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82 Cards in this Set
- Front
- Back
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A few examples of harmful or potenitally fatal inflammatory responses
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Asthma
Atherosclerosis Anaphylaxis to drug or insectbite Pericarditis-->pericardial effusion-->Cardiac tamponade rheumatoid arthritis |
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Acute inflammation
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-duration=minutes-days
-fluid and protein from blood--->into tissues -NEUTROPHILS infiltrate the tissue (come and try to resolve the situation, and dilute whatever the toxin is, adn isolate and kill things off) -Inflammation usually resolves with little or no damage |
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Chronic inflammation
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-Duration=days-years
-LYMPHOCYTES & MACROPHAGES infiltrate the tissue -casues tissue DESTRUCTION -tissue repair by FIBROSIS and NEOVASCULARIZATION (sccarred tissue) |
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3 main components of acute inflammation
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1. local hyperemia: red, warm
2. vascular permeability: swollen and painful 3. Leukocyte emmigration |
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Critical function of the acute inflammatory response
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to deliver neutorphils to the site of injury in order to destroy invading microbes. neutrophiles may prolong the inflammation and induce tissue damage by releasing enzymes, free radicals and chemical mediatiors.
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Local hyperemia
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ARTEROILAR VASODILATION--site becomes red and warm.
more RBCs to the site, meaning more neutrophils to the side. vasodilation causes and increase in the flow volume, but decrease in the flow velocity. |
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Vascular permeability
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structural changes int he microvasculature permit leakage of water, plasma proteins, and neutrophils into the tissue---site becomes painful and swollen
-release of histamine from the mast cells surrounding the vessels contributes to endothelial cell leakiness. this enhances the loss of fluid into the tissue, thereby increasing blood viscosity, and slowing the rate and permitting stasis of blood cells along the endothelial wall |
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What kind of things cause leakiness?
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direct exogenous injury from mechanical impact, burns, bacterial toxins, or endogenous factors such as ischemia/hypoxia
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Direct exogenous injury from mechanical impact, burn or bacterial toxins or endogenous factors such as ischemia/hypoxia cause the release of
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histamine
bradykinin leukotriens IL-1 TNF (these chemical mediators of inflammation aggravate leakiness mainly in the venules-->endothelial intercellular leakage and edema) |
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Histamine, Bradykinin, Leukotriens, IL-1, and TNF
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chemical mediators of imflammation that aggravate leakiness mainly in the venules.
end result is endothelial intracellular leakage and EDEMA |
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Leukocyte emmigration
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accumulation, leakage and subsequent movemnt of neutrophils into the tissues--complex process.
as blood flow slows, laminar flow decreases--stasis develops, permitting increased contact of neutrophils with the endothelial cells. neutrophils stick transiently, roll along the endothelial cells, adhere and emigrate by DIAPEDESIS between retracted endothelial cell junctions (mainly in the venules) |
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How do neutrophils emigrate?
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they stick transiently, roll along the endothelial cells, finally adhere and emigrate by DIAPEDESIS between retracted endothelial cell junctions (mainly in Venules)
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After the neutrophils get into the tissues, how do they move toward the site of injury?
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they move along gradients of chemotactic factors ("chemical junk")
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When the neutrophils bind to chemotactic factors (chemical junk) what occurs?
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enhances the neutrophils' mobility and initiates new neutro tricks
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leukocyte activation
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--->Arachidonic acid---> prostaglandins and leukotrienes
also -->phagocytosis & lysosome degranulation ---> lysosomal enzyme and free radicals *all very imflammatory things |
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Vasoactive amines
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histamine found in mast cells & circulating basophils and platelets.
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Histamine
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exists in granules
-causes ARTERIOLAR DILATION, VENULAR LEAKAGE & EDEMA |
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Degranulation of histamine
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occurs in response to a variety ofstimuli, such as trauma, immune reactions in which IgE binds mast cells
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Eicosanoids
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-Prostaglandins and leukotrienes
-produced by Arachidonic acid in 2 seperate pathways cyclooxygenase pathway: prostaglandins lipoxygenase pathway:leukotrienes |
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Leukotriene and prostaglandins
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eicosanoids produced by AA.
