Mechanisms of acute inflammation:

1- vascular (events) changes:

  • Transient vasoconstriction of arterioles: seconds to few minutes, mediated by neurogenic mechanism.
  • Persistent Arteriolar vasodilatation:this lead to increase blood flow at the site of inflammation and engorgement of downstream capillary beds, this increment in the blood flow responsible for redness and warmth of the site of inflammation. The engorgement of the capillary bed lead to increase in the hydrostatic pressure and lead to ooze of low protein fluid called transudate to the extra vascular compartment.
  • Increase permeability of the vessel wall that lead to infiltrate of high protein fluid called exudates, to the extra vascular compartment.

Note: accumulation of both exudates and transudate responsible for Oedema at site of inflammation.

Mechanisms of increase vessels permeability:

1-Endothelial cells contraction: reversible process mediated by chemicals (histamine and bradykinin).

2-Junction Retraction: reversible process mediated by chemicals (TNF, AND IL-1).

3-Direct endothelial cells damage.

4-Leukocytes dependant endothelial cells injury, like in burn or infection.

5-Increase transcytosis via an intracellular vesicles pathway.

6-Leakage from newly formed blood vessels (angiogenesis).

  • Increase viscosity of blood due to extravasations of blood plasma.
  • Slow of blood flow ( Stasis).

2- cellular (events) changes:

  • (Margination): Accumulation of leukocytes along the endothelial surface and leaving the normal axial stream.
  • (Pavement): Adhesion of the leukocytes to the endothelial cells.
  • After tight adhesion of the leukocytes to the endothelial cells, the leukocytes start (transmigration), by squeezing between endothelial cells at the intercellular junctions.
  • (Chemotaxis):Its migration of leukocytes toward site of inflammation along a chemical gradient.

Types of chemotactic factors:

The chemotactic factors are either endogenous or exogenous, and these are:

1-Bacterial products.

2-Complement component (C5a).

3-Arachidonic acid (A.A.), and leukotriene B4.

4-Cytokines (IL-8).

  • (Phagocytosis):

It’s the process of engulfment and internalization of particular materials include (micro-organisms, damaged cells and tissue debris), by phagocytic cells which are (neutrophils, monocytes and tissue macrophages).

Opsonization:

Phagocytosis is enhanced if the material to be phagocytosed is coated with certain plasma proteins called (opsonins), this process called Opsonization, so the opsonins promote the adhesion between the particular material and the phagocyte cell membrane.

Types of opsonins:

1-specific antibodies of IgG class.

2-C3b component of complement.

3-Plasma fibronectin.

Microbial killing:

  • Oxygen independent mechanism by lysosomal enzymes.
  • Oxygen dependent mechanism, by free radicals like super-oxide anion O2ˉ, and OH˚

Mediators of acute inflammation:

Function “role of mediators” / Type of mediators
Vasodilatation / Histamine, prostaglandins, nitric oxide, and bradykinin
Increase vessel permeability / Histamine, leukotrienes, nitric oxide, and bradykinin
Neutrophil adhesion / IL – 1, TNFα, C5a, and LTB4
Neutrophil chemotaxis / C5a, LTB4, and bacterial components.
Fever / IL – 1, TNFα, and prostaglandins
Pain / Prostaglandins, and bradykinin
Tissue necrosis / Lysosomal granules contents, and free radicals generated by neutrophils

Mediators secretes from macrophages:

Arachidonic acid metabolites, and platelets activating factor “mediators of acute inflammation”.

Highly reactive oxygen metabolites “bacterial and cell killing” .

Proteases and hydrolytic enzymes. “ removing damaged material from areas of injury”.

Cytokines , IL – 1 , and TNF α “ stimulate fibroblast proliferation, and collagen synthesis”.

Growth factors “ PDGF, EGF, and FGF “stimulate growth of blood vessels, division and migration of fibroblasts”.