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Inflammation and Repair

Inflammation Presented by Dr.RINCE MOHAMMEDJ.R 1 O.M.F.S,G.D.C Kottayam

ContentsIntroductionDefinitionCardinal SignsTypes of inflammationAcute inflammation PathogenesisChemical mediators of acute inflammationSystemic & laboratory manifestationsExudate Vs TransudateOut comes of Acute Inflammation

Chronic inflammationChronic inflammatory cellsChronic inflammation typesSummary and conclusionReferences

Introduction

Inflammation is thereactionoflivingtissuetoinjuryorinfection.It is a protective vascular connective tissue reaction or response intended to remove injurious stimuli as well as the necrotic cells.Repair-causes the replacement of damaged tissues by regeneration of parenchyma cells or by filling of any residual defect by fibrous scar tissues. (Healing)

inflammation repair closly related.inflmn-response phase repair healing phase...3

jayalakshmi jayakumar (jj) - inflammation repair closly related.inflmn-response phase repair healing phase...DefinitionA local response to cellular injury that is marked by capillary dilatation, leukocytic infiltration, redness, heat, and pain and that serves as a mechanism initiating the elimination of noxious agents and of damaged tissues.(Websters medical dictionary)

Sometimes harmful hypersensitivity reactions,immune diseses.Repair also can cause scarring ,fibrosis that may lead to obstruction of movement.Anti inflammatory drugs - enhance favourable effects of inflammation and controls its harmful sequelae.The nomenclature used to describe inflammation in different tissues employs the tissue name and the suffix - itis e.g pancreatitis meningitis pericarditis arthritis

allergy to drugs insect bite,toxins.immune diseases like rhumatoid artritis,5

jayalakshmi jayakumar (jj) - allergy to drugs insect bite,toxins.immune diseases like rhumatoid artritis,Cardinal Signs (Celsus)Rubor- redness due to increased blood flow and vasodilationCalor- or heat due to increase blood flow to the peripheryTumor- swelling from inflammatory edemaDolor-pain from swelling and presence of inflammatory mediatorsFunctio laesa-loss of function due to main and structural necrosis (Virchow 1793)

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Types of inflammation

Acute inflammation immediate and early response to an injurious agent,short duration usually less than 48 hrsPMN as inflammatory cells

Chronic inflammation longer duration,occurs either after the causative agent of acute inflammation persist for a long time or the stimulus induces chronic inflammation from the beginningLymhocytes,plasma cells,macrophages inflammatory cells

Acute inflammation

Stimuli for acute inflammationInfections (bacterial, viral, fungal, parasitic) and microbial toxins.Tissue necrosis from any cause, including ischemia (as in a myocardial infarct),trauma, and physical and chemical injuryForeign bodies Dirt, sutures etcImmune reactions (hypersensitivity reactions) are reactions in which the normally protective immune system damages the individual's own tissues.

jayalakshmi jayakumar (jj) - physical injury-thermal injury, as in burns or frostbite; irradiation; exposure to some environmental chemicals). Several molecules released from necrotic cells are known to elicit inflammationAcute inflammation - Pathogenesis3 major components:Alteration of vascular flow and caliber (vasodilation leads to increased blood flow)Increased Vascular Permeability (Vascular Leakage)Emigration of leukocytes from microcirculation (leukocyte activation leads to elimination of offending agent)

jayalakshmi jayakumar (jj) - jayalakshmi jayakumar (jj) - 1 and 2 vascular changes 3 cellular changeVascular changesMajor role in acute inflammation

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Leukocyte Emigration AdhesionTransmigrationChemotaxisPhagocytosis

Termination

Stasis Vascular permeabilityVasodilation

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1.Changes in Vascular Flow and CaliberTransient constriction of arterioles immediate vascular response after an injury.Vasodilation Arterioles are involved, and leads to increased blood flow, which is the cause of heat and redness at the site of inflammation. Induced by the action of mediators like histamine and nitric oxide, on vascular smooth muscle.

events13

jayalakshmi jayakumar (jj) - eventsIncreased permeability of the microvasculature leads to exudation of protein rich fluid into the extravascular space causing swelling (tumor).Stasis of the blood flow -Loss of fluid from the vessels leads to Concentration of red cells resulting in decreased velocity and stasis of the blood flowLeukocytic margination-Neutrophils, accumulate along the vascular endothelium.At the same time endothelial cells are also activated by mediators produced at sites of injury, and express increased levels of adhesion molecules.

