Chronic InflammationBahrain version October 2023FINALv2 (2).pptx
Transcript
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
