
(20% of mediastinal tumors), usually found in the posterior
mediastinum, followed bythymoma (15-20%) located in the
anterior mediastinum
Masses in the anterior portion of the mediastinum can include
thymoma, lymphoma,
pheochromocytoma, germcelltumors including
teratoma, thyroid tissue, and parathyroid lesions. Masses in this
area are more likely to be malignant than those in other
compartments
Masses in the posterior portion of the mediastinum tend to be
neurogenic in origin, and in adults tend to be of neural sheath
origin including neurilemomas and neurofibromas.
Lung cancer typically spreads to the lymph nodes in the
mediastinum
Thymoma is a tumor originating from the epithelial cells of
the thymus. Thymoma is an uncommon tumor, best known for
its association with the neuromuscular disorder myasthenia
gravis. Once diagnosed, thymomas may be removed surgically.
In the rare case of a malignant tumor, chemotherapy may be
used.
Lymphoma is a type of blood cancer that occurs
when B or T lymphocytes, the white blood cells that form a part
of the immune system and help protect the body
from infection and disease, divide faster than normal cells or live
longer than they are supposed to. Lymphoma may develop in
the lymph nodes, spleen,bone marrow, blood or other
organs[2] and eventually they form a tumor.
GIT
6. Diarrhea treatment
Definition
 Diarrhea
o Passage of 3 or more liquid stools in a 24 hour period.
o Acute = few hours or days, Persistent = lasting > 2 weeks
o Dysentery – bloody diarrhea
 Dehydration
o Loss of fluid without loss of supporting tissues
o Contraction of extracellular volume in relation to cell
mass.
Secretory
Secretory diarrhea means that there is an increase in the active
secretion, or there is an inhibition of absorption. There is little
to no structural damage. The most common cause of this type
of diarrhea is a cholera toxin that stimulates the secretion
of anions, especially chloride ions.
Osmotic
Osmotic diarrhea occurs when too much water is drawn into the
bowels. If a person drinks solutions with excessive sugar or
excessive salt, these can draw water from the body into the
bowel and cause osmotic diarrhea. Osmotic diarrhea can also be
the result of maldigestion (e.g., pancreatic disease or Coeliac
disease), in which the nutrients are left in the lumen to pull in
water. Or it can be caused by osmotic laxatives (which work to
alleviate constipation by drawing water into the bowels). In
healthy individuals, too much magnesium or vitamin C or
undigested lactose can produce osmotic diarrhea and distention
of the bowel. A person who has lactose intolerance can have
difficulty absorbing lactose after an extraordinarily high intake
of dairy products.
Exudative
Exudative diarrhea occurs with the presence of blood and pus in
the stool. This occurs with inflammatory bowel diseases, such
as Crohn's disease or ulcerative colitis, and other severe
infections such as E. coli or other forms of food poisoning.
Motility-related
Motility-related diarrhea is caused by the rapid movement of
food through the intestines (hypermotility). If the food moves
too quickly through the gastrointestinal tract, there is not
enough time for sufficient nutrients and water to be absorbed.
This can be due to a vagotomy or diabetic neuropathy, or a
complication of menstruation. Hyperthyroidism can produce
hypermotility and lead to pseudodiarrhea and occasionally real
diarrhea. Diarrhea can be treated with antimotility agents (such
as loperamide). Hypermotility can be observed in people who
have had portions of their bowel removed, allowing less total
time for absorption of nutrients.
Inflammatory
Inflammatory diarrhea occurs when there is damage to the
mucosal lining or brush border, which leads to a passive loss of
protein-rich fluids and a decreased ability to absorb these lost
fluids. Features of all three of the other types of diarrhea can be
found in this type of diarrhea. It can be caused by bacterial
infections, viral infections, parasitic infections, or autoimmune
problems such as inflammatory bowel diseases. It can also be
caused by tuberculosis, colon cancer, and enteritis.
Dysentery
Generally, if there is blood visible in the stools, it is not diarrhea,
but dysentery. The blood is trace of an invasion of bowel tissue.
Dysentery is a symptom of, among others, Shigella, Entamoeba
histolytica, and Salmonella.
Dehydration Assessment: Furazolidone,
Cholera Tetracycline
A B C TMP-SMX
Eyes Normal Sunken Very Sunken Shigella TMP-SMX Nalidixic Acid
Tears Normal Absent Absent Amoebiasis Metronidazole
Mouth & Giardiasis Metronidazole Quinacrine HCl
Moist Dry Very Dry
Tongue
Thirst Drinks Drinks 8. Fecalysis normal values
Thirsty
normally poorly
Skin Goes Quickly <2 Slowly >2 Under normal circumstances, the results of fecalysis will show
Very slowly no presence of parasites. If a person does show the presence of
Back secs secs
>2 signs = >2 signs = parasites, then the type of parasite will need to be addressed.
No Signs of
Some Severe
Dehydration color: brown
Dehydration Dehydration
consistency: soft
parasites: no parasites or ova seen
Plan A
muscle fibers: none
 More fluids than usual  prevent dehydration vegetables cells: none
 Plenty of food  prevent undernutrition rbc: 0-1/hfp
 Take child to health worker if child does not get better in 3 pus cells: 0-1/hpf
days macrophage: none
 ORS solution at home if been on Plan B or C, diarrhea gets bacteria: none
worse fat globules: none
After Each Loose
Age Use at home
Stool 12. Alcoholic liver disease
<2yrs 50-100 mL 500 mL/day
2-10 Encompasses the hepatic manifestations
100-200 mL 1000 mL/day
yrs of alcohol overconsumption, including fatty liver, alcoholic
>10 yrs As much as wanted 2000 mL/day hepatitis, and chronic hepatitis with hepatic fibrosis or cirrhosis
Threshold for developing alcoholic liver disease
Plan B Men: >60-80g/day alcohol for 10 years
Amount of ORS in First 4 hours Women: 20-40g/day
Age Weight mL The following contain ~12g of alcohol
<4 mos < 5 kg 200-400 -one bottle of beer
-four ounces of wine
1-11 mos 5-7.9 kg 400-600
-one ounce of 80% spirits
12-23 mos 8-10 kg 600-800
2-4 years 11-15.9 kg 800-1200
5-14 years 16-29.9 kg 1200-2200
>15 years > 30 kg
 After 4 hours, reassess the child  A,B,C

Plan C
 Start IV fluids  100 mL/kg Ringer’s Lactate Solution
o < 1 year – 30 mL/kg for 1 hour, 70 mL/kg for 5 hours
o Older – 30 mL/kg for 30 mins, 70 mL/kg for 2.5 hours
 Repeat if radial pulse is weak
 Give ORS as soon as the patient can drink
 If no IV fluids available  Give ORS 20 mL/kg/hour for 6 hours
by NGT.

Other Problems
 Blood in stool  treat Shigella  TMP-SMX for 5 days
 Diarrhea >14 days  refer if <6 mos old, dehydration is
present  teach mother to feed child with Plan A  Tell
mother to bring the child back after 5 days if diarrhea has not
stopped
 Severe malnutrition  refer to hospital, provide ORS
Cause Drug of choice Alternative
Labs -Polyuria is a condition of excessive production of urine (> 2.5
L/day)
Alcoholic hepatitis: -Oliguria when < 400 mL per day
AST or ALT increased 2 to 7 fold -Anuria when < 100 mL per da
AST/ALT ratio >1
Increased bilirubin -The first step in urine formation is the filtration of blood in the
kidneys. In a healthy human the kidney receives between 12 and
Alcoholic cirrhosis: 30% of cardiac output, but it averages about 20% or about 1.25
Low albumin L/min.
Prolonged PT -The basic structural and functional unit of the kidney is
Increased bilirubin the nephron. Its chief function is to regulate
Thrombocytopenia (due to portal HPN + hypersplenism) the concentration of water and soluble substances like sodium
CT/UTZ: nodular liver, splenomegaly, venocollaterals salts by filtering the blood, reabsorbing what is needed and
excreting the rest as urine.
MX: Complete abstinence is cornerstone of treatment -In the first part of the nephron, the renal corpuscle blood is
Glucocorticoids may be used for severe alcoholic hepatitis being filtrated from the circulatory system into the nephron. A
defined as: Discriminant function >32, MELD score >20 pressure difference between forces the filtrate from the blood
across the filtration membrane. The filtrate includes water,
GUT small molecules and ions that easily pass through the filtration
membrane. However larger molecules such
2. Urine Formation as proteins and blood cells are prevented from passing through
the filtration membrane.
-The amount of filtrate produced every minute is called
the glomerular filtration rate or GFR and amounts to a
staggering 180 liters per day. About 99% of this filtrate is then
reabsorbed as it passes through the nephron and the remaining
1% becomes urine.
The urinary system is regulated by the endocrine
system by hormones such as antidiuretic hormone, aldosterone,
and parathyroid hormone.

Regulation of concentration and volume:

The urinary system is under influence of the blood

pressure, nervous system and endocrine system.
-Antidiuretic hormone (ADH) is a neurohypophysial
hormone found in most mammals. Its two primary functions are
to retain water in the body and to constrict blood vessels.
-Vasopressin regulates the body's retention of water by acting
to increase water absorption in the collecting ducts of the
kidney nephron. Vasopressin increases water permeability of
the kidney's collecting duct and distal convoluted tubule by
inducing translocation of aquaporin-CD water channels in the
kidney nephron collecting duct plasma membrane.[4]

5. Urinalysis normal values

PHYSICAL CHARACTERISTICS:
Color
-Normal: Pale to dark yellow
-Abnormal: No color - kidney disease/diabetes, Red - blood in
the urine
Transparency
-Normal: Clear
-Average urine production in adult humans is 1 – 2 L per day, -Abnormal: Cloudy (pus, WBC, RBC, sperm, bacteria, yeast)
depending on state of hydration, activity level, environmental
factors, weight, and the individual's health.
CHEMICAL TEST:
pH
-Normal: 4.6-8.0
-Abnormal: High (alkaline) = severe vomiting, kidney disease,
some UTI, asthma. Low (acidic) = emphysema, uncontrolled
diabetes, severe diarrhea, dehydration, starvation
Specific Gravity (urine concentration)
-Normal: 1.005-1.030
-Abnormal: High = very concentrated urine, either from fluid
loss or kidney problem, with substances (sugar/protein) in the
urine. Low = dilute urine, from too much fluid, severe kidney
disease, diuretic use
Albumin
-Normal: None
-Abnormal: Possible kidney damage, infection, cancer,
hypertension, diabetes, SLE, glomerulonephritis, heart failure
Sugar
-Normal: None
-Abnormal: Uncontrolled diabetes, adrenal gland problem, liver
damage, brain injury, some types of kidney diseases
Leukocytes
-Normal: Few/None.
-Abnormal: Leukocytes in the urine typically indicate a past or
current infection in the urinary tract.
Erythrocytes
-Normal: None
-Abnormal: Blood in the urine is an abnormal finding. However,
it is not possible to determine the cause of the bleeding without
further testing. Common causes include infection, trauma,
kidney stones, cancer, surgery on an area of the urinary tract,
kidney disease, trauma related to the insertion of a urinary
catheter.
Bilirubin
-Normal: None
-Abnormal: Increased levels due to biliary tract disease,
cirrhosis, gallstones, hepatitis, liver disease
Nitrite
-Normal: None
-Abnormal: Bacteria that cause a UTI make an enzyme that
changes urinary nitrates to nitrites. Nitrites in urine show a UTI
is present.
Ketones
-Normal: None
-Abnormal: Ketones in the urine can mean uncontrolled
diabetes, a very low-carbohydrate diet, starvation or eating
disorders, or alcoholism. Ketones are often found in the urine
when a person does not eat (fasts) for 18 hours or longer. This
may occur when a person is sick and cannot eat or vomits for
several days.
Urobilinogen
-Normal: None
-Abnormal: Formed by the breakdown of bilirubin and passed
from the body in stool. Can be a sign of liver disease
(cirrhosis,hepatitis) or that the flow of bile from the gallbladder
is blocked.
MICROSCOPIC FINDINGS (CAST):
Hyaline, Granular, Waxy
-Normal: None
-Abnormal: Depending on the type, casts can mean
inflammation or damage to the tiny tubes in the kidneys, poor
blood supply to the kidneys, metal poisoning (such as lead or
mercury), heart failure, or bacterial infection
A cast, which may be referred to as a red, white, or hyaline cast,
typically looks like a small clump of egg white suspended in the
urine. The presence of casts is not normal and may be
suggestive of kidney issues.
CELLS:
RBC, Pus, Yeast, Squamous, Renal, Transitional, Epithelial,
Bacteria, Mucus Thread
-Normal: Few/None
-Abnormal: Bacteria, yeast cells = UTI
Very few or no WBCs should be present in the urine. Significant
numbers typically indicate the presence of infection.
Like white blood cells, there should be very few or no red blood
cells found in the urine.
The presence of bacteria may indicate an infection or
contamination of the sample.
Squamous/Epithelial cells may mean that the sample is not as
pure as it needs to be. New sample needed.
CRYSTALS:
Amorphous urate, Uric acid, Calcium oxalate, Amorphous
phosphate, Triple phosphate
-Normal: Few
-Abnormal: Large amounts of crystals, or certain types of
crystals, can mean kidney stones, damaged kidneys, or problems
with metabolism. Some medicines and UTI can increase the
number of crystals in urine.
6. Renal syndromes
Acute Kidney Injury
Acute kidney injury is a syndrome in which glomerular filtration
declines over a period of hours to days. The patient with acute
renal failure is approached best by evaluation for prerenal,
renal, and postrenal causes.
Generally it occurs because of damage to the kidney
tissue caused by decreased renal blood flow (renal ischemia)
from any cause (e.g. low blood pressure), exposure
to substances harmful to the kidney, aninflammatory process in
the kidney, or an obstruction of the urinary tract which impedes
the flow of urine.

