PATOLOGI INFLAMASI

BAGIAN PATOLOGI ANATOMI

FAKULTAS KEDOKTERAN UKDW

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INFLAMASI
• Respon lokal jaringan bervaskuler terhadap
infeksi dan kerusakan jaringan
 Sel-sel dan molekul-molekul pertahanan tubuh dari sirkulasi
 Eliminasi agen penyebab cedera, membatasi kerusakan dan
mempercepat pemulihan jaringan

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 Terminologi peradangan
Ditambahkan sufiks -itis
Kondisi klinisnya (waktu): akut atau kronik
Tipe eksudat yang terbentuk: serosa,
fibrinosa, hemoragis, purulen, supuratif,
abses, serofibrinosa, fibrinopurulen

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 Perhatikan terminologi berikut ini

Apendisitis Serosa
Neuritis Akut Fibrinosa
Artritis Kronik Hemoragis
Kolesistitis Purulen
Hepatitis Supuratif
Gastritis Abses
Miokarditis Serofibrinosa
Stomatitis
Fibrinopurulen
Peridontitis
Pulpitis
 Etiologi Radang

Infeksi (bakteri, virus, parasit) dan toksin

mikrobial
Jaringan nekrotik
Benda asing (serpihan- serpihan kaca,
kayu; benang jahit, debu)
Trauma (tumpul atau penetrasi)
Reaksi imun (hipersensitivitas)
Agen- agen fisika dan kimiawi ( cedera
termal, beberapa agen kimiawi)
dll 5
• Cardinal Signs of Acute Inflammation: Celsus,
Roman, 1st AD
- tumor swelling
- rubor  redness
- calor  warmth
- dolor  pain
+ functiolaesa impair of function : Virchow (1821–
1902)
 Karakteristik respon radang adalah tergantung modulasi
dari:
 Agen patogen
 Durasi
 Kerusakan jaringan
 Lingkungan mikro
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Acute Inflammation Componen
Respon-respon Gejala/Symptoms
Fisiologi
Melepaskan mediator-mediator solubel

Heat (calor)
Vasodilatasi

Redness (rubor)
Aliran darah meningkat

Ekstravasasi cairan (permeabilitas)

Swelling (tumor)

Influks seluler(chemotaxis)
Pain (dolor)

Metabolisme seluer meningkat

• Komponen respon inflamasi
 Pembuluh darah: dilatasi –
perlambatan aliran darah –
pemeabilitas meningkat –
menarik protein-protein sirkulasi
 Respon seluler leukosit:
marginasi – adesi – migrasi –
teraktivasi – ingesti mikroba
dan agen-agen perusak
 Tahap- tahap respon inflamasi akut
1. Inisiasi: pengenalan agen
patogen
2. Amplifikasi: pengerahan
leukosit pmn dan makrofag
3. Destruksi: menyingkirkan agen
patogen
4. Terminasi: regulasi respon
radang
5. Resolusi: penyembuhan
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Pengenalan Mikroba dan Sel-sel Cedera
dan Rusak

• Langkah awal dari semua respon inflamasi

• Dikenali oleh beberapa reseptor seluler
dan protein sirkulasi:
Reseptor seluler mengenali mikroba: Toll Like
Receptor
Sensor kerusakan sel: Inflammasome
Reseptor seluler lain: Opsonisasi
Protein sirkulasi: Mannose binding Lectin

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Tipe-tipe Inflamasi

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INFLAMASI AKUT

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Respon awal dan segera terhadap agen
penyebab cedera
• Fenomena vaskuler berperan utama :
– Perubahan diameter vaskuler menyebabkan
meningkatnya aliran darah – redness and
warmth ( rubor & calor )
– Perubahan structural di mikrovaskuler
memungkinkan protein plasma dan leukosit keluar
dari sirkulasithat - ( tumor & dolor )
– Emigrasi leukosit dari mikrosirkulasi dan
terakumulasi dalam lokasi cedera
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 Inflamasi Akut

PERUBAHAN VASKULER PERUBAHAN SELULER

PERUBAHAN HEMODINAMIK EKSUDASI

 Vasokonstriksi sesaat  Protein
 Vasodilatasi arteriol prekapiler  Cairan
 Permeabilitas vaskuler meningkat
 Vasokonstriksi venula postkapiler EMIGRASI LEUKOSIT
→Tekanan osmotik turun  Marginasi, Rolling dan Adesi
→Tekanan hidrostatik naik  Migrasi lewat endotelial dan dinding
→ Aliran darah melambat (stasis) vaskuler
 Kemotaksis
MEKANISME PERUBAHAN FAGOSITOSIS
PERMEABILITAS VASKULER  Opsonisasi / recognition & attachment
 Kontraksi sel-sel endotel  Engulfment
 Cedera sel-sel endotel  Degradasi mikroorganisme intraseluler