-induce fever, pain, edema, vasodilation and bronchospasm |
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leukotrienes
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several thousand times more potent than histamine in their ability to cause increased vascular permeability and bronchospasm
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treatment of pain and inflammation
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NSAIDs (non-steroidal anti-inflammatory drugs)
& Steroids |
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NSAIDs
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block the cyclooxygenase pathway (prodiction of prostaglandins)
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Steroids
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Block phospholipase-inducted production of AA
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Arachidonic acid
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Cell injury of C5a activates phospholipases, which chew up membrane phospholipids and release AA.
AA productes the eicosanoids (prostaglandins and leukotrienes) in 2 seperate pathways |
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Mast cell stabilizers
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Intal, Tilade
*used to treat asthma |
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Steroids (Inhaler)
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Vanceril
*used to treat asthma |
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latest asthma research efforts
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aimed at blocking the effects of leukotrienes
-Leukotriene receptor agonists (Accolate and Singulair) -5 lipoxygenase inhibitor (Zyflo) |
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Leukotriene receptor agonists
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-accolate and singulair
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5-lipoxygenase inhibitor
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zyflo
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Cytokines
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IL-1, IL-6 and TNF
-induce systemic inflammatory effects, or acute phase reactions, associated with injury or infections |
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IL-1, IL-6, TNF
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cytokines that induce ACUTE PHASE REACTIONS associated with injury & infx:
-fever, lethargy, decreased appetite, increased neutrophil count, ACTH RELEASE->corticosteroid release; hepatic synthesis of various proteins (acute phase reactants): complement, c-reactive protein and fibrinogen |
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fibrinogen and C-reactive protein
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acute phase reactants that are often used as diagnostic tools
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erythrocyte sedimentation rate test (ESR or sed rate)
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whole blood stands in a thin tube and the rate at which the RBCs settle is measures as the mm lenght of translucent plasma that develops at the top of the tube in 1 hr.
normal rate = 8-20 mm/hr Inflammation=increased levels of fibrinogen in the blood cause sed rate to increase significantly, even to 100 or more mm/hr |
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ESR
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non-specific test.
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normal ESR (sed rate)
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8-20 mm/hr
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ESR (sed rate) during inflammation
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could be up to 100 or more mm/hr.
(increased levels of fibrinogen in blood causes ESR to increase) |
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measurement of C-reactive protein
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done by immunologic methods.
--C-Reactive protein level rises very rapidly with onset of inflammation and clears rapidly as inflammation subsides -being useed to differentiate b/w viral and bacterial meningitis: viral meningitis: CSF-CRP increases bacterial meningitis: CSF-CRP goes MUCH HIGHER |
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TNF and subsequent NO production
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possible roles in the profound HYPOTENSIVE EFFECTS OF SEPTIC SHOCK (intense peripheral vasodilation and decreased myocardial contractility)
-Sepsosemia---vasodilation caused by NO, dilates vessels so much that it could lead to brain ischemia, local organs shut down due to loss of blood |
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NO
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synthesis is induced by TNF (a cytokine)
-most signifcant role is in VASODILATION septosemia-vasodilation causd by NO, vessels dilate so much that can lead to brain ischemia (local organs shut down due to loss of blood) |
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Lysosomal enzymes
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alpha1-antitrypsin counteracts elastase.
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alpha1-antitrypsin
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counteracts elastase. (smoking leads to emphysema by causing persistent, low grade inflammation, chronic release of elastase and dysfunction of the antitrypsin)
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homozygotic alpha1-antitrypsin deficiency
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emphysema is caused in the absence of smoking
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outcomes of acute inflammation
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1. complete resoultion
2. scarring 3. abscess formation 4. progression to chronic inflammation |
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complete resolution
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if injury is slight, lymphatic drainage and macrophages remove accumulated fluid, inflammatory cells and necrotic debris
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scarring
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fibrosis; occurs in tissues that can't regenerate parenchyma, or when tissue destruction is substantial
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abscess formation
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occurs when injury is due to PHYOGENIC BACTERIA, such as strep, staph, pneumococci, meningococci and H. influenzae
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progression to chronic inflammation
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may follow acute inflammation when the acute response cant be resovled, either because the injurious agent persists or because of interference iwth normal healing
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Chronic inflammation-characterized by:
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tissue infiltration with destruction by mononuclear (chronic inflammatory) cellls: macrophages, lymphocytes and plasma cells
-repair by fibrosis and neovascularization (angiogenesis) |
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In what settings are chronic inflammation seen
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persistent infx: syphilis, tuberculosis
prolonged exposure to toxic agents: silicosis, atherosclerosis autoimmune diseases- rheumatoid, systemic sclerosis, others -sarcoidosis |
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chronic inflammatory cells
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monocytes: 1/2 life of 1 day
macrophages: secret active substances that mediate microbe death and tissue destruction, angiogneesis and fibrosis typical of chronic inflammation lymphocytes: T and B lymphs emigrate to site of injury plasma cells: B lymphos Eosinophils: allergies, asthma |
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where do chronic inflammatory cells derive from?
