3. FM2004 PM2004 Chronic Inflammation 23-24.pdf

FM2004 & PM2004 Chronic Inflammation Dr Collette Hand UCC Department of Pathology [email protected] January 2024 Dr C. Hand Textbooks R9 R10 Robbins & Cotran Pathologic Basis of Disease U6 U7 Underwood General & Systemic Pathology RBP9 RBP10 Kumar, Abbas, Aster Robbins Basic Pathology Robbins & Cotran A...

FM2004 & PM2004 Chronic Inflammation Dr Collette Hand UCC Department of Pathology [email protected] January 2024 Dr C. Hand Textbooks R9 R10 Robbins & Cotran Pathologic Basis of Disease U6 U7 Underwood General & Systemic Pathology RBP9 RBP10 Kumar, Abbas, Aster Robbins Basic Pathology Robbins & Cotran Atlas of Pathology A2 W5 Young, Stewart, O’Dowd Wheater’s Basic Pathology Dr C. Hand Acute Inflammation Minutes -> days Blood vessels dilate and leak Neutrophils enter surrounding tissue Questions? Dr C. Hand Chronic Inflammation Duration: weeks / months / years CELLS: macrophages, lymphocytes and plasma cells Main Characteristics 1. Active inflammation 2. Attempts at healing by connective tissue 3. Tissue destruction all proceeding simultaneously Dr C. Hand Histological features U6/U7: Fig 9.14 Active Inflammation – macrophages, lymphocytes and plasma cells Attempts at healing by connective tissue – proliferation of fibroblasts & small blood vessels Tissue destruction – induced by the inflammatory cells Dr C. Hand Causes of Chronic Inflammation Progression from acute inflammation Eg abscess – osteomyelitis Recurrent episodes of acute inflammation Eg chronic choleocystitis – gallstones Primary chronic inflammation Dr C. Hand Primary Chronic Inflammation Most cases; no initial phase of acute inflammation Common diseases, Tuberculosis (TB), Rheumatoid arthritis Dr C. Hand Mononuclear phagocytes Macrophage is main player in chronic inflammation Blood monocytes migrate to tissues -> macrophages Extravasation similar to neutrophils: adhesion molecules, chemical mediators R9/R10: Fig 3.19; RBP10: Fig 3.18 Dr C. Hand Macrophage activation R10: Fig 3.20; ~RPB10: Fig 3.19 IFN-y comes from activated t cells Classical (M1) Alterative (M2) Induced by Microbial products, IFN Cytokines Produces NO, ROS, enzymes, cytokines Growth factors Role Phagocytosis, inflammation End inflammation, promote tissue repair Dr C. Hand Secreted Products Oxygen metabolites: cytotoxic Proteases: ECM breakdown Cytokines, chemotactic agents: attract cells Growth factors: fibroblasts, angiogenesis Powerful defence against invaders Can induce considerable tissue destruction tissue destruction is one of the hallmarks of chronic inflammation Dr C. Hand Lymphocyte – macrophage interaction Reciprocal relationship → Persistence of the inflammatory response Activated lymphocytes and macrophages stimulate each other and both release mediators that affect other cells RBP9: Fig 2.22; RBP10: Fig 3.20; R9: Fig 3.21 Dr C. Hand Granulomatous Inflammation Dr C. Hand Granulomatous Inflammation Distinctive pattern of chronic inflammation Activated macrophage with epithelioid appearance Few but widespread chronic immune and infectious diseases: eg leprosy, tuberculosis Causes: – Specific infections: mycobacteria, parasites, larvae, eggs, worms – Foreign bodies: endogenous : cholesterol crystals exogenous : talc, sutures, silica – Unknown: Crohn’s disease, sarcoidosis Dr C. Hand Granuloma Focal area of granulomatous inflammation Accumulated mass of mixed chronic inflammatory cells 1. epithelioid cells/ histioctyes 2. giant cells 3. mantle of lymphocytes Dr C. Hand Epithelioid histiocytes Modified macrophages Transformed into epithelium-like cells – Abundant pink granular cytoplasm Little phagocytic activity – Adapted to a secretory function Dr C. Hand Giant cells Frequently epithelioid cells fuse a "committee" of epithelioid macrophages May develop ‘by accident’ –  2 macrophage attempt to engulf a particle – cell membranes fuse and cells unite – multinucleate (50 → 100!) Indigestible particulate matter – silica, tubercule bacilli Dr C. Hand Giant cells Langhan Giant cell Horseshoe arrangement Characteristically seen in tuberculosis Foreign body Giant cell nuclei scattered throughout cytoplasm foreign-body material Touton Giant cell Central ring of nuclei around lipid cytoplasm Seen at sites of adipose breakdown Dr C. Hand Foreign-body Giant cells A foreign body type giant cell (arrow) adjacent to a segment of vegetable material aspirated into the lung. http://library.med.utah.edu/WebPath/INFLHTML/INFL056.html Dr C. Hand Types of Granuloma 1. Foreign body granuloma Relatively inert foreign bodies eg talc, sutures Sutures, fibres too large for phagocytosis Epithelioid and giant cells encompass body Usually in centre of granuloma 2. Immune granuloma Insoluble particles eg persistent microbe or self antigen Induce cell mediated immune response Macrophages engulf particle and present antigens to T- cells -> activation; cytokines Dr C. Hand Foreign body granuloma Seen under polarized