KULIAH PATOLOGI ANATOMI BLOK 7

ACUTE & CHRONIC INFLAMMATION

By : dr.Henny Sulastri, SpPA(K)

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GENERAL FEATURES

Definition The response of vascularized

living tissue to injury

may be avoked by :
microbial infections

physical agents

Chemicals

necrotic tissue

immune reactions

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The ultimate goals:
to rid the organism
to repair tissue
replaced injuried or dead cell by regeneration of
parenchymal cell
The steps of the inflammatory response
the five Rs:
(1) Recognition of the injurious agent
(2) Recruitment of leukocytes
(3) Removal of the agent
(4) Regulation (control) of the response,
(5) Resolution (repair). 3
 Characteristic of inflammation
2 main components
vascular reaction
cellular response
mediated by :
circulating plasma protein
vessel wall
inflamatory cells
outcome :
elimination of the noxious stimulus followed by
decline of the reaction
repair of the damaged tissue
persistent injury resulting in chronic
inflammation. 4
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 Types of inflammation

Acute inflammation Chronic inflammation

early onset
onset later onset (days)
(second to minutes)

short duration longer duration

duration
(minutes to day) (weeks to years)

polymorphonuclear cells
Involved cells lymphocytes & macrophages
(neutrophil)

blood vessels proliferation &

effect fluid exudation (edema)
scarring
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 ACUTE INFLAMMATION
Definition is a rapid response to injury or microbes and other
foreign substances that is designed to deliver leukocytes and
plasma proteins to sites of injury.
may be triggered by :
Infections bacterial, viral, fungal, parasitic
Trauma (blunt and penetrating)
physical and chemical agents (thermal injury, e.g., burns or
frostbite; irradiation; some environmental chemicals)
Tissue necrosis (from any cause), including ischemia (as in a
myocardial infarct) and physical and chemical injury.
Foreign bodies (splinters, dirt, sutures)
Immune reactions (also called hypersensitivity reactions)
against environmental substances or against self tissues.
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The cardinal signs of inflammation
1. Heat (calor)
2. Redness (rubor)
3. Edema (tumor)
4. Pain (dolor)
(+) Loss of function
(fungtio laesa)

cardinal signs

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 The typical reactions of acute
inflammation and its morphologic
features
Alterations in vascular caliber head & redness
blood flow

Structural changes in the

microvasculare plasma proteins
& leukocytes leaves the circulation edema
produce inflammatory exudates

Leukocyte migrates from blood

vessels accumulation at the edema & pain
site of injury

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Hyperaemia/heat
Injury

Damaged cells

Direct effect Nervous reaction

CHEMICAL MEDIATORS (axon reflex)
on vessels

VASCULAR DILATATION

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VASCULAR CHANGES IN INFLAMMATION

Normally, fluid
exchange in vascular
beds depends on 2
opposing forces :
Hydrostatic
pressure
fluid moves out of
the circulation
Plasma coloid
osmotic pressure
fluid moves into
capillaries

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VASCULAR CHANGES

Immediately after injury

vascular wall changes in caliber & permeabillity that
effect flow
Vasodilatation, causes increase flow into areas of
injury, thereby increases hydrostatic pressure.
Increased vascular permeability causes exudation
plasma protein & decreases plasma osmotic pressure

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 Formation of venule
intercellular
endothelial gaps Inducing
Direct endothelial
injury
Delayed prolonged
leaked
Leukocyte-mediate
endothelial injury Vascular permeability
Increased transcytosis
Leakage from new
blood vessels

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fluid accumulation in the interstitial spaces

Inflammatory edema
characterized by protein rich exudate

EDEMA

Non inflammation edema

characterized by a transudate of low protein

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 EXUDATION/EDEMA
PROTEIN PASSAGE Endhotelial contraction-formation gaps

Chemical mediators

Increased permeability
FLUID MOVEMENT
Loss of protein Interstitial tissue
Hyperaemia protein increase
from capillaries

Capillary blood Reduced plasma Increased tissue

pressure rises osmotic pressure osmotis pressure

INCREASED FILTRATION PRESSURE

Local swelling (EDEMA)

Increased lymph flow from area 15

Non Inflammatory Edema
hydrostatic pressure due to thrombosis or
congestive heart failure

plasma osmotic pressure caused by albumin loss

due to kidney disease or decreased liver or
malnutrition

Alteration of osmotic pressure due to abnormalities of

sodium &/or water retention

Obstruction of lymphatic flow

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INFLAMMATORY EDEMA

The inflammatory response will increase

vascular permeability important in
enabling cells & factors to reach the side
of injury & some edema occur

