Lecture 10 (P) PDF

Lecture 4 PMED-DENT-PHRM Pathology Team By the end of this session students should be able to: ◦ Define and list the causes of chronic inflammation. Session’s Objectives ◦ List the characteristic features of chronic inflammation. ◦ Enumerate the cells and mediators of chronic inflammation. ◦ Discuss...

Lecture 4 PMED-DENT-PHRM Pathology Team By the end of this session students should be able to: ◦ Define and list the causes of chronic inflammation. Session’s Objectives ◦ List the characteristic features of chronic inflammation. ◦ Enumerate the cells and mediators of chronic inflammation. ◦ Discuss granulomatous inflammation regarding definition, mechanism, and cause. ◦ Enumerate and discuss the systemic effects of inflammation. Chronic Inflammation ◦ Inflammation of prolonged duration (weeks, months to years) in which active inflammation, tissue injury and healing proceed simultaneously. ◦ Acute inflammation progressing to chronic inflammation. Chronic Inflammation Causes ◦ Persistent Infection by microbes which are difficult to eradicate e.g. mycobacterium tuberculosis, treponema pallidum, certain viruses and fungi. ◦ Prolonged Exposure to toxic Agents ◦ Exogenous (Silicosis) ◦ Endogenous (Atherosclerosis) ◦ Immune-mediated diseases ◦ Autoimmune diseases Chronic Inflammation Morphologic Features ◦ Infiltration with mononuclear cells (macrophages, lymphocytes & plasma cells) ◦ Indicates persistent reaction to injury ◦ Tissue destruction, done by ◦ Inflammatory cells ◦ Macrophages which ingest the dead tissue & the causative agents ◦ Repair involving the process of angiogenesis and fibrosis. Inflammation Chronic inflammation in the lung, showing collection of chronic inflammatory cells Acute inflammation of the lung Neutrophils fill the alveolar spaces and blood vessels are congested. Cells of Chronic Inflammation 1- Mononuclear Phagocyte System: ◦ In Bone marrow - Monoblasts ◦ In the Circulating Blood Monocytes ◦ In Tissues – Macrophages ◦ Sinus Histiocytes (spleen) ◦ Kupffer cells (liver) ◦ Microglia (CNS) ◦ Alveolar Macrophages (lung) ◦ Mechanism Of Macrophage Accumulation: ◦ Continued recruitment of monocytes from the circulation Cells of Chronic Inflammation ◦ Local proliferation of macrophages ◦ Immobilization of macrophages at the site of inflammation ◦ Activation Signals for macrophages include: ◦ Microbial products e.g. endotoxin ◦ Mediators of acute inflammation e.g. Fibronectin ◦ IFN-γ by sensitized T lymphocytes ◦ Activated Macrophages show: ◦ Increase in cell size & lysosomal enzymes. ◦ Increased ability to kill ingested organisms. Chronic Inflammation ◦ ACTIVATED MACROPHAGES secrete active products that if unchecked can result in the tissue injury and fibrosis Activated macrophage and its effects 2- Lymphocytes: ◦ Play important role in Antibody mediated and Cell mediated immunity. ◦ Both T and B lymphocytes migrate using cell adhesion molecules(CAM) and chemokines. Cells of Chronic Inflammation ◦ Macrophages display antigens to T lymphocytes and produce IL-12 that stimulates T-cell. ◦ Activated T lymphocytes produce IFN-γ which is a powerful activator of macrophages. ◦ Plasma cells develop from activated B lymphocytes and produce antibodies. ◦ Strong chronic inflammatory reactions: tissues may assume the features of lymph nodes with well-formed germinal centers. Lymphocytes and macrophages bidirectional interaction Cells of Chronic Inflammation ◦ Plasma Cells ◦ Develop from B lymphocytes ◦ Produce antibodies ◦ Mast Cells ◦ Participate in both acute and chronic inflammatory reactions ◦ Binds the Fc portion of the IgE antibody ◦ Eosinophils ◦ Parasitic infections ◦ Mediated by IgE ◦ Eotaxin – chemokine to prime eosinophils for chemotaxis ◦ Neutrophils ◦ Chronic inflammation may continue to show neutrophilic infiltrates, due to persistent microbes or necrotic cells Clinically chronic inflammation is subdivided into: 1. Non-specific ◦ Nonspecific histological appearance. Types of Chronic inflammation ◦ Diffuse accumulation of lymphocytes, plasma cells and macrophages. 