Thursday, May 27, 2010

What is inflammation

Characteristics of inflammation:

We all have inflammation in our body at one point or the other caused during activities, physical stress, accidents, animal or insect bites, pathogenic organisms etc. Inflammation can occur on the skin and subcutaneous tissue, respiratory tract, urinary tract, gastrointestinal tract etc. Usually we find swelling, pain, redness, or infection in that area. What is inflammation and what all happens when our body has an inflammation and what are the clinical features of inflammation?

When an area of the body is injured or altered from its normal structure, it is invaded by bacteria, virus, or parasite etc. and the body produces a defense mechanism by which the harmful antigens are destroyed or removed. A series of actions occur which protects our body from the harmful agent and all these constitute an inflammation or inflammatory reaction. These are detected by its clinical features, which are the 5 signs of inflammation.

Cardinal signs of inflammation:

1. Rubor (redness)
2. Calor (heat)
3. Dolor (pain)
4. Tumor (swelling)
5. functio laesa (loss of function).

 The area becomes hot, red, and painful. There will be swelling all over the area and subsequently loss of function of the body part. The redness and heat are due to the increased blood flow to the inflamed site, swelling is caused due to accumulation of fluid and pain is due to the release of chemicals that stimulate the nerve endings.

Process of inflammation: The inflammatory process is initiated by cells present in the tissues such as resident macrophages, dentritic cells, histiocytes, Kuppfer cells and mastocytes. When a burn, injury, or infection occurs these cells undergo activation and release inflammatory mediators responsible for the clinical signs of inflammation mentioned above. Inflammation is characterized by marked vasodilation, increased permeability, and slowing of blood flow. Vasodilation or the dilation of the blood vessels in the affected area produce a net increase in the blood flow to that area causing redness (rubor) and heat (calor). The increased permeability of the blood vessels results in exudation or leakage of the of plasma proteins and fluid into the tissue which manifests as the swelling (tumor). The mediators that are released such as histamine and bradykinin increases the sensitivity to pain and cause pain(dolor). Increased permeability of the blood vessel results in movement of plasma proteins and fluid into the tissues with resultant stasis of blood due to increased concentration of cells in the blood, a condition characterized by engorged blood vessels filled with blood cells. Stasis or slowing of the blood occurs and results in migration of the white blood cells or leukocytes which is mainly neutrophils that move towards the walls of the blood vessel into the tissues called margination. The neutrophils migrate along a chemotactic gradient created by the local cells to reach the site of injury. The loss of function (functio laesa) is the result of a neurological reflex in response to pain.

Neutrophil margination during inflammation

Cellular changes: The main cellular component that takes part in inflammation are the leukocytes or the white blood cells. These cells move from the blood into the inflamed tissue by extravasation to assist inflammatory process. Some act as phagocytes ingesting bacteria, virus, and cellular debris etc. Others release enzymatic granules which damage the pathogenic invaders and releases substances which mediate and develop the inflammatory response. When the bacteria have invaded the inflamed area, the emigrated leukocytes are attracted to the bacteria in the infected tissues by a process called chemotaxis.The leukocytes which include neutrophils, eosinophils, and monocytes, phagocytose (swallow) the bacteria and digest them. So bacteria and other foreign bodies are digested and destroyed from the site of inflammation. Some leucocytes die along with other degenerated tissue and dead bacteria is turned into a white liquified form called the pus.

Mediators of inflammation: There are a number of cellular and plasma based mediators which helps in modifying the inflammatory process

1) The cell based (RBC, WBC, platelets) mediators are lysosome granules, histamine, IFN-y, IL-8, leucotriene B4, nitrous oxide, prostaglandins, TNF-alfa, and IL-1.
Lysosome granules are present in granulocytes. These cells contain a large number of enzymes which perform certain functions to facilitate inflammation.
Histamines are vasoactive amines present in mast cells, basophils, and platelets. Histamine causes areteriolar dilation and increased venous permeability.
Interferons are found in T-cells and NK cells. They have antiviral, immunoregulatory, and anti-tumour properties.
Interleukins are found primarily in macrophages. It helps in activation and chemoattraction of neutrophils, monocytes, and eosinophils.
Leukotrienes are found in leukocytes. It is ble to mediate leukocyte adhesion and activation, allowing them to bind to the endothelium and migrate across it.
Nitric oxide is found in macrophages and endothelial cells. It is a potent vasodilator. It relaxes smooth muscle, reduces platelet aggregation, aids in leukocyte recruitment, and antimicrobial activity in high concentrations.
Prostaglandins are found in mast cells. These are a group of lipids which can cause vasodilation, fever, and pain.

2) The plasma based (fluid in the blood)  mediators include bradykinin, plasmin, thrombin, C3, C5a, Factor XII etc.
Bradykinin is produced by the kinin sytem. It is a vasoactive protein which is able to induce vasodilation, increase vascular permeability, cause smooth muscle contraction, and induce pain.
C3 is produced by the complement system. It cleaves to produce C3a and C3b. C3a stimulates histamine release by mast cells and thereby producing vasodilation. C3b  binds to bacterial cell wall and act as an opsonin, which marks the invader as a target for phagocytosis.
C3a is produced by the complement system. It stimulates histamine release by mast cells, thus producing vasodilation. It also act as a chemoattractant to direct cells by chemotaxis to the site of inflammation.
Factor XII is produced in the liver. It is a protein which circulates inactively in the blood plasma, until activated by collagen, platelets, or exposed basement membranes. When activated, it is able to activate three plasma systems involved in inflammation: the kinin system, fibrinolysis system, and coagulation system.
Plasmin is produced by the fibrinolysis system. It is able to break down fibrin clots, cleave complement protein C3, and activate Factor XII.
Thrombin is produced by the coagulation system. It cleaves the soluble plasma protein fibrinogen to produce insoluble fibrin, which aggregates to form a blood clot.

An acute inflammation usually resolve with resolution of symptoms and relief of associated infection if proper measures are undertaken. It can also go into a severe or more chronic phase when those underlying causes are not controlled or eliminated.

These are some of the processes that happen when an acute inflammation occurs in the part of our body. Hope you get an idea about what actually inflammation is, what the signs of inflammations are, what processes that happen in an acute inflammation at the cellular level and about the mediators of inflammation.

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