AKI is diagnosed on the basis of characteristic laboratory

findings, such as elevated blood urea nitrogen and creatinine, or
inability of the kidneys to produce sufficient amounts of urine.

BUN is an indication of renal health. Normal ranges 8-

20 mmol/L. If Glomerular Filtration Rate (GFR) and blood
volume decrease (hypovolemia) then BUN will increase. Other
factors responsible for its increment are fever,
increased catabolism, high-protein diet and gastrointestinal
bleeding.

Serum creatinine is an important indicator of renal health

because it is an easily measured byproduct of muscle
metabolism that is excreted unchanged by the kidneys. The
typical human reference ranges for serum creatinine are 0.5 to
1.0 mg/dl for women and 0.7 to 1.2 mg/dl for men.

BUN-to-creatinine ratio:

RIFLE criteria - For staging of AKI

Risk: GFR decrease >25%, serum creatinine increased 1.5 times

or urine production of < 0.5 ml/kg/h for 6 hours

Injury: GFR decrease > 50%, doubling of creatinine or urine

production < 0.5 ml/kg/h for 12 hours

Failure: GFR decrease > 75%, tripling of creatinine or creatinine

> 355 μmol/l (with a rise of > 44) (> 4 mg/dl) OR urine output
below 0.3 ml/kg/h for 24 hours or anuria for 12 hours.

Loss: persistent AKI or complete loss of kidney function for more

than 4 weeks

End-stage renal disease: need for renal replacement therapy

(RRT) for more than 3 months
Chronic Kidney Disease (CKD)
-Abnormal kidney function and progressive decline in
glomerular filtration rate (GFR) brought about by various
etiologies.
-Generally defined as kidney damage >=3months with
GFR<60mL/min and structural or functional abnormalities in the
kidney
-Leading causes: diabetic glomerular disease,
glomerulonephritis, hypertensive nephropathy
Clinically manifested by Uremia: in kidney failure, urea and
other waste products, which are normally excreted into
the urine, are retained in the blood. Early symptoms
include anorexia and lethargy, and late symptoms can include
decreased mental acuity and coma. Other symptoms include
fatigue, nausea, vomiting, cold, bone pain, itch, shortness of
breath, and seizures.
Stage 1
Slightly diminished function; kidney damage with normal or
relatively high GFR (≥90 mL/min/1.73 m2). Kidney damage is
defined as pathological abnormalities or markers of damage,
including abnormalities in blood or urine test or imaging studies.
Stage 2
Mild reduction in GFR (60–89 mL/min/1.73 m2) with kidney
damage. Kidney damage is defined as pathological abnormalities
or markers of damage, including abnormalities in blood or urine
test or imaging studies.
Stage 3
Moderate reduction in GFR (30–59 mL/min/1.73 m2). British
guidelines distinguish between stage 3A (GFR 45–59) and stage
3B (GFR 30–44) for purposes of screening and referral.
Stage 4
Severe reduction in GFR (15–29 mL/min/1.73 m2) Preparation
for renal replacement therapy
Stage 5
Established kidney failure (GFR <15 mL/min/1.73 m2, permanent
renal replacement therapy (RRT), or end stage renal disease
(ESRD)
.
Nephritic Syndrome
The acute nephritic syndrome is an uncommon but dramatic
presentation of an acute glomerulonephritis The hallmark of the
acute nephritic syndrome is the presence of dysmorphic RBCs
and RBC casts, but their absence does not exclude the
syndrome. The acute nephritic syndrome can be caused by any
of the rapidly progressive glomerulonephropathies, all of which
warrant urgent and usually inpatient evaluation.
-1-2g/24h proteinurea
- Hematuria with RBC casts
- Pyuria, Hypertension, Fluid retention, Rise in serum creatinine
Nephrotic Syndrome
The nephrotic syndrome is characterized by the presence of
proteinuria of greater than 3.5 g/day, hypoalbuminemia
(<30g/L), with accompanying edema, hypertension, and
hyperlipidemia. In general, the diseases associated with
nephrotic syndrome do not cause acute kidney injury, although
acute kidney injury may be seen with minimal change disease,
HIV-associated nephropathy, and bilateral renal vein
thrombosis. The causes of primary idiopathic nephrotic
syndrome, in decreasing order of prevalence, are focal and
segmental glomerulosclerosis, membranous nephropathy,
minimal change disease, and membranoproliferative
glomerulonephritis. Secondary causes of the nephrotic
syndrome include diabetic nephropathy, amyloidosis, and SLE
with membranous nephropathy.
- >3gram/24 hour proteinurea
-Hypertension, Hypercholesterolemia, Hypoalbuminemia,
Edema/anasarca, microscopic hematuria
Nephrolithiasis (kidney stones)
-One of the most common urologic problems
-Calcium (75-85%), salts, uric acid, cysteine, and struvite make
up most kidney stones
-Common cause of isolated hematuria
-Pain gradually increases in severity as stone traverses ureter
-DX: Helical CT scan
-MX: alpha-blockers, nephrolithotomy, ureteroscopy
Renal Tubular Acidosis
-Disorder of renal acidification out of proportion to the
reduction in GFR
-Characterized by hyperchloremic metabolic acidosis with
normal anion gap
-Type 1 Distal, Type 2 Proximal, MX: alkali supplementation
-Type 4 most common, with impaired secretion of distal H+ and
K+ ions -> hyperchloremic acidosis with hyperkalemia. MX:
correct hyperka
7.BUN
Reference Range
Blood urea nitrogen (BUN) testing is commonly part of the basic
metabolic panel (BMP) or comprehensive metabolic panel
(CMP), which is commonly obtained as part of a routine medical Drugs that can increase BUN levels include the following:
examination. It is also obtained in patients in emergency or
urgent care settings, as it can provide valuable information that  Allopurinol
may provide clues to various clinical presentations that may be  Aminoglycoside antibiotics
caused by chemical imbalances in the body that require prompt  Amphotericin B
and immediate attention.  Aspirin (high doses)
 Bacitracin
Urea production occurs primarily in the liver (urea cycle, also  Carbamazepine
referred to as the ornithine cycle) and is regulated by N-  Cephalosporins
acetylglutamate. Urea is found dissolved in blood and is  Chloral hydrate
excreted by the renal tubules. In addition, a small amount of  Cisplatin
urea is also excreted in sweat. Therefore, the BUN level may
 Colistin
reflect functioning of the liver and/or kidneys.
 Furosemide
The reference range of the BUN level is 3-20 mg/dL. Individual  Guanethidine
laboratories may have different reference ranges, since the  Indomethacin
procedure may vary.  Methicillin
 Methotrexate
Interpretation  Methyldopa
As with serum creatinine, the BUN level varies inversely with the  Neomycin
glomerular filtration rate (GFR).[1] However, certain conditions  Penicillamine
can result in elevated BUN levels that may not truly reflect renal  Polymyxin B
functioning.[2]  Probenecid
The rate of urea production is not constant. It is elevated in  Propranolol
those who consume a diet fairly high in protein and in  Rifampin
conditions characterized by enhanced tissue breakdown (eg,  Spironolactone
hemorrhage, trauma, glucocorticoid therapy). Certain  Tetracyclines
antibiotics, such as tetracyclines, may interfere with protein  Thiazide diuretics
synthesis and tend to be catabolic, thereby also increasing BUN  Triamterene
levels. On the other hand, a low-protein diet or liver disease can  Vancomycin
decrease the BUN level without affecting GFR or renal
function.[3] The following drugs can decrease BUN levels:

Liver disease may be associated with near-normal values of both  Chloramphenicol

BUN (due to decreased urea production) and serum creatinine
(due to muscle wasting), despite a significant decline in renal
function manifested by decreased GFR.[4]
Approximately 40%-50% of the filtered urea undergoes passive
reabsorption in the proximal tubule. In states of intravascular
volume depletion, proximal sodium and water reabsorption
increases, coupled with a parallel increase in the reabsorption of
urea. This results in a disproportionate rise in BUN levels relative
to any change in serum creatinine levels. This elevation in the
BUN-to-creatinine ratio is one of the laboratory indicators of
decreased renal perfusion. The ratio is indicative of prerenal
injury when the BUN-to-creatinine ratio is greater than 20.
 Streptomycin
BUN levels tend to increase with age. In infants and children,
BUN levels are about two thirds of those found in healthy young
adults, while levels in adults older than 60 years are slightly
higher than those in younger adults. They are also slightly higher
in males than in females, probably reflective of the lower
muscle mass in the latter. During pregnancy, physiologic
changes in blood flow can also lower BUN levels.

The ratio is may also be useful for diagnosing gastrointestinal

bleeding in some patients who do not present with overt blood
loss. In children, a BUN-to-creatinine ratio of 30 or greater has a
sensitivity of 68.8% and a specificity of 98% for upper
gastrointestinal bleeding.

The value of this ratio is limited by other factors that can affect
BUN independently, such as various drugs.
8.Renal Functions – filtration, reabsorption, secretion
Endocrine hydrocortisone
Supportive therapy
1. Thyroid Storm
IV fluids
Definition Temperature control (cooling blankets, paracetamol)
Thyroid storm refers to the heightened and life-threatening
O2 if needed
manifestations of thyroid hyperactivity.
Digitalis for congestive failure and to slow ventricular
Etiology/Pathophysiology response
In the past, thyroid storm classically began a few hours after Treatment of precipitating event (e.g. infection)
a thyroidectomy performed on a patient taken too soon to
Sedation and nutrition
surgery. Most cases of thyroid storm are secondary to toxic
diffuse goiter (Graves’ disease). Precipitating factors
associated with thyroid storm include infections, stress, Prevention of thyroid storm
trauma, thyroidal or non-thyroidal surgery, diabetic  Patients should be rendered euthyroid to mild
ketoacidosis, labor, heart disease and RAI treatment due to hyperthyroidism before RAI treatment or surgery
RAI thyroiditis. The mechanism by which such factors  Patients should be educated on the importance of
worsen thyrotoxicosis may be related to cytokine release compliance with antithyroid medications
and acute immunologic disturbance caused by the
precipitating condition.
2. Thyroid hormone synthesis
Clinical manifestations
Clinical features are similar to those of thyrotoxicosis, but
more exaggerated. Fever is almost invariable and may be
severe; sweating is profuse. Marched tachycardia of sinus
or ectopic origin and arrhythmias may be accompanied by
pulmonary edema or CHF. Early on, tremulousness and
restlessness are present; delirium or frank psychosis may
supervene. N/V, and abdominal pain occur early in the
course. As the disorder progresses, apathy, stupor, and
coma may supervene. Coma and death may ensue in up to
20% of patients.

