1. Inflammation
Lecture II

2. 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

3. 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).

4. Mediators of acute inflammation
Plasma factors synthesized mainly in liver
Kinin system
Factor XII = coagulation system (Hageman factor) activation
Coagulation system
Plasma proteins
C3a
C5a
C3b
C5b-C9
anaphylatoxins
Complement activation
opsonin
MAC

5. 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.

6. 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.

7. 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:
Aggregation of neutrophils
-LTC4, LTD4, LTE4
Vasoconstriction
Bronchospasm
Increase vascular permeability

8. 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.

9. Polypeptides produced by activated lymphocytes & macrophages.
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.

10. 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.

11. F) Lysosomal Constituents
Potentially act as inflammatory mediators when released from neutrophils & macrophages.
Effect:
Destruction of ECM.
Direct cleavage of C3 & C5.

12. G) Oxygen Free Radicals Superoxide (O2-), OH-, H2O2 & NO Effects
Endothelial cell damage causing increase vascular permeability.
Activation of proteinases.
Injury to surrounding cells.

13. Present as inactive form in the plasma
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.

14. Activated by activation of Hageman factor (XII)
2) Kinin System
Activated by activation of Hageman factor (XII)
Bradykinin: increase vascular permeability , V.D., pain & smooth muscle contraction.
Kallikrein: has chemotactic activity.

15. 3) Clotting System
A cascade activated by Hageman factor (XII) resulting in conversion of fibrinogen to fibrin.
Fibrinopeptides: increase vascular permeability & chemotaxis.

16. 4) Fibrinolytic System:
Plasmin: lyses fibrin clots, degrades fibrin to fibrin degradation products.
Fibrin degradation products: Increase vascular permeability.

17. Microscopic appearance of acute inflammation
Congestion of blood vessels.
Exudation of fluid.
Exudation of inflammatory cells mainly neutrophils.

18. 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.

19. Morphologic patterns of acute inflammation
Serous inflammation:
Tissue fluid accumulation indicating a modest increase in vascular permeability
Pleura , pericardium,
peritoneum: effusion
Blister in burns

21. 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

23. 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.