Inflammation Lecture III

fate of acute inflammation

Fates (outcomes) of acute inflammation 1-Complete resolution: restoration of site of acute inflammation to normal. It involve: removal of the exudate, fibrin & debris. reversal of the microvascular changes. regeneration of lost cells. 2-Healing & organization:connective tissue replacement. Occurs in substantial tissue destruction. tissue cannot regenerate. extensive fibrinous exudate.

Complete resolution

Fates (outcomes) of acute inflammation (cont.) 3-Suppuration : It may be diffuse in tissue, localized in tissue (abscess) , on the surface of a wound, or in serous cavity. 4-Progression to chronic inflammation: Acute inflammation progress in to chronic inflammation when there is persistent infection, when there is foreign body, etc.

-Ulcer is defined as loss of continuity in an epithelial surface. or excavation of the surface of an organ or tissue produced by the sloughing of inflammatory necrotic tissue.

Acute inflammation Chronic inflammation Short duration: hours -days –weeks. Exudative fluid (protein rich fluid + inflammatory cells + debris). Main inflammatory cells N & Macrophage. Chronic inflammation Long duration: months – years. Fibrosis. Main inflammatory cells L, M, plasma cells + fibroblasts & endothelial cells.

Chronic Inflammation A prolonged process in which inflammation and attempt of healing proceed at the same time. It is less uniform & productive. The main cells are mononuclear cells.

It is joined by lymphocytes and plasma cells, The dominant cellular player in chronic inflammation is the tissue macrophage Blood monocyte Tissue macrophage (RES) migrate into tissue within 48 hours after injury Kupffer cell (liver) Microglia (CNS) Histiocytes (spleen) Alveolar macs (lung) and differentiate It is joined by lymphocytes and plasma cells, however mast cells and eosinophils are as well involved in chronic allergic diseases Plasma cell Lymphocyte

Chronic Inflammation Inflammation of long duration, characterized by predominance of lymphocytes, plasma cells & Mac. productive (fibrous tissue) rather than exudate through formation of granulation tissue. It may arise in 3 ways 1-Progression from acute inflammation persistent inflammation & suppuration. presence of indigestible endogenous (e.g dead bone), or exogenous (e.g suture). 2-Repeated episodes of acute inflammation (e.g. Chronic Cholecystitis ). 3-Primary chronic inflammation.

Causes of chronic inflammation : 1 Causes of chronic inflammation : 1. Persistent infection by certain micro- organisms. 2. Prolonged exposure to potentially toxic agents-( exogenous or endogenous agents ) e.g. silica, asbestose ect. 3. autoimmunity e.g. rheumatoid arthritis.

Outcome of chronic inflammation Ulcers Fistulas Granulomatous diseases Fibrotic diseases (Scaring) and combinations of the above

Morphologic features of chronic inflammation. 1 Morphologic features of chronic inflammation. 1. Infiltration with, -lymphocytes -plasma cells -eosinophils -mast cells -macrophage, activated to epitheliod cells ,or fused together forming giant cell. 2. Tissue destruction. 3. Attempts of healing.

Primary chronic inflammation No initial phase of acute inflammation e.g., Certain infections e.g T.B, leprosy, brucellosis, viral Prolonged exposure to potential toxic agents e.g. silica, lipids. Foreign body reactions. Some autoimmune diseases e.g. rheumatoid fever. Specific diseases of unknown etiology e.g. ulcerative colitis. Primary granulomatous diseases e.g. sarcoidosis.

Granulomatous inflammation Special type of chronic inflammation in which the predominant cell type is an epitheloid macrophage Epitheloid macrophages: Activated macrophage that has acquired an enlarged, elongated squamous cell-like appearance. They have secretory rather than phagocytic activity Macrophage giant cell: A large cell having numerous nuclei. 2 main types: Foreign body GC. Langhan’s GC.

Granuloma: An aggregate of epitheloid macrophages. surrounding rim of mononuclear infl cells. surrounding rim of fibroblast & fibrosis. giant cells. central necrosis e.g., caseating necrosis in T.B.

Causes of granulomatous inflammation Specific infections Mycobacteria (T.B, leprosy, atypical mycrobacteria ). Parasites (larvae, eggs & worms). Fungi, Brucellosis, Syphilis, cat-scratch disease & Yersina. Foreign bodies Endogenous (keratin, necrotic bone, sodium ureate). Exogenous (talk, silica, suture material, oil, silicon). Chemicals Berrylosis Drugs Unknown Crohn’s disease, sarcoidosis, Wegener’s granulomatosis.

Macroscopic appearance of chronic inflammation Chronic ulcer. Chronic abscess cavity. Induration & fibrosis. Thickening of the wall of the hallow viscous. Caseous necrosis.

Systemic effects of acute inflammation acute phase response Fever (temperature > 37.8oC or >100 F) Increased pulse, blood pressure, Chills and anorexia Leukocytosis Neutrophilia and left shift of neutrophils points to bacterial infection Lymphocytosis points to viral infection Eosinophilia point to allergy or parasitic infection Acute phase protein production in liver fibrinogen, CRP, leads to increased ESR

Increased Erythrocyte Sedimentation Rate as a result of the presence of acute phase reactants ESR = rate at which erythrocytes settle out of unclotted blood in one hour Normally, Erythrocytes are very buoyant and settle slowly Erythrocytes are negatively charged and repel each other (no aggregation occurs) In presence of acute phase reactants (fibrinogen) erythrocytes aggregate due to loss of their negative charge resulting in increased sedimentation ESR is a widely performed test to detect occult processes and monitor inflammatory conditions

- weight loss in chronic inflammation, its due to actions of IL-1 and TNF alpha which increase catabolism in skeletal muscles, adipose tissue and the liver. - Other manifestations (increase pulse and decreased blood pressure, sweating, rigors, chills, anorexia, somnolence, and malaise). - In sepsis -DIC, hypoglycemia, cardiovascular failure (septic shock).