Class Notes (838,052)
Canada (510,627)
Nursing (97)
NURS 2090 (20)
Lecture

Inflammation and Tissue Repair.docx

18 Pages
172 Views
Unlock Document

Department
Nursing
Course
NURS 2090
Professor
Heather Helpard
Semester
Fall

Description
Inflammation and Tissue Repair Goals of inflammation 1. Vascular Response- Increase blood flow to the site 2. Cellular Response- Increase healing cells at the site 3. Repair- Prepare for tissue repair (remove injured tissue) Lines of Defense First: Skin and mucous membranes. Areas not covered by skin are covered by chemically coated mucous membranes that neutralize/ destroy invaders. Second: Inflammatory response. Activated when first line is not adequate. It’s a non specific response. Inflammatory response is identical regardless of cause. Third: Immune response. Specific defense. 1. Vascular Response to Injury (increase in blood flow) • Facilitated by chemical mediators • Induces vasodilation (to accommodate ↑ BF) • Increased capillary permeability/ BM loosens to allow cells to injured tissue • Acute inflammation is triggered by tissue injury (damage = alteration to cells and tissues- invasion by microorganisms, cellular mutations, hypoxia, nutritional deficiencies, physical or chemical damage) Increased BF needed: 1. Phagocytosis/ promote healing 2. Dilute harmful substances - Response at the blood vessel near the site of injury; blood vessels dilate or widen to accommodate increased blood flow to the site; - the lining of the blood vessel is more permeable to allow cells to move from the vessel into the injured tissues. -This loosening occurs at the basement membrane of the blood vessel and adjacent endothelial cells; the vessel is separated from the tissues of the body. The vessel walls are needed to confine blood cells and plasma, but the injury must be loosened to allow for movement of healing fluids and cells into damaged tissues. - Watery exudate that accumulates at the site of injury has a high protein and leukocyte concentration; sign that the vessels are more permeable and that cells active in phagocytosis (engulfing and removing harmful agents) and ready to fend off microorganisms. The whole process is caused by inflammatory mediators: - specifically vasoactive inflammatory mediators - facilitate the process of widening and loosening of blood vessels at the site. - located in the blood plasma and in many cells, including platelets, mast cells, basophils, neutrophils, endothelial cells, macrophages and monocytes. Inflammatory Mediators Cell-derived Plasma-derived -white blood cells -Complement system -platelets -Kinin system -endothelial or damaged tissue cells -Clotting system - Some inflammatory mediators are formed within blood plasma and some are formed within cells (most in cell plasma membrane or made up of proteins in the cell). - Most commonly it is the WBC that produce and release inflammatory mediators, platelets, endothelial cells and injured cells are also potential sources. Mast cell / Basophil - They are leukocytes that are housed in the connective tissues of the body and near all blood vessels. (their placement allows for rapid response) - Responsible for the production and immediate release of inflammatory mediators through the process of degranulation: where mast cell breaks apart and releases inflammatory mediators in the form of grain like particles Inflammatory mediators released by mast cells: histamine, leukotrienes and prostaglandins Signals to trigger, enhance and discontinue the inflammatory response are also generated by lymphocytes, monocytes, macrophages. Cytokines: more than 100 distinct proteins found in white blood cells that have a role in regulating inflammation - active through the whole process -examples: interleukins, growth factors, interferons, chemokines Platelets: active in generating and releasing inflammatory mediators to promote vasodilation, clotting, attraction of WBC and healing of injured tissues - Serotonin/Histamine is a mediator found in platelets (vasodilation and increased vascular permeability). Endothelial cells or injured tissue cells- can release inflammatory mediators: 1. Platelet activating factor: in the cell membrane- vasodilation, clotting, attracting WBC to site of injury 2. Arachidonic acid: from plasma membrane of injured cell - Stimilates inflammatory mediators through chemical conversion. - Includes: prostaglandins, lipoxins, leukotrienes and thromboxane - Processes of vasodilation and vasoconstriction, increased vascular permeability, bronchodilation and bronchoconstriction and attraction of leukocytes - Corticosteroids block this acid (therefore decrease the inflammatory response) In Plasma - Impaired activiation of inflammation can lead to inadequate blood flow; impairing phagocytosis, clot formation and repair. - Impaired inhibition of the inflammatory response: uncontrolled; depletion of proteins for the pathways; and leads to autoimmunity (A self attack against body tissues). - Proteins are needed in the complement pathway (produced in the liver; triggered by presence of microorganisms; make bacteria vulnerable to phagocytosis and cell lysis) clotting (promotes coagulation through a cascade of clotting factors; suppresses coagulation when clotting complete, various clotting factors release inflammatory mediators) kinin (highly potent vasoactive inflammatory mediators and triggers other inflammatory mediators) 2. Cellular Response: Once the vessels are dilated and permeable, the cells essential for healing are needed at the injury site; the cellular response is regulated by inflammatory mediators. 