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TERM USED DESCRIBE THE
PATHOLOGY OF EDEMA

Effusion : excess fluid in body cavities

(e.g. peritoneum or pleura)

Transudate : edema fluid without protein

content, causes increase hydrostatic
pressure

Exudate : edema fluid with high protein

content; appears early in mild injuries;
may contains inflammatory cells.
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 B. CELLULAR EVENTS : LEUKOCYTE
EXTRAVASATION & PHAGOSITOSIS
Margination, rolling, &
adhesion of leukocytes
to the endothelium
Emigration/
Transmigration across
the endothetium 3 steps of leukocyte
extravasation
(diapedesis )
Migration in interstitial
tissues toward a
chemotactic stimulus

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LEUKOCYTE ADHESION & TRANSMIGRATION

occurs by interactions between

complementary adhesion molecules on
leukocytes & endothelium.
The major adhesion molecule :
Selectins
Imunoglobulin family molecules
Integrins

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CELLULAR RESPONSE OF LEUKOCYTES :
MIGRATION

Definition : is the passage of inflammatory

leukocytes between endothelial cells into the
adjacent interstitial tissue.
Before migration, leukocytes circulate from the
central blood flow move toward the endothelial
surface.

a. Margination leukocytes localized to the outer

margin of the blood, flow adjacent to the vascular
endothelium

b. Pavementing leukocytes line the endothelial

surface 22
c. Rolling (tumbling)
mediated by the action of endothelial
selectins loosely binding to leukocytes,
producing a characteristic rolling
movement of leukocytes along the
endothelial surface
d. Adhesion
leukocytes adhere to the endothelial surface
mediated by the interaction of integrins
on leukocytes binding to immunoglobulin-
family adhesion proteins on endothelium
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e. Transmigration
isthe movement of leukocyte across the
endothelium
mediated by platelet endothelial cell
adhesion molecule-1 (PECAM-1) on both
leukocytes & endothelium.

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Chemotaxis
Adherent leukocytes migrate through
interendothelial junctions & tranverse basement
membrane to the site of injury will need a
chemotactic agents.
Chemotatic agent
Exogenous : bacterial products
Endogenous : complement fragments,
arachidonic acid metabolites & chemokines

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PHAGOCYTOSIS

Definition: is the ingestion of particulate

material (e.g., tissue debris, living or dead
bacteria, other foreign cells) by phagocyte cells
Involves three step :
Recognized & binding
Engulfment
Killing & degradation

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 Recognized & binding
Microorganisme may be coated with
opsonins
2 major opsonins are :
- Immunoglobulin G (IgG) Fc fragment
- The complement fragment C3b
Fragment opsonized by IgG are bounded to
phagocytic cells-surface receptors for the Fe
portion of the IgG molecule.
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 Engulfment
By encircling pseudopods (involving actin
polymerization) & enclosure of the particle
within intracellular phagosome
Phagocytic vacuole fuse with lysosomes,
resulting in enzyme discharge into resulting
phagolysosome.

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 Killing & degradation
1. Oxygen dependent microbial killing
is the most important intracellular microbicidal
process.
Activating of the hexose monophasphat shunt
causing activation of NADPH oxidase in the
phagosomal membran.
Converting oxygen to superoxide anion

(O2-) & H2O2

Lysosomal myeloperoxidase (MPO) then concerts
H2O2 & Cl- into the highly bactericidal HoCl
H2O2 + Cl- MPO HOCL 30
2. Oxygen-independent microbicidal
killing
<<< effective than oxygen dependent
microbicidal killing.
mediated by protein;
lysozyme lactoferrin

mayor basic protein of eosinophils

cationic proteins

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CHEMICAL MEDIATORS OF INFLAMATION

Vasoactive Amines:
Histamin vasodilatation, vascular
Serotonin permeability
Plasma Protein
complement system
kinin system
clotting system
Arachidonic Acid Metabolites
Prostagl&ins
Leukotrines
lipoxins
Platelet-activating Factor
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 Cytokines & chemokines
TNF & Interleukin
Chemokines
Nitric Oxide
Lysosomal Constituens of Leokocytes
Oxygen-Derived Free Radicals
Neuropeptides
Other Mediators

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Chemical mediators of inflammation

