Help
Options
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't Know
Remaining cards (0)
Know
retry
shuffle
restart
0:00
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
Inflammation
BMS263
| Term | Definition |
|---|---|
| Signs of Inflammation | Redness, Heat, Swelling and Pain |
| Cause of Inflammation Symptoms | Increased vasodilation & local blood flow, increased local vascular permeability, excess local interstitial fluid compressing nerves, & chemical mediators of inflammation activate nociceptors |
| Benefits of Inflammation | Increased local blood flow and permeability of blood vessels allows migration of leukocytes, entry of chemical mediators, destruction of invading microbes & deposition of fibrin to isolate damaged tissue to inhibit further invasion of microbes |
| Stages of Tissue Healing | Coagulation, Inflammation, Migration and Proliferation, Remodeling |
| Vasodilation | Vasodilation of arterioles, capillary beds opens, increasing permeability. Protein-rich fluid enters tissue (dilutes noxious agents) decreasing fluid inside blood vessel (more RBC, platelets, & clotting factors, slower blood flow, increase blood clotting) |
| Vascular Permeability | Formation of endothelial gaps primarily in venules. Chemical mediators bind to endothelial cell receptors & stim endothelial cell contraction. Separation of intercellular junctions. allowing leukocytes & chemical mediators into damaged tissue |
| Regeneration | Damaged tissue replaced with same tissue |
| Scar Formation | Damaged tissue replaced by connective tissue |
| Tissue Repair | May involve regeneration or the formation of scar tissue. Whether or not regeneration or scar formation occurs depends upon the extent of damage & the tissue damaged |
| Tissue Healing | Allow regeneration &/or form a scar to replace damaged tissue. Superficial wounds more likely to involve regeneration. More tissue types destroyed, more difficult repair will be = scar |
| Platelet Activation | Activated platelets release many proteins (over 300). Many of these proteins are thought to stimulate inflammation. Some known potent inflammatory mediators. Increase vascular permeability & stimulate chemotaxis & extravasation of leukocytes |
| Inflammation | Damaged cells release inflamm mediators. These stim leukocyte infiltration & inflamm. Destroys invading pathogens & fence off damaged tissue. Clean up cell debris in preparation for repair (phagocytosis). Macrophages ‘resolve’ inflamm & initiate healing |
| Migration and Proliferation | Overlaps with inflamm stage. Cells involved in replacing damaged tissue prolif & migrate into wound. Allow regeneration &/or scar tissue to form. Fibroblast prolif. Capillary growth, macrophage and mast cell activity |
| Remodelling | Conversion of initial granulation tissue to scar tissue. Collagen synthesis increases & fibroblast proliferation slows. Vascular degeneration occurs. Scar tissue forms that contains dense EC material, mainly consisting of densely packed collagen fibres |
| Haemostasis | Prevention of Blood Loss |
| Cellular Changes of Inflammation | Migration of leukocytes into the inflamed area- Phagocytes (neutrophils & then macrophages), Lymphocytes (to subsequently allow adaptive immunity). Must attach to blood vessel wall to extravasate |
| Leukocyte Adhesion Deficiency | Leukocytes are unable to adhere to endothelial cells. Therefore they can’t efficiently extravasate into underlying tissue. Very susceptible to infections. LAD type I is a hereditary congenital defect in an attachment molecule (integrin) |
| Endothelial Cells & Inflammation | Selectively permeable barrier. Regulate leukocyte extravasation. Release inflammatory mediators. Regulate immune cell proliferation (secrete haematopoietic colony-stimulating factors (CSFs)). Tissue repair |
| Inflammatory Chemicals | Cytokines (attract & activate leukocytes & simulate immune reactions, IL-1 & TNF-a), Prostaglandins & Leukotrienes, Histamine, Complement, Kallikrein/kininogen/kinin system Fibrin |
| IL-1 & TNF-a | 2 important cytokines with different functions. Important to both local & systemic inflamm. Major source of both is macrophages. Both are pyrogens. Act on endothelial cells, stimulate leukocyte adhesion, release of chemotactic factors, & other cytokines |
| Prostaglandins | Synthesised from cell membrane phospholipids. Cycloxygenase (COX) pathway produces it. Stim inflam (including fever) & enhance effects of histamine & other chemical mediators. Normally inhibit gastric acid secretion & protect mucosal lining of GI tract |
