Chronic Inflammation - Bahrain Version October 2024 PDF

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 i...

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 Pneumoconiosis-anthracosis  Diseases of unknown aetiology  e.g. Inflammatory bowel disease  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 Foreign body reaction  Silicosis Unknown aetiology  Sarcoidosis  Crohn’s disease  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 Ziehl Neelson M. tuberculosis PCR  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