Diagnostic tests
The serum thyroid hormone levels in crisis are not
appreciably greater than those in uncomplicated
thyrotoxicosis. Therefore thyroid storm is primarily a
clinical diagnosis. Electrolytes, BUN, blood sugar, LFT and
plasma cortisol should be monitored. The diagnosis of (1) Thyroglobulin is synthesized from tyrosine in the
thyroid storm is incomplete until a search for some cause of thyroid follicular cells, packaged in secretory vesicles,
the crisis, especially infection, has been made. and extruded into the follicular lumen (step 1).
(2) The iodide (I-) pump, or Na+ I- cotransport
Management of Thyroid Storm
 Is present in the thyroid follicular epithelial
Inhibition of thyroid hormone formation and secretion cells
PTU  Actively transports I- into the thyroid follicular
Sodium iodide cells for subsequent incorporation into thyroid
hormones (step 2)
Sympathetic blockade
 Is inhibited by thiocyanate and perchlorate
Propranolol anions
Glucocorticoid therapy
(3) Oxidation of I- to I2
 Is catalyzed by a peroxidase enzyme in the
follicular cell membrane (step 3)
 I2 is the reactive form , which will be
“organified” by combination with tyrosine on
thyroglobulin
 The peroxidase enzyme is inhibited by
propylthioruacil, which is used therapeutically
to reduce thyroid hormone synthesis for the
treatment of hyperthyroidism
 The same peroxidase enzyme catalyzes the
remaining organification and coupling
reactions involved in the synthesis of thyroid
hormones
(4) Organification of I2
 At the junction of the follicular cells and the
follicular lumen, tyrosine residues of
thyroglobulin react with I2 to form
monoiodotyrosine (MIT) and diiodotyrosine
(DIT) (step 4)
 High levels of I- inhibit organification and,
therefore, inhibit synthesis of thyroid
hormone (Wolff-Chaikoff effect)
(5) Coupling of MIT and DIT
 While MIT and DIT are attached to
thyroglobulin, 2 coupling reactions occur (step
5)
 When two molecules of DIT combine,
thyroxine (T4) is formed
 When one molecule of DIT combines with one
molecule of MIT, triiodothyronine (T3) is
formed
 More T4 than T3 is synthesized, although T3 is
more active
 Iodinated thyroglobulin is stored in the
follicular lumen until the thyroid gland is
stimulated to secrete thyroid hormones
(6) Stimulation of thyroid cells by TSH
 When thyroid cells are stimulated, iodinated
thyroglobulin is taken back into the follicular
cells by endocytosis (step 6). Lysozomal
enzymes then digest thyroglobulin, releasing
T4 and T3 into the circulation (step 7).
 Leftover MIT and DIT are deiodonated by
thyroid deiodinase (step 8). The I2 that is
released is reutilized to synthesize more
thyroid hormones. Therefore, deficiency of
thyroid deiodinase mimcs I2 deficiency.
(7) Binding of T3 and T4
 In the circulation, most of the T3 and T4 is
bound to the thyroxine-binding globulin (TBG)
 In hepatic failure, TBG levels decrease, leading
to a decrease in total thyroid hormone levels,
but normal levels of free hormone
 In pregnancy, TBG levels increase, leading to
an increase in total thyroid hormone levels,
but normal levels of free hormone (i.e.
clinically euthyroid)
(8) Conversion of T4 to T3 and reverse T3 (rT3)
 In the peripheral tissues, T4 is converted to T3
by 5’-iodinase (or to rT3)
 T3 is more biologically active than T4
 rT3 is inactive
3. Hypertensive vs. DM retinopathy
Diabetic Retinopathy
Clinical stages
a) Background or nonproliferative DM reninopathy
 Microaneurysms, dot blot hemorrhage, flame
shaped hemorrhages, hard exudates (outer
plexiform layer)
b) Pre-proliferative DM retinopathy
 Cotton wool spots (soft exudates, nerve fiber
layer)
c) Proliferative DM retinopathy
 Neovascularization into vitreous and optic
disc, vitreous hemorrhage, tractional RD
Tx: Panretinal photocoagulation (principle:
destruction of ischemic retina to reduce O2
demand hence reduce angiogenic stimulus for
neovascularization)
Hypertensive Retinopathy
Scheie Grading
I – Slight generalized attenuation retinal arterioles
II – Obvious attenuation/further narrowing
III – Changes in I and II + exudates and hemorrhages
IV – I, II, III + optic disc edema
Tx: BP control, PRP if necessary
4. DM and GDM
TYPE 1 DIABETES MELLITUS
Type 1 diabetes is a chronic illness characterized by the
body’s inability to produce insulin due to the autoimmune
destruction of the beta cells in the pancreas. Onset most
often occurs in childhood, but the disease can also develop
in adults in their late 30s and early 40s.
Signs and symptoms
The classic symptoms of type 1 diabetes are as follows:
 Polyuria
 Polydipsia
 Polyphagia
 Unexplained weight loss
Other symptoms may include fatigue, nausea, and blurred
vision.
The onset of symptomatic disease may be sudden. It is not
unusual for patients with type 1 diabetes to present with
diabetic ketoacidosis (DKA).
Diagnosis
Diagnostic criteria by the American Diabetes Association
(ADA) include the following :
 A fasting plasma glucose (FPG) level ≥126 mg/dL (7.0
mmol/L), or
 A 2-hour plasma glucose level ≥200 mg/dL (11.1
mmol/L) during a 75-g oral glucose tolerance test
(OGTT), or
 A random plasma glucose ≥200 mg/dL (11.1 mmol/L) in
a patient with classic symptoms of hyperglycemia or
hyperglycemic crisis
Lab studies
 A fingerstick glucose test is appropriate for virtually all
patients with diabetes
 HbA1c assay for diagnosing type 1 diabetes only when
the condition is suspected but the classic symptoms are
absent
Management
Glycemic control
Benefits of tight glycemic control include not only
continued reductions in the rates of microvascular
complications but also significant differences in
cardiovascular events and overall mortality.
Self-monitoring
Self-monitoring of blood glucose levels allows rational
adjustments in insulin doses. All patients with type 1
diabetes should learn how to self-monitor and record their
blood glucose levels with home analyzers and adjust their
insulin doses accordingly.
Insulin therapy
Patients with type 1 diabetes require lifelong insulin
therapy. Most require 2 or more injections of insulin daily,
with doses adjusted on the basis of self-monitoring of blood
glucose levels. Insulin replacement is accomplished by
giving a basal insulin and a preprandial (premeal) insulin.
The basal insulin is either long-acting (glargine or detemir)
or intermediate-acting (NPH). The preprandial insulin is
either rapid-acting (lispro, aspart, or glulisine) or short-
acting (regular).
Diet and activity
 Daily caloric intake prescription
 Recommendations for amounts of dietary
carbohydrate, fat, and protein
 Instructions on how to divide calories between meals
and snacks
 Exercise
TYPE 2 DIABETES MELLITUS
Type 2 diabetes mellitus consists of an array of dysfunctions
characterized by hyperglycemia and resulting from the
combination of resistance to insulin action, inadequate
insulin secretion, and excessive or inappropriate glucagon
secretion.
Signs and symptoms
Many patients with type 2 diabetes are asymptomatic.
Clinical manifestations include the following:
 Classic symptoms: Polyuria, polydipsia, polyphagia, and
weight loss
 Blurred vision
 Lower-extremity paresthesias
 Yeast infections (eg, balanitis in men)
Diagnosis
 A fasting plasma glucose (FPG) level of 126 mg/dL (7.0
mmol/L) or higher, or
 A 2-hour plasma glucose level of 200 mg/dL (11.1
mmol/L) or higher during a 75-g oral glucose tolerance
test (OGTT), or
 A random plasma glucose of 200 mg/dL (11.1 mmol/L)
or higher in a patient with classic symptoms of
hyperglycemia or hyperglycemic crisis
Whether a hemoglobin A1c (HbA1c) level of 6.5% or higher
should be a primary diagnostic criterion or an optional
criterion remains a point of controversy.
Management
Goals of treatment are as follows:
 Microvascular (ie, eye and kidney disease) risk
reduction through control of glycemia and blood
pressure
 Macrovascular (ie, coronary, cerebrovascular,
peripheral vascular) risk reduction through control of
lipids and hypertension, smoking cessation
 Metabolic and neurologic risk reduction through
control of glycemia
The European Association for the Study of Diabetes (EASD)
and the American Diabetes Association (ADA) position
statement contains 7 key points:
1. Individualized glycemic targets and glucose-lowering
therapies
2. Diet, exercise, and education as the foundation of the
treatment program
3. Use of metformin as the optimal first-line drug unless
contraindicated
4. After metformin, the use of 1 or 2 additional oral or
injectable agents, with a goal of minimizing adverse
effects if possible
5. Ultimately, insulin therapy alone or with other agents if
needed to maintain blood glucose control
6. Where possible, all treatment decisions should involve
the patient, with a focus on patient preferences, needs,
and values
7. A major focus on comprehensive cardiovascular risk
reduction
Approaches to prevention of diabetic complications include
the following:
 HbA1c every 3-6 months
 Yearly dilated eye examinations
 Annual microalbumin checks
 Foot examinations at each visit
 Blood pressure < 130/80 mm Hg, lower in diabetic
nephropathy
 Statin therapy to reduce low-density lipoprotein
cholesterol
Gestational Diabetes
Gestational diabetes mellitus is defined as glucose
intolerance of variable degree with onset or first
recognition during pregnancy. Infants of mothers with
preexisting diabetes mellitus experience double the risk of
serious injury at birth, triple the likelihood of cesarean
delivery, and quadruple the incidence of newborn intensive
care unit (NICU) admission.
Maternal-Fetal Metabolism in Normal Pregnancy
In the pregnant woman, each meal sets in motion a
complex series of hormonal actions, including a rise in
blood glucose and the secondary secretion of pancreatic
insulin, glucagon, somatomedins, and adrenal
catecholamines. These adjustments ensure that an ample,
but not excessive, supply of glucose is available to the
mother and fetus.
Compared with nonpregnant subjects, pregnant women
tend to develop hypoglycemia (plasma glucose mean = 65-
75 mg/dL) between meals and during sleep. This occurs
because the fetus continues to draw glucose across the
placenta from the maternal bloodstream, even during
periods of fasting. Interprandial hypoglycemia becomes
increasingly marked as pregnancy progresses and the
glucose demand of the fetus increases.
Levels of placental steroid and peptide hormones (eg,
estrogens, progesterone, and chorionic
somatomammotropin) rise linearly throughout the second
and third trimesters. Because these hormones confer
increasing tissue insulin resistance as their levels rise, the
demand for increased insulin secretion with feeding
escalates progressively during pregnancy. By the third
trimester, 24-hour mean insulin levels are 50% higher than
in the nonpregnant state.
Maternal-Fetal Metabolism in Diabetes
If the maternal pancreatic insulin response is inadequate,
maternal and, then, fetal hyperglycemia results. This
typically manifests as recurrent postprandial hyperglycemic
episodes. These postprandial episodes are the most
significant source of the accelerated growth exhibited by
the fetus.
Surging maternal and fetal glucose levels are accompanied
by episodic fetal hyperinsulinemia. Fetal hyperinsulinemia
promotes excess nutrient storage, resulting in macrosomia.
The energy expenditure associated with the conversion of
excess glucose into fat causes depletion in fetal oxygen
levels.
These episodes of fetal hypoxia are accompanied by surges
in adrenal catecholamines, which, in turn, cause
hypertension, cardiac remodeling and hypertrophy,
stimulation of erythropoietin, red cell hyperplasia, and
increased hematocrit. Polycythemia (hematocrit >65%)
occurs in 5-10% of newborns of diabetic mothers. This
finding appears to be related to the level of glycemic
control and is mediated by decreased fetal oxygen tension.
High hematocrit values in the neonate lead to vascular
sludging, poor circulation, and postnatal
hyperbilirubinemia.
During a healthy pregnancy, mean fasting blood sugar levels
decline progressively to a remarkably low value of 74 ± 2.7
(standard deviations [SD]) mg/dL. However, peak
postprandial blood sugar values rarely exceed 120 mg/dL.
Meticulous replication of the normal glycemic profile during
pregnancy has been demonstrated to reduce the
macrosomia rate. Specifically, when 2-hour postprandial
glucose levels are maintained below 120 mg/dL,
approximately 20% of fetuses demonstrate macrosomia. If
postprandial levels range up to 160 mg/dL, macrosomia
rates rise to 35%.
Screening for diabetes mellitus during pregnancy
Gestational diabetes
The following 2-step screening system for gestational
diabetes is currently recommended in the United States:
 50-g, 1-hour glucose challenge test (GCT)
 100-g, 3-hour oral glucose tolerance test (OGTT) - For
patients with an abnormal GCT result
Postdiagnostic testing
Once the diagnosis of diabetes is established in a pregnant
woman, continued testing for glycemic control and diabetic
complications is indicated for the remainder of the
pregnancy.
Management
Diet
The goal of dietary therapy is to avoid single large meals
and foods with a large percentage of simple carbohydrates.
The diet should include foods with complex carbohydrates
and cellulose, such as whole grain breads and legumes.
Insulin
The goal of insulin therapy during pregnancy is to achieve
glucose profiles similar to those of nondiabetic pregnant
women. In gestational diabetes, early intervention with
insulin or an oral agent is key to achieving a good outcome
when diet therapy fails to provide adequate glycemic
control.
Glyburide and metformin
The efficacy and safety of insulin have made it the standard
for treatment of diabetes during pregnancy. Diabetic
therapy with the oral agents glyburide and metformin,
however, has been gaining in popularity. Trials have shown
these 2 drugs to be effective, and no evidence of harm to
the fetus has been found, although the potential for long-
term adverse effects remains a concern.[6]
5. Insulin preparation