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Perubahan Ukuran dan Diameter Pembuluh
Darah

• Vasodilatasi
• Permeabilitas meningkat
• Aliran darah melambat – viskositas
meningkat – stasis
• Akumulasi neutrofil di sepajang dinding
pembuluh darah

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Permeabilitas Vaskuler Meningkat

• Kontraksi sel-sel endotel – ruang inter endotel

melebar – mekanisme vaskular leakage
Histamin
Bradikinin
Leukotriene
• Cedera endotel – nekrosis dan terkelupas
Defek langsung
Perlengketan leukosit
• Transitosis
Peningkatan transport cairan dan protein
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Reaksi Pembuluh Darah

• Eksudasi
• Transudasi
• Edema
• Pus

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Karakteristik transudat, eksudat
dan pus

FLUID TYPE CONDITION CONTENT SPECIFIC

GRAVITY
---------------------------------------------------------------------------------------------------------------------

TRANSUDATE INCREASED HYDROSTATIC LOW PROTEIN < 1.020

PRESSURE

EXUDATE ACUTE INFLAMMATION HIGH PROTEIN > 1.O20

PUS ACUTE INFLAMMATION HIGH PROTEIN + > 1.020

NEUTROPHILS

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TIPE INFLAMASI BERDASARKAN JENIS EKSUDAT
INFLAMASI SEROSA
Develops in mucous and serous membranes, interstitial tissue, skin,
and kidneys glomes capsules. The amount of cells in the serous
exudate is not large. The serous exudate conduces of microorganisms
washing off and their toxins from the damaged surfaces. But the
serous exudate in brain coats can squeeze the brain and violate its
function. The serous infiltration of the lungs alveolar septs can cause
the development of acute respiratory insufficiency syndrome.
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 TIPE INFLAMASI BERDASARKAN JENIS EKSUDAT

INFLAMASI HEMORAGIK
The hemorrhagic inflammation, as the form of
serous inflammation, the fibrinous one or the
purulent one, is characterized by erythrocytes
impurity to the exudate (Siberian ulcer, natural
smallpox, influenza).
 TIPE INFLAMASI BERDASARKAN JENIS EKSUDAT

INFLAMASI FIBRINOSA
contains a plenty of fibrinogene, which forms clots of fibrin in tissues
(occures when an organism is affected by corinebacterium
diphtheriae, pneumococcus, Fridlander's bacillus, Frencel's
diplococcus, streotococcus, and mycobacterium of tuberculosis. Such
type of an inflammation occurs on mucous or serous coats more often
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 TIPE INFLAMASI BERDASARKAN JENIS EKSUDAT

INFLAMASI PURULENTA

Reason - staphylococcus,
streptococcus, gonococcus,
meningococcus, and Frenkel’s
diplococcus

Purulent exudate smell bad, consist of

of many viable leukocytes and
purulent bodies (perishing
leukocytes), cells detritus,
microorganisms, plenty of proteins
(especially globulines)

Is characterise by low рН
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 TIPE INFLAMASI BERDASARKAN JENIS EKSUDAT

DECAYING INFLAMMATION
The decaying inflammation develops after the invasion of
decaying microorganisms into the purulent inflammation
site. During this type of inflammation necrosis of injurious
tissues progresses, the inflammation area isn’t localized,
and this provokes the penetration of alien agent and toxic
products into vessels, development of intoxication due to
which the patients usually die.
 TIPE INFLAMASI BERDASARKAN JENIS EKSUDAT

Ulcers
• An ulcer is a local defect, or excavation, of the surface of
an organ or tissue that is produced by the sloughing
(shedding) of inflamed necrotic tissue.
• Ulceration can occur only when tissue necrosis and
resultant inflammation exist on or near a surface. It is
most commonly encountered in
(1) the mucosa of the mouth, stomach, intestines, or
genitourinary tract, and
(2) the skin and subcutaneous tissue of the lower
extremities in older persons who have circulatory
disturbances that predispose to extensive
ischemic necrosis.
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Penarikan Leukosit ke Tempat Inflamasi

• Eliminasi agen perusak

• Neutrofil dan makrofag – fagositosis
• Multistep proses - leukosit dari aliran
darah ke dalam jaringan

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Sequence of leukocytes events in
inflammation

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Scanning electron micrograph of
moving leukocyte

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 Endothelial / leukocyte adhesion molecules

