Pathology Mod 1: Inflammation and Repair PDF

PATHOLOGY 08/07/2024. MOD 1: INFLAMMATION AND REPAIR Dr. Baut...

PATHOLOGY 08/07/2024. MOD 1: INFLAMMATION AND REPAIR Dr. Bautista Trans Group/s: Volunteers I. INFLAMMATION B. MAJOR COMPONENTS OF ACUTE INFLAMMATORY Protective response which rids the host of both the RESPONSE cause of cell injury and consequence of such injury (such as necrotic tissue). 1. DILATATION OF SMALL VESSELS Response of vascularized tissue to infections and Induced by several mediators: histamine (vascular damaged tissues that brings cells and molecules of host smooth muscle) defense from the circulation to the sites where they are Increases blood flow needed to eliminate the offending agents. 2. INCREASED MICROVASCULAR PERMEABILITY Promoted by increased blood flow Leakage of plasma proteins and leukocytes → engorgement of blood vessels and loss of fluid → induces stasis 3. EMIGRATION, ACCUMULATION, AND ACTIVATION OF LEUKOCYTES Promoted by stasis LEUKOCYTE RECRUITMENT Metabolites Description Leukocytes line up along MARGINATION endothelium Microbes and damaged tissues are recognized by Allows membrane complexes to macrophages and other cells, which then release ROLLING interact with markers to activate mediators that trigger the vascular and cellular integrin reactions of inflammation. ADHESION Stable/firm adhesion to endothelium A. CAUSES OF INFLAMMATION Infections ○ Microbes Transmigration across endothelium DIAPEDESIS ○ Toxins and vessel wall (into tissue) Tissue necrosis ○ Ischemia Migration into tissue guided by ○ Trauma CHEMOTAXIS chemotactic stimulus (like cytokines ○ Physical Injury and other mediators) ○ Chemical Injury Foreign body Immune reactions (hypersensitivity) II. ACUTE INFLAMMATION Initial, rapid response to infections and tissue damage Develop within minutes or hours Short duration: lasting for several hours or only a few days Main characteristics: ○ Edema: exudation of fluid or proteins ○ Neutrophils: immigration of leukocytes A. CARDINAL SIGNS OF INFLAMMATION Rubor (redness) C. MEDIATORS OF INFLAMMATION Tumor (swelling) Substances that initiate and regulate inflammatory Calor (heat) reactions Dolor (pain) The most important mediators of acute inflammation are: Clinical: functio laesa (loss of function) ○ Vasoactive amines ○ Lipid products ○ Cytokines ○ Products of complement activation Pathology - Mod 1 MOD1-PATHO-Inflammation and Repair 1 of 6 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Secreted by cells or generated from plasma proteins Produced ONLY in response to stimuli Short-lived One mediator stimulate the release of other mediators 1. VASOACTIVE AMINES VASOACTIVE AMINES HISTAMINE SEROTONIN Vasodilator Vasoconstrictor Increases Importance to permeability of inflammation is unclear venules 2. ARACHIDONIC ACID METABOLITES Prostaglandins Leukotrienes 4. CHEMOKINES ○ The lipid mediators prostaglandin and Acts as chemoattractants for specific types of leukotrienes are produced from arachidonic acid leukocytes present in membrane phospholipids. Functions: Lipoxins ○ Inflammatory chemokines → attach to endothelium ○ Homeostatic chemokines Types of chemokines ○ C-X-C chemokines (PMNs) ○ 2 C-C chemokines (macrophages) ○ 3 C chemokines (lymphocytes) ○ 4 CX3C chemokines (fractalkine) 5. COMPLEMENT SYSTEM Collection of soluble proteins and membrane receptors Function as host defense against microbes and in pathologic inflammatory reactions. 3. CYTOKINES Proteins produced by many cell types that mediate and regulate immune and inflammatory reactions. Tumor Necrosis Factor (TNF) and Interleukin 1 (IL-1) serve roles in leukocyte recruitment by: ○ Promoting adhesion of leukocyte to endothelium ○ Increasing venule permeability to aid in migration D. MORPHOLOGIC PATTERNS OF ACUTE MAJOR ROLES OF TNF AND IL-1 IN ACUTE INFLAMMATION INFLAMMATION 1. SEROUS INFLAMMATION 1 Endothelial activation Marked by exudation of cell-poor fluid into spaces created by cell injury or body cavities 2 Activation of leukocytes and other cells 3 Systemic acute-phase response Pathology - Mod 1 MOD1-PATHO-Inflammation and Repair 2 of 6 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Skin blisters showing the separation of epidermis from the dermis due to the focal collection of serous effusion. 2. FIBRINOUS INFLAMMATION This develops when vascular leaks are large or there is a local procoagulant stimulus This type of inflammation is characteristic in the lining of body cavities Abscess (center), which contains neutrophils and cellular debris, surrounded by congested blood vessels. 4. ULCERS These are local defect or excavation of the surface of an organ or tissue Fibrin deposits on the surface of the pericardium. Ulcer. E. POSSIBLE OUTCOMES OF ACUTE INFLAMMATION Complete resolution Healing by connective tissue replacement Progression to chronic inflammation Pink meshwork of fibrin exudate (F) overlying a pericardial tissue (P). 