| Leukotrienes | Synthesised from cell membrane phospholipids. Lipoxygenase pathway produces it. Increase venule permeability, & leukocyte extravasation & chemotaxis. Also stimulate bronchoconstriction & are thought to be important in asthma |
| Histamine | Released from activated mast cells, basophils, & platelets. Stimulates vasodilation, increased vascular permeability & smooth muscle contraction (occurs in most smooth muscle, but not VSMC) |
| Complement | Stimulates vasodilation. Increases vascular permeability. Promotes leukocyte adhesion, chemotaxis & activation. Increases phagocytosis (opsonisation of antigens) |
| Kininogen/ Kinin System | Kinins are produced from plasma proteins. Kininogens --> Kinens. Stimulate vasodilation. Increase vascular permeability (hypotension). Stimulate nociceptors. Attract neutrophils. Activate coagulation & fibrinolysis. Bronchoconstriction e.g. Bradykinin |
| Kinins | Important mediators of pain, inflammation & blood clotting. Bradykinin in particular is important for increasing vascular permeability and pain |
| Fibrin | Converted from fibrinogen. Forms a mesh-like network of filaments that trap cells to cause coagulation and wall off damaged tissue (outside of blood vessels). Some wounds, lot of fibrinogen enters damaged tissue (fibrinous exudate) |
| Effects of Inflammation | Causes pain, can impair function (Temporary or permanent loss of function caused by oedema &/or tissue damage). Can be more damaging than the infection or original tissue damage that initiated it. May prolong & exacerbate injuries |
| Oxygen Free Radicals | Released from leukocytes after exposure to microbes, cytokines, immune complexes & during phagocytic process. Highly reactive chemicals can attach to other molecules. Can amplify inflamm. High levels will damage cells |
| Acute Local Inflammation | Inflamm of short-duration in 1 area initiated by harmful stimuli & injury. Severity of reaction depends upon cause. Substantial area of necrotic tissue abscesses or ulcerations develop. Can progress to chronic inflam |
| Purulent | Containing pus |
| Chronic Local Inflammation | Last from wks to yrs. May develop from originally acute inflam response,or low-grade but continuous response. Usually involves tissue necrosis & more fibroblast prolif (fibrosis & scaring) & vascularisation. 2 types: Non-specific & Granulomatous |
| Non-Specific Chronic Inflammation | Diffuse accumulation of macrophages & lymphocytes. Fibroblast proliferation. Scar tissue forms, replacing normal tissue e.g, chrones |
| Granulomatous Inflammation | Discrete mass of macrophages surrounded by lymphocytes. CT surrounds & isolates mass. Caused by foreign bodies that are not easily digested by phagocytes, or controlled by other inflamm mechanisms e.g asbestos |
| Systemic Inflammation Symptoms | Fever (leukocytes release pyrogens), lethargy (cytokines affect CNS), muscle loss, sore lymph nodes, increase in WBC numbers, production of pro-inflammatory molecules & more fibrinogen by the liver, hypotension & shock |
| Systemic inflammatory Response Syndrome | Occurs if levels of chemical mediators increase too much. Release high amounts of IL-1 and TNFa into systemic circulation. Sudden & big increase in vasodilation & vascular permeability through body. Loss blood V & hypotension leading to shock e.g. sepsis |
| Systemic Inflammation Process | Leukocytosis (increase in neutrophils), liver synthesis of factors involved in innate immunity increases substantially. Fibrinogen. C-reactive protein (bind to pathogens to induce phagocytosis & stimulates complement to destroy microbes) |
| Rheumatoid Arthritis | An autoimmune disorder. Primarily destroys joints due to chronic joint inflam & abnormal prolif of synovial tissue. Genetic predisposition & immunological trigger. Synovial inflam & joint damage (reduced joint motion/ joint fusion). Formation of pannus |
| Rheumatoid Arthritis Effects | Usually systemic inflam & symptoms involved. Initially, general fatigue, weakness, aching & stiffness. Gradually more systemic effects e.g. Inflam of arteries, dryness of mucosal membranes, ulcerations & neuropathy, pulmonary fibrosis, pericarditis |
| NSAIDS | ‘Traditional’ (inhibit COX1 & 2) & Coxibs (more selective for COX2). Include Aspirin, Ibuprofen & Paracetamol. 3 main functions: 1. Analgesic - Pain relief. 2. Anti-inflam (Decrease vasodilation, not leukocyte migration) 3. Antipyretic - Reduces fever |
