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105 Cards in this Set
- Front
- Back
When does repair begins in inflammation?
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At the early phases.
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Who are inflammatory connective tissue cells?
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MAST CELLS, fibroblasts, resident macrophages and lymphocytes.
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Where are Mast cells located?
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Connective tissue.
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Redness, swelling, pain, heat- symptoms of which inflammation?
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Acute.
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What causes Exudate (SG>1.020)?
What causes Transudate (SG<1.015)? |
Exudate: changes in permeability of small blood vessels.
Transudate: changes in hydrostatic/oncotic pressure. |
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What is pus?
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EXUDATE, rich in leukocytes (mostly neutrphiles), debris of dead cells and often microbes.
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What are some stimuli for acute inflammation I never think about?
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Blunt trauma
Burns Tissue necrosis |
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Which vessels are affected by vasodilation?
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First arterioles, and then you see opening of new capillary beds.
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What causes vasodilation in inflammation?
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Histamine and NO, that affect smooth muscle cells.
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What does the permeability cause?
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Loss of fluid -> concentration of RBC -> increased viscosity -> STASIS.
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What is the "immediate transient response"? Which vessel is affected?
(permeability) |
Permeability due to gaps between endothelial cells.
Venules. |
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How long does the immediate transient response last?
(permeability) |
15-30 minutes.
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Immediate transient response: which mediators cause it? What is the mechanism in each reponse?
(permeability) |
Histamine: contraction of endothelial cells (contractile proteins).
Cytokines: structural reorganization of cytoskeleton. |
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What is the difference between the effect of Histamine vs. Cytokines in the Immediate Transient Response?
(permeability) |
Cytokines requires reorganization of cytoskeleton, and thus take longer to and are more long-lived.
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What is the Immediate Sustained Reponse?
(permeability) |
Direct endothelial damage, causing necrosis and detachment.
(burns) Affects all microvasculature. |
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What is Delayed Prolonged Leakage?
(permeability) |
begins 2-12 hours, lasts for several hours/days.
(sunburn) |
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Where does Leukocyte-mediated endothelial injury usually occur?
(permeability) |
Vascular sites, like the glomerulus, where they can adhere for prolonged periods.
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What is Transcytosis?
What mediator cause it? (permeability) |
Channels consisting of interconnected, uncoated vesicles- mostly in venules.
VEGF. |
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What are the 3 phases of increased permeability in acute inflammation?
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1. Immediate transient response- venules- 30 min or less.
2. Delayed response, 2-8 hours. 3. After direct endothelial injuru: Prolonged response. |
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Can any endothelial cell bind leukocytes?
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No, it has to be activated (by histamine, PlateletActivatingFactor, thrombin).
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What causes margination of leukocytes?
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Blood stasis
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Where can you find P-Selecting?
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Endothelial cells, Platelets.
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Which cells express ICAM1/VCAM1? What do they bind?
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Endothelial cells, bind integrins on leukocytes.
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What is CD31? What does it bind?
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Also called PECAM on endothelial cells.
Binds ... CD31 on leukocytes. |
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What causes rolling of leukocytes?
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P,E Selectins that bind Sialyl-Lewis X on leukocytes.
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Which cytokines induce expression of VCAM1/ICAM1 on endothelial cells?
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TNF, IL-1.
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How are rolling leukocytes activated?
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Chemokines cause change of integrins to high affinity state, so they can stick and stop rolling.
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Common chemokines?
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Exogenous factors like bacterial products.
C5a, Leukotrienes, IL-8. |
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What type of receptor do chemokines have?
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GPCR.
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What does leukocyte activation cause?
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1. Increase in Ca.
2. Activatoin of Protein C. 3. Activation of Phospholipase A2 (causes production of Arachinodic Acid metabolites). |
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Which receptors are involved in leukocyte activation?
(4) |
1. TLR (cause production of microbicidal substances).
2. GPCR. 3. Cytokine receptors in phagocytes. 4. Opsonin receptors in phagocytes. |
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What receptors activate phagocytosis?
(meaning, they exist on neutrophiles and macrophages) |
Mannose receptor.
Scavenger Receptor (also activate uptake of LDL by macrophages). |
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Popular opsonins?
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IgG, C3b, MBL, CRP, fibronectin, fibrinogen.
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What happened (cytoskeleton-wise) during phagocytosis?
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Polymerization of actin.
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What does NADPH Oxidase do?
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Reduce oxygen to O2-. Can spontaneously go -> H2O2, that can be reduced to OH.
