Inflammation: From L. inflammare-to set on fire A complex progression of vascular changes in response to tissue injury. It is a defensive response which destroys, dilutes or neutralizes harmful agents (microbes, toxins) and repairs the damaged tissues. Components of Acute and Chronic Inflammation Components of Inflammation Circulating cells – neutroplils, eosinophils, basophils, monocytes, lymphocytes, thrombocytes Circulating Proteins – clotting factors, kininogens, and complement factors Vascular wall cells – Endothelial cells, smooth muscle cells Connective tissue cells – mast cells, macrophages, lymphocytes, fibroblasts Exracellular matrix – collagen and elastin, proteoglycans, adhesive glycoproteins Types: Inflammation is of two types: acute and chronic. Acute inflammation is of short duration – a few hours or days and characterized by exudation of fluid and plasma proteins (edema) and emigration of leukocytes, mainly neutrophils. Chronic inflammation is of longer duration (weeks and months) and associated with mononuclear cells (lymphocytes and macrophages) and proliferation of fibrous connective tissue and blood vessels. Acute Inflammation: Causes: 1. Infectious agents including bacteria, viruses, fungi, protozoa, helminths etc. 2. Chemical agents like toxins, acids, alkalies etc. 3. Physical agents such as burns, electricity, radiation, excessive cold, trauma etc. 4. Immunological reactions: Tissue damaging antigen-antibody reactions like hypersensitivity and autoimmune diseases. 5. Necrotic tissue: Ischemia, toxins and infectious agents may directly cause necrosis and necrotic tissues release mediators which cause inflammation. Cardinal signs of inflammation: Celsus, a roman philosopher, described 4 principal signs of inflammation in 38 AD i.e. redness, swelling, heat and pain. The 5th cardinal sign, loss of function, was added in 1858 by Virchow. 1. Redness (L. rubor) It is due to increase of blood in the inflamed area as a result of hyperemia. 2. Swelling (L.tumor) Due to hyperemia and exudation of protein – rich fluid and leukocytes. 3. Heat (L.calor) Due to increased arterial blood flow and increased metabolism in the area of acute inflammation. 4. Pain (L. dolor) Caused by pressure on sensory nerve endings by the exudate and irritation by the chemical mediators like 5HT (serotonin) kinins (bradykinin) and prostaglandins. 5. Loss of function (L. functio laesa) Due to combination of pain, swelling and tissue destruction. Vascular changes in inflammation: Vascular changes, first described by the German pathologist – Cohnheim in 1877 play an important role in acute inflammation. The cardinal signs of inflammation are attributed to the vascular changes including: 1) Changes in the blood vessels: a) Momentary constriction: Immediately after the injury (irritation) arterioles undergo vasoconstriction lasting for only a few seconds, possibly caused by neurogenic stimuli or chemical mediators. b) Vasodilation: Normally many capillaries remain collapsed but in an area of inflammation all the arterioles and capillaries are dilated by the action of chemical mediators of inflammation. The area appears to be more vascular, with heat and redness. Vascular Changes 2) Changes in the rate of flow: i) Increased vascular permeability: Vasodilation is immediately followed by increased blood flow and then a slowdown and exudation of protein – rich fluid into the interstitial spaces, forming inflammatory edema (exudate). Plasma proteins – albumin, fibrinogen, globulins etc leave the blood vessels due to increased vascular permeability resulting in hemoconcentration, increased blood viscosity and stasis. Mechanism of increased vascular permeability a) Formation of endothelial gaps in venules: chemical mediators of inflammation increase vascular permeability by opening endothelial cell junctions – due to contraction of endothelial cells 0.5-1.0um gaps appear between them. Most commonly it is produced by histamine, bradykinin and leukotrienes. Called immediate transient response (15 to 30 minutes), is reversible and affects only venules. b) Endothelial cell retraction: Cytokines interleukin – 1, tumour necrosis factor and interferon – gamma cause changes in cellular cytoskeleton, cellular retraction and formation of endothelial gaps. This change occurs after 4-6 hours and lasts for 24 hrs or longer. c) Direct endothelial injury: It follows necrosis and detachment of endothelial cells after severe injuries due to burns or injuries. It persists until vessel is thrombosed or repaired. d) Delayed prolonged leakage: It is caused by mild to moderate thermal injuries, some bacterial toxins, u.v. radiation etc. It continues for several hours and days. e) Leukocyte - Dependant Endothelial Injury: Leukocytes release toxic oxygen – free radicals and proteolytic enzymes which cause endothelial injury. ii) Slowing down of circulation: Early vasodilation results in increased blood flow, followed by slowing of circulation which is essential for emigration of leukocytes. Retardation of blood flow is caused by: a) Increased capillary bed. b) Swelling of endothelial cells. c) Hemoconcentration. d) Margination of leukocytes. iii) Stasis: A condition of stasis is produced following slowing down of circulation. This is ideal for escape of large molecules and cellular elements from blood vessels and formation of exudate. Sequence of events in leukocyte emigration in inflammation 3) Changes in the bloodstream: Slowing down of blood circulation changes the blood stream from axial to laminar flow i.e. from centripetal to centrifugal. This leads to margination, rolling and adhesion or pavementing of leukocytes to the endothelium. 4) Exudation of plasma: The fluid part of blood escapes blood vessels due to increased vascular permeability and produces exudate. 5) Emigration of leukocytes: 5 The Process by which leukocytes come out of the blood vessels is called emigration. 6) Diapedesis of erythrocytes: Erythrocytes are pushed out of the vessels passively by increased hydrostatic pressure. These bring oxygen and nutrients to cells and tissues.
Pages to are hidden for
"factors for Inflammation.ppt"Please download to view full document