First-trimester laboratory studies Pharmacokinetics of Available Insulin Preparations

Onset Peak Effective
 HbA1C
Duration
 Blood urea nitrogen (BUN)
Rapid Acting
 Serum creatinine
Insulin aspart 5-15 mins 30-90 mins <5h
 Thyroid-stimulating hormone
injection
 Free thyroxine levels
Insulin lispro 5-15 mins 30-90 mins <5h
 Spot urine protein-to-creatinine ratio
injection
 Capillary blood sugar levels
Insulin 5-15 mins 30-90 mins <5h
glutisine
Second-trimester laboratory studies
injection
 Spot urine protein-to-creatinine study in women with Slow Acting
elevated value in first trimester Regular 30-60 min 2-3 h 5-8 h
 Repeat HbA1C Intermediate, basal
 Capillary blood sugar levels NPH 2-4 h 4-10 h 10-16 h
Long Acting
Ultrasonography Insulin 2-4 h No peak 20-24 h
glargine
 First trimester - Ultrasonographic assessment for injection
pregnancy dating and viability Insulin 3-8 h No peak 5.7-23.2 h
 Second trimester - Detailed anatomic ultrasonogram at detemir
18-20 weeks and a fetal echocardiogram if the injection
maternal glycohemoglobin value was elevated in the Premixed
first trimester 75% insulin 5-15 min Dual 10-16 h
 Third trimester - Growth ultrasonogram to assess fetal lispro
size every 4-6 weeks from 26-36 weeks in women with protamine
overt preexisting diabetes; perform a growth suspension /
ultrasonogram for fetal size at least once at 36-37 25% insulin
weeks for women with gestational diabetes mellitus lispro
injection  Injection immediately before a meal affords
(Humalog mix hypoglycemic control similar to regular insulin
75/25) given 30 minutes before the meal
50% insulin 5-15 min Dual 10-16 h 2. Insulin Aspart
lispro
protamine  Substitution of the B28 proline with aspartic acid
suspension /  The modification reduces ProB28 and GlyB23
50% insulin monomer-monomer interaction inhibiting self-
lispro aggregation
injection  Rapidly breaks into monomers after SC injection
(Humalog mix
 Absorption and activity profile similar to insulin
50/50) (4)
70% insulin 5-15 min Dual 10-16 h lispro
aspart 3. Insulin Glusine
protamine  Asparagine is substituted for lysine at B3 and
suspension / glutamic acid for lysine at B29
30% insulin
aspart Short Acting Insulin
injection
1. Regular or Soluble Crystalline Zinc Insulin
(Humalog mix
70/30) (4)  Predominantly dimeric and hexameric causing
70% NPH / 30-60 mins Dual 10-16 h delay in onset and prolonging time to peak action
30% regular  Given 30 mins SC before a meal to control
postprandial hyperglycemia
Indications for Insulin  Preparation of choice for IV therapy during
 Persons with Type 1 (insulin dependent) diabetes or surgery, acute infections, diabetic ketoacidosis
post-pancreatectomy diabetes
 Acutely decompensated diabetes (with diabetic Intermediate Acting Insulin
ketoacidosis or hypersomolar, hyperglycemic coma) 1. NPH
 Hyperglycemic pregnant diabetic not controlled by diet  Mixes insulin and protamine in an equal ratio and
alone neurtral pH with small amount of zinc
 Short-term treatment of type 2 or impaired glucose  Converts the normally rapidly absorbed insulin to a
tolerance during intercurrent events (operations, preparation with longer duration of action
infections, myocardial infarction)
 Persons with Type 2 diabetes, but good blood glucose Long Acting Insulin
control cannot be achieved/maintained by diet, 1. Insulin Glargine
exercise, oral hypoglycemic  Insulin analog
 Emergency treatment of hyperkalemia. Insulin is given  Provides constant basal insulin supply and mimics
with glucose to lower ECF K+ via distribution into cells physiological post-absorptive basal insulin
secretion
Characteristics of Insulin Preparation  Used in conjunction with short-acting insulin
Rapid Acting Insulin  Lowers post-absorptive plasma glucose but
 Very fast onset, short duration reduces the risk of nighttime hypoglycemia
Insulin Analogs 2. Insulin Detemir
1. Insulin Lispro  Terminal threonine is dropped from B30 and
 Same AA as human insulin except B28 contains myristic acid is attached to the terminal B29 lysine
lysine and B29 contains proline  This modification prolongs the availability of the
 Switching results in insulin molecule that resists injected analog by increasing both self-aggregation
formation of hexamers and tends to remain in SC and reversible albumin binding
monomeric, thus promoting a more rapid rate of  Dose dependent onset of action of 1-2 h and
absorption for SC injection. Shorter duration of duration of action for more than 24 h
action (2-4 hours)
 Insulin Mixtures
 Combination of intermediate acting and rapid or
short acting insulin in premixed ratio
 Useful for patients with physical impairments
(visual or manual) who are on mixed insulin
regimens
 Not ideal for most diabetics who may achieve
better control by separately mixing short-acting
and intermediate acting insulins to arrive at a ratio
that is better suited to manage their diabetes
Degree of Control of Plasma Glucose is Modified By
 Changes in insulin absorption
 Factors that alter insulin absorption
 Diet and exercise
Factors that Affect the Absorption of Insulin
 Site of injection – abdominal wall > arm > buttocks
> thigh
 Type of insulin
 Subcutaneous blood flow
 Regional muscular activity at site of injection
 Depth of injection
 Species source – human insulin absorbed faster
 A burst of estradiol synthesis at the end of the
follicular phase has a positive feedback effect on
the secretion of FSH and LH (LH surge)
 Estrogen levels decrease just after ovulation (but
rise again during the luteal phase)
 Cervical mucus increases in quantity; it becomes
less viscous and more penetrable by sperm
(3) Luteal phase (days 14-28)
 The corpus luteum begins to develop, and
synthesizes estrogen and progesterone
 Vascularity and secretory activity of the
endometrium increase to prepare for receipt of a
fertilized egg
 Basal body temperature increases because of the
effect of progesterone on the hypothalamic
thermoregulatory center
 If fertilization does not occur, the corpus luteum
regresses at the end of the luteal phase. As a
result, estradiol and progesterone levels decrease
abruptly.
(4) Menses (days 0-4)
 The endometrium is sloughed because of the
abrupt withdrawal of estradiol and progesterone

Complications of Insulin Therapy

 Hypoglycemia
 Weight gain
 Insulin lipodystrophy (atrophy and/or hypertrophy)
 Insulin allergy and resistance
 hypokalemia

Reproductive

1. Menstrual cycle
(1) Follicular phase (days 0-14)
 A primordial follicle develops to the graafian
stage, with atresia of neighboring follicles
 LH and FSH receptors are upregulated in theca and
granulosa cells
 Estradiol levels increase and cause proliferation in
the uterus
 FSH and LH levels are suppressed by negative
feedback effect of estradiol on the anterior
pituitary
(2) Ovulation (day 14)
 Occurs 14 days before menses, regardless of cycle
length. Thus, in a 28-day cycle, ovulation occurs on
day 14; in a 35-day cycle, ovulation occurs on day
22
 2. HPO Axis Regional lymph nodes (N)
(Hypothalamic-Pituitary Gonadal Axis, or
Hypothalamic-Pituitary Ovarian Axis) Clinical

N0 No regional lymph node metastasis

N1 Metastasis to movable ipsilateral level I, II axillary lymph

node(s)

N2 Metastases in ipsilateral level I, II axillary lymph nodes that

are clinically fixed or matted or in clinically detected*
ipsilateral internal mammary nodes in the absence of
clinically evident axillary lymph node metastasis

N3 Metastases in ipsilateral infraclavicular (level III axillary)

lymph node(s), with or without level I, II axillary node
involvement, or in clinically detected * ipsilateral internal
mammary lymph node(s) and in the presence of clinically
evident level I, II axillary lymph node metastasis; or
metastasis in ipsilateral supraclavicular lymph node(s), with
or without axillary or internal mammary lymph node
involvement

Distant metastasis (M)

Hypothalamic control – GnRH
M0 No clinical or radiographic evidence of distant metastasis
 Pulsatile GnRH stimulates the anterior pituitary to
secrete FSH and LH
M1 Distant detectable metastases as determined by classic
Anterior lobe of the pituitary – FSH and LH clinical and radiographic means and/or histologically
proven > 0.2 mm
FSH and LH stimulate the following in the ovaries:

 Steroidogenesis in the ovarian follicle and corpus

luteum
Stage T N M
 Follicular development beyond the antral stage
 Ovulation IA T1 N0 M0
 Lutenization IB T0 N1mi M0

3. Breast Cancer T1 N1mi M0

IIA T0 N1 M0
Breast Cancer Staging
T1 N1 M0
Primary tumor (T)
T2 N0 M0
T0 No evidence of primary tumor IIB T2 N1 M0
T3 N0 M0
T1 Tumor ≤ 20 mm in greatest dimension
IIIA T0 N2 M0
T2 Tumor > 20 mm but ≤ 50 mm in greatest dimension
T1 N2 M0

T3 Tumor > 50 mm in greatest dimension T2 N2 M0

T3 N1 M0
T4 Tumor of any size with direct extension to the chest wall
and/or to the skin (ulceration or skin nodules) T3 N2 M0
IIIB T4 N0 M0  Family history of BRCA1 and BRCA2 mutations
 Late age at first pregnancy, nulliparity, early onset of
T4 N1 M0 menses, and late age of menopause
 Obesity, sedentary lifestyle
T4 N2 M0
 Dietary (eg, charred and processed meats)
IIIC Any T N3 M0  Regular, moderate consumption of alcohol (3-5
alcoholic beverages per week)
IV Any T Any N M1  Tobacco smoke (both active and passive exposure)
 Environmental carcinogens (eg, exposure to pesticides,
Pathophysiology radiation, and environmental and dietary estrogens)

The current understanding of breast cancer etiopathogenesis is Signs and symptoms

that invasive cancers arise through a series of molecular
alterations at the cell level. These alterations result in breast
epithelial cells with immortal features and uncontrolled growth.
Genomic profiling has demonstrated the presence of discrete
breast tumor subtypes with distinct natural histories and clinical
behavior. The exact number of disease subtypes and molecular
alterations from which these subtypes arise remains to be fully
elucidated, but these generally align with the presence or
absence of estrogen receptor (ER), progesterone receptor (PR),
and human epidermal growth factor receptor 2 (HER2).
Early breast cancers may be asymptomatic, and pain and
discomfort are typically not present. If a lump is discovered, the
following may indicate the possible presence of breast cancer:
 Change in breast size or shape
 Skin dimpling or skin changes
 Recent nipple inversion or skin change, or nipple
abnormalities
 Single-duct discharge, particularly if blood-stained
 Axillary lump

Diagnosis
Breast cancer is often first detected as an abnormality on a
mammogram before it is felt by the patient or health care
provider.