light are numerous bright white crystals of talc in a patient who was an intravenous drug user. The injected drug was diluted with the talc. Such foreign material can produce a granulomatous reaction. http://library.med.utah.edu/WebPath/INFLHTML/INFL058.html Dr C. Hand Tuberculosis Prototype of granulomatous disease Granuloma = tubercule Central caseous necrosis – rare in other granulomatous diseases Mycobacterium tuberculosis inhaled into lung Immune mediated response Cell walls resistant to degradation Chronic inflammation Dr C. Hand Tuberculous granuloma diagram Dr C. Hand Tuberculous granuloma image 1 Dr C. Hand Tuberculous granuloma image 2 Fibroblasts Lymphocytes Giant cell Dr C. Hand Summary Granulomatous Inflammation Specific type of chronic inflammation Accumulations of modified macrophages (epithelioid cells) Initiated by infectious and non-infectious agents Dr C. Hand Morphological patterns of Acute and Chronic Inflammation Dr C. Hand Morphological patterns 1 Acute and Chronic Inflammation Severity of reaction Specific cause Tissue Site Dr C. Hand Morphological patterns 2 Serous Fibrinous Suppurative / purulent Ulcer Haemorrhagic Membraneous / Pseudomembraneous Necrotising / gangrenous Dr C. Hand Serous Inflammation Inflammation of the serous cavities Outpouring of thin fluid – serum – secretions of mesothelial cells of peritoneal, pleural, pericardial cavities Skin blister from burn, viral infection – accumulation of serous fluid – within or beneath epidermis RBP10: Fig 3.12; R9: Fig 3.13 Serous inflammation. Epidermis separated from dermis by collection of serous effusion Dr C. Hand Fibrinous Inflammation 1 More severe injuries – larger molecules eg fibrin pass through vascular barriers Exudation of large amounts of plasma proteins including fibrinogen Precipitation of masses of fibrin Inflammation of body cavities – Pericardium , pleura Dr C. Hand Fibrinous Inflammation 2 fibrinous exudate pericardial cavity fibrinous pericarditis with strands of stringy pale fibrin (arrow). https://webpath.med.utah.edu/INFLHTML/INFL014.html Dr C. Hand Fibrinous Inflammation 3 R10/RBP10: Fig 3.13; R9: Fig 3.14 Fibrinous pericarditis A Deposits of fibrin on pericardium B A pink meshwork of fibrin exudate (F) overlie the pericardial surface (P) Dr C. Hand Suppurative/ Purulent U6/U7: Fig 9.9 Pus produced – dying and degenerative neutrophils – infecting organisms – liquefied tissues Certain microbes Empyema: hollow area filled with pus eg gallbladder, appendix Dr C. Hand Purulent Inflammation R10/RBP10: Fig 3.14; R9: Fig 3.15 Purulent Inflammation A Multiple bacterial abscesses in the lung, in a case of bronchopneumonia B Abscess contains neutrophils and cellular debris and is surrounded by congested blood vessels ABSCESS: Focal localised collection of purulent inflammatory tissue Dr C. Hand Ulcer Local defect or excavation of surface of an organ/ tissue produced by shedding of inflammatory necrotic tissue Commonly encountered: – – Inflammatory necrosis of mucosa of mouth, stomach, intestines, GU tract Subcutaneous inflammation of lower extremities in older persons with circulatory disturbances RBP10: Fig 3.15; R9/R10: Fig 3.16 Morphology of an ulcer Low power cross section of a duodenal ulcer with an acute inflammatory exudate in the crater Dr C. Hand Peptic Ulcer Dr C. Hand Dr C. Hand Chronic Peptic Ulcer Sl: necrotic slough V: vascular granulation tissue (HP in b) F: fibrous granulation tissue (HP in c) Sc: fibrous scar M: Muscular wall W4: Fig 3-2 Dr C. Hand Systemic effects of Inflammation Cytokine-induced systemic reactions/ Acute-phase response Fever / Pyrexia – Response to pyrogens eg LPS released by microbes -> TNF, IL-1 -> ↑ prostaglandins -> ↑ temp. (NSAIDs inhibit) Acute-phase proteins – – – Plasma proteins, produced by liver, elevated eg C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen CRP, SAA: bind microbial cells- opsonins → eliminate Fibrinogen: binds to RBCs → increase ESR Leukocytosis – Esp bacterial infection, cytokines stimulate production Constitutional symptoms – Malaise, somnolence: probably effects of cytokines Dr C. Hand Inflammation Feature Acute Chronic Onset Fast: minutes or Slow: days hours Monocytes/ macrophages and lymphocytes Cellular infiltrate Mainly neutrophils Tissue injury, fibrosis Usually mild and May be severe and self-limited progressive Local and systemic signs Prominent R10: Table 3.2; RBP10: Table 3.1 Less Dr C. Hand Learning Objectives Compare and contrast acute and chronic inflammation with respect to causes, nature of the inflammatory response, and tissue changes. Describe the histological features / cellular elements of the chronic inflammatory response. Describe granulomatous inflammation, list the causes and describe / recognise the cellular components. Distinguish between different types of inflammation ie purulent, serous, fibrinous, ulcer. Identify the settings in which these types of reactions occur. Dr C. Hand