2.Increased Vascular Permeability

15Hallmark of acute inflammation as it causes escape of protein rich exudate leading to edema. loss of protein from plasma reduces intravascular osmotic pressure, and increases that of interstitium.So marked outflow of fluid Edema

pathogenesis-3 components.1 vasodilation (Alteration of vascular flow and caliber) 2 Vascular Leakage)3 Emigration of leukocytes15

jayalakshmi jayakumar (jj) - jayalakshmi jayakumar (jj) - pathogenesis-3 components.1 vasodilation (Alteration of vascular flow and caliber) 2 Vascular Leakage)3 Emigration of leukocytesMechanism of vascular leakageContraction of endothelial cells

Resulting in gaps in endothelium.most common mechanism.Elicited by histamine, bradykinin, leukotrienes,and substance P.It is called the immediate transient response because it occurs rapidly and is short-lived.

Endothelial retractionStructural reorganization of cytoskeleton of endothelial cellsReversibile retraction of intercellular junctionsDelayed and prolongedDirect endothelial injury Resulting in endothelial cell necrosis.Eg:Burns,bacterial infectionsImmediate and sustained reaction.

Leukocyte-dependent endothelial cell injuryMarginating leukocytes may damage the endothelium through activation and release of toxic oxygen radicals and proteolytic enzymes making the vessel leaky.Transcytosis occurs across cellular channels.

Shows the difference between normal and inflamed tissues....vasodilation19

jayalakshmi jayakumar (jj) - Shows the difference between normal and inflamed tissues....vasodilationCellular Events

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Leukocyte EmigrationAdhesionTransmigrationChemotaxisPhagocytosis

Termination

Stasis Vascular permeabilityVasodialtion

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3.Emigration of leukocytescritical function of inflammation is to deliver leukocytes to the site of injury and to activate the leukocytes to eliminate the offending agents.Leukocytes leave the vasculature routinely through the following sequence of events:Margination, rolling, and adhesion to endotheliumDiapedesis (trans-migration across the endothelium)Migration toward a chemotactic stimuli from the source of tissue injury.

Margination and RollingWith increased vascular permeability, fluid leaves the vessel causing leukocytes to settle-out of the central flow column and marginate along the endothelial surfaceEndothelial cells and leukocytes have complementary surface adhesion molecules which briefly stick and release causing the leukocyte to roll along the endothelium until it adhire firmly.Rolling and adhesion are mediated by selectins, integrins, Immunoglobulin superfamily adhesion molecules.

There are three types of selectins: one expressed on leukocytes (L-selectin), one on endothelium (E-selectin), and one in platelets and on endothelium (P-selectin).The expression of selectins and their ligands is regulated by cytokines produced in response to infection and injury.23

jayalakshmi jayakumar (jj) - jayalakshmi jayakumar (jj) - There are three types of selectins: one expressed on leukocytes (L-selectin), one on endothelium (E-selectin), and one in platelets and on endothelium (P-selectin).The expression of selectins and their ligands is regulated by cytokines produced in response to infection and injury.Transmigration (diapedesis)After adhesion leukocytes insert their pseudopods into endothelial cell junction and squeeze through this layer into the extarvascular space..It cross basement membrane by damaging it locally with Collagenases

Chemotaxis.Once they have exited the capillary, the leukocytes move through the tissue guided by secreted cytokines, bacterial and cellular debris, and complement fragments (C3a, C5a),leukotrienes (LTB4).Most chemotactic agents signal via G-protein-coupled receptors resulting in intracellular Ca2+ release and activation of small GTPases. This leads to actin/myosin polymerization and filopodia formation directed to the chemical agent.

The process by which leukocytes migrate in response to a chemical signal is called chemotaxis.25

jayalakshmi jayakumar (jj) - The process by which leukocytes migrate in response to a chemical signal is called chemotaxis.

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Phagocytosis and DegranulationDuring the next and final stage of the cellular response, the neutrophils and macrophages engulf and degrade the bacteria and cellular debris in a process called phagocytosis.It involves

RecognitionEngulfmentKilling (degradation/digestion)

Recognition and BindingThe phagocytic cells are recognized by chemotactic factors released by bacterial products.It is made easier by opsonisation-coating with natural opsonins like C3b, IgG,lectins.EngulfmentAfter a particle is bound to phagocyte receptors,pseudopods flow around it, and form a vesicle (phagosome) that encloses the particle.It fuses with lysosome-phagolysosome.

mpo myeloperoxidase29

jayalakshmi jayakumar (jj) - mpo myeloperoxid

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