ACUTE INFLAMMATION

Reaction of vascularised living tissue to injury General Comments – -Closely linked to process of repair -Purpose is to destroy/dilute injurous agent -Without it wound would never heal -But if unchecked it may be potentially harmful -Role of anti-inflammatory agents.

HISTORY Celsus – four cardinal signs of inflammation- rubor,calor,dolor,tumor Virchow – added ‘functio laesa’ Elie Metchnikoff – phagocytosis Sir Thomas Lewis – chemical substances – mediators.

TYPES OF INFLAMMATION Acute – short duration characterised by exudation of fluid, plasma protein – edema emigration of leucocytes. Chronic – longer duration lymphocytes,macrophages proliferation of blood vessels, fibrosis, tissue necrosis

INFLAMMATORY RESPONSE

ACUTE INFLAMMATION Immediate and early response to an injurous agent 3 components – -Alteration in vascular caliber – increased blood flow -Structural changes in microvasculature that allow plasma proteins and leucocytes to leave the circulation -Emigration of leucocytes from microcirculation Definitions – Exudation Edema Transudate Exudate

VASCULAR EVENTS -Changes in vascular flow and caliber -Changes in vascular permeability Transient vasoconstriction of arterioles – 3-5 secs Vasodialation – arterioles and opening of new beds Increased blood flow Heat Redness Transudation

Slowing of circulation Concentration of RBC’s Increased viscosity of blood Stasis Peripheral orientation of leucocytes (margination) Emigration

Changes in vascular permeability Mechanisms- Gaps – Endothelial contraction – venules – vasoactive mediators -Gaps – Cytoskeletal reorganisation – mostly venules,capillaries cytokines hypoxia -Direct Injury – arterioles,capillaries,venules toxins,burns,chemicals -Leucocyte dependent injury – venules pulmonary capillaries late response -Increased transcytosis – across endothelial cytoplasm -Leakage from new blood vessels – angiogenesis - VEGF

CELLULAR EVENTS OF INFLAMMATION

Margination – Axial blood flow Pavementing Adhesion – Specific interactions between complementary’adhesion molecules’ present on the leucocytes and endothelial surfaces Emigration – Process by which motile white cells escape from blood vessels to perivascular tissues Neutrophils,eosinophils,basophils,monocytes,lymphocytes Insert large pseudopods Widened intercellular junctions assume position between endothelial cells and basement memb Traverse

Chemotaxis – Unidirectional migration of cells towards an attractant Locomotion oriented along chemical gradient Agents – Bacterial products Components of complement system Products of lipo-oxygenase pathway Cytokines – IL-8 Phagocytosis and degranulation Recognition and attachment Engulfment Killing and degradation of ingested material

Leucocyte Activation – Microbes Products of necrotic cells Antigen-antibody reactions Cytokines Signalling pathway – increased cytosolic calcium-activation of enzymes like protein kinase C and phospholipase A2

CHEMICAL MEDIATORS OF INFLAMMATION General Principles – Mediators originate from plasma/cells Production of active mediators Most mediators perform activity by binding to specific receptors on target cells One mediator can stimulate release of other mediators Secondary mediators may amplify/counteract actions Mediators can act on one/few target cells May have different effect on different cells Once activated – short lived action System of checks and balances Most mediators have potential to cause harmful effects

CHEMICAL MEDIATORS Cellular – Preformed – Histamine Serotonin Lysosomal enzymes Newly formed – Prostaglandins Leucotreines PAF NO Cytokines Plasma – Factor XII – Kinin system Coagulation /Fibrinolytic Complement activation – C 3a C 5a C 3b C 5b-9

MOST LIKELY MEDIATORS OF INFLAMMATION Vasodialation – Ptostaglandins Increased vascular permeability – vasoactive amines C 3a and C 5a Bradykinin Leukotreine C4 D4 E4,PAF Chemotaxis –C 5a Leukotreine B4 Other chemotactic lipids Bacterial products Fever – IL-1,TNF Prostaglandins Pain – Prostaglandins Bradykinin Tissue Damage – Neutrophil and macrophage lysosomal enzymes Oxygen metabolites

OUTCOME OF ACUTE INFLAMMATION Injury Acute Inflammation Abscess Resolution Chronic Inflammation Healing Regeneration Scarring Mediators Persistent infections Persistence toxins Autoimmune dis

MORPHOLOGIC PATTERNS OF ACUTE INFLAMMATION 1.Serous inflammation – Outpouring of thin fluid - Derived from plasma / mesothelial cell secretion e.g.Skin blister due to burns/viral infection 2.Fibrinous inflammation – Severe injury - Deposition of fibrin in extracellular space e.g – Pericardial cavity,meninges 3.Suppurative /Purulent – Pus/purulent exudate -containing neutrophils, necrotic cells & edema fliud e.g – acute suppurative – acute appendicitis, abscesses 4.Ulcers – local defect, excavation of the surface of an organ /tissue produced by shedding of inflammatory necrotic tissue e.g – mucosa of mouth, stomach,intestine peptic ulcer