1. Chemotaxis- the process of moving certain cells to the site of injury - Chemotactic factors are activated to attract specific cells (neutrophils; eosinophils) 2. Cellular adherence- means attraction or binding for effective phagocytosis - Regulated by: 1. chemotactic factors released by endothelial cells; 2. receptors that bind leukocytes to the surface of endothelial cells near the site of injury 3. Cellular migration- depends on ability of cells to migrate or move across epithelial cells and to get to the exact site of injury (primarily leukocytes, erythrocytes and platelets) Diapedesis : Cells can move between and through epithelial junctions Leukocyte: global term for many kinds of WBC. Phagocytosis: removal of dead tissue; Neutrophils: earliest phagocytic responders; Macrophages: a type of white blood cell; large long lived phagocytes associated with prolonged chronic inflammation; Monocytes: immature macrophages. Erythrocytes: carry oxygen to tissues Platelets: trap harmful substances; stop bleeding; form structural organ of repair. ** Tissue destruction is minimized by the work of the inhibitor proteins in the plasma derived complement, clotting and kinin systems. General Manifestations: mostly due to vasodilation/ ↑BF • Erythema (redness) • Heat • Swelling • Pain - accumulation of fluid/compression tissues • Lymphadenitis (enlargement of nearby lymph nodes filtering and draining micro- organisms) • Pyrexia- fever (which stimulates phagocytosis and inhibits growth of microorganisms) • Leukocytosis (elevation of WBC in lab work) normal= 5-10,000 - demonstrates the increased circulation of WBC to aid in healing • Incapacitation: related to damage, pain and swelling Blood Tests: Acute Inflammation • WBC: elevated with increased WBC circulation • WBC count differential: measures proportions of the five types of white blood cells • ESR: elevated for red blood cell clumping or stacking (due to increased fibrinogen which causes cells to stick together) • CRP: elevation for significant inflammatory disease (shows presence of a protein triggered during the inflammatory process) • PT: elevated result in a reduced time to coagulate Treatment of Acute Inflammation Drug intervention goal is to block inflammatory mediators to reduce swelling, pain redness & warmth: • Aspirin: inhibits conversion of arachidonic acid to prostaglandins to suppress inflammation, reduce pain and fever • NSAIDS: similar to aspirin: ibuprofen and naproxen • Glucocorticoids: inhibit synthesis of chemical mediators and reduce pain, warmth, redness and swelling; suppress infiltration of phagocytes and avert tissue damage from release of lytic enzymes, reduce immune component of inflammation Initial TX Principles: (RICE: Rest, ice, compression, elevation) 1. Reduce blood flow to area 2. Decrease swelling 3. Block the action of inflammatory mediators 4. Decrease pain 3. Healing and Tissue Repair Clotting Factors Stop bleeding and form fibrin clot Inflammatory mediators Promote chemotaxis to affected area Proteinases (enzymes) Degrade dead tissue Proteinase inhibitor Prevent healthy tissue break down Matrix proteins Rebuilds structural supports Molecule Receptor Attract cells needed to form matrix Adhesion molecules Provides stickiness to cells Growth factors Promote regeneration of new cells and tissues 1. Inflammatory phase: 1. Acute inflammatory response 2. Cover the wound- hemostasis: platelets releases, blood vessel constriction, thrombus forms - inflammatory mediators are released from the platelets and other cells constrict blood vessels and form a clot at the site (a protective scab: called a thrombus) - The role of the thrombus is to form a physical barrier for protection and prevents the loss of plasma. - Epithelial skin cells regenerate under the thrombus - Once this is complete; the enzymes degrade the scab. 2. Proliferative phase: 1. Clean the debris- remove necrotic tissue - chemical mediators activate the neutrophils to move into the injured area and begin the work of healing (neutrophils/ macrophages engulf, digest and remove harmful substances and debris) - healing cannot begin until necrotic cells and tissues are removed. 