Chronic InflammationBahrain version October 2023FINALv2 (2).pptx
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RCSI School of Medicine
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LEARNING OUTCOMES • Define chronic inflammation • List the causes of chronic inflammation • Describe the microscopic features of chronic inflammation • Describe the clinical patterns of chronic inflammation • List the systemic effects of chronic inflammation • List the clinical terms of chronic infl...
LEARNING OUTCOMES • Define chronic inflammation • List the causes of chronic inflammation • Describe the microscopic features of chronic inflammation • Describe the clinical patterns of chronic inflammation • List the systemic effects of chronic inflammation • List the clinical terms of chronic inflammation • List the outcome of chronic inflammation • Explain TB and sarcoidosis and granuloma formation CHRONIC INFLAMMATION • Inflammation of a prolonged duration and delayed response • Results from a balance between progressive tissue damage caused by a persistent damaging stimulus and attempted eradication of the damaging agent followed by tissue repair • The chronic inflammatory cells are lymphocytes and macrophages • Begins insidiously (ab initio) • Preceded by acute inflammation • Stimulus that either persists or recurs CHRONIC INFLAMMATION FOLLOWING ACUTE INFLAMMATION • Progression of acute inflammation Organisation of an abscess - e.g. progression of acute osteomyelitis to chronic osteomyelitis Presence of indigestible material - Wood implanted into wound - Surgical sutures • Recurrent episodes of acute inflammation e.g. chronic cholecystitis CHRONIC INFLAMMATION- AB INITIO • Persistent infection Mycobacterium tuberculosis Treponema pallidum Fungi • Prolonged exposure to toxic agents e.g. pneumoconiosis silica or asbestos, carbon dust Autoimmune diseases e.g. Rheumatoid arthritis, SLE Diseases of unknown aetiology e.g. Inflammatory bowel disease Pneumoconiosis-anthracosis FEATURES OF CHRONIC INFLAMMATION • Mononuclear cells -macrophages, lymphocytes and plasma cells • Fibrosis MACROPHAGES • The main effector cells in chronic inflammation • Extravasation of monocytes (adhesion molecules and chemical mediators) • Transformation into larger macrophages ROLE OF MACROPHAGES • Activated by cytokines and bacterial endotoxins • Phagocytosis • Are ‘professional’ antigen presenting cells • Release inflammatory mediators, causing Tissue destruction Proteases and other enzymes AA metabolites Toxic oxygen metabolites Nitric oxide Coagulation factors Neutrophil chemotactic factors Vascular proliferation (angiogenesis) and fibrosis Growth factors Cytokines Remodelling collagenase and metalloproteinase M1 AND M2 MACROPHAGES DENDRITIC CELLS • Dendritic cells derive from bone marrow progenitors • Circulate in blood as immature precursors and settle in tissues where they differentiate • They are professional antigen presenting cells- stimulate naive T cells to initiate the immune response • There are different types depending on location e.g. Langerhans cells of the skin T-LYMPHOCYTES • Produced in the bone marrow, maturation in the thymus: TCR rearrangement • CD4 helper cells- MHC class II • CD8 cytotoxic cells- MHC class I • Activation of T cells requires binding of antigen/MHC complex • T lymphocytes release lymphokines • T cells regulate macrophage activation and recruitment via lymphokines T-HELPER CELLS B-LYMPHOCYTES • B cells are produced in the bone marrow • Differentiate to form either memory B cells or plasma cells • Plasma cells are rich in rough endoplasmic reticulum and make antibodies NATURAL KILLER (NK) CELLS MAST CELLS/BASOPHILS • Basophils are the least common leukocyte in the blood, they migrate into tissue to become mast cells EOSINOPHILS • Common in many allergic inflammatory reactions • Effective killers of parasites • Phagocytic • Major basic protein-MBP (toxic to parasites and contributes to tissue damage) • Mediate tissue damage GRANULOMATOUS INFLAMMATION • Specific form of chronic inflammation • Aggregation of macrophages having an enlarged, epithelium-like appearance (called ‘epithelioid’ macrophages), surrounded by a rim of lymphocytes • Giant cells- large cells with multiple nuclei (fusion of macrophages) • Seen in response to persistent irritating agent which is poorly digestible and/or which initiates a cell mediated immune response: • Substances resist lysosomal degradation • Substances that induce T-cell hypersensitivity • Its aim is to control or remove the damaging agent GRANULOMATOUS INFLAMMATION-CAUSES • Infection (specific types) • Foreign body – Exogenous • Splinter • Suture • Graft material – Endogenous • Keratin • Hair shafts in pilonidal sinus • Response to tumours • Metal/dust Berylliosis Silicosis • Unknown aetiology Sarcoidosis Crohn’s disease Foreign body reaction GRANULOMATOUS INFLAMMATION –INFECTIOUS CAUSES Bacteria Tuberculosis Leprosy Cat scratch disease Spirochaetes Syphilis Fungi Histoplasmosis Blastomycosis Parasites Schistosomiasis Toxoplasmosis Leishmaniasis Schistosomiasis TUBERCULOSIS • Is Type IV hypersensitivity • Histological features (lungs, lymph nodes) Caseating granuloma, central necrosis Epithelioid macrophages and Langhans giant cells T-helper cells (within the granuloma) Occasional plasma cells Peripheral rim of suppressor T cells and fibroblasts ZN stain • Culture • Fluorescent staining with auramine • PCR Ziehl Neelson M. tuberculosis SARCOIDOSIS • Granulomatous condition of unknown aetiology • Young adults, blacks > whites • May affect any tissue • Non caseating ‘naked’ granuloma • Schaumann bodies - concentric calcification (calcium oxalate crystals) • Asteroid bodies Schaumann bodies Asteroid bodies TYPE IV DELAYED HYPERSENSITIVITY Interactions between CD4 T helper cells and macrophages • Macrophages present antigens via MHC II to CD4 helper cells causing their activation • T cells produce cytokines (IL-2 and IFN-γ) TB Fungal infection Sarcoidosis HYPERSENSITIVITY REACTIONS MORPHOLOGIC PATTERNS IN ACUTE AND CHRONIC INFLAMMATION • Serous inflammation • Fibrinous inflammation • Suppurative inflammation • Ulcers • Sinus • Fistula SEROUS INFLAMMATION • Accumulation of thin fluid derived from the blood serum or secretion of fluid from mesothelial lining Effusion • Peritoneal • Pleural • Pericardial Skin blisters • Viral infection • Burn FIBRINOUS INFLAMMATION • Accumulation of fluid and fibrin due to increased vessel permeability • Common locations include the serosal linings of the pericardium, peritoneum and pleura • May be removed by fibrinolysis (resolution) SUPPURATIVE INFLAMMATION • Purulent inflammation is a localized proliferation of pus-forming organisms • Can be seen in association with certain organisms as Staphylococcus aureus (e.g., skin abscess). • Staphylococcus aureus contains coagulase, which cleaves fibrinogen into fibrin and traps bacteria and neutrophils, thereby keeping the infection localised • Cellulitis is a spreading type of bacterial infection of subcutaneous tissue that usually follows some type of skin trauma ABSCESS • Localised collection of pus Dead and degenerate leucocytes (mainly neutrophils) Dead and degenerate host tissue cells Oedema fluid Dead microorganisms ULCER • Local defect in an epithelial surface • Produced by shedding of dead epithelial cells • Skin and mucosal surfaces e.g., peptic ulcer • They are distinguished from erosions by the extent of tissue loss ULCERS • Acute ulcers Loss of the full thickness of the epithelium May or may not be associated with scarring at the base of the ulcer • Chronic ulcers Usually, deep penetrating Always associated with scarring at the base of the ulcer SINUS • Tract lined by granulation tissue leading from a chronically inflamed cavity to a surface, for example: – Sinuses associated with osteomyelitis – Pilonidal sinus FISTULA • Track open at both ends, through which abnormal communication between two surfaces is established – e.g. gastrointestinal fistula in Crohn's disease