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Who breaks down most of the H2O2?
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Catalase enzyme.
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What does the enzyme MPO do?
Which cells contain it? |
Converts H2O2 to HOCL (bleach).
Neautrophiles (Azuraphilic granules). |
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When do the acid hydrolases begin to work?
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After killing in the phagolysosome.
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What products do neutrophiles and macrophages release to the extracellular fluid during phagocytosis?
(3) |
1. Lysosomal enzymes.
2. ROS intermediates. 3. Products of AA metabolism. |
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What causes release of products to the extracellular fluid during phagocytosis?
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1. Regurgiation during feeding.
2. Frustrated phagocytosis- ingestible materials. 3. Cytotoxic release- after damage to the membrane of the phagolysosome (like asfter engluding urate crystals). 4. Sometimes, exocytosis.. |
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What do neutrophiles do after phagocytosis?
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Apoptosis.
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What are LAD1/2?
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Defects in leukocyte adhesion.
LAD1: recurrent baterial infections, impaired wound healing. LAD2: milder. |
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What happens in Chediak-Higashi syndrome?
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AR.
Defect in forming phagolysosomes. (thought to result from aberrant organelle fusion). |
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What happens in Chronic Granulomatose Disease?
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Inherited defects in NADPH oxidase.
Recurrent bacterial infections. |
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How is acute inflammation terminated?
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1. Mediators have short half-lives.
2. Mediators are degraded after release. 3. Active anti-inflammatory mechniasms ("stop signals"). |
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Are plasma-derived mediators active, or precursors?
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Precursors.
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Which cells secrete Histamine?
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MAST CELLS, basophils, platelets.
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Which cells secrete Serotonin?
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Platelets (after aggregation), Enterochromaffin.
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What are the actions of Serotonin?
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Similar to histamine.
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What are the 3 complement pathways?
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1: Classical- C1 is fixated to antibody+antigen.
2. Alternative: Triggered without antibody. 3. Lectin: MBL binds the microbe, and activates C1. |
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What do C3a, C5a and C4a do?
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Cause release of Histamine from Mast cells.
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What does C5a do?
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1. Cause release of Histamine from Mast cells.
2. Activate the Lipooxygenase pathway in neutrophiles and macrophages. 3. Chemotactic factor for many leukocytes. |
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Who are the most important inflammatory mediators among the complement components?
What can activate them? |
C3 and C5.
Can be activated by proteolytic enzymes within the inflammatory exudate, like plasmic. |
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What are Kallikreins?
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Proteases, cleave Kininogen to create Bradykinin.
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What activates Kallikreins?
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Activated Hageman factor (12a).
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What are the effects of Bradykinin?
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Similar to Histamine.
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What does Kallikrein do, besides cleavage of Kininogen to create Bradykinin?
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1. Activate Hageman factor.
2. Convert C5 to C5a. |
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What does Thrombin do?
(just some) |
1. Activate fibrin, from fibrinogen.
2. Activate PAR1 (induces inflammation). |
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What does Hageman factor do?
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1. Initiate the Kinin system.
2. Initiate the instrinsic clotting system. 3. Initiate the fibrinolytic system (via plasmin). 4. Activate the complement system. |
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Which are the most important plasma proteases?
(clotting) |
Bradykinin, C3a, C5a, Thrombin.
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What is an Autocoid?
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Short-range hormone.
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How do we obtain Arachidonic Acid?
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1. Dietary sources.
2. Conversion from linoleid acid. |
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What are Eicasinoids?
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AA metabolites.
Synthesized by COX & Lipooxygenase. |
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What does the COX pathway create?
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Prostaglandins (also Thromboxane).
COX1 - constitutive and during inflammation. COX2 - only during inflammation (the bad guy). |
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What do prostaglandins cause during inflammation?
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Pain and fever.
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What is created by the lipooxygenase pathway? What do the products do?
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Leukotrienes.
Cause vasoconstriction and increase permeability much more than Histamine. |
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What are Lipoxins?
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Eicasinoids- precursor created in neutrophiles, final factor in platelets.
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What do you use Lipooxygenase inhibitors for?
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Asthma, as leukotrienes cause bronchospasm.
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What is effected by C-X-C chemokines?
C-C chemokines? |
C-X-C : Neutrohpiles
C-C: Everybody else. They use GPCR receptors. |
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What other effects does NO have?
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Microbicidal!
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What is the difference between specific and azuophil granules in neutrophiles?
