Patologi Umum Penyakit Infeksi

Kompetensi Dasar
 Mempelajari dan memahami penyakit infeksi (virus dan
bakteri)
 Mempelajari dan memahami proses penyakit infeksi di
dalam tubuh
 Mempelajari dan memahami respon sel, jaringan, organ,
dan sistem terhadap penyakit infeksi
 Respon imun tubuh terhadap penyakit infeksi
 Manifestasi tubuh terhadap penyakit infeksi
 Komplikasi penyakit infeksi
INFEKSI
 Patogenik: agen penyebab infeksi yg menyebabkan
penyakit

 Infeksi terjadi bila MO menyerang jaringan tubuh internal

yg steril

 Penyakit infeksius terjadi bila infeksi berhubungan dengan

kerusakan jaringan yang bermanifestasi secara klinis

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Mekanisme bagaimana organisme infeksiosa
menimbulkan penyakit tergantung:
Sifat spesifik
organisme
penyebab
infeksi
Respon host
terhadap agen
penyebab
infeksi
 V
Agen Penyebab Infeksi
i
r
u
Bakteri
s
Jamur
Protozoa
Parasit / Cacing
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 Sejumlah bakteri secara normal berkoloni pada
permukaan luar tubuh (kulit, sistem pencernaan, saluran
nafas atas). Kebanyakan patogenik rendah dan terkadang
justru menguntungkan tubuh seperti:

 Menghasilkan bahan nutrisi tubuh: Vitamin B12

 Berkompetisi dan menyingkirkan patogen

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Rute masuknya organisme infektif:
1. Kulit & membran mukosa
a) Kontak langsung  peny kelamin, HIV
b) Kontaminasi dr luka & abrasi  infeksi luka, rabies
c) Inokulasi  gigitan serangga, tusukan jarum; DBD,
hepatitis B
2. Ingesti  kontaminasi makanan & air; cholera,
hepatitis A
3. Inhalasi  debu, droplet ; influenza, TBC

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Faktor yg mempengaruhi terjadinya infeksi:

1. Faktor host : kondisi tubuh yg sehat & nutrisi baik

 mencegah & membatasi infeksi
a) Barier fisika: epitel gepeng pd kulit
b) Sekresi: air mata, urin
c) Filtrasi: bulu hidung
d) Musin: pd silia sal nafas
e) Bahan kimia: sekresi asam pd lambung & sal kemih,
lisosom, imunoglobulin A, substansi inhibitor non
spesifik seperti urin, keringat, sebum

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2. Faktor MO (mikroorganisme)
a) Jml kuman; makin >> kuman  makin mudah mekanisme
pertahanan diserang
b) virulensi

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Faktor yg mempengaruhi perjalanan
infeksi:

 Saat infeksi terjadi, mk mekanisme pertahanan yg

penting akan bekerja yaitu:
1. Inflamasi pd reaksi lokal akut u/ membatasi
penyebaran mo
2. Fagositosis
3. Respon imunitas
 Reaksi Ab humoral  aglutinasi, opsonisasi, lisis melalui
komplemen
 Reaksi seluler  tu pd infeksi virus
4. Interferon : sekelompok agen antivirus non spesifik
yg dihasilkan oleh sel host yg terinfeksi
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 Public Enemy #1 : The Bacteria

•Modus operandi :
 Set up shop in tissues but remain
EXTERNAL to cells
 Reproduce rapidly
 Secrete exotoxins or contain
endotoxins as part of cell wall
Examples: Escherichia coli,
Clostridium botulinum, Salmonella

Figure from Holt Biosources

Mekanisme terjadinya penyakit:
Reaksi lokal thd infeksi biasanya adalah inflamasi & ini dipicu oleh kerusakan
selular & sel-sel mati. Mekanisme detilnya berbeda pd bakteri & virus

 Bakteri
1. Produksi toksin
 Eksotoksin : disekresikan oleh bakteri hidup, berupa
protein sederhana, dinetralisir oleh Ab spesifik
(antitoksin), seringnya memiliki enzim spesifik & bekerja
pd organ/jar spesifik

