Chemical Mediators of Inflammation Dr. Raid Jastania.
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Transcript of Chemical Mediators of Inflammation Dr. Raid Jastania.
Chemical Mediators of Inflammation
Dr. Raid Jastania
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.
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)
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
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
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
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.
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.
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.
Morphologic Patterns of Inflammation
• Serous Inflammation
• Fibrinous Inflammation
• Suppurative Inflammation
• Ulceration
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.
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.
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.
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.
Defect in Leukocyte Function
1. 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.
2. Defect in microbial killing:– Chronic granulomatous disease results from defect in
oxidative burst function.
3. Defect in phagolysosome formation– Chediak-Higashi syndrome result from impaired
lysosomal degranulation.
Home work
• Exercise
• Case discussion