INFLAMMATION Dr. Saleem Shaikh Introduction Inflammation is defined as local response of living tissues to injury by any agent It is a body defense reaction in order to eliminate or limit the spread of injurious agent. Inflammation can be caused by ◦ Infectious agents ◦ Immunologic agents ◦ Physical agents ◦ Chemical agents ◦ Inert materials Inflammation is different from infection Though it is protective in nature it may cause considerable harm to the body as well Signs of Inflammation 4 cardinal signs - Celsus Rubor – redness Tumor – swelling Calor – heat Dolor – pain Functio lessa – loss of function (virchow) Types Acute inflammation – early body reaction, lasts for less than 2 weeks. The main features of acute inflammation are – ◦ Accumulation of fluid and plasma at the affected site ◦ Intravascular activation of platelets ◦ Neutophils as inflammatory cells Chronic inflammation is of longer duration and occurs either after the causative agent of acute infection persists for a long time, or the stimulus is such that it induces chronic inflammation from the beginning. presence of chronic inflammatory cells – lymphocytes, plasma cells etc. Granulomatous inflammation – variant of chronic inflammation Acute inflammation The events happening during inflammation can be divided into Vascular events Cellular events Vascular events – alteration in the vasculature is the earliest change to tissue injury 1. Hemodynamic changes – the first vascular response is transient vasoconstriction; the blood flow is re-established very quickly. next follows is progressive vasodilation. This results in increased blood volume in the capillaries. vasodilation increases the local hydrostatic pressure; this causes fluid to come out of cappilaries (transudate). This is responsible for swelling at the location. Stasis or slowing of circulation – this facilitates the movement of leucocytes from inside to outside of the blood vessel. Lewis experiment – ‘triple response’ or ‘red line response’ Firm stroking of inners aspect of the forearm with a blunt point shows the following changes ◦ Redline – after few seconds; due to local vasodilatation ◦ Flare – spreading of the white line; due to vasodilation of adjacent arterioles ◦ Wheal – swelling or odema of the surrounding area 2. Altered Vascular permeability- initial swelling produced in inflammation is because of elevated hydrostatic pressure (transudate) in later stages there is migration of cells and fluid into the extracellular spaces (exudate). This is due to increased vascular permeability. Mechanisms Contraction of endothelial cells- most common (venules); immediate, transient Retraction of endothelial cells – delayed and prolonged Direct injury to endothelial cells – immediate, prolonged Endothelial cell injury caused by leucocytes - delayed, prolonged Cellular events: ◦ Exudation of leucocytes ◦ Phagocytosis 1. Exudation of leucocytes: escape of neutrophils from the lumen of vessels to the tissue. Mechanism – In normal pattern of blood flow, the cells of the blood will be in the center and the cell free plasma will be at the periphery (near the vessel wall). due the vascular events (stasis), the cells come closer to the vessel wall. (margination & pavementing) As the neutrophils come close to the vessel wall, they start rolling over the endothelial cells (rolling phase). This is followed by bonding between the neutrophils and endothelial cells (adhesion phase). Next the neutrophils move along the endothelial cells till they come to a suitable site where they can move out (Emigration). Once the neutrophils are out of the vessel, they move towards the site of injury. This movement is guided by chemical messengers (Chemotaxsis) 2. Phagocytosis – it is the process of engulfing solid material by cell (cell eating). The neutrophils once they reach the site of injury produce many enzymes which kill the bacteria and also degrades some of the tissues. The phagocytic cells develop receptors for the bacteria, the bacteria are also coated by certain chemicals (opsonins) which makes them more recognisable by the bacteria. (recognition and attachment) Once the bacteria is attached, the cell develops cytoplasmic extensions around the particle. This bacteria is then taken inside as a phagocytic vacuole. Inside the cell the vacuole fuses with a lysosome. (Engulfment) Killing and Degradation of the bacteria can occour by many different mechanisms. ◦ Oxidative mechanism by oxygen free radicals ◦ Oxidative mechanism by Lysosomal granules ◦ Nonoxidative bacterial mechanism Extracellular mechanisms