Inflammation and Events of acute inflammation

Inflammation is a process by which the body's white blood cells and substances they produce protect us from infection with foreign organisms, such as bacteria and viruses. However, in some diseases, like arthritis, the body's defense system -- the immune system -- triggers an inflammatory response when there are no foreign invaders to fight off
Inflammation is a process by which the body's white blood cells and substances they produce protect us from infection with foreign organisms, such as bacteria and viruses

Events of acute inflammation:

Acute inflammation is categorized into an early vascular and a late cellular responses.

1) The Vascular response has the following steps:

a) Immediate (momentary) vasoconstriction in seconds due to neurogenic or chemical stimuli.
b) Vasodilatation of arterioles and venules resulting in increased blood flow.
c) After the phase of increased blood flow there is a slowing of blood flow and stasis due to increased vascular permeability that is most remarkably seen in the post-capillary venules. 

The increased vascular permeability oozes protein-rich fluid into extravascular tissues. Due to this, the already dilated blood vessels are now packed with red blood cells resulting in stasis. The protein-rich fluid which is now found in the extravascular space is called exudate. The presence of the exudates clinically appears as swelling. Chemical mediators mediate the vascular events of acute inflammation.

2) Cellular response

The cellular response has the following stages:
A. Migration, rolling, pavementing and adhesion of leukocytes
B. Transmigration of leukocytes
C. Chemotaxis
D. Phagocytosis
Normally blood cells particularly erythrocytes in venules are confined to the central(axial) zone and plasma assumes the peripheral zone. As a result of increase cardiovascular permeability, more and more neutrophils accumulate along the endothelial surfaces (peripheral zone).

A) Migration, rolling, pavementing, and adhesion of leukocytes

Migration is a peripheral positioning of white cells along the endothelial cells.
Subsequently, rows of leukocytes tumble slowly along the endothelium in a process known as rolling. In time, the endothelium can be virtually lined by white cells. 

This appearance is called pavementing. Thereafter, the binding of leukocytes with endothelial cells is facilitated by cell-adhesion molecules such as selectins, immunoglobulins, integrins, etc which result in adhesion of leukocytes with the endothelium.

B). Transmigration of leukocytes

Leukocytes escape from venules and small veins but only occasionally from capillaries. The movement of leukocytes by extending pseudopodia through the vascular wall occurs by a process called diapedesis. The most important mechanism of leukocyte emigration is via widening of interendothelial junctions after endothelial cells contractions. The basement membraneis disrupted and resealed thereafter immediately.

C). Chemotaxis:

A unidirectional attraction of leukocytes from vascular channels towards the site of inflammation within the tissue space guided by chemical gradients (including bacteria and cellular debris) is called chemotaxis. The most important chemotactic factors for neutrophils are components of thecomplement system (C5a), bacterial and mitochondrial products of arachidonicacid metabolism such as leukotriene B4 and cytokines (IL-8). 

All granulocytes, monocytes and to lesser extent lymphocytes respond to chemotactic stimuli.
How do leukocytes "see" or "smell" the chemotactic agent. This is because receptors on cell membrane of the leukocytes react with the chemo-attractants resulting in the activation of  phospholipase C that ultimately leads to release of cytocolic calcium ions and these ions trigger cell movement towards the stimulus.

D) Phagocytosis

Phagocytosis is the process of engulfment and internalization by specialized cellsof particulate material, which includes invading microorganisms, damaged cells,and tissue debris.
These phagocytic cells include polymorphonuclear leukocytes (particularly neutrophiles), monocytes and tissue macrophages.
Effects of acute inflammation

Beneficial effects

 Dilution of toxins: The concentration of chemical and bacterial toxins at the site of inflammation is reduced by dilution in the exudate and its removal from the site by the flow of exudates from the venules through the tissue to the lymphatics.

Protective antibodies: Exudation results in the presence of plasma proteins including antibodies at the site of inflammation. Thus, antibodies directed against the causative organisms will react and promote microbial destruction by phagocytosis or complement-mediated cell lysis.

Fibrin formation: This prevents bacterial spread and enhances phagocytosis by leukocytes. 

Plasma mediator systems provisions: The complement, coagulation, fibrinolytic, and kinin systems are provided to the area of injury by the process of inflammation.

Cell nutrition: The flow of inflammatory exudates brings with it glucose, oxygen and other nutrients to meet the metabolic requirements of the greatly increased numberof cells. It also removes their solute waste products via lymphatic channels.

Promotion of immunity: Micro-organisms and their toxins are carried by the exudates, either free or in phagocytes, along the lymphatics to local lymph nodes where they stimulate an immune response with the generation of antibodies and cellular immune mechanisms of defense.

Harmful effects

Tissue destruction: Inflammation may result in tissue necrosis and the tissue-necrosis may, in turn, incite inflammation.

Swelling: The swelling caused by inflammation may have serious mechanical effects at certain locations. Examples include acute epiglottitis with interference in breathing; acute meningitis and encephalitis with effects of increased intracranial pressure.

Inappropriate response: The inflammatory seen in hypersensitivity reactions is inappropriate (i.e. exaggerated).

Acute inflammation may end up in:

Resolution: That is complete restitution of normal structure and function of the tissue,eg. Lobar pneumonia.

Healing by fibrosis (scar formation).

Abscess formation {Surgical law states -Thou shall (you should) drain all abscesses.} However, if it is left untouched, it may result in
- Sinus formation - when an abscess cavity makes contact with only one epithelial lining.
- Fistula formation: when an abscess tract connects two epithelial surface.Or very rarely to septicemia or Pyemia with subsequent metastatic abscess in heart, kidney and  brain


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