Chemical Mediators of Inflammation

1
Chemical Mediators of Inflammation

• Dr. Raid Jastania

2
(No Transcript)
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 NSAIDs 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 WBCs from the
  bone marrow and result in Leukocytosis
  (15,000-20,000 per microliter).
• They also induce the bone marrow to produce
  WBCs.
• IL-6 acts on the liver to increase the
  production of complement components and
  coagulation factors.

11
(No Transcript)
12
(No Transcript)
13
(No Transcript)
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.

17
(No Transcript)
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