INFLAMMATIONAcute inflammationChronic inflammationRepairResolutionAbscessInjury“Inflame” to set fire.Inflammation is “A dynamic response of vascularised tissue to injury.”It is a protective response.It serves to bring defense & healing mechanisms to the site of injury.What is Inflammation?A reaction of a living tissue & its micro-circulation to a pathogenic insult.A defense mechanism for survival .Reaction of tissues to injury, characterized clinically by: heat, swelling, redness, pain, and loss of function.Pathologically by : vasoconstriction followed by vasodilatation, stasis, hyperemia, accumulation of leukocytes, exudation of fluid, and deposition of fibrin.How Does It Occur?The vascular & cellular responses of inflammation are mediated by chemical factors (derived from blood plasma or some cells) & triggered by inflammatory stimulus.Tissue injury or death - Release mediators EtiologiesMicrobial infections: bacterial, viral, fungal, etc.Physical agents: burns, trauma-like cuts, radiationChemicals: drugs, toxins, or caustic substances like battery acid.Immunologic reactions: rheumatoid arthritis. Cardinal Signs of InflammationRedness : Hyperaemia.Warm : Hyperaemia.Pain : Nerve, Chemical mediators.Swelling : ExudationLoss of Function: PainTime courseAcute inflammation: Less than 48 hoursChronic inflammation: Greater than 48 hours (weeks, months, years)Cell typeAcute inflammation: Neutrophils Chronic inflammation: Mononuclear cells (Macrophages, Lymphocytes, Plasma cells).Pathogenesis: Three main processes occur at the site of inflammation, due to the release of chemical mediators :Increased blood flow (redness and warmth).Increased vascular permeability (swelling, pain & loss of function).Leukocytic Infiltration. Mechanism of Inflammation 1.Vaso dilatation2.Exudation - Edema3.Emigration of cells4.ChemotaxisThe major local manifestations of acute inflammation, compared to normal.(1)Vascular dilation and increased blood flow (causing erythema and warmth).(2)Extravasation and deposition of plasma fluid and proteins (edema).(3)leukocyte emigration and accumulation in the site of injury.Changes in vascular flow (hemodynamic changes) Slowing of the circulationoutpouring of albumin rich fluid into the extravascular tissues results in the concentration of RBCs in small vessels and increased viscosity of blood. Leukocyte marginationNeutrophi become oriented at the periphery of vessels and start to stick.Time scaleVariableminor damage- 15-30 minutessevere damage- a few minutes Lymphatics in inflammation:Lymphatics are responsible for draining edema.Edema: An excess of fluid in the interstitial tissue or serous cavities; either a transudate or an exudateTransudate: An ultrafiltrate of blood plasmapermeability of endothelium is usually normal.low protein content ( mostly albumin)Exudate:A filtrate of blood plasma mixed with inflammatory cells and cellular debris. permeability of endothelium is usually alteredhigh protein content.Pus:A purulent exudate: an inflammatory exudate rich in leukocytes (mostly neutrophils) and parenchymal cell debris.Leukocyte exudationDivided into 4 steps Margination, rolling, and Margination, rolling, and adhesion to endotheliumadhesion to endothelium Diapedesis (trans-migration across the endothelium)Diapedesis (trans-migration across the endothelium) Migration toward a chemotactic stimuli from the Migration toward a chemotactic stimuli from the source of tissue injury.source of tissue injury. PhagocytosisPhagocytosisPhagocytosis3 distinct steps Recognition and attachmentEngulfmentKilling or degradationDefects in leukocyte function:Margination and adhesionsteroids, leukocyte adhesion deficiencyEmigration toward a chemotactic stimulusdrugschemotaxis inhibitorsPhagocytosisChronic granulomatous disease (CGD)Inflammation OutcomeAcute InflammationResolutionChronic InflammationAbscessSinusFistulaFibrosis/ScarUlcerInjuryFungusVirusCancersT.B. etc.Chemical Mediators:Chemical substances synthesised or released and mediate the changes in inflammation.Histamine by mast cells - vasodilatation.Prostaglandins Cause pain & fever.Bradykinin - Causes pain.Morphologic types of acute inflammationExudative or catarrhal Inflammation: excess fluid. TB lung.Fibrinous pneumonia fibrin Membranous (fibrino-necrotic) inflammationSuppuration/Purulent Bacterial - neutrophilsSerous excess clear fluid Heart, lungAllergic inflammationHaemorrhagic b.v. damage - anthrax.Necrotising inflammation.Acute inflammation has one of four outcomes:Abscess formationProgression to chronic inflammationResolution-tissue goes back to normalRepair-healing by scarring or fibrosisAbscess formation:A localized collection of pus (suppurative inflammation) appearing in an acute or chronic infection, and associated with tissue destruction, and swelling.Site: skin, subcutaneous tissue, internal organs like brain, lung, liver, kidney,.Pathogenesis: the necrotic tissue is surrounded by pyogenic membrane, which is formed by fibrin and help in localize the infection.Carbuncle- It is an extensive form of abscess in which pus is present in multiple loci open at the surface by sinuses.- Occur in the back of the neck and the scalp.Furuncle or boil- It is a small abscess related to hair follicles or sebaceous glands, could be multiple furunclosis.Cellulitis - It is an acute diffuse suppurative inflammation caused by streptococci, which secrete hyaluronidase & streptokinase enzymes that dissolve the ground substances and facilitate the spread of infection.-Sites: -Areolar tissue; orbit, pelvis, -Lax subcutaneous tissue