InflammationDr. Raid Jastania

StressInjuryOverloadCell DeathResponseAdaptationInflammationInsultResults

Causes of InflammationInjury and cell DeathInflammationPhysicalChemicalInfectionsIschemiaImmuneMetabolic

Types of InflammationInjury and cell DeathInflammationPhysicalChemicalInfectionsIschemiaImmuneMetabolicAcuteChronicGranuloma

Immune ReactionInjury and cell DeathInflammationPhysicalChemicalInfectionsIschemiaImmuneMetabolicAcuteChronicGranulomaImmune

Chronic Inflammatory DiseasesInjury and cell DeathInflammationPhysicalChemicalInfectionsIschemiaImmuneMetabolicAcuteChronicGranulomaImmuneChronic Inflammatory Diseases

Acute Inflammation

Chronic Inflammation

Chemical Mediators of Inflammation

Intended Learning Outcomes:Students should be able to define inflammation and understand clinical features of inflammation and its systemic effect.Students should know the vascular and cellular events in acute inflammation and understand its morphology. Students should know the cellular events in chronic inflammation.Students should be able to define granulomatous inflammation and know its causes. Students should be able to apply the rules of acute and chronic inflammation to predict the features of inflammation in the different organs of the body.

InflammationInflammation is a protective response of connective tissue to injury. Aim: to eliminate the injury and start the process of repair. Inflammation starts with activation of endothelial cells and white blood cells. Changes in vesselsCellular events. Chemical mediators

InflammationInflammation is divided into acute and chronic type. Acute inflammation is the immediate response to injury, and neutrophils are the main cell type. Chronic inflammation is mediated by mononuclear cells (macrophages, lymphocytes, plasma cell)

Clinical Features:Exercise:During a foot ball game, a player was injured and had twist in ankle joint.What are the signs/symptoms that he would have?

Clinical Features:Exercise:19 year old boy has inflammation of the appendix, Appendicitis.What are the signs/symptoms that he would have?

Clinical Features:Localized or systemic. The localized features are: Redness, Swelling, Heat, Pain and Loss of function. The systemic features include: Fever, elevated WBC, malaise, anorexia, and hypotension, Acute phase reaction

Acute Inflammation

Acute Inflammation:It is the immediate early response to injury. It is characterized by neutorphil infiltrate and fluid exudates.The changes in acute inflammation may be divided to: vascular changes and cellular events.

Vascular changes:Change in the vascular caliber and flowinitial transient vasoconstriction of the arterioles followed by vasodilatation. The end result is blood stasis.Increase in vascular permeabilityincrease in the hydrostatic pressure and leakage of fluid to the extravascualr space (Transudate).increase in the osmotic pressure of the interstitium leading to leakage of protein-rich fluid (Exudate). The end result is Edema.

Mechanisms of increased vascular permeability:Endothelial contraction: histamine, PG, Immediate transient responseEndothelial retraction: 4-6 hours after injuryDirect endothelial damage: Immediate sustained Response Delayed prolonged leakage:

Mechanisms of increased vascular permeability:5. Leukocyte-dependent endothelial injury6. Increased Transcytosis: Through intracellular vesicular pathway, and occurs after exposure to VEGF.7. Leakage from new blood vessels (angiogenesis)

Cellular Events

Cellular Events:Margination and Rolling:WBC slow down and are pushed to the side of the vessel near endothelial cells. This process is MarginationWBCs transiently stick to endothelial cells. This process is Rolling The adhesion is facilitated by the action of adhesion molecules called Selectins.

Cellular Events:Margination and Rolling:Selections are present on WBC, endothelial cells and platelets. E-Selectin: on endothelial cellP-Selectin: on Platelets and endothelial cellsL-Selectin: on WBCsSelectins are up regulated by IL-1, and TNF.Selectins bind to sugar molecules. Example: Sialyl-Lewis X

Cellular Events:2. Adhesion and Transmigration:Firm adhesion of WBCs to endothelial cells. Integrins on WBCs and Immunoglobulins on endothelial cells. Example of immunoglobulins: ICAM (intercellular adhesion molecule), VCAM (vascular adhesion molecule)ICAM binds to LFA-1 (integrin)VCAM binds to VLA-4 (integrin)

Cellular Events:2. Adhesion and Transmigration:IL-1 and TNF induce the expression of ICAM and VCAMIntegrins bind only when WBCs are activated.Transmigration occurs as the WBCs pass through intercellular junction. This process is facilitated by PECAM (platelet endothelial cell adhesion molecule, CD31).

Cellular Events:3. Migration in interstitium: ChemotaxisMigration of WBCs is facilitated by chemotactic agents. These are molecules that attract WBCs. They include:Bacterial productsComplement system, C5aLeukotriene B4 (LTB4)Cytokines (IL-8)

Leukocyte Activation:by G-protein activation WBC activation is characterized by:Degranulation of WBC granules and formation of oxidative burstSecretion of arachidonic acid metabolites (Leukotrienes and prostaglandins)Expression of adhesion molecules.

Phagocytosis1. Recognition and attachment:opsonins: immunoglobulins IgGC3b molecule of the complement systemCollectinsWBCs have specific receptors to these opsonins.

Phagocytosis2. Engulfment in phagocytic vacuole:phagosome.3. Killing and degradation:Phagosome fuses to lysosome to form phagolysosome. Killing is facilitated by:a. Oxygen free radicals (oxidative burst)b. Lysosomal enzymes (myeloperoxidase)

Outcome of Acute Inflammation:ResolutionAcute persists with complications: Abscess Progression to chronic inflammationScarring and Fibrosisorganization and fibrosis

Inflammation-Induced Tissue Injury