| Action of NSAIDS | Inhibit cyclo-oxygenase (COX) enzymes which inhibits the production of prostaglandins & thromboxanes. 2 main isoforms of COX enzyme (COX1 & COX2) Classical inhibit COX 1 & 2. Some are “selective” & primarily inhibit only COX1 or 2 |
| Inhibition of Prostaglandins | Inhibit IL-1 stim pyretic activity. Decrease nociceptor sensitivity to inflamm mediators like bradykinnin. Decrease inflamm vasodilation (decrease blood flow, oedema & cerebral vasodilation Can decrease fever, pain & swelling assoc with inflamm |
| Inhibition of Thromboxane | Inhibits platelet activity & timulation of vascular spasm by platelet activation etc. Inhibit platelet plug formation & blood clotting. Decreases the risk of thrombosis & formation of emboli but increases the risk of uncontrolled bleeding & haemorrhage |
| Action of COX1 | Constitutive enzyme. Expressed in most tissues. Many ‘house-keeping’ roles. Protection of gastric mucosa. Platelet aggregation Renal blood flow |
| Action of COX2 | Expression induced in inflammatory cells when they are injured, infected, or activated. Production of inflammatory mediators. Constitutive in some tissues (e.g. CNS) |
| Common Unwanted-Effects of NSAIDS | Gastric irritation. Effect on renal blood flow in compromised kidneys. Prolonged bleeding - inhibition of platelets. Skin reactions. Increased hypertension risk (thrombosis, MI & stroke*). Long-term continual use can produce rheumatoid arthritis |
| Gastric Irritation | Inhibit prostaglandins activity in GI tract, protection of mucosal lining is lost. Increase risk mucosal damage & ulcers. Often asymptomatic. Increase risk of bleeding or perf. COX2 selective inhibitors cause less GI damage. May decrease healing ability |
| Reduced Renal Blood Flow | Prostaglandins involved in maintenance of renal blood flow (RBF). PGE2 mediates vasodilation in response to noradrenaline & angiotensin II. Block this, RBF wont increase. Can cause abnormal reduction in RBF & cause acute renal failure. Low risk for most |
| DMARD (Disease Modifying Anti-Rheumatic Drugs | Used for rheumatoid arthritis (RA). Slow onset (months). Combo of drugs used. Reduce # swollen & tender joints + progression of damage & plasma concentration of markers of RA. Decrease pain. Allow decrease in use of other drugs (NSAIDs or glucocorticoids) |
| Gout | High uric acid levels in blood. Insufficient excretion of uric acid in urine. Urate crystals form in joints stimulating inflamm. Treat acute attack (NSAIDS), then treat underlying uric acid accumulation (Drugs inhibit uric acid synth & increase excretion) |
| Glucocorticoids | Inhibit inflam by stim synthesis & release of anti-inflammatory proteins & blocking activity inflam cells. Inhibit cell-mediated immunity (inhib cytokine synthesis). Affect expression of MANY genes. Potent. Used for autoimmune disease & transplant reject |
| Unwanted Effects of Glucocorticoids | Mostly to do with metabolism. Includes: Cushing’s syndrome, Osteoporosis, Hypergylcaemia, Muscle wasting, Inhibition of growth in children, CNS effects (euphoria, mood swings), Acute adrenal insufficiency . Effects are worse with long-term & high dose |
| Cushing's Syndrome | Caused by excessive exposure to glucocorticoids. Symptoms include: Osteoporosis, moon face, euphoria, buffalo hump, increased abdominal fat, muscle wasting (thin arms & legs), easy bruising, poor wound healing, increased infection susceptibility |
| Acute Adrenal Insufficiency | Sudden withdrawal after prolonged treatment of glucocorticoids. Decreased endogenous ACTH levels. Endogenous corticosteroid synthesis inhibited. Endog adrenal androgens decrease. Cytokine & prostaglandin levels increase. Effects on CNS. Aldosterone normal |
| Acute Adrenal Insufficiency Symptoms | Fever, Headache, Diarrhoea, cramping, vomiting &/or nausea, Weakness and fatigue, Hypotension, Depression, Vitiligo (depigmented patches of skin), Desquamation |
| Glococorticoid Pharmacokinetics | Some systemic, some topical (Oral, Intra-articular, nasal sprays, eye/nasal drops, creams & ointments). Topical reduce side-effects. Metabolised in liver. Small, lipophilic molecules (simple diffusion BUT often bound by transport proteins in plasma) |
| Anti-Cytokine Drugs | Allow some specificity. Block specific step in inflam or adaptive immune response. Recombinant proteins. Expensive. Admin by SC injection or IV. Targets TNFa, IL-1 & 2, Leukocyte receptors. Many cause hypersensitivity or mild GI symptoms |
| Opsonins | Molecules that enhance phagocytosis by marking an antigen for an immune response or marking dead cells for recycling |
Created by:
Mandyrox300
Popular Pharmacology sets