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The Process of

ACUTE INFLAMMATIONObjectives:1. Understand the sequence of vascular and cellular events in the histological evolution of acute inflammation2. Learn the roles of various chemical mediators of acute inflammation3. Know the three possible outcomes of acute inflammation4. Visualize the three morphologic patterns of acute inflammation

@CBBitangcor Presentations A.Y.2012-2013

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Sequence of Events• Normal Histology• Vasodilation• Increased Vascular Permeability• Leakage of Exudate• Margination, Rolling and Adhesion• Transmigration (Diapedesis)• Chemotaxis• PMN Activation• Phagocytosis: Recognition, Attachment, Engulfment, Killing (degradation

or digestion)• Termination• 100% Resolution, Scar, or Chronic Inflammation as the three possible

outcomes

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Vascular Changes• Changes in Vascular Flow and Caliber• Increased Vascular Permeability

DilationEndothelial gapsDirect InjuryLeukocyte InjuryTransocytosis (endo/exo)New Vessels

Leakage of Proteinaceous EXUDATE, not TRANSUDATE

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Extravasation of PMNs• Margination (PMN's go toward the wall)• Rolling (Tumbling and heaping)• Adhesion• Transmigration (Diapedesis)

Adhesion Molecules(glycoproteins)

affecting Adhesion and Transmigration• Secretins (from endothelial cells)• Integrins (from many cells)

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ChemotaxisPMNs going to the site of injury AFTER Transmigration

Leukocyte Activationtriggered by the offending stimuli for PMNs to:-Produce eicosanoids (arachidonic acid derivatives)Prostaglandins (and thromboxanes)LeukotrienesLipoxins-undergo DEGRANULATION-secrete CYTOKINES

PhagocytosisRecognitionEngulfmentKilling (Degradation/Digestion)

Chemical MediatorsFrom plasma or cellsHave "triggering" stimuliUsually have specific targetsCan cause a "cascade"Are shortlivedA.Y.2012-2013

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Sources of Chemical Mediators

• The chemical mediators of inflammation can be derived from plasma or cells.

Plasma-derived mediators:i) Complement activation• increases vascular permeability (C3a,C5a)• activates chemotaxis (C5a)• opsoninization (C3b,C3bi)ii) Factor XII (Hegman factor) activation• Its activation results in recruitment of four systems: the kinin,

the clotting, the• fibrinolytic and the compliment systems.A.Y.2012-2013

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Cell-derived Chemical MediatorsCellular mediators Cells of origin FunctionsHistamine Mast cells, basophiles Vascular leakage &

plateletsSerotonine Platelets Vascular leakageLysosomal enzymes Neutrophiles Bacterial & tissue

destruction, macrophages

Prostaglandines All leukocytes Vasodilatation, pain, fever

Leukotriens All leukocytes LB4Chemoattractant LC4, LCD4, & LE4

Broncho and vasoconstriction

Platlete activating factor All leukocytes Bronchoconstriction and WBC priming

Activated oxygen species All leukocytes Endothelial and tissue damage

Nitric oxide Macrophages Leukocyte activationCytokines Lymphocytes,

macrophages Leukocyte activation

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Morphologic Patterns of Acute Inflammation

• 100% Resolution• Scar• Chronic Inflammation

3 Outcomes of Acute Inflammation

• Serous (watery)• Fibrinous (hemorrhagic, rich in Fibrin)• Suppurative (PUS)• UlcerativeA.Y.2012-2013

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Serous (watery)

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Fibrinous (hemorrhagic, rich in Fibrin)

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Suppurative (PUS)

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Ulcerative

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