2. Specific (Chronic Granulomatous) ◦ Focal response that leads to the formation of a specific lesion – Granuloma. ◦ Examples: Tuberculosis, leprosy, syphilis. Chronic Granulomatous Inflammation: ◦ Granuloma: is a localized collection of modified macrophages called epithelioid cells, surrounded by lymphocytes, giant cells and fibroblasts. Chronic Inflammation ◦ Giant cells are formed by fusion of macrophages and contain many nuclei (multi-nucleated giant cells). ◦ Types of Giant Cells: ◦ Langhan Giant Cells: the nuclei are arranged at the periphery in a horse shoe shaped manner. ◦ Foreign body giant cell: no specific arrangement, many nuclei are present haphazardly within the cytoplasm. Chronic Granulomatous Inflammation Chronic Inflammation ◦ Morphologically Granulomas can be of two types: ◦ Caseating granulomas, there is a central mass of necrotic tissue called caseation. ◦ Non-caseating granulomas, no central caseation Chronic Inflammation Microscopic picture of a granuloma ◦ Epithelioid cells have pink granular cytoplasm, combined to make granuloma which is surrounded by a collar of lymphocytes & fibroblasts. Non-caseating granulomas ◦ Multinucleated giant cells may also be seen. ◦ Granulomas associated with tuberculosis have a central zone of caseous necrosis Microscopically, necrotic material appears as amorphous, granular debris. ◦ Healing of granulomas is by fibrosis Caseating granulomas Granuloma Non-caseating granulomas Caseating granulomas Caseating Granuloma Classification of Granulomas based on etiology: 1. Infective Granulomas: ◦ Tuberculosis ◦ Leprosy ◦ Syphilis ◦ Cat-scratch disease Chronic Granulomatous Inflammation ◦ Listeriosis ◦ Brucellosis. 2. Foreign Body Granulomas: ◦ Silicosis ◦ Asbestosis ◦ Talc and sutures 3. Immune Granulomas: ◦ Crohn’s disease Granulomatous diseases: Disease: Cause: ◦ Tuberculosis. ◦ Mycobacterium TB ◦ Leprosy. ◦ Mycobacterium Leprae ◦ Syphilis. ◦ Treponema Pallidum ◦ Listeriosis. ◦ Listeria ◦ Brucellosis. ◦ Brucella ◦ Asbestosis. ◦ Asbestos ◦ Silicosis. ◦ Silica ◦ Berylliosis. ◦ Beryllium ◦ Acute-phase reaction/Systemic inflammatory response syndrome: ◦ Cytokines TNF, IL-1,IL-6 are important mediators. Systemic Effects of Inflammation ◦ Produced by leukocytes and other cells and are released systemically. ◦ IL-6 stimulates the hepatic synthesis of opsonins e.g. Creactive protein, fibrinogen, and serum amyloid A protein. ◦ Raised Erythrocyte Sedimentation Rate (ESR) ◦ Fibrinogen binds to erythrocytes and causes them to form stacks (rouleaux). Leukocytosis: ◦ TNF and IL-1 cause release of cells from the bone marrow Systemic Effects of Inflammation ◦ Leukocyte count rises to 15,000 or 20,000 cells/μL, ◦ Bacterial infections - increase in the blood neutrophil count (Neutrophilia). ◦ Viral infections - increased numbers of lymphocytes (Lymphocytosis). ◦ Allergic conditions and parasite infestations increased number of eosinophils (Eosinophilia). ◦ Certain infections (typhoid fever, some viruses, rickettsiae, and certain protozoa) - decreased number of circulating white cells (leukopenia) Systemic Effects of Inflammation ◦ Fever: ◦ Elevation of body temp. by 1-4 C in response to Pyrogens: ◦ Exogenous pyrogens (bacterial lipopolysaccharides) stimulate leukocyte release of Endogenous pyrogens (IL-1,TNF) ◦ These stimulate synthesis of PGs by endothelial cells of hypothalamus which resets body temp. at a higher level ◦ Increased heart rate, rigors, chills, anorexia. Systemic Effects of Inflammation ◦ Cachexia: Wasting syndrome due to TNF mediated appetite suppression. ◦ In severe bacterial infections, high levels of TNF cause clinical triad: ◦ Disseminated intravascular coagulation (DIC), ◦ Hypoglycemia, and ◦ Hypotensive shock - Septic Shock. Summary