Evaluation of breast cancer includes the following:

 Clinical examination
 Imaging
 Needle biopsy

Physical examination

If a palpable lump is found and possesses any of the following

features, breast cancer may be present:

 Hardness
 Irregularity
 Focal nodularity
 Fixation to skin or muscle

Screening

Early detection remains the primary defense in preventing

breast cancer. Screening modalities include the following:

 Breast self-examination
 Clinical breast examination
 Mammography
 Ultrasonography
 Magnetic resonance imaging
Etiology
Risk factors for breast cancer: Biopsy
 Increasing age and female sex Core biopsy with image guidance is the recommended
 Family history of breast cancer diagnostic approach for newly diagnosed breast cancers. This is
a method for obtaining breast tissue without surgery and can
eliminate the need for additional surgeries. Open excisional
biopsy is the surgical removal of the entire lump.
Differential Diagnoses
 Breast Abscess and Masses
 Breast, Fibroadenoma
Management
Pediatrics
Surgery
Surgery is the primary treatment for breast cancer. Lumpectomy
or total mastectomy may be indicated.
Radiation therapy may follow surgery in an effort to eradicate
residual disease while reducing recurrence rates. Adjuvant
treatment for breast cancer involves radiation therapy and a
variety of chemotherapeutic and biologic agents. There are 2
general approaches for delivering radiation therapy:
 External-beam radiotherapy (EBRT)
 Partial-breast irradiation (PBI)
 Surgical resection with or without radiation is the
standard treatment for ductal carcinoma in situ.
Pharmacologic agents
Hormone therapy and chemotherapy are the 2 main
interventions for treating metastatic breast cancer. Common
chemotherapeutic regimens include the following:
 Docetaxel
 Cyclophosphamide
 Doxorubicin
 Carboplatin
 Methotrexate
 Trastuzumab
Two selective estrogen receptor modulators (SERMs), tamoxifen
and raloxifene, are approved for reduction of breast cancer risk
in high-risk women.
4. Lactation
 Estrogens and progesterone stimulate the growth and
development of the breasts throughout pregnancy
 Prolactin levels increase steadily during pregnancy
because estrogen stimulates prolactin secretion from
the anterior pituitary
 Lactation does not occur during pregnancy because
estrogen and progesterone block the action of
prolactin on the breast
 After parturition, estrogen and progesterone levels
decrease abruptly and lactation occurs
 Lactation is maintained by suckling, which stimulates
both oxytocin and prolactin secretion
 Ovulation is suppressed as long as lactation continues
because prolactin has the following effects
a. Inhibits hypothalamic GnRH secretion
b. Inhibits the action of GnRH on the anterior
pituitiary, and consequently inhibits LH and
FSH secretion
c. Antagonizes the actions of LH and FSH on the
ovaries
1. EPI vaccines
Expanded Program on Immunization – Philippines
 Immunization is the process of inducing immunity
against a specific disease
 Immunity can be induced either passively through
administration of preformed antibodies or actively
through administration of a vaccine or toxoid
Active immunization
 Involves administration of whole or parts of a
microorganism or a modified product of that
microorganism (toxoid, purified antigen)
 This will evoke an immunologic response mimicking
that of the natural infection
 Usually presents little or no risk to the recipient
 Vaccines can consist of:
a. Live attenuated virus – measles, MMR, OPV,
varicella, rotavirus vaccines
b. Live attenuated bacteria – BCG
 Contraindication to ALL VACCINES
a. Serious allergic reaction (anaphylaxis) after a
previous vaccine dose
b. Serious allergic reaction to a vaccine
component
 Contraindications to ALL LIVE VACCINES
a. Immunocompromised patients
b. Patients given immunoglobulin and blood
products for the past 3 months
c. Pregnancy and possibility of getting pregnant
within 3 months
d. Household contacts of immunocompromised
patients (for OPV only)
Vaccine Minimum Dose Route and Min  0.05 ml ID from birth to 4 weeks, 0.1 ml ID beyond 1
Age (No) Site of interval month at right upper deltoid
Admin b/w
doses
Hepatitis B Vaccine
BCG 1 Birth; or 0.05 ml ID, deltoid R  Inactivated viral antigen
any time for NB; arm  0,1 & 6 months
after birth 0.1 ml
 If mother is HBsAg (+), give HIBG and Hep B vaccine
for
infants within 12 hours of birth
(1)  After birth, the 2nd dose should be given at age 1-2
months
DTP 6 weeks 0.5 ml IM, upper 4
(3) outer weeks  The 3rd dose should be given at 6 months
portion of  Dose: up to 19 years old – 10 mcg (0.5 ml)
thigh 19 years odl and above – 20 mcg (1 ml)
OPV 6 weeks 2 drops PO, mouth 4
(3) weeks Diphtheria, Tetanus and Pertussis (DTP) Vaccine
DTap
Hep B 6 weeks or 0.5 ml IM,
 DT are toxoids
at birth (3) – 0, anterolateral
1 & 6 aspect of  aP is killed/inactivated acellular pertussis
months thigh DTP or DTwP
 DT are toxoids
Measles 9 mos; 6 0.5 ml SC, outer
mos if (1) part of thigh  P is killed/inactivated whole cell pertussis
epidemic  DTP/DTaP vaccine usual side effect: fever up to 72
hours
BCG 2 At school 0.1 ml ID, deltoid L
entry, (1) arm
whether or Poliomyelitis Vaccine
not child  6 weeks, then at least 4 week intervals
has BCG  Inactivated or killed polio vaccine (IPV) – 0.5 ml, IM
scar
Tetanus Women of 0.5 ml IM, deltoid TT1 at Measles vaccine
Toxoid childbearing (5) region first  live attenuated
age contact  0.5 ml SC
TT2 at  Recommended at age 9 months but may be given as
least 4 early as 6 months when there is an epidemic
weeks
after
Hemophilus influenzae b (Hib) Vaccine
TT3 6  0.5 ml IM given at 2, 4, 6, and 12-15 months old
weeks
after
Measles, Mumps, Rubella (MMR) Vaccine
TT4 at  Live attenuated viral vaccine
least 1
 0.5 ml SC
year
after  Given at 12-15 months, a booster dose is
recommended at 4-6 years old
TT5 at
least 1
Varicella Vaccine
year
after  live attenuated vaccine
 0.5 ml SC
 Routinely given at age 12 months and up but can be
BCG Vaccine given as early as 9 months
 Live attenuated vacterial vaccine  Dose: single dose for ages 1-12 years; a booster dose is
 At birth or anytime after birth recommended at 4 to 6 years old
 2 doses 6-10 weeks apart in children >13 years  Lifts head momentarily on prone
 Head lags when pulled to sit
Hepatitis A Vaccine  Begins to regard surroundings
 Inactivated viral antigen  Follows objects to midline
 Given to children 1 years and above in 2 doses 6 to 12 2 months
months apart  Motor activity generalized
 Dose for 1-18 years old: 0.5 ml IM  Smiles and coos socially
>19 years old: 1ml IM  Follows objects past midline
 Indications  Head lags on pull to sit
- Persons travelling to areas with high prevalence of 3 months
Hep A  Visually tracks objects well
- Occupational hazards  Begins to have hand regard
- Hemophiliacs – contacts of infected persons  Good head control on prone and looks around
 Improved head control on sitting position
Pneumococcal Vaccine  Sustained smiling and cooing
 PCV is given at 2, 4, 6 and 12-15 months or 1 dose at 2 4 months
years of age  Begins to reach for toys symmetrically
 PPV is given for children 2 years and above  Regards toys and puts them into mouth
 0.5 ml IM  Removes diaper on face
 Good head control on sitting position
Influenza Vaccine
 Midline regard (plays with hands)
 Inactivated vaccine
 Laughs
 Dose for 3 years and above: 0.5 ml IM or SC 6 months
6-36 months: 0.25 ml IM or SC
 Reaches with either hand
 Indications:
 Chest up when prone
- Prophylaxis in children older than 6 months and
 Rolls over
adult over 60 years
 May sit briefly when placed
- CV or metabolic disease, cystic fibrosis, chronic
 Laughs and plays with examiner
respiratory disease, chronic renal insufficiency
 Imitates speech sounds
8 months
Rotavirus Vaccine
 Sits alone
 Inactivated vaccine
 Begins to creep
 Given at 2, 4 and 6 months
 Regards self in mirror
 0.5 ml IM
 Babbles
 Crude prehension
Human Papilloma Virus Vaccine
 Transfer object from 1 hand to the other
 Inactivated vaccine
 Says papa and mama indiscriminately
 Given from 9-45 years old at 0, 1, and 4 months; or 0, 2,
and 6 months  Responds to commands of “no”
10 months
 0.5 ml IM
 Crawls and pulls to stand
2. Developmental milestones  Begins to cruise around the crib or furniture
 Better prehension (thumb and forefinger
Newborn period (1st 4 weeks) opposition)
 Lies in flexed position, turns head side to side  Utters “mama” or “dada”
 Head lags on ventral suspension  Holds bottle
 May fixate face on light in line of vision  Feed self with crackers
 Doll’s eye movement of eye when turning body  Waves bye-bye
 Visual preference for human face  Gesture language
1 month
 Spontaneous motor activity
12 months  Hops on one foot
 Walks alone with one hand held  Throws ball overhead
 Stands alone  Draws person with head, trunk, arms or legs
 2 words other than mama and dada  Counts 3 objects
 Beings to feed with fingers  Draws a triangle, copies a square
 Kisses on request :*  Names one or more colors
 Releases object on request  Sings songs
 Obeys commands with gestures  Toilet trained
15 months  Role plays
 Independent walking 5 years
 Creeps upstairs  Skips
 3-4 words other than mama, dada  Draws a person
 Drinks from cup  Dresses / undresses unaided
 Begins to feed with spoon  Names 4 or more colors
 Vocalizes and points to something  Counts > 10
 Obeys simple commands without gesture  Ties shoelaces
18 months  Asks meaning of words
 Walks well 6 years
 Throws a ball  Draws a person with hands and clothes
 Stacks 3-4 blocks  Repeats 4-5 digits forward
 10 word vocabulary  Knows morning and afternoon
 Pulls toy on string  Knows right and left sides
2 years  Copies a diamond
 Runs well, jumps
 Uses pronouns and produces 3 word sentences 3. SMR Staging
 Feeds self with spoon Classification of Sex Maturity States in Girls
 Toilet-trained by day SMR Stage Pubic Hair Breasts
 Removes clothes 1 Preadolescent Preadolescent
 Points to body parts
2 Sparse, lightly Breast and
2 ½ years
pigmented, papilla elevated
 Partially undresses self medial border of as small mound;
 Draws vertical and horizontal lines labia diameter of
 Knows full name, uses “I” areola increased
 Helps to put things away 3 Darker, beginning Breast and areola
3 years to curl, increased enlarged, no
 Alternate feet in climbing stairs amount contour
 Pedals a tricycle separation
 Builds a tower of 6-8 blocks 4 Coarse, curly, Areola and
 Plays simple games abundant, but papilla form
 Names drawing less than in adult secondary
mound
 Copies a circle, later a cross
 Uses plurals and obeys prepositional commands 5 Adult feminine Mature, nipple
 Knows age and sex triangle, spread projects, areola
to medial surface part of general
 Buttons and unbuttons
of thighs breast contour
 Puts on shoes
 Counts 1-10
4 years
 Runs and climbs well
 Descends stairs on alternate feet
 Surgery
Classification of Sex Maturity in Boys
SMR Pubic hair Penis Testes 1. Trauma