• Endothelial Mol. Leukocyte Rec. Major role

P-Selectin Sialyl-Lewis X Rolling
PSGL-1
E-Selectin Sialyl-Lewis X Rolling, adhesion
ESL-1,PSGL-1
ICAM-1 CD11/CD18(integrin) Adh,arrest,transm
(LFA-1,Mac-1)
VCAM-1 alphaB1(VLA4) adhesion
(integrin)
alpha B7(LPAM-1)
GlyCam-1 L-selectin Lymphocyte homing
CD34 to high end.venules

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CHEMOTAXIS
• After exiting the circulation leukocyte emigrate in
tissues towards the site of injury by a process
called chemotaxis.
• Exogenous and endogenous substance can act
as chemoattractants.
• Exogenous – bacterial products.
• Endogenous- 1) cytokines- IL-8
2) Leukotriene- B4
3) components of complement
system.
4) soluble bacterial products
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 PHAGOCYTOSIS

The process of engulfment of solid particulate

material by the cell.
2 types:
a) Microphages
b) macrophage
RECOGNITION &
s
ATTACHMENT

KILLING OR
ENGULFMENT
DEGRADATION

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 PHAGOCYTO
SIS

RECOGNITION AND ATTACHMENT

Opsonins - C3b, IgG, lectins
ENGULFMENT STAGE
Cytoskeletal mechanisms
Degranulation
KILLING / DEGRADATION
O2-Dependent - H2O2 HOCl
O2-Independent - lysozyme, cationic proteins,
defensins, lactoferrin
NO -Dependent
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Sel-sel dalam Proses Inflamasi
• Neutrofil memfagositosis substansi asing cth.
bakteria, dan kemudian mengoksidasi dan
mendigestinya melalui oksidase dan protease.
Didapatkan terutama dalam fase akut.
• Eosinophils juga sel fagositik dan memiliki
banyak enzim seperti neutrofil, melepaskan
histamin. Berhubungan dengan respon alergi.
Didapatkan dalam inflamasi akut maupun kronik.

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Defek Fungsi Leukosit
• Defect in leukocyte adhesion (LAD)
LAD type 1 : recurrent bacterial infections
impaired healing
LAD type 2 : milder than lad1, but also
recurrent bacterial infections

• Defect in phagolysosome function :

Chediak-Higashi : neutropenia, defective
degranulation and delayed microbial
killing. 46
Defect in Leukocyte Function . . . .
• Defect in microbicidal activity
example : chronic granulomatous disease – TBC
patient susceptible to recurrent bacterial infection
( defect in bacterial killing )

• Bone marrow supression (the most frequent cause) :

leading to reduce production of leukocytes –
seen following therapies for cancer ( Radiation
therapy or chemotherapy ) and when the marrow
space
is compromise by tumor metastases to bone.

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Cells of the inflammatory process
• Simple-appearing cells with varied and complex functions
• Briefly, some lymphocytes are in the T-cell system and
produce various types of lymphokine, which have local
effect.
• Immunoglobulin or antibodies can also be produced by
this cells as a B cells
• Characterizes chronic inflammation, antibody production
is the function of the plasma cells, a specialized B cell,
which is also found in chronic inflammation. It is
particularly prominent in chronic inflammation involving
mucosal surfaces

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Cells of inflammation
CELL ACTIVITY PHAGOCYTOSIS INFLAMMATION
---------------------------------------------------------------------------------------------------------
NEUTROPHIL PROTEASES, OXIDASES + ACUTE

EOSINOPHIL ANTIHISTAMINE + ACUTE, CHRONIC

MACROPHAG ANTIGEN PROCESSING, + LATE ACUTE, CHRONIC

DIGESTION

LYMPHOCYTE LYMPHOKINES - CHRONIC

PLASMA CELL ANTIBODY PRODUCTION - CHRONIC

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ACUTE INFLAMMATION

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MICROSCOPIC APPEARANCE
OF ACUTE INFLAMMATION

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 Chemical Mediators
• Mediators originate either from plasma and from cells

• Mediators perform their biologic activity by binding to

specific receptors on target cells. But some have direct
enzymatic activity or mediate oxidative damage

• A chemical mediator can stimulate the release of

mediators by target cells themselves

• Mediators can act on one or few target cell types

• Once activated and released from the cell, most of

these mediators are short-lived

• Most mediators have the potential to cause harmful

effects

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Chemical Mediator

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 MEDIATOR OF ACUTE
INFLAMMATION

MEDIATOR VASODILATATION INCREASED PERMEABILITY CHEMOTAXIS OPSONIN PAIN

---------------------------------------------
IMMEDIATE SUSTAINED
--------------------------------------------------------------------------------------------------------------------------------------------------------------
HISTAMINE + +++ _ _ _ _

