INFLAMMATION

 

OVERVIEW

Inflammation  is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators.

The goal of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair.

Types of Inflammation:-

1.      Acute inflammation

2.      Chronic inflammation

1.     Acute Inflammation:-

·        Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma & leukocytes from the blood in to the injured tissue.

·        A series of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, and various cells within the injured tissue.

2.     Chronic Inflammation:-

                      Chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation, such as mononuclear cells, and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process.

SIGN OF INFLAMMATION:-

·         Dolor (pain):- Pain is due to the release of chemicals such as Bradykinin and histamine that stimulate nerve endings.

·         Calor (heat):- heat are due to increased blood flow to the inflamed site.

·         Rubor (redness):- Redness  due to increased blood flow at body  to the inflamed site

·         Tumor (swelling):- swelling is caused by accumulation of fluid

 Functio laesa (loss of function):- The loss of function (functio laesa) is probably the result of a neurological reflex in response to pain.

                      The first four classical signs were described by Celsus  while loss of function was probably added later by Galen.

 INFLAMATORY PROCESS:-

·        The process of acute inflammation is initiated by resident immune cells which are already present in the involved tissue, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mast cells.

·        These cells possess surface receptors known as pattern recognition receptors (PRRs), which recognize  two subclasses of molecules: pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).

·        PAMPs are compounds that are associated with various pathogens & which are distinguishable from host molecules.

·        DAMPs are compounds that are associated with host-related injury and cell damage.

·        Any infection-----activation of PPPs-------PRRs recognise whether it is PAMP or DAMP----Release inflammatory madiaters.

·        In addition to cell-derived mediators, several acellular biochemical cascade systems consisting of preformed plasma proteins act in parallel to initiate and propagate the inflammatory response.

·        These include the complement system activated by bacteria and the coagulation and fibrinolysis systems activated by necrosis, e.g. a burn or a trauma.

Acute inflammation:-

·        Acute inflammation can be broadly divided into two phases:-

                                           I.            vascular phase that occurs first

                                        II.            cellular phase involving immune cells .

·        The vascular phase of acute inflammation there is movement of the plasma fluid which contains proteins such as fibrin & immunoglobulin in to the inflamed tissue.

·        With the  contact with PAMPs, tissue macrophages and mastocytes release vasoactive amines such as histamine and serotonin, prostaglandin E2 and leukotriene B4 to remodel the local vasculature.

·        Macrophages and endothelial cells release nitric oxide mediators which cause vasodilatation and permeable  the blood vessels, which results in the net distribution of blood plasma from the vessel into the tissue space.

·        The increased collection of fluid into the tissue causes it to swell (edema).

·         This exuded tissue fluid contain various antimicrobial mediators from the plasma such as lysozyme, antibodies, which can immediately deal damage to microbes, and opsonise the microbes in preparation for the cellular phase.

·        If the inflammatory stimulus is a lacerating wound, exuded platelets, coagulants, plasmin and kinins can clot the wounded area and provide haemostasis in the first instance.

Cellular component:-

·        The cellular component involves leukocytes, which normally reside in blood and must move into the inflamed tissue via extravasations to aid in inflammation.

·        Some act as phagocytes, ingesting bacteria, viruses, and cellular debris. Others release enzymatic granules that damage pathogenic invaders.

·        Leukocytes also release inflammatory mediators that develop and maintain the inflammatory response.

·        In general, acute inflammation is mediated by granulocytes, whereas chronic inflammation is mediated by mononuclear cells such as monocytes and lymphocytes.

·        Neutrophils migrate from blood vessels to the infected tissue via chemotaxis, where they remove pathogens through phagocytosis and degranulation

·        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. In these diseases, called autoimmune diseases, the body's normally protective immune system causes damage to its own tissues. The body responds as if normal tissues are infected or somehow abnormal.

PROCESS OF ACUTE INFLAMMATION

Tissue injury

Activation of surface receptor

Activation of (PRRs) pattern recognition receptor

Check  whether PAMPs or DAMPs

Cell release mediators

Vasodilatation & increase permeability

Increase blood flow to injury site

Causes redness & swelling in injury site

Neutrophil & macrophages reaches the injury site

Destroy & kill the micro organism & remove dead cell

Plasma cascade systems:-

·         The complement system, when activated, creates a cascade of chemical reactions that promotes opsonization, chemotaxis, and agglutination.

·         The kinin system generates proteins capable of sustaining vasodilation and other physical inflammatory effects.

·         The coagulation system or clotting cascade, which forms a protective protein mesh over sites of injury.

·         The fibrinolysis system, which acts in opposition to the coagulation system, to counterbalance clotting and generate several other inflammatory mediators.

Plasma-derived mediators

1.      Bradykinin:- A vasoactive protein that is able to induced vasodilatation, increase vascular permeability causes smooth muscle contraction & induced pain.

2.      C3:- Cleaves to produce C3a & C3b. C3a stimulates histamines which is released by mast cell there by producing vasodilatation. C3b bind the bacterial cell wall & act as opsonin which make the invader as a target for ohagocytosis.

3.      C5a:- It act as chemo attractant which direct cells via chemotaxis to the site of inflammation.

4.      Factor XII:-Its a protein that circulate in blood inactively, it activated by collagen, platelets or exposed basement membrane. When it activated it activated it activate three plasma system involve in inflammation: the Kinin system, the fibrinolysis system & coagulation system.

5.      Membrane attack complex:- The complement proteins C5b,C6,C7, C8 & C9 join together & form membrane attack complex which insert in to bacteria cell wall causes cell lysis.

6.      Plasmin: - Help to break fibrin clots.

7.      Thrombin: - Help to form clot.