Chronic Inflammation Lecture Notes PDF

D2 Lecture 9 Chronic Inflammation; Granulomatous inflammation Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1  Outcome of Acute Inflammation Depends on the nature and intensity of injury, the site and tissue affected and the ability of...

D2 Lecture 9 Chronic Inflammation; Granulomatous inflammation Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1  Outcome of Acute Inflammation Depends on the nature and intensity of injury, the site and tissue affected and the ability of host to mount a response However, the process has one of four outcomes: 1) Complete Resolution, with regeneration of native cells and restoration of the site of acute inflammation to normal. 2) Abscess formation, particularly in infection with pyogenic organism. 3) Healing by connective tissue replacement (fibrosis) and scaring, which occurs after substantial tissue destruction, when the inflammation occurs in tissues that do not regenerate or when there is abundant fibrin exudation. 4) Progression to chronic inflammation  Chronic Inflammation “Chronic inflammation is a response of prolonged duration (weeks or months) in which inflammation, tissue injury and attempts at repair coexist, in varying combinations”  Chronic Inflammation Chronic Inflammatory conditions Hepatitis Chronic cystitis Inflammatory bowel disease Chronic cholecystitis Pancreatitis Barret esophagus Gastritis Osteomyelitis Sialadenitis  Causes of Chronic Inflammation 1.Persistent infections: By microorganisms that are difficult to eradicate, such as mycobacteria and certain viruses , fungi, and parasites. These organisms often evoke an immune reaction called delayed-type hypersensitivity Sometimes develop a specific pattern called a granulomatous reaction Unresolved acute inflammation may evolve into chronic inflammation 2. Hypersensitivity diseases (autoimmune) 3. Prolonged exposure to potentially toxic agents: Toxic exogenous substances: Lung in silicosis due to silica particles and asbestosis due to asbestos particles Toxic endogenous substances : Atherosclerosis due to cholesterol in blood vessels.  Morphologic Features of Chronic Inflammation Chronic inflammation is characterized by: 1) Infiltration with mononuclear cells, including macrophages, lymphocytes, and plasma cells. 2) Tissue destruction or necrosis, largely induced by the products of the inflammatory cells. Induced by persistence of offending agent. 3) Attempts at healing (repair), by connective tissue replacement of damaged tissue: new vessel proliferation (angiogenesis) or Fibrosis.  Chronic vs Acute Inflammation in Lung A, Chronic inflammation in the lung, showing the characteristic histologic features: collection of chronic inflammatory cells (asterisk); destruction of parenchyma, in which normal alveoli are replaced by spaces lined by cuboidal epithelium (arrowheads); and replacement by connective tissue, resulting in fibrosis (arrows). B, by contrast, in acute inflammation of the lung (acute bronchopneumonia), neutrophils fill the alveolar spaces and blood vessels are congested  Cells and mediators of Chronic Inflammation: 1. Macrophages. Note: Although neutrophils are 2. Lymphocytes characteristic of acute inflammation, many forms of chronic inflammation 3. Eosinophils. continue to show large numbers of 4. Plasma Cells neutrophils 5. Mast cells.  1. Macrophages Macrophages are the dominant cells in most of the chronic inflammation. Function of Macrophages: Tissue Name of Macrophages Liver Kupffer cells. Phagocytosis. Central Nervous System Microglial cells. Initiates tissue repair. (CNS) Secrets inflammatory mediators Lungs Alveolar Macrophages. TNF-a, IL-1 & Chemokines. Spleen & Lymph Nodes. Sinus Histiocytes. Display antigen to T lymphocytes. Responds to signals from T lymphocytes.  2. Lymphocytes Major drivers of inflammation in autoimmune and chronic inflammatory diseases. Activation of B and T lymphocytes is a part of adaptive immune response. B lymphocytes on activation develop into plasma cells which secrete antibodies T lymphocytes on activation secrete cytokines: CD4+ T lymphocytes promote inflammation and influence the nature of the inflammatory reaction.  