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- Endotoksin : bgn integral dr dinding sel bakteri,
dilepaskan organisma mati, berupa komplek lipo-
polisakarida, tdk merangsang produksi antitoksin,
menyebabkan demam & syok endotoksik, bekerja
menyebabkan kerusakan kapiler, mengganggu sistem
koagulasi, mengaktifkan fibrinolitik & kaskade
komplemen, memfasilitasi pelepasan mediator
inflamasi akut

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2. Reaksi hipersensitifitas menyebabkan jejas jar: reaksi
antara protein bakteri & limfosit yg disensitifikasi
memicu reaksi inflamasi
3. Invasi jaringan: penyebaran limfatik & invasi pembuluh
darah

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 Bakterimia: adanya bakteri yg hidup di dlm darah. Merup
bgn integral dr bbrp infeksi spt demam thypoid, biasanya
tidak ada makna yg serius.

 Septikemia / sepsis / toksemia: bakterimia dgn respon

inflamasi dr tubuh menyebabkan sindroma inflamasi
sistemik. Ditandai dg nafas cepat, TD rendah, demam dll.

 Pyemia : salah satu tipe septikemia yg menyebabkan

penyebaran abses secara luas. Merup kondisi serius dg
toksemia berat, organisme lepas ke dlm aliran darah dlm
btk agregat kecil membentuk mikroemboli

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Infeksi bakteri akut
Bakteri pyogenik
- Staphylococcus aureus : bakteri gram (+), tersusun
berkelompok. Menghasilkan enzim koagulase yg
menimbun fibrin pd tempat lokasi infeksi 
pembentukan pus & abses
- Streptococcus pyogenes : bakteri gram (+), tersusun
dlm btk rantai. Menghasilkan sejumlah enzim spt
hyaluronidase, streptokinase & leucocidin

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- Neisseria (meningococcus, gonococcus): diplococcus
intraselular gram (-)
 Basil gram (-): biasanya komensal pd sal cerna,
anaerob obligat & fakultatif.
 Gangren: salah satu bentuk nekrosis yg sering
mengalami infeksi bakteri. Bakteri berproliferasi &
mencerna jar mati & kmdn menghasilkan gas.
 Gangren basah: ok udem / kongesti vena  jar
lembab
 Gangren kering: tu pd kaki & tumit, orang tua yg
menderita oklusi arteri bertahap

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 Tetanus
etio: Clostridium tetani, anaerob, gram (+) 
sekresi eksotoksin
metode infeksi: kontaminasi luka dg kondisi
anaerob (luka penetrasi dalam) / luka dg kerusakan
jar lunak yg hebat (kecelakaan lalin)
efek eksotoksin  spasme otot paroksismal 
makin hebat  fatal
Imunitas : imunisasi aktif dg Toksoid (profilak),
imunisasi pasif dg antitoksin (terapi)

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Infeksi bakteri kronik
 Tuberkulosis
 Aktinomikosis
 Lepra
 Sifilis

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 Public Enemy #2 : The Viruses
•Modus Operandi :
 Dock with receptors on target cell
surface
 Insert viral DNA or RNA into
host cell
 Use host cell machinery to
replicate new viruses
 Lyse host cell and spread to
nearby cells
Lytic vs. Lysogenic life cycles

Examples: smallpox, chickenpox,

polio, HIV
Infeksi virus akut
 Pd periode inkubasi terjadi hal sbb: penetrasi virus pd
sel tempat infeksi  replikasi virus di dlm sel secara
lokal  sel mati, membebaskan virus  penyebaran
virus ke KGB lokal  replikasi lanjutan virus &
kematian sel
 Pd keadaan di atas : ditemukan gejala lokal berupa spt
pd influenza, enteritis ok virus

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 Pd keadaan peny lanjut: virus dibebaskan ke dlm
aliran darah  penyebaran virus oleh darah ke KGB
secara umum  replikasi lanjut virus  sel mati &
membebaskan virus ke aliran darah  penyebaran
virus secara umum ke seluruh tubuh dg efek terutama
terlihat pd organ / jar yg memiliki reseptor spesifik
untuk virus tsb
 Pd keadaan ini tdp gejala yg lebih jelas pd organ /
jaringan yg rusak spt pd poliomyelitis-sel saraf