3. SUPPURATIVE INFLAMMATION It is characterized by the production of pus Pus: exudate consisting of neutrophils, the liquefied debris of necrotic cells, and edema fluid Outcomes of Acute Inflammation. III. CHRONIC INFLAMMATION A response of prolonged duration which could be weeks or months in which inflammation, tissue injury, and attempts in repair coexist May follow acute inflammation or arise de novo Pathology - Mod 1 MOD1-PATHO-Inflammation and Repair 3 of 6 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Associated with: ○ More tissue destruction ○ Presence of lymphocytes and macrophages ○ Proliferation of blood vessels ○ Deposition of connective tissue A. CAUSES OF CHRONIC INFLAMMATION Persistent infections such as mycobacteria, viruses, fungi, and parasites Hypersensitivity diseases such as autoimmune and allergic disease Prolonged exposure to potentially toxic agents such as silicosis or atherosclerosis B. MORPHOLOGIC FEATURES OF CHRONIC INFLAMMATION Infiltration with mononuclear cells such as D. GRANULOMATOUS INFLAMMATION macrophages, lymphocytes, and plasma cells A form of chronic inflammation characterized by Tissue destruction collections of activated macrophages often with T Attempts at healing such as connective tissue lymphocytes and sometimes associated with central replacement accomplished by angiogenesis and fibrosis necrosis Cellular attempt to contain an offending agent that is difficult to eradicate Epithelioid macrophage fuse to form giant cells ○ Epithelioid macrophages: activated macrophages that develop abundant cytoplasm and resemble epithelial cells. Types of Granuloma: ○ Foreign body: caused by inert foreign bodies with NO T-cell mediated immune response Morphologic Features of Chronic Inflammation. ○ Immune: caused by persistent T-cell response C. CELLS AND MEDIATORS OF CHRONIC INFLAMMATION These include macrophages, lymphocytes, and other cells such as eosinophils, mast cells, and neutrophils 1. MACROPHAGES Dominant cell in most chronic inflammatory reactions Secrete cytokines and growth factors Two major pathways: ○ Classical ○ Alternative Examples of Diseases With Granulomatous Inflammation. IV. SYSTEMIC EFFECTS OF INFLAMMATION Classical and Alternative Macrophage Activation. A. FEVER Caused by prostaglandins 2. LYMPHOCYTES LPS stimulate leukocytes to release cytokines such as IL-1 and TNF Microbes and other environmental antigen activate T PGE2 stimulates the production of neurotransmitters and B lymphocytes, which amplify and propagate that reset the temperature set point at a higher level. chronic inflammation Pathology - Mod 1 MOD1-PATHO-Inflammation and Repair 4 of 6 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited. B. ACUTE-PHASE PROTEINS STEPS IN SCAR FORMATION Mostly synthesized in the liver C-reactive protein: stimulated by IL-6 Vasodilatation (NO) and Fibrinogen: stimulated by IL-6 increased permeability Serum amyloid A: stimulated by IL-1 or TNF (VEGF) Acts as opsonins and fix complement Separation of pericyte, breakdown of basement C. LEUKOCYTOSIS membrane Migration of EC to the site of V. TISSUE REPAIR 1 Angiogenesis injury Restoration of tissue architecture and function Proliferation of EC AFTER injury Remodelling Two types of reactions: Recruitment of pericytes ○ Regeneration: replacement of injured cells by Suppression of EC proliferation of cells or tissue stem cells proliferation and deposition ○ Connective tissue deposition: replacement of of BM. injured cells by connective tissues Migration and proliferation of fibroblasts and deposition of loose connective tissue, together with the vessels and interspersed leukocytes. TGF-β Formation of ○ Stimulates fibroblast 2 granulation migration and tissue proliferation ○ Increase synthesis of collagen and fibronectin ○ Decreased degradation of ECM by inhibiting metalloproteinases Balance between synthesis and degradation of ECM Remodeling of Matrix metalloproteinase- 3 connective include interstitial tissue collagenase, gelatinase, stromelysin Tissue Repair. B. FACTORS THAT INFLUENCE TISSUE REPAIR A. SCAR FORMATION Infection Diabetes SCAR FORMATION Nutritional Status Glucocorticoids 1 Injury to a tissue Mechanical factors Poor perfusion 2 Induces inflammation Foreign bodies Type, extent, location of tissue injury 3 Clearing of dead cells and microbes VI. HEALING OF SKIN WOUNDS 4 Formation of granulation tissue A. HEALING BY FIRST INTENTION 5 Deposition of extracellular matrix to form the scar Involves only the epithelial layer Healing of a clean, uninfected surgical incision approximated by surgical sutures 3 processes: ○ Inflammation ○ Proliferation ○ Maturation B. HEALING BY SECOND INTENTION Cell or tissue loss is more extensive Large wounds, abscesses, ulceration, ischemic necrosis in parenchymal organs Repair process involves regeneration and scarring C. HEALING BY SECOND INTENTION Scar Formation. Inadequate formation of granulation tissue (e.g., wound dehiscence and ulceration) Pathology - Mod 1 MOD1-PATHO-Inflammation and Repair 5 of 6 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Excessive formation of the components of repair (e.g., hypertrophic scars and keloid) Exuberant granulation (e.g., blocking of reepithelialization) Contractures Pathology - Mod 1 MOD1-PATHO-Inflammation and Repair 6 of 6 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.