2. Restore Structural Integrity- formulates provisional matrix/granulation tissue, and rebuild ECM (includes BM/ Connective tissue) - depends on the balance of tissue destruction and construction - ECM building depends on growth factors and matrix proteins Basement Membrane: (must be restored before re-epithelialisation can occur) 1. Provides supportive architectural support 2. Supports Re-epitheliaziation (movement of epithelial cells to form a covering over the wound) 3. Store growth factors 4. Restore neuromuscular function 5. Support development of parenchymal tissue (tisses made of cells with specific fx, ie. Neurons, myocardial cells, epithelial cells) Connective Tissue: (aka. Stromal/ interstitial tissue) - Collagen, elastin and glycoprotein Provides: 1. Storage of proteins, 2. Architectural support and physical protection from trauma 3. An exchange medium btw proteins and other cells Cells that stimulate replacement of connective Tissue: FIBROBLASTS 1. Fibroblasts - Stimulated by macrophages. - Actively manufacture/secrete collagen (which helps fill the gaps left after removal of damaged tissues). ** excess collagen leads to tissue fibrosis and scarring Elastin: allows stretching and recoil of tissue - resistant to damage, but slow and difficult to replace ** less flexible after injury Glycoproteins: are essential with the basement membrane 1. Regulate cell movement across the matrix 2. Provide a place for attachment of cells to the matrix 3. Prompt cells to function provisional matrix: is a temporary matrix that forms in response to injury. - decreases blood and fluid loss at the site. - attracts fibroblasts, endothelial cells and epidermal cells - Macrophages convert this into granular tissue (tissue with macrophages/ fibroblasts, and promotes angiogenesis, promotion of new blood vessels) 3. Remodelling: 1. Restore functional integrity- Resolution, Regeneration, Replacement Resolution- healing in response to mild injury with minimal disruption to the cells (i.e. small scratch). Healing is rapid and ‘business as usual’ Regeneration-occurs in celss that undergo mitotic division 1. Proliferation: growth and reproduction 2. Differentiation: cells mature and become more specialized 3. Diapedesis: migration of nearby cells 2. Remodeling- maturation of cells, degradation of provisional matrix Labile cells- cells that constantly regenerate, like epithelial Re-epithelialization- When basal cells are re-established through mitosis - requires the presence of a basement membrane. Skin cells at the periphery of the wound undergo mitosis and micrate inward until the process is complete. Stable cells: cells that stop regenerating when growth is complete, but can resume if injured. Replacement: through the production of scar tissue in extensive wounds when regeneration is not possible; Permanent cells: Cells that do not undergo mitosis and are unable to regenerate. i.e. neurons, cardiac myocytes, lens of the eye. - When these cells are damanged they are replaced with connective tissue (scar tissue) - Does not function as before. Healing: Primary Intention: the wound is basically closed with all areas of the wound healing simultaneously Secondary Intention: heal from the bottom up. More prone to infection and scaring Chronic Inflammation - Recurrent or persistent inflammation lasting several weeks or longer - Monocytes, macrophages and lymphocytes more prominently involved - Formation of granulomas and scarring often occur - Occurs when acute inflammatory and immune responses are unsuccessful. Can be related to an unrelenting injury, persistent infectious process, or an autoimmune condition (when body identified self cells as foreign) - Monocytes mature into macrophages in the tissues; producing proteinases (which destroy elastin and other tissue complements). These enzymes don’t discriminate, and kill healthy tissue at the area and surrounding skin. - Fibroblasts are also involved, which are responsible for collagen development and contribute to scarring (which leads to loss of fx and deformity). Granulomas : Are nodular inflammatory lesions that encase harmful substances. - They are regulated by macrophages - Form when injury is too difficult to control by usual inflammatory processes and immune mechanisms - Example mycobacterium tuberculosis: by forming a granuloma, macrophages are able to protect surrounding tissue from damage. Macrophages adapt into giant cells/ epithelioid cells that phagocytise particles. As a result, necrosis fills the inside of the granuloma. Gradually, the necrosis diffuses through the granuloma wall and a fibrotic capsule remains. Symptoms :  fever  anorexia  malaise  weight loss  anemia  weakness  fatigue Complications of Healing 1. Infection: invasion by microorganisms which destroys the first line of defense and leads to poor inflammatory and immune response -This impairs wound healing - Tissue healing needs adequate perfusion (oxygenated blood to the site) or ulceration can occur 2. Ulcers: are circumscribed, open and craterlike lesions of the skin or mucous membranes These areas are necrotic and open to further invasion by microorganisms.Resistant to healing because of lack of perfusion to the site and persistant habitation by microorganisms ***Ulcers are a common cause of gastritis 3. Dehiscence: problem of deficient scar formation; in which the wound splits or bursts open, often at the suture line. Opens area to microorganisms. Possible complication post surgery due to movement and coughing Often caused by poor development of extracellular matrix and ineffective or inadequate collagen 4. Keloid: hypertrophic scars that result from excessive collagen production at the site of injury. Hi
More Less

Related notes for NURS 2090

Log In


OR

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


OR

By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.


Submit