Chronic Inflammation PDF - Causes, Pathogenesis & Granuloma

Chronic inflammation Assistant a Professor R.F. Zibirov  Chronic Inflammation: Persists for weeks to months Extravascular accumulation of lymphocytes and macrophages Tissue destruction and attempts to healing by proliferation runs simultaneously, i.e., Proli...

Chronic inflammation Assistant a Professor R.F. Zibirov  Chronic Inflammation: Persists for weeks to months Extravascular accumulation of lymphocytes and macrophages Tissue destruction and attempts to healing by proliferation runs simultaneously, i.e., Proliferative lesion Not stereotype  Chronic inflammation is inflammation of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist in varying combinations. It may follow 1. acute inflammation 2. or chronic inflammation may begin insidiously, as a low-grade, smoldering response without any manifestations of an acute reaction.  CAUSES OF CHRONIC INFLAMMATION 1. Persistent infections by microorganisms that are difficult to eradicate, such as mycobacteria, and certain viruses(hepatitis C), fungi and parasites 2. Immune-mediated inflammatory diseases. Chronic inflammation plays an important role in a group of autoimmune diseases (rheumatoid arthritis and multiple sclerosis) 3. Prolonged exposure to potentially toxic agents, either exogenous (silica), or endogenous (toxic plasma lipid component in atherosclerosis  Pathogenesis of chronic inflammation Local persistence of the antigen leads to accumulation of activated T lymphocytes, plasma cells, and macrophages at the site of injury. Macrophages (monocytes) are recruited to the lesion from the blood by such chemotactic factors as C5a and TGF-β. Local activation occurs under the influence of cytokines (particularly interferon-γ (INF-γ) and IL-4 (from T-cells)), microbial products. Macrophages in turn release a variety of factors (IL-1, IL-6, TNF-α, complement components, prostaglandin) that perpetuate the developing immune response and various growth factors such as fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), TGF- β which can cause of fibrosis and angiogenesis Pathogenesis of chronic inflammation  MORPHOLOGIC FEATURES OF CHRONIC INFLAMMATION 1. Infiltration with mononuclear cells, which include macrophages, lymphocytes, and plasma cells 2. Tissue destruction, induced by the persistent agent or by the inflammatory cells 3. Attempts at healing by connective tissue replacement of damaged tissue (fibrosis)  Classification of chronic inflammation Nongranulomatous chronic inflammation is characterized by the accumulation of sensitized lymphocytes, plasma cells, and macrophages, necrosis, formation of granulation tissue and healing by fibrosis in the injured area. The cells do not form granulomas. Examples: chronic osteomyelitis, chronic ulcer, chronic viral hepatitis, autoimmune diseases (cytotoxic B and T cell responses - Hashimoto's thyroiditis, chronic ulcerative colitis), chronic toxic diseases (chronic alcoholic liver disease, chronic alcoholic pancreatitis) Chronic inflammation with chronic endometritis with lymphocytes accumulation lymphocytes as well in synovium after as plasma cells in the rheumatoid arthritis endometrial stroma. Hashimoto's Autoimmune Thyroiditis cytotoxic T cell-mediated hypersensitivity reaction chronic cervicitis; lymphocytes accumulation Chronic hepatitis; the portal tract in the center of the photomicrograp h contains an increased number of lymphocytes.  Classification of chronic inflammation Granulomatous chronic inflammation is characterized by the formation of epithelioid cell granulomas. Epithelioid cells are activated macrophages. Epithelioid cells appear to have enhanced abilities to secrete variety of enzymes but decreased phagocytic potential. An epithelioid cell granuloma is an aggregate of these activated macrophages. Macrophage aggregation is induced by lymphokines produced by activated T cells. Granulomas are usually surrounded by lymphocytes, plasma cells, fibroblasts, and collagen. Epithelioid cells around the center of a granuloma. Langhans-type giant cells in the granuloma  Granuloma is circumscribed lesion of granulomatous inflammation, built from macrophages and aggregation of inflammatory cells Two types of granuloma are recognized: 1) epithelioid cell granuloma, which represents an immune response in which the macrophages are activated by lymphokines of specifically stimulated T cells; 2) foreign body granuloma, which represents nonimmune phagocytosis of foreign nonantigenic material by macrophages.  Granuloma Epithelioid cell granulomas form when two conditions are satisfied: 1) macrophages have successfully phagocytosed the injurious agent but it survives inside them. 2) T lymphocyte-mediated cellular immune response occurs. Lymphokines produced by activated T lymphocytes inhibit migration of macrophages and cause them to aggregate in the area of injury and form granulomas  Granuloma Cell types in granulomas : 1. Epitheloid cells 2. Giant cells: fused epitheloid cells (20 or more nuclei) (foreign body type, Langhans-type, Touton-type) 3. Lymphocytes, plasma cells 4. Fibroblasts (in older granulomas) In many infectious granulomas central caseous necrosis is a common feature. numerous granulomas in upper lung in a case of pulmonary tuberculosis Сaseating granuloma; Epithelioid cells surround central area of necrosis  Granulomatous chronic inflammation Foreign body granuloma forms around inert (incites no inflammatory response), nonantigenic (incites no immune response) material (such as talc, sutures). Macrophages aggregate around the particles and form granulomas which frequently contain foreign body giant cells Immune granuloma: Infectious granulomas (tuberculosis, syphilis, lepra, cat-scratch disease, Whipple-disease, brucellosis, leishmaniasis, schistosomiasis, fungal infections) Immune granuloma: Non infectious granulomas – Unknknown etiology (sarcoidosis, Crohn-disease). – Rheumatic fever, granulomas associated with vasculitis (polyarteritis nodosa), hypersensitiv pneumonitis. Talc granulomas in the lung. A section of lung from an intravenous drug abuser viewed under polarized light reveals a granuloma adjacent to a pulmonary artery. The refractile material is talc that was used to dilute the drug prior to its intravenous injection. noncaseating granuloma, with Sarcoidosis multinucleated giant cells. Within the giant cells are asteroid bodies noncaseating granulomas (arrowheads). with giant cells Berylliosis. A noncaseating granuloma consists of a nodular collection of epithelioid macrophages and multinucleated giant cells.  NEGATIVE SIDES OF INFLAMMATION 1. Inflammatory reactions underlie life-threatening hypersensitivity reactions to insect bites, drugs, and toxins as well as some, of the common chronic diseases such as rheumatoid arthritis, atherosclerosis, and lung fibrosis. 2. Repair by fibrosis may lead to disfiguring scars or fibrous bands that cause intestinal obstruction or limit the mobility of joints. 3. Several chronic infectious diseases are associated with development of malignancies. For example, schistosomiasis of the urinary bladder leads to squamous cell carcinoma of that organ. Ulcerative colitis are at higher risk for adenocarcinoma in this organ. Thank you for attention