Morphologic Patterns of Acute Inflammation Dr Shoaib Raza

Morphologic Patterns of Acute Inflammation Dr Shoaib Raza

Morphologic Patterns of Acute Inflammation • Acute inflammation is morphologically characterized by – Dilatation of small blood vessels – Slowing of blood flow – Leukocyte infiltration – Fluid accumulation in interstitial space • Special morphologic patterns are seen – Severity of reaction – Specific cause of reaction – Particular tissue/site involved

Serous Inflammation �Marked by • Outpouring of thin fluid derived from �Plasma �Secretions of mesothelial cells • Accumulation of fluid in these cavities is called as EFFUSION • Skin blister represent accumulation of serous fluid

Fibrinous Inflammation • • Characterized by deposition of fibrin in the extracellular spaces Fibrinous exudate develops when – Vascular leaks are large, or – Local procoagulant stimulus • Fibrinous exudate is characteristic of: – Inflammation in the lining of body cavities • Conversion to fibrous tissue (organization) within pericardial sac leads to fibrous thickening (Fibrinous pericarditis)

Suppurative/purulent Inflammation • Characterized by production of large amounts of pus (purulent exudate), consist of – PMN, liquefactive necrosis, edema fluid • • Pyogenic bacteria produce this Abscess are localized collection of purulent inflammatory exudate – Suppuration buried in an organ, tissue or confined space • Central necrotic area • Preserved PMN around this necrotic focus • Vascular dilatation, parenchymal and fibroblastic proliferation occurs peripherally

Ulcers • • • A local defect or excavation, of the surface of an organ or tissue, produced by the sloughing (shedding) of inflamed necrotic tissue Occur when tissue necrosis and inflammation exist on or near a surface Encountered in – Mouth, stomach, intestine, genital or urinary tract – Skin & subcutaneous tissues

Outcomes of Acute Inflammation �Complete resolution �Healing by connective tissue replacement • Fibrosis, organization, scar formation �Progression to chronic inflammation

Chronic Inflammation �Inflammation of the prolonged duration (weeks or months) in which inflammation, tissue injury and attempts at repair coexist �It may • Follow acute inflammation • Begin insidiously as low grade smoldering response without any manifestation of the acute reaction

Causes of Chronic Inflammation � Chronic inflammation arises in following settings: • Persistent infection by microorganism �Mycobacteria, fungi, viruses, parasites etc • Immune mediated inflammatory diseases �Autoimmune diseases (Allergic disorders) • Prolonged exposure to potentially toxic agents �Exogenous �Silica, carbon �Endogenous �Atherosclerosis

Morphologic Features �Chronic inflammation is characterized by: • Infiltration with mononuclear cells �Macrophages, lymphocytes, plasma cells • Tissue destruction �Induced by persistence of offending agent • Attempts at healing by connective tissue replacement of damaged tissue �Proliferation of small blood vessels (Angiogenesis) �Fibrosis

Macrophages � Macrophages are the predominant cells of chronic inflammation • Component of mononuclear phagocyte system �Liver �Spleen & Lymph nodes �Lung �CNS �Bone Kupffer cells Sinus histiocytes Alveolar macrophages Microglia Osteocytes • Arise from common precursor in bone marrow • Monocytes enter tissue & differentiate into macrophages

Role of Macrophages in Chronic Inflammation � Migration begins early in acute inflammation � Predominant cells after 48 hours � Macrophages activation occur via: • Microbial products via TLRs • IFN-γ secreted by sensitized T Cells, NK cells, � Activation results in: • Increased level of lysozyme • ROS & NO production • Production of cytokines, growth factors, etc

Role of Macrophages in Chronic Inflammation �Activation of macrophages result in: • Toxicity to microbes & host cells • Release of protease etc • Influx of other cell types via cytokines • Fibroblast proliferation • Angiogenesis �Arsenal of mediators make them powerful allies in the defense, but the same weaponry can induce tissue destruction

Fate of Macrophages �In acute inflammation: • If irritant is eliminated, macrophages disappear �Either dying off �Drain to regional lymph nodes via lymphatics �In chronic inflammation: • Accumulation of macrophages persists �As a result of continuous recruitment from the circulation and local proliferation at the site of inflammation

Other cells in Chronic Inflammation �Lymphocytes: • Cell mediated or antibody mediated reactions • Selectins, integrins and chemokines help in their recruitment • TNF, IL-1, etc promote leukocyte recruitment, �Persisting the inflammatory response • Macrophages present antigens to T Cells �Plasma cells • May transform the inflammatory site into tertiary lymphoid organ

Other cells in Chronic Inflammation � Eosinophils: • Abundant in immune reaction mediated by Ig. E and parasitic infestations (infections) • Eotaxin is a potent chemotactic agent for eosinophil • Eosinophil produce: �Major Basic Proteins � Mast Cells: • Widely distributed in connective tissue • Participate in both acute & chronic inflammation • Express FcεRI • Release histamine, prostaglandins, serotonin • Cytokines production

Granulomatous Inflammation Distinctive (Specific) pattern of chronic inflammation � Immune reactions are usually involved in granuloma formation � Granuloma is an attempt to contain an offending agent � Granuloma composed of: � • Modified macrophages (epitheliod cells) • Collar of lymphocytes • Giant cells (multinucleated cells) • + Necrosis (caseous) � Granulomas are of two main types: • Foreign body granuloma • Immune granulomas �Delayed type hypersensitivity reactions

Fungal Infections: Bacteria: • Histoplasmosis • Blastomycosis • Tuberculosis • Leprosy Metal/Dust • Berylliosis • Silicosis Foreign body • Splinter • Suture • Graft material Sarcoidosis Parasites: • Schistosomiasis

Systemic Effects of Inflammation � Acute Phase Response (systemic inflammatory response syndrome) • Fever: �Usually seen in infections �Pyrogens stimulate hypothalamus to form PG • Acute Phase proteins: �CRP, Fibrinogen, Serum Amyloid A (SAA) • Leukocytosis: �Leukemoid reactions, leukopenia • Others: �Increased pulse rate, Increased blood pressure, decreased sweating, rigors, chill, anorexia, somnolence, malaise

Pain is perfect misery, the worst of evils, and excessive, overturns All patience. - John Milton,

Inappropriate Inflammatory Responses � Defective Inflammation: • Increased susceptibility to infections • Delayed wound healing � Excessive Inflammation: • Hypersensitivity reactions • Autoimmune disorders • Other non-immune related disorders �AS, CHD, Alzheimer’s Disease • Pathology in many infections, metabolic disorders, etc.

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