1 None Preadolescent Preadolescent Goal

Primary survey initial management and Identify and treat
2 Scanty, Minimal Enlarged concurrent resuscitation conditions which are an
long, slightly change or scrotum, immediate threat to life
pigmented enlargement pink, texture Secondary survey diagnostic evaluation Examination of patient
and definitive care in a systematic fashion
altered
3 Darker, Lengthens Larger ABC – airway, breathing, circulation
starting to Airway Management
curl, small All patients with blunt trauma require cervical spine immobilization (hard collar,
amount sand bags).
4 Resembles Larger, glans Larger,
Px who are conscious with normal voice and no tachypnea, do not need early
adult type and breadth scrotum dark
attention to the airway.
but less increase size
quantity, Px who have an abnormal voice and altered mental status require further airway
coarse, curly evaluation.
5 Adult Adult size Adult size
distribution, Altered mental status is the most common indication for intubation as px is not
spread to able to protect airway.
medial
Types of intubation
surface of Nasotracheal intubation Only in px breathing spontaneously and is
thighs contraindicated in apneic px
Orotracheal intubation  In px with potential cervical
spine injuries
 Able to directly visualize vocal
cords, use large diameter
endotracheal tubes, use in
apneic px
 Conscious px need
neuromuscular blockade or
sedation
Surgical intubation Cricothyroidotomy

Breathing Management
All injured px should receive supplemental oxygen and be monitored with pulse Four life threatening injuries that must be identified during the circulation
oximetry. section of the primary survey
Massive >1500ml of blood Tube thoracostomy
Conditions that may constitute an immediate threat to life due to compromised hemothorax or 1/3 of patient’s for quantifying blood
ventilation blood volume in loss and lung re-
the pleural space in inflation; surgical
pediatric px intervention
Tension Respiratory distress w/ Immediate Cardiac Tamponade Occurs most Beck’s Triad often not
pneumothorax  Tracheal deviation tube commonly after seen due to chaos of
away from the thoracotomy penetrating trauma site, UTZ best
affected side without thoracic injuries for dx;
 Decreased breath awaiting pericardiocentesis for
sounds on the chest relief, thoracotomy to
affected side radiograph address injury
 Distended neck confirmation Massive Blood in the Laparotomy for
veins hemoperitoneum peritoneal cavity identification and
 Systemic control bleeding
hypotension Mechanically Severe pelvic Pelvic binder to
 Subcutaneous unstable pelvic fractures leading to stabilize pelvis,
emphysema on the fractures mechanical hemorrhage control –
affected side instability and pelvic/retroperitoneal
Open Full thickness loss of the chest Wound vascular disruption packing, intraaortic or
pneumothorax wall permitting a free closure and as a consequence intrailiac balloon
communication between tube of the displacement occlusion
pleural space and atmoshpere thoracostomy of tissues at the
Flail Four or more ribs are Px frequently moment of impact
chest/pulmonary fractured in at least two have
contusion locations underlying
pulmonary Shock and initial fluid resuscitation
contusion; Signs of shock:
respiratory  Tachycardia
failure not  Hypotension
immediately
 Tachypnea
evident,
 mental status changes
requires
 diaphoresis
frequent
 pallor
reassessment

Circulation

First, approximate px’s CV status by palpating peripheral pulses.

Systolic BP needed for palpation

Carotid 60mmHg
Femoral 70mmHg
Radial 80mmHg

External hemorrhage control is needed before restoring circulating volume

Extremities – manual compression and splints

Penetrating injuries to head, neck, thoracic outlet, groin, and extremities –

digital control (gloved finger through the wound directly on the bleeding vessel
wit enough pressure to control active bleeding)

Scalp laceration involving the aponeurotic layer – Rainey clips, large nylon
continuous stitch

*Do not do blind clamping! There is potential risk to damage adjacent

structures.
Fluid resuscitation

IV access for fluids – two peripheral catheters, gauge 16 or larger for adult
bolus of isotonic crystalloid, typically Ringer's lactate

If two attempts at percutaneous peripheral access fail, in children <6 y/o,

 2 L (adult)
perform interosseous canulation through proximal tibia or distal femur
 20 mL/kg (child) IV
For persistent hypotension, this is repeated once in an adult and twice in a child Secondary Survey
before red blood cells (RBCs) are administered. Patients who have a good
response to fluid infusion are presumed to have adequate overall perfusion. Patient is examined in a systematic fashion. The patient and surrogates should
be queried to obtain an AMPLE history (Allergies, Medications, Past illnesses or
*watch out for pxs on beta blockers and in good physical condition – may not be Pregnancy, Last meal, and Events related to the injury). The physical
able to raise their heart rate and may have tachycardia in the 90s respectively examination should be head to toe, with special attention to the patient's back,
axillae, and perineum, because injuries here are easily overlooked.
*hypotension not reliable indicator of hypovolemia - >30% fluid loss must occur
before hypotension occurs A nasogastric tube should be inserted in all intubated patients to decrease the
risk of gastric aspiration
Classification of pxs based on response to initial fluid therapy
Responders stable or have a good response *NGT contraindicated in px with complex facial fractures, oral tube placement
- normalization of vital signs, instead
mental status, urine output;
unlikely to have significant
A Foley catheter should be inserted in patients unable to void to decompress the
ongoing hemorrhage
bladder, obtain a urine specimen, and monitor urine output
Transient Responders respond initially to volume
loading by an increase in blood
pressure only to then
hemodynamically deteriorate
once more *deferred if patient with signs of urethral injury
Nonresponders persistent hypotension -
require immediate  blood at the meatus
identification of the source of  perineal or scrotal hematomas
hypotension with appropriate
 high-riding prostate
intervention

2. Burns
Persistent hypotension
 Initial evaluation
Pxs with persistent hypotension require systemic and prompt intervention  Airway management
 Evaluation of other injuries
First consider shock. Two most common types for persistent hypotension in  Estimation of burn size
trauma are hemorrhagic and cardiogenic.  Diagnosis of carbon monoxide and cyanide poisoning

The two are distinguished by CVP monitoring
 Px with flat neck veins and a CVP of <5 cm H2O is hypovolemic and is
likely to have ongoing hemorrhage
 Px with distended neck veins or a CVP of >15 cm H2O is likely to be in
cardiogenic shock
Burn patients should be first considered trauma patients
Hypothermia is one of the common prehospital complications that contributes
to resuscitation failure – wrap px in clean blankets during transport, avoid
cooling blankets

In patients without clear operative indications and persistent hypotension, one Never give prophylactic antibiotics – promotes fungal growth and resistant
should systematically evaluate the five potential sources of blood loss. organisms; give tetanus booster

 Scalp Rule of 9s for fluid requirement

 Chest
 Abdomen
 Pelvis
 Extremities

Thoracoabdominal trauma should be evaluated with a combination of chest

radiograph, FAST, and pelvic radiograph.

If negative, do a diagnostic peritoneal aspiration

Examine extremites. Extremity related blood loss when additive can be

substantial.

Blood loss
Each rib 100-200ml
Tibia 300-500ml
Femur 800-1000ml
Pelvis >1000ml
Inhalation poisoning Three zones in a burn injury

TX Zone of coagulation Most severely burned portion

and is typically in the center of
CO Hemoglobin has Administer 100% the wound, will need excision
200-250 times O2 and grafting
greater affinity for
CO than O2 Zone of stasis Has a local response of
vasoconstriction and resultant
Hydrogen Cyanide Inhibits cytochrome Sodium thiosulfate ischemia, resuscitation and
oxidase – inhibits – transforms wound care may help prevent
cellular cyanide into conversion to a deeper wound
oxygenation; lactic thiocyanate,
acidosis, S-T hydroxocobalamin, Zone of hyperemia Will heal with minimal or no
elevation in ECG 100% O2 scarring

Burn classification Resuscitation

Thermal Most common Most commonly used formula, the Parkland or Baxter formula, consists of 3 to 4
mL/kg per percent burned of lactated Ringer's
Electrical Can cause arrhythmias,
compartment syndromes with Give half over 8 hours, the other half over the next 16 hours
rhabdomylosis
MAP is at 60 mmHg – to ensure end organ perfusion
Chemical Can be absorbed and cause
metabolic derangements Urine output at 30ml/h in adults

1 to 1.5 ml/kg/hr in pediatric patients

Burn depth Inhalation Injury Management

Treatment of inhalation injury consists primarily of supportive care. Aggressive

pulmonary toilet and routine use of nebulized bronchodilators such as albuterol
are recommended

Treatment of Burn wounds

Drug Indication Adverse effects

Silver sulfadiazine prophylaxis against Silver sulfadiazine

burn wound will destroy skin
infections rather grafts and is
than treatment of contraindicated on
existing infections burns in proximity
to newly grafted
areas

Mafenide acetate Effective topical absorbed

antimicrobial, systemically, and a
effective even in major side effect is
the presence of metabolic acidosis
eschar, excellent
antimicrobial for
fresh skin grafts

Silver nitrate broad-spectrum topical application

antimicrobial can lead to
activity electrolyte
extravasation with
resulting
hyponatremia
 Wound healing

bacitracin, Wounds that are Used for superficial Hemostasis and inflammation
neomycin, nearly healed partial thickness
polymyxin B facial burns, Wounding – disruption of tissue integrity, leading to division of blood vessels
meshed skin grafts and direct exposure of extracellular matrix to platelets
where the
interstices are Exposure of subendothelial collagen to platelets results in:
closed
 platelet aggregation
 degranulation
 activation of the coagulation cascade
Surgery Platelet alpha-granules release a number of wound-active substances
 PDGF
Full-thickness burns with a rigid eschar can form a tourniquet effect as the  TGFB
edema progresses, leading to compromised venous outflow and eventually  Platelet activating factor
arterial inflow. The resulting compartment syndrome is most common in  Fibronectin
circumferential extremity burns, but abdominal and thoracic compartment  Serotonin
syndromes also occur. Formed fibrin clot achieves hemostasis and acts as scaffolding for wound
inflammatory cells
Warning signs of compartment syndrome
Order of cellular infiltration
 Paresthesias
 Pain PMN 24-48 hrs Phagocytosis of
 Decreased capillary refill bacteria and tissue
 Progression to loss of distal pulses debris
Escharotomies are rarely needed within the first 8 hours – not performed unless
indicated due to terrible aesthetic sequelae. Macrophage 48-96 hrs Activation and
Digital escharotomies do not usually result in any meaningful salvage of recruitment of
functional tissue and are not recommended other cells via
mediators;
Early excision and grafting in burned patients has greatly decreased mortality. regulates
angiogenesis and
3. Inflammation matrix deposition
and remodeling
Inflammatory response to injury or infection involves cell signaling, cell
migration, and mediator release
T lymphocytes 1 week Modulation of
tissue
Five cardinal signs
environment;
downregulating
 Dolor (pain)
effect on fibroblast
 Calor (heat)
collagen synthesis
 Rubor (redness)
 Tumor (swelling)
 Functio laesa (loss of function)
Proliferation
The process of acute inflammation is triggered by macrophages, dendritic cells,
histiocytes, Kupfer cells and mastocytes. These cells have pattern recognition 2nd phase of wound heaing
receptors which recognize molecules that are broadly shared by pathogens but Spans days 4 to 12
distinguishable from host molecules. At the onset of an infection, burn, or other Where tissue continuity is re-established
injuries, these cells undergo activation and release inflammatory
mediators responsible for the clinical signs of inflammation. Vasodilation and its Fibroblasts primary function of matrix
resulting increased blood flow causes the redness (rubor) and increased heat synthesis remodeling
(calor). Increased permeability of the blood vessels results in an exudation
(leakage) of plasma proteins and fluid into the tissue (edema), which manifests Endothelial cells formation of new capillaries,
itself as swelling (tumor). Som of the mediators such as bradykinin increases migrate from intact venules
sensitivity to pain (dolor). The mediator molecules also alter the blood vessels close to the wound
to permit the migration of leukocytes, mainly neutrophils, outside of the blood
vessels (extravasation) into the tissue. The neutrophils migrate along
a chemotactic gradient created by the local cells to reach the site of injury.
Matrix Synthesis

Collagen synthesis

Type I collagen is the major component of extracellular matrix in skin

Type III, which is also normally present in skin, becomes more prominent and protein synthesis. Failure to provide adequate nonprotein energy sources will
important during the repair process lead to consumption of lean tissue stores.