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Plasma Protein-Derived
Mediators : complement
numbered C1 to C9) & present in plasma in inactive
forms
Upon activation, different complement proteins coat
(opsonize) particles, such as microbes, for phagocytosis
and destruction, and contribute to the inflammatory
response by increasing vascular permeability and
leukocyte chemotaxis.
C3a & C5a increase vascular permeability & cause
vasodilation by inducing mast cells to release histamine.
C3 cleavage occurs
(1) via the classical pathway
(2) through the alternative pathway
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(3) by the lectin pathway,
The activation and functions of
the complement system

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CELLS OF INFLAMATION

1. Neutrophils
2. Monocyte/Macrophage
3. Eosinophils
4. Basophils
5. Platelets
6. Mast cells
7. Endothelial Cells

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Neutrophils
Hallmarks of acute inflamation
Originate in bone marrow from myelocyte
progenitors
Contain two main types of granules & a
multilobed nucleus
When activated, they migrate out of blood into
the tissues, where they phagocytose invading
microbes & dead tissue
dont return to blood
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Monocyte/Macrophage
Accumulate at sites of acute inflamation in
response to inflamatory mediators

Important in maintenance of a chronic

inflamatory state

Have single-lobed & kidney-shape nucleus

Migrate out of to become resident tissue

macrophages
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Activated tissue macrophages histiosit
phagocytose microbes, debris

Can process & present antigen to

lymphocytes

Produce bactericidal & proinflammatory

mediators

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Eosinophils
Involved in defense against parasites
Associated with allergic reactions
Usually have a bilobed nucleus
tissue in a manner similar to neutrophils
Contains in blood; recruited to
Produce major basic protein & cationic
protein

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 Basophils

Cellular sources of vasoactive mediators,

particularly in response to allergens
Rarest of bloods leukocytes
Have receptors for IgE on their surface
Binding of antigen specific to surface IgE
causes release of granules containing
inflammatory mediators (histamine & heparin)
The granulation may also be induced by
physical agonist (cold & trauma)
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Platelets
Small, anucleated membrane bounded
cytoplasmic fragments
Derived from bone marrow megakaryocytes.
Contain granules rich in serotonin, histamine,
coagulation proteins & pletelet-derived growth
factor (PDGF)
Platelets adherence, aggregation, &
degranulation occur folowing vascular injury
exposing the ECM
Activation of platelets results in increased
vascular permeability
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Mast cells
appearance & function similar basophils

Especially prevalent along mucosal surfaces of

the lung, GI tract, skin dermis, &
microvasculature

Products play an important role in vascular

permeability & bronchial smooth muscle tone,
especially in allergic hypersensitivity reactions
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Endothelial Cells
Flattened cells lining blood vessels & lymphatics
Maintain vessel patency & blood flow by the
production of antithrombotic agents
Regular vascular tone through the production of
vasodilators & vasoconstrictors
Injured endothelium leads to a local procoagulant
signal

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 Important inflammatory mediators of endothelium are :
Nitric oxide vasodilatation; inhibits platelet
aggregation
Endothelins induce prolonged vasoconstriction
Arachidonic acid derivated constriction & relaxing
factors
Anticoagulants inactivate the coagulation cascade
Fibrinolytic factors such as tissue-type
plasminogen activator
Prothrombic agents such as von Willebrand factor
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 Complete Resolution
with regeneration of
native cells &
restoration to
OUTCOMES OF normalcy
ACUTE
INFLAMMATION Healing by conective
tissue replacement
(firosis)

Progression to
chronic inflammation
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 Bacterial kill
RESOLUTION

SUPPURATION

Discharge of pus

ACUTE Excessive exudate REPAIR &

INFLAMMATION Excessive necrosis ORGANISATION

FIBROSIS

Persistence of causal agent

CHRONIC
INFLAMMATION

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 Serous exudate or
effusion
Serosanguinous
exudate
Fibrinous exudate
MORFOLOGY PATERNS
OF ACUTE Purulent exudate or
effusion
INFLAMMATION
Supurative
inflammation
Catharralhis
inflammation
Ulcers
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OUTCOMES OF ACUTE INFLAMMATION:
RESOLUTION, HEALING BY SCARRING
(FIBROSIS), OR CHRONIC INFLAMMATION

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 CHRONIC INFLAMMATION

Is a prolonged process (weeks or months) in

which active inflammation, tissue destruction,
& attempts at healing may all proceeding
simultaneously