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 Tdk seluruh perubahan/evolusi virus tsb dpt terjadi secara
lengkap ok replikasi / penyebaran virus dilawan oleh
mekanisme pertahanan tubuh.
 Infeksi virus memiliki 3 variasi yaitu:
1. latent
2. onkogenik
3. lambat

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Reaksi yg terjadi pd host thd infeksi virus:

1. Perubahan sel yg terinfeksi

 Degenerasi sel
 Fusi sel yg terinfeksi dg sel di dekatnya  sel datia
 Proliferasi sel
 Pembentukan badan inklusi di dlm sitoplasma / inti (tdr
dr agregat virus &/ produk dr degenerasi sel)
 Tdk ada perubahan pd sel tp virus tetap laten 
reaktifasi
 Tdk ada perubahan  proliferasi malignan

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2. Produksi interferon: sekelompok molekul protein  sgt
penting utk pertahanan
3. Respon imun dimulai 4 -7 hari setelah infeksi inisial
4. Respon inflamasi

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Infeksi opportunistik
 Disebabkan oleh MO yg seringnya nonpatogenik /
virulensi derajat rendah, terjadi pd individu dg
ketahanan tubuh yg rendah thd infeksi.
 Penyebab rendahnya ketahanan tubuh:

1. Defisiensi imunologi kongenital

2. Defisiensi imunologi didapat
 Ok penyakit: infeksi HIV, tumor ganas
 Ok terapi: immunosupresi pd transplantasi

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 So what’s a body to do?

 First line defenses: Nonspecific anatomical barriers and

secretions that prevent entry, such as skin, saliva, tears
(lysozyme), mucus, stomach acid, fever

Second line defenses: Inflammation

A nonspecific response triggered by histamine secreted by
basophils when tissue is damaged
Lines of Defense

Nonspecific Defense Mechanisms……

First line defenses:
A. Body Surfaces
 Intact skin
 keratin layers, acidity (pH 3-5), antibacterial sebum
 Mucous membranes
 acidic vaginal secretions, stomach (HCl and proteases), saliva
and tears (Lysozyme), mucous (trapping of pathogens, outward
transport via cilia)
B. Cellular & Chemical Defenses
 If surface barriers are breached:
 Phagocytes (phagocytotic cells)
 macrophages (develop from WBC [monocytes]) after leaving
blood vessels, found in nearly all tissues, also capable of
respiratory burst (release of free radicals attacking pathogen)
 neutrophiles (production of defensins)
 eosinophiles (parasitic worms, not true phagocytosis “external
digestion” of pathogens)
 potential long term damage by DNA damage through radicals 
cancer
Cellular & Chemical Defenses
 Natural Killer Cells
 large granular lymphocytes, attack abnormal (cancerous),
and virus-infected cells
 non-specific attack, via non-self recognition of cell surface
carbohydrates
 destroy cells via cytotoxic compounds, induction of
membrane channels on target, disintegrate the nucleus
 release of inflammatory compounds
Second line defenses:
Inflammation

 Any tissue damage causes inflammation

 mechanical (blows, cuts)
 chemical (acids, bases, solvents, etc.)
 heat, intense radiation
 infection via viruses, bacteria, fungi

 Five Cardinal Symptoms:

 Redness, Heat, Swelling, Pain and Loss of function
 The Inflammatory Response
 1- Tissue injury; release of chemical signals~
• histamine (basophils/mast cells): causes Step 2...
• prostaglandins: increases blood flow & vessel permeability

 2/3- Dilation and increased permeability of capillary~

• chemokines: secreted by blood vessel endothelial cells mediates phagocytotic migration of WBCs

