Dr Soekimin Sp.

PA
Dr Suryani Eka Mustika Sp.PA
BAGIAN PA UISU
2011
CHAPTER 2
Inflammation
(5 OBJECTIVES)
1) (Concept) Understand the chain,
progression, or sequence of
vascular and cellular events in
the histologic evolution of acute
inflammation
2) (Rote?) Learn the roles of various
“chemical mediators” of acute
inflammation
3) Know the three possible outcomes of
acute inflammation
4) Visualize the three morphologic
patterns of acute inflammation
5) Understand the causes, morphologic
patterns, principle cells, minor cells, of
chronic and granulomatous
inflammation
 SEQUENCE OF EVENTS
• NORMAL HISTOLOGY 
• VASODILATATION 
• INCREASED VASCULAR PERMEABILITY 
• LEAKAGE OF EXUDATE 
• MARGINATION, ROLLING, ADHESION 
• TRANSMIGRATION (DIAPEDESIS) 
• CHEMOTAXIS 
• PMN ACTIVATION 
• PHAGOCYTOSIS: Recognition, Attachment,
Engulfment, Killing (degradation or digestion) 
• TERMINATION 
• 100% RESOLUTION, SCAR, or CHRONIC
INFLAMMATION are the three possible outcomes
 Radang akut

Radang yang disebabkan oleh rangsangan yang berlangsung sesaat /

mendadak (akut)

Makroskopik:
1. Tumor Mikroskopik:

2. Rubor 1. Infiltrasi sel-sel radang akut (PMN)

3. Kalor 2. Vasodilatasi

4. Dolor 3. Oedem

5. Functiolesia
 Radang Kronik

Radang / inflamasi yang disebabkan oleh jejas atau injury yang

berlangsung beberapa minggu, bulan, atau bersifat menetap dan
merupakan kelanjutan dari radang akut

Sinonim radang fibroblastik karena selalu diikuti dengan

terjadinya proliferasi fibroblast (jaringan ikat)

Mikroskopis:
• Infiltrasi sel-sel radang kronis (MN)
• Proliferasi jaringan fibroblast
• Neovaskularisasi
ACUTE INFLAMMATION
•“PROTECTIVE”
RESPONSE
•NON-specific
ACUTE INFLAMMATION
• VASCULAR EVENTS
• CELLULAR EVENTS (PMN or
PolyMorphonuclear Neutrophil,
Leukocyte?, “POLY”, Neutrophil,
Granulocyte, Neutrophilic
Granulocyte
• “MEDIATORS”
 ACUTE
INFLAMMATION
Neutrophil
Polymorphonuclear
Leukocyte, PMN, PML
“Leukocyte”
Granulocyte, Neutrophilic
granulocyte
“Poly-”
Polymorph
 HISTORICAL
HIGHLIGHTS
(Egypt, 3000 BC)

Rubor
Calor
Tumor
Dolor
5th (functio laesa)
 STIMULI
for acute inflammation
• INFECTIOUS
• PHYSICAL
• CHEMICAL
• Tissue Necrosis
• Foreign Bodies (FBs)
• Immune “responses”, or “complexes”
Vascular Changes
• Changes in Vascular Flow
and Caliber

• Increased Vascular
Permeability
INCREASED PERMEABILITY
• DILATATION
• Endothelial “gaps”
• Direct Injury
• Leukocyte Injury
• Transocytosis (endo/exo)
• New Vessels
 LEAKAGE OF
PROTEINACEOUS FLUID
( EXUDATE, NOT
TRANSUDATE)
 EXTRAVASATION of
PMNs
• MARGINATION
(PMN’s go toward
wall)
• ROLLING (tumbling
and HEAPING)
• ADHESION
• TRANSMIGRATION
(DIAPEDESIS)
 ADHESION MOLECULES
(glycoproteins) affecting
ADHESION and TRANSMIGRATION

• SECRETINS (from
endothelial cells)
• INTEGRINS (from many
cells)
 CHEMOTAXIS
PMNs going to the site of “injury”
AFTER transmigration
 LEUKOCYTE
“ACTIVATION”
• “triggered” by the offending stimuli for PMNs to:
– 1) Produce eicosanoids (arachidonic acid
derivatives)
• Prostaglandin (and thromboxanes)
• Leukotrienes
• Lipoxins
– 2) Undergo DEGRANULATION
– 3) Secrete CYTOKINES
PHAGOCYTOSIS
• RECOGNITION

