CHAPTER 14: 14: Inflammation, Tissue Repair, and Wound Healing Cardinal Signs of Inflammation Rubor (redness) Tumor (swelling) Calor (heat) Dolor (pain) Functio laesa (loss of function) • • • • •
Factors Involved in Protective Responses and Bodily Repair Inflammatory reaction: damage cells release inflammatory mediators which stimulate inflammation Immune response Tissue repair and wound healing •
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Causes of Inflammation Immune response to infectious microorganisms Trauma Surgery Caustic chemicals Extremes of heat and cold Ischemic damage to body tissues • • • • • •
Granulomatous Inflammation Associated with foreign bodies such as: splinters; sutures; silica, asbestos Associated with microorganisms that cause: Tuberculosis; Syphilis, sarcoidosis; deep fungal infections; brucellosis •
Vascular Changes that May Occur with Inflammation An immediate transient response response:: Occurs with minor injury An immediate sustained response response : Occurs with more serious injury and continues for several days and damages the vessels in the area A delayed hemodynamic response: response: Involves an increase in capillary permeability that occurs 4 to 24 hours after injury Cellular Stage of Acute Inflammation Phagocytic white blood cells enter the injured tissue: destroying infective organisms; removing damaged cells; releasing more inflammatory mediators to control further inflammation and healing Two types of leukocytes participate in the acute inflammatory response: Granulocytes (neutrophils, eosinophils, and basophils) Monocytes (the largest of the white blood cells) cells ) *The immediate effect of platelets to plug a wound; the function of both histamine from mast cells and serotonin from platelets in vasoconstriction and activation of further clotting mechanisms • •
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Direction of Cellular Response
Margination, adhesion, transmigration Cytokines: Adhesion molecules Selectins, integrins, and immunoglobulin Initiation of adhesion Aggregation of inflammatory cells Movement into underlying tissue *The interaction of adhesion molecules, chemokines, and cytokines in leukocyte adhesion, migration, and phagocytosis, which are part of the cellular phase of inflammation. *The cellular phase of inflammation is very tightly controlled by the c ytokines. Cytokines are chemical road signs that organize the response. •
Inflammatory Mediators Histamine Cytokines Arachidonic acid metabolites Eicosanoids (Prostaglandins; Leukotrienes; Omega-3 polyunsaturated fatty acids Platelet-activating factor Plasma proteins • • •
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Classification of Inflammatory Mediators by Function Those with vasoactive and smooth muscle–constricting properties Chemotactic factors such as complement fragments and cytokines Plasma proteases that can activate complement and components of the clotting system Reactive molecules and cytokines liberated from leukocytes, which when released into the extracellular environment can damage the surrounding tissue • • •
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QUESTION Which of the following molecules will induce endothelial cell retraction? A. Omega-3 fatty acids B. Leukotrienes C. Histamine D. VCAM ANSWER C. Histamine - Rationale: Histamine is the primary activator of endothelial retraction and increased permeability of the vessels. •
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Types of Inflammatory Exudates Serous Exudates: Watery Exudates: Watery fluids low in protein content; Result from plasma entering the inflammatory site Hemorrhagic Exudates: Exudates: Occur when there is severe tissue injury that causes damage to blood vessels or when there is significant leakage of red cells from the capillaries Membranous or Pseudomembranous Exudates: Exudates : Develop on mucous membrane surfaces; Are composed of necrotic cells enmeshed in a fibropurulent exudate •
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Purulent or Suppurative Exudates: Contain pus; composed of degraded white blood cells, proteins, and tissue debris Fibrinous Exudates: Contain large amounts of fibrinogen and form a thick and sticky meshwork
Basic Patterns of Inflammation Acute inflammation inflammation:: Of relatively short duration; nonspecific early response to injury; Aimed primarily at removing the injurious agent and limiting tissue damage Chronic inflammation: inflammation: Longer duration lasting for days to years; A recurrent or progressive acute inflammatory process or a low-grade smoldering response that fails to evoke an acute response •
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Chronic Versus Acute Inflammation Acute inflammation inflammation—self-limited and of short duration Infiltration of neutrophils Exudate Chronic inflammation—self-perpetuating and may last for weeks, months, or even years Infiltration by mononuclear cells (macrophages) and lymphocytes Proliferation of fibroblasts •
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Most Prominent Systemic Manifestations of Inflammation Acute-phase response Alterations in white blood cell count (leukocytosis or leukopenia) Fever Sepsis and septic shock (severe) • • • •
QUESTION Permanent cells, once damaged, can easily be regenerated and their functions recovered? True or False ANSWER False False - Rationale: Many Rationale: Many cells in the body cannot be replaced once they die. Neurons and cardiac cells are such examples. •
Types of Structures of Body Organs and Tissues Parenchymal: Tissues contain the functioning cells of an organ or body part ( e.g., hepatocytes, renal tubular cells) The Stromal Tissues: Consist of the supporting connective tissues, blood vessels, extracellular matrix, and nerve fibers •
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Types of Body Cells Labile: Labile: Continue to divide and replicate throughout life, replacing cells that are continually being destroyed Stable: Stable : Normally stop dividing when growth ceases Permanent Cells: Cells: Cannot undergo mitotic division •
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Healing by Primary or Secondary Intention The objective of the healing process is to fill the gap created by tissue destruction and to restore the structural continuity. Primary healing—small, clean wound Secondary healing—great loss of tissue with contamination •
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Basic Components of the Extracellular Matrix (ECM) Fibrous structural proteins: Collagen and elastin fibers Water-hydrated gels that permit resilience and lubrication: Proteoglycans and hyaluronic acid Adhesive glycoproteins glycoproteins that connect connect the matrix matrix elements to each each other and to cells: cells: Fibronectin and laminin Basic Forms of the ECM Basement Membrane: Surrounds epithelial, endothelial, and smooth muscle cells Interstitial Matrix: Matrix : Present in the spaces between cells the connective tissue and between the epithelium and supporting cells of blood vessels • •
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Stages of Wound Healing Inflammatory phase (healing process as cleaning out the wound) Proliferative phase (regenerating the missing or damaged tissue) Maturational or remodeling phase (maturation to regain function) • • •
Steps in Development of a New Capillary Vessel Proteolytic degradation of the parent vessel basement membrane, allowing for formation of a capillary sprout Migration of endothelial cells from the original capillary toward an angiogenic stimuli Proliferation of the endothelial cells behind the leading edge of the migrating cells Maturation of the endothelial cells and proliferation of pericytes (for capillaries) and smooth muscle cells (for larger vessels) •
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QUESTION Which of the following will promote wound healing? A. Malnutrition B. Increased blood flow and oxygen delivery C. Infection C. Infection D. Foreign bodies ANSWER B. Increased blood flow and oxygen delivery - Rationale: Increasing Rationale: Increasing blood flow and • oxygen delivery is one of the main objectives of the the inflammatory response. This will allow for greater energy production and faster removal of dead material. •
Factors Regulating the Healing Process Action of chemical mediators and growth factors that mediate the healing process Interactions between the extracellular and cell matrix • •
Two Phases of Scar Formation Emigration and proliferation of fibroblasts into the site of injury Deposition of the ECM by these cells * Explain the effects of malnutrition; ischemia and oxygen deprivation; impaired immune and inflammatory responses; and infection, wound separation, and foreign bodies on wound healing. No tissue functions well under these conditions, and wound healing is no different. • •
Causes of Impaired Wound Healing Malnutrition Impaired blood flow and oxygen delivery Impaired inflammatory and immune responses Infection Wound separation Foreign bodies Age effects • • • • • • •
