1. Chemical Mediators of Inflammation
Dr. Raid Jastania

3. Chemical Mediators of Inflammation
Mediators can be plasma proteins, typically synthesized in the liver and released to the circulation in an inactive form. complement system, Kinins, and coagulation factors.
Mediators can be produced by cells (WBC, endothelial cells, fibroblast). This include arachidonic acid metabolites, cytokines and vasoactive amines.

4. Chemical Mediators of Inflammation
List of chemical mediators:
Vasoactive amines (eg. histamine)
Plasma proteases (Kinins, Clotting factors, Complement system)
Arachidonic Acid metabolites (PG, Leukotrienes)
Cytokines (Interleukins, chemokines)

5. Chemical Mediators of Inflammation
act on specific receptor on cell surface.
may induce the production other mediators.
may act by autocrine, paracrine, or endocrine fashion.
may act on one cell type or many cell types.
tightly regulated by their short half-life and by inhibitors.
Mediators may have harmful effect

6. Chemical Mediators of Inflammation
Histamine:
Source: mast cells
Action: vasodilation and increase vascular permeability by endothelial contraction.
Stimuli: trauma, heat, IgE reaction, C3a, C5a (anaphylatoxins), IL-1, IL-8

7. Chemical Mediators of Inflammation
Arachidonic Acid metabolites:
Source: phospholipid of cells by the action of Phospholipase A2.
Stimuli: physical, chemical injury, C5a
2 pathways:
1.      Cyclooxygenase: produce prostaglandins PG, action: vascular changes, pain, platelet function
2.      Lipoxygenase: produce Leukotrienes, eg. LTB4 act as chemotactic agent

8. Chemical Mediators of Inflammation
Arachidonic Acid metabolites:
Aspirin and NSAID’s inhibit cyclooxygenase activity and result in decrease in PG production and control of pain and fever.
Steroids inhibit Phospholipase A2, and hence all arachidonic acid metabolites.

9. Chemical Mediators of Inflammation
Cytokines: IL-1, and TNF:
Source: macrophages
Stimuli: injury, immune complex, other mediators
Action: activation of endothelial cells, neutrophils and fibroblasts, They have systemic effect as well.

10. Chemical Mediators of Inflammation
Cytokines: IL-1, and TNF:
IL-1 and TNF act on the thermoregulatory center in the hypothalamus and induce the production of PGE and result in Fever.
They also enhance the release of WBC’s from the bone marrow and result in Leukocytosis (15,000-20,000 per microliter).
They also induce the bone marrow to produce WBC’s.
IL-6 acts on the liver to increase the production of complement components and coagulation factors.

14. Morphologic Patterns of Inflammation
Serous Inflammation
Fibrinous Inflammation
Suppurative Inflammation
Ulceration

15. Morphologic Patterns of Inflammation
Serous Inflammation:
abundant watery effusion fluid (exude/transudate).
Serous inflammation commonly occurs in the serosal surfaces (peritoneum, pericardium, pleura).
Examples: peritonitis, pericarditis, pleuritis, skin burn, viral infections.

16. Morphologic Patterns of Inflammation
Fibrinous Inflammation:
severe injury to the vessels.
Example: trauma, bacterial infections.
excessive blood clotting and fibrin
organization,
may lead to fibrous adhesions. Example: restrictive pericarditis, fibrous adhesion in the peritoneum.

18. Morphologic Patterns of Inflammation
Suppurative Inflammation:
pus accumulation (neutrophils, exudate fluid and cellular debris)
typical in bacterial infections eg. staph infection of skin
may lead to abscess formation.

19. Morphologic Patterns of Inflammation
Ulceration:
Ulcer can be acute or chronic.
Ulceration is necrosis of the epithelial surface (of skin, GIT, respiratory, urogenital tract) with underlying inflammation (acute or chronic).
Peptic ulcer is a typical example.
Ulcer may result from physical or chemical injury, or ischemic necrosis.

20. Defect in Leukocyte Function
Defect in adhesion:
Leukocyte adhesion deficiency-1 (LAD-1) is a defect in the integrin LFA-1
Leukocyte adhesion deficiency-2 (LAD-2) is due to absence of sialyl-Lewis X.
Defect in microbial killing:
Chronic granulomatous disease results from defect in oxidative burst function.
Defect in phagolysosome formation
Chediak-Higashi syndrome result from impaired lysosomal degranulation.

21. Home work
Exercise
Case discussion