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Specific granules are secreted extra-cellulary, and more readily (=by lower concentrations of agonist).
Azuraphil granules are more destructive, and release their content into phagolysosomes less readily. |
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What do extra-cellular ROS do?
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Amplify inflammatory cascade.
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What is substance P?
What does it do? Who secretes it? |
Neuropeptide, plaus a role in the initiation and propagation of the inflammatory response.
Secreted from nerve fibers. |
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What causes Gout?
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The pro-inflammatory action of uric acid.
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What do we need in order to achieve complete resolution after acute inflammation?
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Limited/short lived injury.
Little tissue destruction. The parenchymal cells can regenerate. |
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When do we resort to healing by fibrosis?
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Substantial tissue destruction, or the parenchymal cells cannot regenrate, or there is abundant fibrin exudation.
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What is Serous Inflammation?
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Outpouring of fluid (effusion)- can be in pleura etc. or under/within epidermis.
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What is Gibrinous inflammation?
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Comes with more severe injuries- such great permeability that larger molecules, like fibrinogen, pass and deposit fibrin.
Can also happen is there is a procoagulant stimulus in the interstitium (like cancer cells). |
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What is "organization"?
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conversion of fibrin exudate to scar tissue.
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What is purulent inflammation?
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Large amounts of pus.
(also abscesses) |
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What are abscesses?
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localized collection of purulent inflammatory tissue, in a confined space.
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What is an Ulcer?
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Defect of the surface of an organ, produced by the shedding of inflammatory necrotic tissue.
Obviously, can only occur when it exists on/near a surface.. (in mouth, legs in people with circulatory disturbances) |
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What happens in chronic inflammation?
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Active inflammation, tissue destruction and repair, simultaneously.
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What kind of immune reaction is chronic inflammation caused by organisms?
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Delayed-type hypersensitivity.
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What type of cells infiltrate in chronic inflammation?
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Mainly mononuclear- macrophages and lymphocytes.
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Which cell type is dominant in chronic inflammation?
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Macrophages.
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What is the half-life of blood monocytes?
Tissue macrophages? |
Monocytes: 1 day.
Macrophages: months. |
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When do macrophages emigrate during acute inflammation?
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Pretty early- after 48 hours they are often the dominant cell.
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What causes macrophage accumulation during chronic inflammation?
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1. Recruitment of monocytes from the circulation.
2. Local proliferation of macrophages (happens in atheromatous plaques). 3. Immobilization of macrophages. |
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What do the products of activated macrophages do in chronic inflammation?
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Tissue injury.
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What is one of the major hallmarks of chronic inflammation?
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Tissue destruction.
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What can happen in strong chronic inflammation, lymphocytes-wise?
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The reaction, because of the accumulation of lymphocytes, APC and plasma cells, may look like a lymph node- germinal follicles and all.
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What is a granuloma?
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Focus of chronic inflammation, consisting of aggregation of epitheloid cells, surrounded by a collar of mononuclear leukocytes (mainly lymphocytes).
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What do older granulomas develop?
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an enclosing rim of fibroblasts and connective tissue.
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What are giant cells?
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Fusion of several epitheloid cells.
20+ small nuclei. |
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What is a difference between granulomatous inflammation and other granulomatous diseases?
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Granolumatous inflammation often has central caseous necrosis (think tuberculosis).
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What happens to lymph flow during inflammation?
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Increases, to help drain the edema.
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What is Lymphangitis?
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Inflammation in Lymph.
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What is Lymphadenitis?
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Inflammation in lymph nodes.
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What usually causes nodal enlargement?
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HyperPLASIA of lymphoid follicles and phagocytic cells (lining the sinuses).
Termed Reactive Lymphadenitis. |
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What happens in Acute Phase Response?
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1. Fever (in response to pyrogens).
2. Leukocytosis (left shift)- called Leukemoid Reaction. 3. Acute Phase Proteins, made by the liver, appear. |
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Name two acute phase proteins
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CRP, Fibrinogen.
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What do acute phase proteins do?
(3) |
1. Act as opsonins.
2. Aid in the clearing of necrotic cell nuclei (bind chromatin). 3. Target HDL to macrophages, so they have more sources for energy. |
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What affects the Erythrocyte Sedementation Rate?
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Fibrinogen makes RBCs form stacks, which decreases ESR.
Since Fibrinogen is a marker of systemic inflammation, so is ESR.. |
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What can prolonged production of acute phase proteins cause?
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Secondary Amyloidosis.
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