Proteoglycan synthesis

Glycosaminoglycans comprise a large portion of the "ground substance" that

makes up granulation tissue

Major glycosaminoglycans present in wounds are dermatan and chondroitin
sulfate
Fibroblasts synthesize these compounds, increasing their concentration greatly
during the first 3 weeks of healing
It is thought that the assembly of collagen subunits into fibrils and fibers is
dependent on the lattice provided by the sulfated proteoglycans
The Harris-Benedict equations are suitable for estimating energy requirements
in the majority of hospitalized patients. It has been demonstrated that the
provision of 30 kcal/kg per day will adequately meet energy requirements in
most postsurgical patients, with a low risk of overfeeding. After trauma or
sepsis, energy substrate demands are increased, necessitating greater
nonprotein calories beyond calculated energy expenditure.

Maturation and remodeling

Begins during the fibroplastic phase

Collagen is broken down by matrix metalloproteinases

An appropriate nonprotein-calorie:nitrogen ratio of 150:1 (e.g., 1 g N = 6.25 g
There is collagen synthesis and eventually the re-establishment of extracellular protein) should be maintained, which is the basal calorie requirement provided
matrix composed of a relatively acellular collagen-rich scar to limit the use of protein as an energy source.

Deposition of matrix at the wound site follows a characteristic pattern: 5. Surgical Wound Classification

 Fibronectin and collagen type III constitute the early matrix

scaffolding
 Glycosaminoglycans and proteoglycans represent the next significant
matrix components
 Collagen type I is the final matrix

The amount of collagen in the wound reaches a plateau, but the tensile strength
continues to increase for several more months
Scar remodeling continues for many (6 to 12) months postinjury, gradually
resulting in a mature, avascular, and acellular scar

The mechanical strength of the scar never achieves that of the uninjured tissue

Epithelialization

The process is characterized primarily by proliferation and migration of epithelial

cells adjacent to the wound. It begins on day 1 of injury and is seen as thickening
of the epidermis at the wound edge. Marginal basal cells enlarge, and begin to
migrate across the surface of the provisional matrix. Fixed basal cells undergo a
series of rapid mitotic divisions, and migrate by moving over one another in a
leapfrog fashion until the defect is covered. Once the defect is bridged, the
epithelial cells become more columnar in shape, and increase their mitotic Pharmacology
activity. Layering of the epithelium is re-established, and the surface layer
eventually keratinizes. 1. H1 and H2 Histamines

Wound Contraction Histamine is neurotransmitter and mediator of allergic responses.

Myofibroblast has been postulated as being the major cell responsible for Synthesized from histidine and stored in vesicles in mast cells, basophils and
contraction some nerve endings

Typically this cell contains alpha-smooth muscle actin in thick bundles called Histamine’s effects are mediated by three G-protein coupled receptors
stress fibers, giving myofibroblasts contractile capability
Receptor G protein Location Function
4. Surgical Nutrition H1 Gq Smooth, Increased IP3
muscle, gland and DAG,
The goals of nutritional support in the surgical patient are to prevent or reverse cells, some smooth
the catabolic effects of disease or injury and meet substrate requirements for nerve endings muscle
contraction
 (except Cortisol – major natural glucocorticoid – rapidly metabolized, short, duration of
vessels); action
increased
secretion Aldosterone – major natural mineralocorticoid
H2 Gs Parietal cells Increased
(stomach), cAMP, Synthetic corticosteroids – longer duration of action, less mineralocorticoid
heart increased
effect
acid
secretion,
cardiac Prednione, triamcinolone and dexamethasone (in order of increasing DOA)
stimulation
H3 ? Nerve Modulation Fludrocortisone – synthetic mineralocorticoid
endings of transmitter
release Clinical uses

Adrenal dysfunction – replacement therapy in Addison’ disease and as

H1 blocking drugs (traditional antihistamines) fall into three groups supplementation in acute adrenal insufficiency states (infection, shock, trauma)

Group Examples Uses Toxicities Nonendocrine uses – use in inflammatory and immune disorders
1st Diphenhydramine Allergy, sleep Strong alpha
Generation aid, motion and Toxicities
sickness, muscarinic
nausea of block; Suppression of ACTH – adrenocortical atrophy
chemotherapy strongly
sedative
Cushingoid state – fat deposition and muscle atrophy
1st Chlorpheniramine Allergy Much
generation, reduced
newer sedative and Metabolic effects – hyperglycemia, increased insulin demand, osteoporosis,
ANS effects aseptic hip necrosis, decreased skeletal growth in children; mineralocorticoid –
2nd Fexofenadine, Allergy Negligible electrolyte imbalance, edema, hypertension
Generation loratidine, CNS and ANS
desloratidine, effects Other toxicities – GI ulcers, decreased wound healing, cataract formation,
cetirizine glaucoma, increased infections, mental dysfunction
H1 blockers are used in the treatment of urticarial, hay fever and other IgE
mediated allergic reactions. Toxicities reflect ther ANS and CNS effects. Corticosteroid Antagonists

H2 blockers Receptor antagonists

 Cimetidine Spironolactone Blocks aldosterone receptors

 Famotidine Mifepristone Blocks glucocorticoid receptors
 Nizatidine
 Ranitidine
Synthesis inhibitors
H2 blockers are used for acid peptic ulcer disease, especially heartburn and
peptic ulcer. Toxicities include inhibition of hepatic cytochrome P450, drug Ketoconazole – inhibits both corticosteroids and gonadal receptors
metabolizing enzymes and an antiandrogenic action.
3. Antibiotics
*most H2 toxicities are from Ranitidine
Inhibitors of cell wall synthesis: Penicillin
2. Steroids
Bactericidal antibiotics that contain a Beta lactam ring necessary for
Corticosteroids bind to cytosolic receptors and the complexes formed undergo antimicrobial activity.
dimerization and then enter the cell nucleus. There they alter gene expression
by binding to tissue specific nuclear response elements. Subclasses