• ENGULFMENT

• KILLING
(DEGRADATION/
DIGESTION)
CHEMICAL MEDIATORS
• From plasma or cells
• Have “triggering” stimuli
• Usually have specific
targets
• Can cause a “cascade”
• Are short lived
 CLASSIC MEDIATORS
• PLATELET
• HISTAMINE ACTIVATING
• SEROTONIN FACTOR (PAF)
• COMPLEMENT • CYTOKINES
• KININS • /CHEMOKINES
• CLOTTING • LYSOSOME
FACTORS CONSTITUENTS
• EICOSANOIDS • FREE RADICALS
• NITRIC OXIDE • NEUROPEPTIDES
HISTAMINE
• Mast Cells,
basophils
• POWERFUL
Vasodilator
• Vasoactive
“amine”
• IgE on mast
cell
 SEROTONIN
• (5HT, 5-Hydroxy-
Tryptamine)
• Platelets and
EnteroChromaffin Cells
• Also vasodilatation, but
more indirect
• Evokes N.O. synthetase
(a ligase)
 COMPLEMENT SYSTEM
• >20
components,
in circulating
plasma
• Multiple sites
of action, but
LYSIS is the
underlying
theme
KININ SYSTEM
• BRADYKININ is KEY component, 9 aa’s
• ALSO from circulating plasma
• ACTIONS
– Increased permeability
– Smooth muscle contraction, NON vascular
–PAIN
 CLOTTING
FACTORS
• Also from circulating plasma
• Coagulation, i.e., production of
fibrin
• Fibrinolysis
 EICOSANOIDS
(ARACHIDONIC ACID DERIVATIVES)
• Part of cell membranes
• 1) Prostaglandins (incl.
Thromboxanes)
• 2) Leukotrienes
• 3) Lipoxins (new)
MULTIPLE ACTIONS AT MANY LEVELS
Prostaglandins
(thromboxanes included)

• Pain
• Fever
• Clotting
 Leukotrienes
• Chemotaxis
• Vasoconstriction
• Increased Permeability
 Lipoxins
• INHIBIT chemotaxis
• Vasodilatation
• Counteract actions of
leukotrienes
 Platelet-Activating Factor
(PAF)
• Phospholipid
• From MANY cells,
like eicosanoids
• ACTIVATE
PLATELETS,
powerfully
CYTOKINES/CHEMOKINES
• CYTOKINES are PROTEINS produced by
MANY cells, but usually LYMPHOCYTES
and MACROPHAGES, numerous roles in
acute and chronic inflammation

–TNFα, IL-1, by
macrophages
• CHEMOKINES are small proteins which are
attractants for PMNs (>40)
 NITRIC OXIDE
• Potent vasodilator
• Produced from the action
of nitric oxide synthetase
from arginine
LYSOSOMAL CONSTITUENTS
• PRIMARY • SECONDARY
• Also called • Also called SPECIFIC
AZUROPHILIC, or
NON-specific • Lactoferrin
• Lysozyme
• Myeloperoxidase • Alkaline Phosphatase
• Lysozyme (Bact.) • Collagenase
• Acid Hydrolases
FREE RADICALS
• O2 – (SUPEROXIDE)
•H2O2 (PEROXIDE)
•OH- (HYDROXYL RADICAL)

•VERY VERY
DESTRUCTIVE
 NEUROPEPTIDES
• Produced in CNS (neurons)
• SUBSTANCE P
• NEUROKININ A
 OUTCOMES OF
ACUTE INFLAMMATION
• 1) 100% complete
RESOLUTION

• 2) SCAR

• 3)CHRONIC inflammation
 Morphologic PATTERNS
of Acute INFLAMMATION
(EXUDATE)
•Serous (watery)
•Fibrinous (hemorrhagic,
rich in FIBRIN)
•Suppurative (PUS)
•Ulcerative
BLISTER, “Watery”, i.e., SEROUS
FIBRINOUS
 PUS
=
PURULENT

ABSCESS
=
POCKET
OF
PUS
PURULENT, FIBRINOPURULENT
ULCERATIVE
 SEQUENCE OF EVENTS
• NORMAL HISTOLOGY 
• VASODILATATION 
• INCREASED VASCULAR PERMEABILITY 
• LEAKAGE OF EXUDATE 
• MARGINATION, ROLLING, ADHESION 
• TRANSMIGRATION (DIAPEDESIS) 
• CHEMOTAXIS 
• PMN ACTIVATION 
• PHAGOCYTOSIS: Recognition, Attachment,
Engulfment, Killing (degradation or digestion) 
• TERMINATION 
• 100% RESOLUTION, SCAR, or CHRONIC
inflammation
CHRONIC INFLAMMATION
(MONOS)

MONOCYTE
LYMPHOCYTE MACROPHAGE
HISTIOCYTE
 CAUSES of
CHRONIC INFLAMMATION
• 1) PERSISTENCE of
Infection
• 2) PROLONGED
EXPOSURE to insult
• 3) AUTO-IMMUNITY
 Cellular Players
•LYMPHOCYTES
•MACROPHAGES
(aka, HISTIOCYTES)
• PLASMA CELLS
• EOSINOPHILS
• MAST CELLS
MORPHOLOGY
• INFILTRATION
• TISSUE DESTRUCTION
• HEALING
 GRANULOMAS
GRANULOMATOUS INFLAMMATION
4 COMPONENTS

FIBROBLASTS

LYMPHS

HISTIOS

“GIANT” CELLS
 GRANULOMAS
GRANULOMATOUS INFLAMMATION

CASEATING (TB)
NON-CASEATING
 LYMPHATIC
DRAINAGE
• SITE REGIONAL LYMPH NODES
 SYSTEMIC MANIFESTATIONS
(NON-SPECIFIC)
• FEVER, CHILLS
• C-Reactive Protein (CRP)
• “Acute Phase” Reactants
• Erythrocyte Sedimentation Rate
(ESR) increases
• Leukocytosis
• Pulse, Blood Pressure
• Cytokine Effects, e.g., TNF(α), IL-1
NORMAL SPE

Serum
Protein
Electrophoresis

In ACUTE
Inflammation
Alpha-1 & alpha-2
are increased,
i.e.,
“acute phase”
reactants.