Sequence of events in acute inflammation ?
Ans. is 'd' i.e., Transient vasoconstriction --> Vasodilatation -+ Increased permeability --> Stasis Acute inflammation o Acute inflammation is a rapid response to an injurious agent that serves to deliver mediators of host defense, i.e., leukocytes and plasma proteins, to the site of injury. o Acute inflammation has three major steps : ? 1.Alteration in vascular caliber that leads to an increase in blood flow, i.e., vasodilatation. Structural changes in the microvasculature that permit plasma proteins and leukocytes to leave the circulation, i.e., Increased vascular permeaility. 3.Emigration of the leukocytes from the microcirculation, their accumulation in the focus of injury, and their activation to eliminate the offending agent i.e., chemotoxis and phagocytosis. o These inflammatory change involve two main components. A.Vascular reaction i.e., changes in blood vssels. B.Cellular reaction i.e., changes in leukocytes. A.Vascular events Vascular changes are essential for inflammation because these changes serve to deliver leukocytes and antibodies (two major mechanisms of host defence against microbes) at the site of injury. Normally leukocytes and immunoglobulins are sequestered inside the vesels and move in the direction of flow. During inflammation blood flow is increased to inflammed area and these leukocytes and immunoglubulin are directed towards the injurious stimulus. 1. Changes in vascular caliber (vasodilatation) o Vasodilatation is one of the earliest manifestations of acute inflammation. o Sometimes, it follows a transient constriction of aerioles, (vasoconstrictions) lasting for a few seconds ---> Though vasodilatation is the earliest manifestation of acute inflammation, it follows a transient period of vasoconstriction. o Vasodilatation first involve aerioles and than results in opening of new capillary beds in the area. o There is increased hydrostatic pressure due to increased blood flow. Change in vascular permeability o Vasodilatation is quickly followed by increased vascular permeability. o Increased vascular permeabily is the hallmark of acute inflammation. o This leads to escape of protein rich fluid (exudate) and leukocytes into extravascular space. o Intravascular osmotic pressure reduces due to exudation of proteins and osmotic pressure of interstitial fluid is increased. o Together with increased hydrostatic pressure and decreased intravascular osmotic pressure leads to fuher outflow of fluid and its accumulation in the interstitial fluid. Change in vascular flow (Stasis) o The loss of fluid results in concentration of red cells and increased viscosity of blood Slower blood flow ---> Stasis B.Cellular events A critical function of inflammation is to deliver leukocytes to the site of injury and to activate the leukocytes to perform their normal functions in host defence. Leukocytes ingest offending agents, kill bacteria and other microbes, and get rid of necrotic tissue and foreign substances. The sequence of events in the journey of leukocytes from the vessel lumen to interstitial tissue is called extravasation. Extravasation involves following steps. 1. In the vessel lumen o As stasis develops, leukocytes principally neutrophils accumulute along the vascular endothelium. This is called margination. o The rows of leukocytes move (tumble) slowly along the endothelium a process called rolling. o Finally coming to at rest, leukocytes adhere firmly to endothelium --> adhesion. o The endothelium can be virually lined by white cells ---> Pavementing. 2. Diapedesis o It is the process of transmigration of leukocytes across the endothelium. o After firm adhesion, leukocytes migrate through interendothelial junctions and assume a position between endothelial cells and the basement membrane. o Eventually, they pierce the basement membrane by secreting collegenase and escape into the extravascular space. o The processes of adhesion and transmigration are regulated largely by the binding of complementry adhesion molecules on the leukocytes and endothelium. o These adhesion molecules include - Selectins, integrins, members of immunoglobulin superfamily and mucin like glycoproteins. o Different cytokines increase surface expression or avidity of these adhesion molecules and enhance adhesion and transmigration of leukocytes. o Leukocyte diapedesis, similar to increased vascular permeability, occurs predominantly in the venules (except in lungs, where it occurs in capillaries). 3. Chemotaxis o After extravasation, leukocytes emigrate into tissues toward the site of injury, along a chemical gradient, a process know as chemotaxis. o The substances that act as chemoattractant may be exogenous (bacterial products) or endogenous (C5a, LT4, IL-8) 4. Leukocyte activation o At the site of inflammation, cytokines induce a number of responses in leukocytes that are pa of defensive functions of leukocytes and are referred as leukocyte activation. o The functional responses that are induced on leukocyte activation are : - i) Production of archidonic acid metabolites (PGs, LTs) as result of activation of phospholipase A,. ii) Degranulation and secretion of lysosomal enzymes and activation of the oxidative burst. iii) Secretion of cytokines iv) Modulation of leukocyte adhesion molecules, allowing a firm adhesion of activated neutrophils to endothelium. 5. Phagocytosis o Phagocytosis and release of enzymes by neutrophils and macrophages are responsible for eliminating the injurious agents. o In phagocytosis, engulfment and killing & degradation of injurious agent takes place.
Vasodilatation - Stasis - Transient - vasoconstriction - Increased permeability
Transient vasoconstriction - Stasis - Vasodilatation - Increased permeability
Transient vasoconstriction - Vasodilatation - Stasis - Increased permeability
Transient vasoconstriction - Vasodilatation - Increased permeability - Stasis