Inflammation Lecture Notes PDF

KAAF UNIVERSITY COLLEGE SCHOOL OF NURSING/MW/PHN PATHOLOGY LECT. RICHMOND KWAKYE INFLAMMATION  INFLAMMATION The term is derived from the Latin "inflammare“ meaning to burn. Inflammation is a local response (reaction) of living vascularized tissues to endogenous and...

KAAF UNIVERSITY COLLEGE SCHOOL OF NURSING/MW/PHN PATHOLOGY LECT. RICHMOND KWAKYE INFLAMMATION  INFLAMMATION The term is derived from the Latin "inflammare“ meaning to burn. Inflammation is a local response (reaction) of living vascularized tissues to endogenous and exogenous stimuli. Inflammation is fundamentally destined to localize and eliminate the causative agent and to limit tissue injury.  INFLAMMATION Thus, inflammation is a physiologic (protective) response to injury, an observation made by Sir John Hunter in 1794 concluded: “inflammation itself not to be considered as a disease but as a salutary operation consequent either to some violence or to some diseases  INFLAMMATION It is fundamentally a protective response, designed to rid the organism of both the initial cause of cell injury (e.g., microbes, toxins) and the consequences of such injury (e.g.,necrotic cells and tissues).  DEFINITION Inflammation is defined as the complex yet systematic biological response of vascularized living tissues to harmful stimuli such as pathogens, damaged cell or irritants. It is a protective mechanism, an attempt by the organism to remove injurious stimuli as well as initiate the healing process for the tissue. Inflammation is a complex reaction in tissues that consists mainly of responses of blood vessels and leukocytes. These vascular and cellular reactions of inflammation are triggered by soluble factors that are produced by various cells or derived from plasma proteins and are generated or activated in response to the inflammatory stimulus.  WHY INFLAMMATION The benefits of inflammation include: Identification of the injurious stimuli curtailment of the progression of the injurious agent, dilution of the toxins produced by the injurious agent, destruction/degradation of the injurious agent and preparation of the tissue for repair  However, inflammation is not always beneficial e.g hypersensitivity reactions. Why?  CAUSES OF INFLAMMATION physical agents - mechanical injuries, alteration in temperatures and pressure, radiation injuries. chemical agents- drugs and toxins. biologic agents (infectious)- bacteria, viruses, fungi, parasites immunologic disorders- hypersensitivity reactions, autoimmunity, immunodeficiency states etc genetic/metabolic disorders- examples gout, diabetes mellitus etc…  Nomenclature: The nomenclatures of inflammatory lesion are usually indicated by the suffix 'itis'. Thus, inflammation of the appendix is called appendicitis and that of meninges as meningitis,  Classification: Inflammation is classified crudely based on duration of the lesion and histologic appearances into acute and chronic inflammation.  ACUTE INFLAMMATION Acute inflammation is an immediate and early response to an injurious agent and it is relatively of short duration, lasting for minutes, several hours or few days. It is characterized by exudation of fluids and plasma proteins (oedema)and the emigration of predominantly neutrophilic leucocytes to the site of injury. The five cardinal signs of acute inflammation Redness (rubor) which is due to dilation of small blood vessels within damaged tissue as it occurs in cellulitis. Heat (calor) which results from increased blood flow (hyperemia) due to regional vascular dilation Swelling (tumor) which is due to accumulation of fluid in the extravascular space which, in turn, is due to increased vascular permeability.  Pain (dolor), which partly results from the stretching & destruction of tissues due to inflammatory edema and in part from pus under pressure in as abscess cavity. Some chemicals of acute inflammation, including bradykinins, prostaglandins and serotonin are also known to induce pain. Loss of function: The inflammed area is inhibited by pain while severe swelling may also physically immobilize the tissue.  Cellular response of A.INFL. A.Migration, rolling, pavementing, & adhesion of leukocytes B. Transmigration of leukocytes( escape from the venules) C. Chemotaxis ( leukocyte to the site of inflammation) D. Phagocytosis Phagocytosis Phagocytosis is the process of engulfment and internalization by specialized cells of particulate material, which includes invading microorganisms, damaged cells, and tissue debris. These phagocytic cells include polymorphonuclear leukocytes (particularly neutrophiles), monocytes and tissue macrophages. Morphology of acute inflammation Characteristically, the acute inflammatory response involves production of exudates. An exudate is an edema fluid with high protein concentration, which frequently contains inflammatory cells.  Effects of acute inflammation Beneficial effects Dilution of toxins: The concentration of chemical and bacterial toxins at the site of inflammation is reduced by dilution in the exudate and its removal from the site by the flow of exudates from the venules through the tissue to the lymphatics. Protective antibodies: Exudation results in the presence of plasma proteins including antibodies at the site of inflammation. Thus, antibodies directed against the causative organisms will react and promote microbial destruction by phagocytosis or complement-mediated cell lysis.  