2. Lymphocytes Subset of CD4+ T lymphocytes: TH1, TH2, TH17 TH1 and TH17 cells are involved in defense against many bacteria and viruses, and in autoimmune diseases TH2 cells are involved in defense against helimenthic parasites and in allergic inflammation  3.Eosinophils Abundant in immune reaction mediated by IgE and parasitic infections. Eotaxin: Chemotactic chemokine for eosinophil. Major protein (MBP): Present in eosinophil granules; Toxic to parasites Eosinophils are of benefit in controlling helminth infections But may also contribute to tissue damage in immune reactions such as allergies  3.Eosinophils Focus of inflammation containing numerous eosinophil  4. Plasma Cells Terminally differentiated B lymphocytes. Produce antibody directed either against persistent foreign antigen in the inflammatory site or against altered tissue component.  5.Mast cells Widely distributed in connective tissues Participate in both acute and chronic inflammatory reactions Cells degranulate and release mediators, such as histamine and prostaglandins This type of response occurs during allergic reactions to foods, insect venom, or drugs, sometimes with catastrophic results (e.g., anaphylactic shock).  Granulomatous Inflammation Granulomatous inflammation is a form of chronic inflammation characterized by collections of activated macrophages, often with T lymphocytes, and sometimes associated with necrosis (Granulomas) Granuloma formation is a cellular attempt to contain an offending agent that is difficult to eradicate. Strong activation of T lymphocytes leads to macrophage activation, which can cause injury to normal tissues.  Morphology of Granuloma Activated macrophages have pink granular cytoplasm with indistinct cell boundaries; these are called epithelioid cells because of their resemblance to epithelia. Surrounded by a cuff of lymphocytes. Older granuloma may show rim of fibroblasts as well. Fusion of macrophages: Multinucleated giant cells: 40 to 50 μm in diameter. Consist of a large mass of cytoplasm and many nuclei, Central necrosis may also be present in some granulomas. Granuloma effectively “walls off” the offending agent and is therefore a useful defense mechanism  Granulomatous Inflammation - Types Types of granulomas: 1.Immune granulomas: Caused by agents that can induce a persistent T cell– mediated immune response such as microbes (mycobacterium tuberculosis) 2.Foreign body granulomas (Nonimmune): Incited by relatively inert foreign bodies such as talc (associated with intravenous drug abuse), sutures, or other fibers that are large enough to preclude phagocytosis by a macrophage  Morphology of Granuloma In granulomas associated with certain infectious organisms (most classically the tubercle bacillus), a combination of hypoxia and free radical injury leads to a central zone of necrosis. Gross: Granular, cheesy appearance and is therefore called caseous necrosis. Microscopy: Necrotic material appears as eosinophilic amorphous, structureless, granular debris, with complete loss of cellular details.  Morphology of Granuloma The granulomas associated with Crohn disease, sarcoidosis, and foreign body reactions are “non-caseating.” No necrotic center  Morphology of Granuloma Granular cheese like appearance on gross  Morphology of Granuloma Non caseating granuloma Caseating granuloma Blue arrow: Caseous necrosis Red arrow: Giant cell (Langhan type) Yellow arrow: Epithelioid cells White arrow: Lymphocyte cuff Examples of diseases with granulomatous inflammation Tuberculosis: Caseating granuloma; Langhan’s giant cells Syphilis: Gummas, Plasma cells Leprosy: Non caseating, Acid fast bacilli present Cat scratch disease: Rounded or stellate granulomas with neutrophils Sarcoidosis: Non caseating granulomas Crohn disease: Non caseating granulomas; dense inflammatory infiltrate  Foreign body granuloma : Nonimmune Granulomatous reaction around Talc powder Suture material  Differences between Acute and Chronic Inflammation Acute Inflammation Chronic Inflammation Response Immediate reaction of tissue to Persisting reactions of tissue to injury. injury. Onset/ Duration. Rapid: hours to weeks. Slow Response: weeks/ months/ years. Immunity Innate Cell mediated Predominant Cell Type / Mainly Neutrophils. Monocytes/ Macrophages & Cellular infiltrate lymphocytes. Tissue injury, Fibrosis Usually mild & self limiting Often sever & progressive. Local & systemic signs Prominent. Less Prominent. Outcome Resolution, abscess formation, Tissue destruction, fibrosis, chronic inflammation. necrosis. Thank You