inflammation

Inflammation

Lecture II

Defect in leukocytes function

Defect in adhesion
Leukocyte adhesion defect-1 due to defect in integrin.
Leukocyte adhesion defect-2 due to defect in sialyl- Lewis X.
Defect in chemotaxis or phagocytosis
Chediak-Higashi syndrome.

Defect in microbicidal activity

Chronic granulomatous disease

Chemical Mediators

A substances which play a role in genesis and modulation of inflammatory reaction.


They are responsible for:
1.Vasodilatation.
2.Increased permeability of the blood vessels.
3.Emigration of WBC (Chemotactic agent).

Mediators of acute inflammation

Plasma factors synthesized mainly in liver
Plasma proteins
Factor XII = coagulation system (Hageman factor) activation

Kinin system

Coagulation system
Complementactivation

C3a

C5a

C3b

C5b-C9

anaphylatoxins
opsonin
MAC

Chemical Mediators of Inflammation

A/ Vasoactive Amines

1) Histamine: secreted from mast cells, basophils & platelets.

2) Serotonin: secreted from platelets, enterochromaffin cells.

Effects: arteriolar vasodilatation & increase vascular permeability.

B/ Arachidonic Acid (AA) Metabolites

AA present in the cell membrane phospholipids.

Release from phospholipids through the action of phospholipase enzyme by mechanical, chemical & physical stimuli.

AA metabolism proceeds along 1 of 2 pathways

Cyclo-oxygenase pathway------Prostoglandins.
Lipo-oxygenase pathway------------Leukotriens.


Arachidonic Acid Metabolites
Cyclo-oxygenase pathway

-Thromboxane A2

Vasoconstriction
Platelet aggregation
-Prostacyclin (PGI2)
Vasodilatation
Inhibits Platelet aggregation
-PGD2, PGE2 & PGF2
VD & edema
-PGE2:
Fever
Pain
Lipo-oxygenase pathway

-HETE:

Chemotaxis

-LTB4:

Chemotaxis
Aggregation of neutrophils
-LTC4, LTD4, LTE4
Vasoconstriction
Bronchospasm
Increase vascular permeability


C/ Platelet-Activating Factor

Synthesized from membrane phospholipids through the action of phospholipase A2 in basophils, endothelial cells & neutrophils.
Effects of platelate –Activating factor
Platelet aggregation.
V.D. & increase vascular permeability.
Chemotaxis.
Smooth muscle contraction.

D) Cytokines

Polypeptides produced by activated lymphocytes & macrophages.
It involved in cellular immunity & inflammatory responses.
IL-1 & TNF
Acute phase reaction including fever & Neutrophilia.
Promote endothelial secretion of PG & NO.
Induce fibroblastic proliferation & collagen synthesis.
IT-6
Acute phase reactions.
IT-8
Chemotactant & neutrophil activating agent.


E) Nitric Oxide (NO)

Soluble free radical gas synthesized by endothelial cells, macrophages & specific neurons in the brain.

Effect

Vascular smooth muscle relaxation causing vasodilatation.
Decreased platelet aggregation & adhesion.
Microbicidal agent.

F) Lysosomal Constituents

Potentially act as inflammatory mediators when released from neutrophils & macrophages.

Effect:

Destruction of ECM.

Direct cleavage of C3 & C5.

G) Oxygen Free Radicals

Superoxide (O2-), OH-, H2O2 & NO

Effects
Endothelial cell damage causing increase vascular permeability.

Activation of proteinases.

Injury to surrounding cells.

H/ Plasma Proteases

1)Complement System

Present as inactive form in the plasma

Vascular effect (anaphylotaxins): C3a, C5a & C4a causing V.D. & increase vascular permeability.

Leukocyte adhesion, chemotaxis & activation: C5a

Phagocytosis: C3b & C3b1 act as opsonin.

2) Kinin System

Activated by activation of Hageman factor (XII)

Bradykinin: increase vascular permeability , V.D., pain & smooth muscle contraction.

Kallikrein: has chemotactic activity.

3) Clotting System

A cascade activated by Hageman factor (XII) resulting in conversion of fibrinogen to fibrin.

Fibrinopeptides: increase vascular permeability & chemotaxis.

4) Fibrinolytic System:

Plasmin: lyses fibrin clots, degrades fibrin to fibrin degradation products.

Fibrin degradation products: Increase vascular permeability.

Microscopic appearance of acute inflammation

Congestion of blood vessels.


Exudation of fluid.

Exudation of inflammatory cells mainly neutrophils.

Types of acute inflammation
1. Catarrhal
Acute inflammation + mucus hyper secretion of mucus membrane (common cold).
2. Serous
Low protein content, low cellular fluid (pleural effusion).
3. Suppurative (Purulent)
Pus: creamy yellow or blood stained fluid consist of N, M.O, & tissue debris (acute appendicitis).
Abscess: Focal localized collection of pus material.
Empyema: Collection of pus in the hallow organ.
4. Fibrinous
Accumulation of thick exudate rich in fibrin, which may resolve by fibrinolysis or organize into thick fibrous tissue. Fibrinous inflammation –bread &butter appearance to the inflamed serous membrane.

Morphologic patterns of acute inflammation

Serous inflammation:
Tissue fluid accumulation indicating a modest increase in vascular permeability
Pleura , pericardium,
peritoneum: effusion
Blister in burns

Fibrinous inflammation:

More marked increase in vascular permeability, with exudates containing large amounts of fibrinogen
Involvement of serosal surfaces ( pericardium or pleura) : fibrinous pericarditis or pleuritis

Suppurative or purulent inflammation:

Production of purulent exudates consisting of leukocytes and necrotic cells.
An abcess refers to a localized collection of purulent inflammatory tissue accompanied by liquefactive necrosis.