SEROTONIN(5-HT) + + _ _ _ _

BRADYKININ + + _ _ _ +++

COMPLEMENT 3a _ + _ _ _ _
COMPLEMENT 3b _ _ _ _ +++ _
COMPLEMENT 5a _ ++ _ +++ _ _

PROSTAGLANDINS +++ +++ +? +++ _ ++

LEUKOTRIENES _ +++ +? +++ _ _

LYSOSOMAL
PROTEASES _ _ ++ _ _ _

OXYGEN RADICALS _ _ ++ _ _ _
--------------------------------------------------------------------------------------------------------------------------------------------------------------

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Events in the resolution of
inflammation

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Summary of the acute inflammatory
response
• Vascular phenomena
Dilatation of arteriolar and capillary beds - increased
bloodflow to the injured area
Increased vascular permeability – Exudate

• Leukocyte activity
Adhesion molecule, transmigrate, migrate to the site of
injury;
phagocytosis of the offending agents.
During chemotaxis and phagocytosis activated leukocyte
may released toxic metabolites and proteases
extracellulary, potentially causing tissue damage.

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INFLAMASI KRONIK

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INFLAMASI KRONIK

• Sel-sel inflamasi dominan adalah

limfosit, sel plasma dan makrofag
• Destruksi jaringan
• Diganti oleh jaringan ikat fibrous

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MEDIATORS OF CHRONIC
INFLAMMATION
AGENT ACTION SOURCE
----------------------------------------------------------------------------------------------
-
Migration inhibition Aggregation of Activated T
Factor (MIF) macrophages at lymphocytes
site of injury

Macrophage Increased Activated T

Activation factor phagocytosis by lymphocytes
(MAF) macrophages

Complement 5a Chemotactic for Complement

macrophages
system
Eosinophil chemo- Chemotactic for Mast cells and
Tactic factor of eosinophils in basophils 61
Anaphylaxis(ECF-A) metazoan infections
CHRONIC INFLAMMATION

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MICROSCOPIC APPEARANCE
OF CHRONIC INFLAMMATION

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Three characteristics histologic
pictures in chronic inflammation

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Maturation of mononuclear
phagocytes

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Macrophage-lymphocyte interaction
in chronic inflammation
• Activated lymphocytes and
macrophages influence each
other and also release
inflammatory mediators that
affect other cells

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Events in the resolution of
inflammation

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Granuloma, chronic inflammation
TBC
• Central necrosis
• Epitheloid cells
• Langhans type
giant cells
• Lymphocytes

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Morphologic Patterns in acute and
chronic inflammation
• Fibrinous
• Suppurative or Purulent
• Cattarhalis
• Pseudomembrane
• Sanguinis / haemorrhagic
• Suppurative / purulent
• Ulcers

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INFLAMASI GRANULOMATOSA

• A distinct pattern of chronic inflammation characterized by

formation of granulation tissue.

• It is a protective response to chronic infection or foreign

material, preventing dissemination and restricting
inflammation.

• Some autoimmune diseases such as rheumatoid arthritis

and Crohn’s disease are also associated with granulomas

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? Granuloma.......

• A granuloma is a localized mass of granulation tissue with aggregations

of chronic inflammatory cells

• The granuloma consists of a kernel of infected macrophages surrounded

by foamy macrophages and a ring of lymphocytes and a fibrous cuff.

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Causes of granuloma......
• Bacteria:
• Tuberculosis, Leprosy, Syphilis, Actinomycosis
• Parasites:
• Schistosomiasis
• Fungi:
• Histoplasmosis, Blastomycosis
• Foreign bodyGranulomas
– Endogenous
• keratin, necrotic bone or adipose tissue uric acid crystals
– Exogenous
• wood, silica, asbestos, silicone
• Unknown cause such as sarcoidosis
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Systemic effects of Inflammation

• Fever – acute phase reaction ( Endocrine

and metabolic, Autonomic, Behavioral )

• Leukocytosis
exception : lymphocitosis, eosinophillia,
leukopenia

• Changes in organ
reactive, degenerative, septicaemia, pyaemia,
bacteriemia
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KESIMPULAN

• Mekanisme pertahanan tubuh terhadap

agen infeksi dan penyebab cedera adalah
inflamasi dan pemulihan yang dapat
meredakan cedera dan membuat
penyembuhan.
• Tanpa inflamasi, infeksi tidak akan
terdeteksi, luka tidak pernnah sembuh dan
jaringan yang cedera akan menetap.
• Meskipun demikian inflamasi dan
penyembuhan dapat berpotensi
merugikan. 79
semoga bermanfaat
tuhan memberkati

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