inflammation 1.pdf

INFLAMMATION BY Prof. Dr. MAHMOUD TAG Head of pathology department MUST University  Introduction  Define: inflammation – exudate- phagocytosis- mediators  Describe: vascular phenomenon  Compare between acute and chronic inflammation  Analy...

INFLAMMATION BY Prof. Dr. MAHMOUD TAG Head of pathology department MUST University  Introduction  Define: inflammation – exudate- phagocytosis- mediators  Describe: vascular phenomenon  Compare between acute and chronic inflammation  Analyze the mechanism of leukocytes extravasation The science of the disease study. Pathology deals with five components of the disease: Definition, Causes, Mechanisms (pathogenesis), Morphologic changes (gross and microscopic), and Complications.  Definition: It is a protective immune-vascular response. It is the reaction of living tissue against injury.  Causes: Infectious agents-immunological- tissue necrosis- chemical and physical agents- nutritional.  Components of inflammation: Cause-Immune cells-Blood vessels- Chemical mediators  Purpose of inflammation: Elimination of the cause-Clear necrotic cells- Initiate repair.  Redness: due to vasodilatation  Swelling: due to inflammatory fluid exudate (edema fluid)  Pain: due to irritation of nerve ending by toxins and chemical mediators or compression by the exudate  Loss of function Transient By direct action of toxins or vasoconstriction trauma on blood vessels Vasodilatation Due to Histamine Slowing of the Due to: Vasodilatation circulation (stasis) Hemoconcentration Swelling of endothelial cells Escape of the plasma To form the fluid part of From inside to outside inflammatory exudate blood vessels Leukocytes Diapedesis through intact extravasation vessels  Swollen endothelium and V. constriction/V. dilatation escape of plasma  Chemo-attraction, margination, activation: [ Recognition of the pathogens by leukocytes- IL1- TNFα- Endothelial cells express E & P selectins]  Rolling : [Carbohydrate ligands on leukocytes surface bind to selectins- Rolling]  Adhesion: [ Activation of integrin molecules in the surface of rolling leukocytes Integrin bind tightly to receptors in endothelial cells causing immobilization of leukocytes]  Transmigration: - Pseudopodia - Leukocytes pass through gaps between intact endothelium. -Proteolytic digestion of basement membrane  Definition: it is a fluid formed of plasma and blood cells (neutrophils). It comes out the blood vessels to do specific immune functions in inflammation area  Function of Neutrophils: Phagocytosis and kill the microbe by[ ROS and Lysosomes] - Dilution of the toxins. - Fibrinogen forms a network of fibrin threads causing localization of infection and facilitates the movement of leucocytes - It contains antibodies  Neutralization [Block antigen receptor]  Opsonization [Coat the microorganism to help phagocytosis]  Agglutination [Clumping the microorganism to prevent spread]  Antibody mediated cell cytotoxicity [NK cell]  Activation of complement : - Phagocytosis - Cell lysis - Inflammation  Part of immune system consists of number of small proteins.  Formed in the liver and circulates in an inactive form.  Stimulated by Antigen-antibody or bacteria  Works by cleavages of specific protein parts  Release of cytokines  Activation of cell killing membrane attack complex.  Functions: A- Cell lysis: C5b bind to C6-C9 forming membrane attack complex which form a hole in cell membrane B- Inflammation: C3a-C5a (anaphylatoxins) stimulate histamine release. C5a is a strong leukocyte chemoattractant. C- Opsonization: C3b binds to specific receptor promotes phagocytosis by neutrophils and macrophages. - Engulfing of foreign body as bacteria and debris. - Neutrophils and macrophage are phagocytic cells. - Function: Clean and clear the area of inflammation for repair. - Factors which help phagocytosis: opsonins, complement, fibrin and mild fever. - Steps of phagocytosis: Chemotaxis -Adherence of microbe to phagocytes- Ingestion- Phagosome- fusion of phagosome with a lysosome to form phagolysosom- Digestion by enzyme- Residual body - Discharge of waste materials. Characters Acute Chronic Onset Rapid Gradual Duration Few days Months or years Cardinal signs Present absent Toxemia Acute Chronic macrophages, Microscopically: lymphocytes, Neutrophil and a) Cells plasma cells, giant macrophages. cells, and fibroblasts b) Edema fluid Present absent Less numerous, Numerous, thin thick walled and c) Blood vessels walled, dilated and show angiogenesis filled with blood. or endarteritis obliterans.  Fever: due to release of chemical mediators  Leukocytosis: increase number of WBCs  Neutrophil: suppurative inflammation and produce proteolytic enzymes  Eosinophil: parasitic inflammation and allergy  Lymphocyte: chronic and viral inflammation  Fibroblast: chronic inflammation and produce collagen in tissue repair  Hyperplasia of the reticulo-endothelial system: a part of immune system consists of phagocytic cells as Kupffer cells of the liver and tissue histiocytes.  Reversible changes: cloudy swelling (Water) or fat accumulation due to toxic effects.  Cell death (necrosis).  Toxemia-sepsis-pyemia.  Beneficial effects: dilution of toxins- phagocytosis- localization by fibrin- immunity.  Harmful effects:  Swelling of inflamed tissues with obstructions and loss of functions.  Healing by fibrosis leads to narrowing- pressure atrophy-cell replacement and organ dysfunction.  Hypersensitivity: exaggerated response of inflammatory cell. The vascular and cellular events of inflammation are mediated by different molecules derived from cells or plasma. Mediators are produced in response to microbial products or factors released by necrotic tissues. 1- Mention three criteria of inflammatory exudate 2- What are selectins and integrin 3- What is opsonization 4- List three functions of complement 5- Define chemical mediators