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 Following acute
inflammation, either
because the inciting
stimulus persists or
because normal healing is
somehow interrupted (ex:
Chronic peptic ulcer, cholecystytis
inflammation cronic)
can occurs by: From repeated bouts of
acute ainflammation (ex:
viral infection)
without prior acute
inflammation (ex: TBC,
leprosy, syphyllis)

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Etiology Persistent infections
Mycobacteria
Treponema pallidum syphilis
viruses
fungi

Prolonged exposure to potentially toxic agents

exogenous: silica silicosis
endogenous: chronically elevated plasma lipid
components atherosclerosis

Immune-mediated inflammatory diseases bronchial asthma

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 Characteristic of
chronic
inflammation:

Infiltration with mononoclear inflammatory

cells macrophages, lymphocytes & plasma
cells.
Tissue destruction, largely induce by
persistent injury & inflammatory cells
Attempt at healing by connective tissue
replacement, accomplished by vascular
proliferation (angiogenesis) & fibrosis 64
Chronic Inflammatory
Cells
Macrophages
the dominant cells of chronic inflammation
normally diffusely scattered in most
connective tissues
the liver (where they are called Kupffer cells)
spleen and lymph nodes (called sinus
histiocytes)
central nervous system (microglial cells)

lungs (alveolar macrophages)

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The roles of activated macrophages
in chronic inflammation

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 Other cells in chronic
Inflammation
Lymphocytes
mobilized in both antibody & cell mediates
immune reactions
involved even in non-immune inflammation.
Eosinophils
characteristic of immune reactions mediated by
IgE & in parasitic infections
Mast cells
widely distribute in connective tissues
participate in acute & chronic inflammation67
Macrophage-lymphocyte interactions in
chronic inflammation

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GRANULOMATOUS INFLAMMATION
Definition: pattern of chronic inflammatory reaction
characterized by focal accumulations of activated macrophages
(granulomas)

GRANULOMATOUS
INFLAMMATION

2 types :
1. Forein body granulomas are incited by relatively
inert foreign bodies (eg: suture, splinter)
2. immune granulomas are formed by immune T cell-
mediated responses to persistent antigen ex:
tuberculosis bacillus (granuloma is called a tubercle &
classically exhibits central caseous necrosis)

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Activated may fuse to form multinucleated
macrophages IFN- giant cells
becoming enlarged & flattened
Epitheloid macrophages

surrounded by collar of lymphocytes elaborating factor necessary to

induce macrophage activation

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 Mediators of chronic
inflammation
Agent Action Source

Aggregation of
Migration inhibition Activated T
macrophages at
factor (MIF) lymphocytes
site of injury

Increased
Macrophage activation Activated T
phagocytosis by
factor (MAF) lymphocytes
macrophages

Chemotactic for
Complement 5a Complement system
macrophages

Eosinophil Chemotactic for

chemotactic factor eosinophyls in Mast cells and
of anaphylaxis metazoan basophils
(ECF-A) infections 71
 LYMPHATICS IN INFLAMATION
Lymphatics & lymph nodes

Function :
filtering & policeekstravascular fluids
representing a secondary line of defense
whenever a local inflammatory response
cannot contain an external agent
In inflammation, lymphatic flow will increased
to drain edema fluid, leucocytes & cell debris
from the extravascular space

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SYSTEMIC EFFECTS OF
INFLAMMATION
Systemic changes associated with inflammation
acute fase response or Systemic inflammatory
response syndrome (SIRS)

These represent responses to cytokines produced either by

bacterial product (ex: endotoxin) or by other inflammation
stimuli.
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 Fever; T (1-4C) is produced in response
to pyrogens that act by stimulating PG
of acute phase proteins (CRP, fibrinogen,
serum amyloid A) synthesis stimulated
by cytokines (IL-6) acting on liver cells
Leukocytosis cytokines stimulate
production of leukocytes from precusors in
bone marrow
Others :
CLINICAL & increase pulse & blood pressure
PHATOLOGIC decrease sweating
CHANGES of SIRS: rigors
Chills
Anorexia
somnolens
malaise, probably due to systemic
effects of cytokines.
Bacterial infections (sepsis) induced by
high level of TNF
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Cancer related chronic
inflammation
HIV sarcoma kaposi
Hepatitis B hepatoma
Schistosomiasis squamous ca pada buli
Chronic gastritis stomach cancer
Chronic prostatitis prostate cancer
inflammatory bowel disease ulcerative
colitis colon cancer
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