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bone marrow stem cells
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what do chronic inflammatory cells circulate the blood as?
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monocytes with a 1/2 life of 1 DAY
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When a monocyte emigrates under the same influences and by teh same mechanisms as neutrophils.....
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it transforms into the larger tissue macrophages with a life span of a few months
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lymphocytes
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T and B lymphos emigrate to site of injury
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plasma cells
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B lymphos
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Eosinophils
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found at sites inflamed by parasites and IgE-mediated immune reactions, such as allergies and asthma
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Granulosmatous inflammation
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characterized by aggregation of activated macros that develop a squamous "epithelioid" appearance.
as the granuloma ages, it becomes surround by fibroblasts and connective tissue, seemingly to contain the injurious agent |
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Tuberculosis
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encysted lung tuberculi (caseating granulomas) and hard scrotal mass
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sarcoidosis
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non-caseating granulomas
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foreign bodies
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suture, breast impant, vascular graft
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silicosis
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slowly progressing fibrosis of the lungs due to long term exposure to silica dust
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net fluid loss into the tissue
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is taken up by small lymphatic vessels (who have less tight cell junctions than those in capillaries and venules)
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thoracic duct
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juntion of the left internal jugular vein and left subclavian vein
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right lymph duct
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at junction of right internal jugular vein and right subclavian vein
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where is lymph dumped back into venus return?
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either at the thoracic or right lymphatic duct
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Does the brain have lymphatics?
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No
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BBB (blood brain barrier)
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how the brain compensates for lack of lymphatics; the BBB are tighter endothelial cell junctions located in the brain capillaries
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What does the BBB do?
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it prevents normal net leakage of plasma proteins into hte brain parenchyma, and prevents exposure of the brain to every drug, toxin or hormone that comes by
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what moeities can penetrate the BBB without the assistance of an active transport system?
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water, oxygen, carbon dioxide, lipid-soluble substances (alcohol, anesthetics) all pass free
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Can electrolytes pass freely through the BBB into the brain?
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No, they permeate less freely (Na, K, and Cl) and other substances are either blocked entirely or need a special active transport system for them to penetrate BBB
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Is it easy to get therapeutic drugs into brain tissue?
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No, the BBB makes it difficult for therapeutic drugs to get into the brain tissue
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What is the most critical need for antibiotic penetration of the BBB?
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bacterial encephalitis (cerebritis). This also causes inflammation (which causes vascular permeability) so in this instance, antibiotics are able to penetrate the BBB
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In absence of brain inflammation, what antibitoic can penetrate the BBB and enter the brain tissue?
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Chloramphenicol
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Lymph flow during inflammation
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lymph flow increases and helps drain edema fluid, emigrated leukocytes, and cellular debris.
-also, a second line of defense: delivers antigents from the peripheral sites to monocytes and T& B lymphos. |
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How could the lymph vessels become inflamed?
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Lympathics provide channels for dissemination of injurious agens, which could in turn cause inflammation of the lympathics
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Lymphangitis
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inflammation of the lymphatics
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lymphadenitis, lymphadenopathy
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inflammation of a lymph node
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bacteremia
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when the lymph nodes are overwhelmed, bacteria may enter the blood
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what is the next line of defense after the lymphatics?
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mononuclear phagocytes of the liver, spleen and bone marrow
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If the mononuclear phagocytes of the liver, spleen and bone marrow fails, what could happen?
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Microbes might be seeded in:
-the heart valves (valvulitis) -kidney (pyelonephritis) -joints (septic arthritis) -meninges (meningitis) |
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morphological patterns in acute and chronic inflammation
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1. serus inflammation
2. fibrinous inflammation 3.suppurative (purulent) inflammation 4. ulceration |