Beneficial effects Fibrin formation: This prevents bacterial spread and enhances phagocytosis by leukocytes. Plasma mediator systems provisions: The complement, coagulation, fibrinolytic, & kinin systems are provided to the area of injury by the process of inflammation.  Promotion of immunity: Micro- organisms and their toxins are carried by the exudates, either free or in phagocytes, along the lymphatic's to local lymph nodes where they stimulate an immune response with the generation of antibodies and cellular immune mechanisms of defense  Harmful effects Tissue destruction Inflammation may result in tissue necrosis and the tissue necrosis may, in turn, incite inflammation. Swelling: The swelling caused by inflammation may have serious mechanical effects at certain locations. Examples include acute epiglottitis with interference in breathing; Acute meningitis and encephalitis with effects of increased intracranial pressure. Inappropriate response: The inflammatory seen in hypersensitivity reactions is inappropriate (i.e. exaggerated). Outcomes of Acute Inflammation. 1) Complete resolution, 2) Healing by connective tissue replacement 3) Progression of the response to chronic inflammation. 4)Abscess formation  When acute inflammation is successful in eliminating the offenders the reaction subsides, but if the response fails to clear the invaders it can progress to a chronic phase CHRONIC INFLAMMATION Chronic inflammation can be defined as a prolonged inflammatory process (weeks or months) where an active inflammation, tissue destruction and attempts at repair are proceeding simultaneously.  Causes of chronic inflammation: Persistent infections Certain microorganisms associated with intracellular infection such as tuberculosis, leprosy, certain fungi etc characteristically cause chronic inflammation. These organisms are of low toxicity and evoke delayed hypersensitivity reactions Prolonged exposure to non- degradable but partially toxic substances endogenous lipid components which result in atherosclerosis or exogenous substances such as silica, asbestos Progression from acute inflammation: Acute inflammation almost always progresses to chronic inflammation following Persistent suppuration as a result of uncollapsed abscess cavities, foreign body materials (dirt, cloth, wool, etc)  Autoimmuniy. Autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosis are chronic inflammations from the outset.  Cells of chronic inflammation: Monocytes and Macrophages T-Lymphocytes B-lymphocytes and Plasma cells Mast cells and eosinophils appear predominantly in response to parasitic infestations & allergic reactions.  Classification of chronic inflammation: Chronic inflammation can be classified into the following two types based on histologic features: Nonspecific chronic inflammation: This involves a diffuse accumulation of macrophages and lymphocytes at site of injury that is usually productive with new fibrous tissue formations. E.g. Chronic cholecystitis ( inflammation of your gall bladder) Specific inflammation (granulomatous inflammation): Granulomatous inflammation is characterized by the presence of granuloma. A granuloma is a microscopic aggregate of epithelioid cells. Epithelioid cell is an activated macrophage, with a modified epithelial cell-like appearance (hence the name epithelioid)  granuloma is a focus of chronic inflammation consisting of a microscopic aggregation of macrophages that are transformed into epithelia-like cells, surrounded by a collar of lymphocytes, with or without giant cells.  Major causes of granulomatious inflammation include: a) Bacterial: Tuberculosis, Leprosy, Syphilis, Cat scratch disease, Yersiniosis b) Fungal: Histoplasmosis, Cryptococcosis, Coccidioidomycosis, Blastomycosis c) Helminthic: Schistosomiasis  d) Protozoal: Leishmaniasis, Toxoplasmosis e) Chlamydia: Lymphogranuloma venerum f) Inorganic material: Berrylliosis SYSTEMIC EFFECTS OF INFLAMMATIONS The systemic effects of inflammation include: a. Fever b. Endocrine & metabolic responses c. Autonomic responses d. Behavioral responses e. Leukocytosis f. Leukopenia g. Weight loss  Fever Fever is the most important systemic manifestation of inflammation. It is coordinated by the hypothalamus & by cytokines (IL -1, IL-6, TNF-α) released from macrophages and other cells.  Endocrine and metabolic responses include: The liver secrets acute phase proteins such as: C-reactive proteins Serum Amyloid A Complement and coagulation proteins Glucocorticoids (increased) Vasopressin (decreased)  Autonomic responses include: Redirection of blood flow from the cutaneous to the deep vascular bed. Pulse rate and blood pressure (increased)  Behavioral responses include: - Rigor, chills, anoroxia, somnolence, and malaise. Leucocytosis is also a common feature of inflammation, especially in bacterial infections. Its usual count is 15,000 to 20,000 cells/mm3. Most bacterial infections induce neutrophilia. Some viral infections such as infectious mononucleosis, & mumps cause lymphocytosis.  Parasitic infestations & allergic reactions such as bronchial ashma & hay fever induce eosinophilia. Leukopenia is also a feature of typhoid fever and some parasitic infections.. Weight loss is thought to be due to the action of IL-1 and TNF-α which increase catabolism in skeletal muscle, adipose tissue and the liver with resultant negative nitrogen balance.  Cellular response( assignment) 2 Briefly explain the ff cellular response to acute inflammation A.Migration, rolling, pavementing, & adhesion of leukocytes B. Transmigration of leukocytes C. Chemotaxis