Metabolic effects: Glucocorticoids increase gluconeogenesis, insulin secretion, Penicillinase-susceptible Pen G, Pen V
narrow spectrum
liogenesis, lipolysis. Catabolic effects nclude muscle and lymphoid tissue
Penicillinase-resistant narrow Methicillin, nafcillin
wasting, osteoporosis and growth inhibition. Mineralocorticoids increase
spectrum
synthesis of ion transporters and sodium channels in renal collecting tubules. Penicillinase-susceptible broad Ampicillin, amoxicillin,
spectrum ticarcillin
Immunosuppressive and anti-inflammatory actions: High doses of
glucocorticoids result in decreased synthesis of prostaglandins and leukotrienes.
There is also decreased leukocyte migration, phagocytosis, lymphocyte MOA: bind to specific proteins (penicillin binding proteins, PBPs) and inhibit
proliferation and activity. transpeptidation, the final step in cell wall synthesis and also activate autolytic
enzymes which cause lesions in th bacterial cell membrane
Natural corticosteroids
MOR:
  Formation of penicillinases (staph, gram-negative bacilli)
 Changes in PBP structure prevent binding (MRSA, NRSA)
 Changes in porin structure prevent access to the cytoplasmic
membrane (pseudomonas resistant to ticarcillin)
Pharmacokinetics
Oral bioavailability: Gastric acids inactivates some penicillins (Pen G)
Elimination: Most are eliminated via active tubular secretion; nafcillin is
eliminated in bile and ampicillin undergoes enterohepatic cycling
Clinical Uses
Pen G Strep, pneumococci,
enterococci, meningococci,
Treponema pallidum,
spirochetes
Nafcillin, oxacillin, related Known or suspected staph
drugs infections (not MRSA)
Amoxicillin and ampicillin Streptococci, E coli,
Haemophilus influenza,
Moraxella catarrhalis, Listeria
monocytogenes, H pylori
Ticarcillin and related drugs Gram negative bacilli including
Pseudomonas aeruginosa
(synergy with aminoglycosides)
*certain penicillins are enhanced by the addition of clavulanic acid and
sulbactam – inhibit bacterial penicillinases
Inhibitors of cell wall synthesis: Cephalosporins, carbapenems, vancomycin
Cephalosporins
MOA: bactericidal B-lactams similar to penicillins. Resistance may occur via B-
lactamase formation and changes in PBP
1st gen Gram-positive cocci (not
MRSA) E coli, Klebsiella
pneumonia and some Proteus
species
2nd gen Gram negative bacilli including
Bacteroides fragilis (cefotetan);
Haemophilus influenza and
Moraxella catarrhalis (cefaclor)
3rd gen Gram (+), gram (-) cocci and
gram (-) bacilli including B-
lactamase forming strains
including Pseudomonas
(ceftazidime), anaerobes
(ceftizoxime) and gonococci
(ceftriaxone, cefixime)
4th gen Cefipime
*none of the cephalosporins has clinically useful activity in the treatment of
infections caused by methicillin-resistant staph, Listeria species, enterococci,
Mycoplasma pnumoniae, chlamydia
Toxicities
Allergic reactions
 Complete cross allergenicity between different cephalosporins
 Partial cross allergenicity with penicillin and cephalosporins
Other effects – nausea, diarrhea, and opportunistic infections;
hypoprothrombinemia (cefotetan) and disulfiram like reactions with ethanol
Carbapenems
Imipenem and meropenem are bactericidal, penicillinase resistant antibiotics
with wide activity against gram (+) and gram (-), including anaerobes.
Carbapenems are IV agents eliminated by the kidney; imipenem is given with
cilastatin, which blocks its metabolism.
Toxicities – nausea, diarrhea, skin rash, seizures
Vancomycin
MOA: Bactericidal inhibitor of cell wall synthesis by inhibiting glycosylation
reactions. Resistance involves decreased binding of the drug.
Pharmacokinetics: renal elimination
Clinical use: DOC for MRSA and for pseudomembranous colitis
Toxicities – fever, chills, potential ototoxicity and nephrotoxicity
Inhibitors of Protein synthesis: Macrolides, Clindamycin, Tetracycline and
Chloramphenicol
MOA and Resistance: All are bacteriostatic inhibitors of protein synthesis at the
ribosomal level.
Macrolides Binds to 50s subunit to block
Clindamycin translocation
Chloramphenicol Binds to 50s subunit but
prevents transpeptidation by
preventing binding of
aminoacyl moiety of charged
tRNA
Tetracyclines Bind to 30s subunit to prevent
binding of charged tRNA to the
acceptor site of the ribosomal
mRNA complex
Resistance – in gram (+) cocci, resistance to macrolides involves methylation of
the 50s receptor, preventing binding of the antibiotics; chloramphenicol –
formation of acetyltransferases that inactivate the drug; tetracycline –
decreased intracellular accumulation
Macrolide antibiotics
Erythromycin, azithromycin, clarithromycin
Good oral bioavailability
Erythromycin (biliary excretion) and clarithromycin (metabolism and renal
clearance) have half-lives of <5 hours.
Azithromycin accumulates in the tissues and undergoes renal elimination with a
half-life of >3days.
Clinical Uses: Gram (+) cocci, Mycoplasma pneumonia, chlamydial species,
ureaplasma urealyticum, Legionella pneumophilia
Azithromycin - Haemophilus influenza and Moraxella catarrhalis
Clarithromycin – H pylori
Toxicities: Erythromycin causes GI distress, cholestasis (avoid in pregnancy).
Both eryhthromycin and clarithromycin inhibit Cytochrome P-450 – may
enhance carbamazepine, theophylline, warfarin. Azithromycin does not inhibit
drug metabolism and is safe in pregnancy.
Clindamycin
Pharmacokinetics: Effective orally, eliminated by metabolism, biliary and renal
clearance.
Clinical Uses: Gram (+) cocci and anaerobes including Bacteroides strains. It is
prophylactic against enterococcal endocarditis in penicillin-allergic patients and
is back up drug for Pneumocystis Carnii and Toxoplasma gondii.
Toxicities: Gi distress, skin rash, opportunistic infections including
pseudomembranous colitis.
Tetracyclines
Tetracyclines and doxycycline
Pharmacokinetics: Good oral bioavailability (avoid antacids); eliminated via the
kidney but a large fraction of doxycycline appears in the feces.
Clinical Uses: Vs Mycoplasma pneumonia, chlamydial species, Rickettsia, and
Vibrio.
Tetracyclines – used in H pylori, back up in syphilis, prophylactically in chronic
bronchitis and acne
Doxycycline – DOC in Lyme disease
Toxicities: GI disturbances, tooth enamel dysplasia and bone growth
irregularities in children
Chloramphenicol
Pharmacokinetics: Orally effective, metabolized by glucoronosyltransferase
Clinical Uses: back up drug in bacterial meningitis, typhoid fever, rickettsial
disease and Bacteroides infections.
Toxicities: opportunistic infections, bone marrow suppression, aplastic anemia,
gray baby syndrome – neonates with inadequate glucoronosyltransferase
Inhibitors of Protein synthesis: Aminoglycosides, Streptogramins, Linezolid
MOA: Aminoglycosides – bacterial inhibitors of protein synthesis
Intracellular accumulation is oxygen dependent – anaerobes resistant
Bind to 30s ribosomal subunit and cause misreading of mRNA
Streptogramins are also bactericidal, binding to a site on the 50s subunit
extrusion of nascent polypeptides; also inhibit tRNA synthetase
Linezolid (bacteriostatic) binds to 50s and blocks initiation
MOR: Resistance to aminoglycosides in gram (+) bacteria via formation of
inactivating transferases.
Pharmacokinetics of aminoglycosides
Absorption – not absorbed orally, needs parenteral administration
Elimination – renal clearance is proportional to GFR, half-life 2-3 hours.
*despite short half-life, once daily dosing is effective
*killing is concentration dependent but nephrotoxicity is dependent on both
time and dosage
Gentamicin, tobramycin and amikacin: aminoglycosides are used for gram (-)
bacilli, E coli, Enterobacter, Klebsiella, Proteus, Pseudomonas and Serratia
*synergism with penicillins against enterococci and Pseudomonas strains
Streptomycin and neomycin: Streptomycin is used for tuberculosis, cholera, and
tularemia. Neomycin is only used topically due to toxicity
Toxicities of aminoglycosides
Nephrotoxicity – ATN
Ototoxicity – auditory or vestibular function which may not be fully reversible
Contact dermatitis – frequent with neomycin
Streptogramins and Linezolid
Streptogramin combination of quinupristin and dalfopristin – IV for MRSA,
vancomycin resistant Staph aureus and enterococcus.
Linezolid – similar clinical indication and active against penicillin resistant
pneumococci
Toxicities: Streptgramins – arthralgia and myalgia, inhibitors of CP-450
Inhibitors of Folic Acid synthesis: Sulfonamides and Trimethoprim
MOA
Sulfonamides: inhibit dihydropteroate synthase (1st step in folic acid synthesis)
Trimethoprim: analog of dihydrofolic acid, inhibits the dihydrofolate reductase
in bacteria
Sequential blockade: combo of sulfamethoxazole and trimethoprim cause
sequential blockade of folic acid synthesis
MOR
Sulfonamides: changed sensitivity of dihydropteroate synthase, increased
production of PABA and decreased intracellular accumulation of the drugs.
Trimethoprim: change in sensitivity of DHFR.
Pharmacokinetics
Most sulfonamides are effective orally
 Eliminated via the kidney – may cause crystalluria in acidic urine
 Sulfonamides bind to plasma proteins and can displace other drugs
(phenytoin and warfarin) and bilirubin
Trimethoprim is well absorbed orally and excreted largely unchanged by the
kidney
Clinical use: UTI, ocular chlamydial infections, burn dressings, ulcerative colitis
Trimethoprim-sulfamethoxazole (TMP-SMX), UTI, respiratory, ear, sinus
infections including those due to Haemophilus influenza and Moraxella
catarrhalis. DOC for prevention and tx of Pneumocystis carinii.
Toxicities
Sulfonamides: hypersensitivity reactions, nausea, diarrhea, hemolysis in G6PD
deficiency, phototoxicity, crystalluria and drug interactions.
TMP-SMX: sulfonamides AE along with anemia and granulocytopenia
Inhibitors of Nucleic Acid synthesis: Fluoroquinolones
Norfloxacin and ciprofloxacin are prototypes
MOA
Fluoroquinolones are bactericidal inhibitors of nucleic acid synthesis. Inhibit
both topoisomerase II and IV, preventing separation of the replicated DNA.
MOR
Resistance is increasing in gram (+) cocci.
 Mechanisms include decreased intracellular accumulation of drug
 Changes in sensitivity to inhibition of the topoisomerases
Pharmacokinetics
 Antacids may interfere with oral bioavailability
 Renal clearance
Clinical uses
General: wide spectrum of activity associated with GU, GI and URTI.
Specific: Ciprofloxacin and ofloxacin – gonorrhea; Levofloxacin and sparfloxacin
– Mycoplasma pneumonia, CAP; Moxifloxacin and trovafloxacin - Mycoplasma
pneumonia, anaerobes, Chlamydia
Toxicities
Common to all – GI distress, skin rash, tendinitis, headache, dizziness
*seizures have occurred in high doses
*not for use on pregnancy due to effects on collagen metabolism
Antimycobacterial drugs Infectious Diseases

HRZES
H and R are used for prophylaxis and latent tuberculosis infection
INH
MOA and resistance: drug is converted to a metabolite that inhibits mycolic acid
synthesis
 High level of resistance – involves deletions in the katG gene that
codes for catalase
 Low-level of resistance – involves deletions in the inhA gene that
codes for the target acyl carrier protein
Pharmacokinetics: INH is metabolized by N-acetyltransferase
Toxicities – neurotoxicity (tx-B6), hepatitis, hemolysis in G6PD deficiency
Rifampicin
MOA and resistance: inhibits DNA-dependent RNA polymerase. Resistance
occurs via changes in polymerase sensitivity to inhibition.
Pharmacokinetics: undergoes hepatic metabolism with red-orange metabolites
Toxicities: GI distress, rash, decreases effect of other drugs including
anticonvulsants and warfarin
Ethambutol and Pyrazinamide
 Ethambutol – inhibits synthesis of arabinogalactan (component of
cell walls); AE – retrobulbar neuritis
 Pyrazinamide – requires bioactivation for activity, target is unknown;
hyperuricemia, phototoxicity, exacerbation of porphyria
Drugs for Mycobacterium avium-intracellulare
Prophylaxis – azithromycin or clarithromycin
Tx – Clarithromycin + ethambutol with or without rifampicin
1. Malaria
Malarial life cycle
Human infection begins when a female anopheline mosquito inoculates
plasmodial sporozoites from its salivary gland during a blood meal. These
microscopic motile forms of the malarial parasite are carried rapidly via the
bloodstream to the liver, where they invade hepatic parenchymal cells and
begin a period of asexual reproduction. The swollen infected liver cell
eventually bursts, discharging motile merozoites into the bloodstream. These
merozoites then invade the red blood cells (RBCs) and multiply six- to
twentyfold every 48–72 h. When the parasites reach densities of 100 million
parasites in the blood, the symptomatic stage of the infection begins. After
entry into the bloodstream, merozoites rapidly invade erythrocytes and
become trophozoites. Attachment is mediated via a specific erythrocyte surface
receptor. In the case of P. vivax, this receptor is related to the Duffy blood-group
antigen Fya or Fyb. By the end of the 48-h intraerythrocytic life cycle (24 h for P.
knowlesi, 72 h for P. malariae), the parasite has consumed two-thirds of the
RBC's hemoglobin and has grown to occupy most of the cell. It is now called a
schizont. Multiple nuclear divisions have taken place (schizogony or merogony),
and the RBC then ruptures to release 6–30 daughter merozoites, each
potentially capable of invading a new RBC and repeating the cycle.
In P. vivax and P. ovale infections, a proportion of the intrahepatic forms do not
divide immediately but remain dormant for a period ranging from 3 weeks to a
year or longer before reproduction begins. These dormant forms, or
hypnozoites, are the cause of the relapses that characterize infection with these
two species.

Drugs for Leprosy

Dapsone – DOC for M leprae and back up for Pneumocystis carinii
Toxicities – Gi irritation, methemoglobinemia and hemolysis in G6PD deficiency
Alternatives – rifampicin, clofazimine

Antibiotics to be avoided in Pregnancy

Aminoglycosides – ototoxicity in developing fetus
Clarithromycin – embryotoxic
Erythromycin estolate – cholestasis in pregnant px
Fluoroquinolones – deleterious effects on collagen metabolism
Tetracyclines – interferes with bone and tooth formation
Sulfonamides – may cause kernicterus when used in 3rd trimester
Metronidazole – mutagenic in Ames test

MISC Antimicrobials
Metronidazole
MOA – forms metabolite that interferes with nucleic acid synthesis
Clinical Use – DOC in amoebiasis, giardiasis, trichomoniasis, Bacteroides fragilis,
Clostridium deficile, Gardnerella vaginalis, H pylori
Toxicity – GI irritation, headache, disulfiram like reactions with ethanol

Fosfomycin
MOA and resistance – inhibits enopyruvate transferase, preventing formation of
N-acetylmuramic acid needed for cell wall synthesis

Urinary antiseptics
Nitrofurantoin – eradication of most urinary pathogens except Proteus and
Pseudomonas; toxicity - Gi irritation, and hemolysis in G6PD deficiency
Nalidixic acid – quinolone with activity similar to nitrofurantoin; toxicity –
glycosuria, skin rash, phototoxicity and ocular dysfunction
Methenamine – urinary acidifier that releases formaldehyde below pH 5.5
 of harm is supported not only by our commonly held moral
convictions, but by the laws of society as well.

3. Beneficence
Health care providers have a duty to be of a benefit to the patient, as
well as to take positive steps to prevent and to remove harm from
the patient. This principle is at the very heart of health care implying
that a suffering supplicant (the patient) can enter into a relationship
with one whom society has licensed as competent to provide medical
care, trusting that the physician’s chief objective is to help.

4. Justice
A form of fairness or as Aristotle once said, "giving to each that which
is his due." This implies the fair distribution of goods in society and
requires that we look at the role of entitlement.

Bioethics Principles

1. Respect for autonomy

Respect for the autonomy of the patient would, in common parlance,
imply that the patient has the capacity to act intentionally, with
understanding, and without controlling influences that would
mitigate against a free and voluntary act. This principle is the basis
for the practice of "informed consent" in the physician/patient
transaction regarding health care.

2. Nonmaleficence
Nonmaleficence requires of us that we not intentionally create a
harm or injury to the patient, either through acts of commission or
omission. In common language, we consider it negligent if one
imposes a careless or unreasonable risk of harm upon another.
Providing a proper standard of care that avoids or minimizes the risk