 4- Phagocytosis of pathogens~
• fever & pyrogens: leukocyte-released molecules increase body temperature
Inflammation
 Cell & tissue damage  release of inflammatory
chemicals:
 histamine, kinins, prostaglandins, complement, and
lymphokines
 all cause local vasodilation
  hyperemia - redness, heat
 all increase vascular permeability
  exudate formation - swelling, pain
 pain enhanced by prostaglandins, kinins
Inflammation
 Extensive infections may cause formation of pus:cell
debris, WBCs, pathogens, etc., if not removed by
macrophages, formation of abscess:collagen fiber
enclosed pus
 granulomas:resistant pathogens may become
enclosed in macrophages and persists, can cause
infectious outbreak later
If all else fails…
The Immune Response
 A highly specific, long lasting response tailored to
combat pathogens
Antigen- a molecule (usually carried on the
surface of a pathogen) that is capable of eliciting
an immune response
B-Lymphocytes- white blood cells that produce
and secrete antibodies
T-Lymphocytes- white blood cells that serve as
part of the cell-mediated immune response
Immune Response - Step by Step
1. Pathogen (carrying foreign antigens) enters and
survives the inflammatory response

2. Some pathogens remain exposed in tissues

where their antigens may be recognized by
circulating B cells
OR
3. Macrophages engulf pathogens and display their
antigens on MHC (major histocompatibility
complex) receptors. Macrophage has now
become an Antigen Presenting Cell (APC)
Humoral Immunity
B cell response
• If a circulating B cell’s receptors bind to
foreign antigens, the B cell becomes activated
• Activated B cells divide into Memory B cells
and Plasma B cells
• Plasma B cells rapidly produce and secrete
antibodies (immunoglobulins)
• Clonal selection amplifies the production of
cells that produce effective antibodies
Humoral response: B cells
 Stimulated by T-dependent
antigens (help from Th cells)
 Macrophage (APCs) with class
II MHC proteins
 Helper T cell (CD4 protein)
 Activated T cell secretes IL-2
(cytokines) that activate B cell
 B cell differentiates into
memory and plasma cells
(antibodies)
 Clonal Selection

Figure from AccessExcellence.org

Mechanism of Antibody Function
 Antibodies bind to
antigens and aggregate
pathogens for removal by
macrophages
 Antibodies disrupt
function of pathogen’s
surface proteins
 Antibody-antigen
complexes trigger the
Complement system, a a
series of enzymes carried
in the bloodstream that
lyse invaders
Figure from AccessExcellence.org
Cell-Mediated Immunity
T cell Response
 Helper T cells (TH or CD-4 T cells) constantly
interact with macrophages
 When T cell finds a macrophage that is presenting
H
antigen (APC) it becomes activated
 Activated T cells secrete cytokines, chemicals that
H
stimulate both T and B cells
 Stimulated cytotoxic T cells (killer or CD-8 T
cells) divide rapidly, bind directly to pathogen
infected cells and secrete enzymes that lyse
infected cells
Helper T lymphocytes
 Function in both humoral & cell-mediated immunity
 Stimulated by antigen presenting cells (APCs)
 T cell surface protein CD4 enhances activation
 Cytokines secreted (stimulate other lymphocytes):
 a) interleukin-2 (IL-2): activates B cells and cytotoxic T cells
 b) interleukin-1 (IL-1): activates helper T cell to produce IL-2
Cell-mediated: cytotoxic T cells
 Destroy cells infected by intracellular pathogens and cancer cells
 Class I MHC molecules (nucleated body cells) expose foreign proteins
 Activity enhanced by CD8 surface protein present on most cytotoxic T
cells (similar to CD4 and class II MHC)
 TC cell releases perforin, a protein that forms pores in the target cell
membrane; cell lysis and pathogen exposure to circulating antibodies
The Immune Response - Overview
Efek umum infeksi
 Demam
 Perubahan metabolisme

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 Steps in Pathogenesis
1. Pathogen enters Host
2. Pathogen clonizes appropriate site
3. Pathogen reproduces rapidly
4. Prodromal signs may appear
5. Acute signs present
6. Decreased reproduction & death of pathogens
7. Recovery – signs subside
8. Total recovery
Development of Infection: Clinical
Signs and Symptoms
 Local signs
 Inflammation
 Purulent exudate if bacterial infection; serous exudate if viral
 Tissue necrosis
 Lymphadenopathy
 Respiratory effects
 Systemic signs
 Fever, fatigue, headache, nausea
Terimakasih