USCSOM: Pathology: Acute Inflammation
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| What are the six cardinal signs of inflammation? | Heat, redness, swelling, pain, loss of fxn, systemic changes
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| What are the three time categories of inflammation? | Acute (0-48hrs), Subacute (2-10days), Chronic>2weeks
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| What inflammatory cells are involved in acute inflammation? | heutrophils
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| WHat inflammatory cells are involved in chronic inflammation? | monocytes, lymphocytes, plasma cells, macrophages, granuloma cells
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| What is the first hemodynamic change that takes place in acute inflammation? | vasoconstriction followed by vasodilation
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| Where does increased permeability take place in the vasculature? | postcapillary venules
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| What is exudation? | leakage of fluid and cells into interstiital space
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| What are the stages of leukocyte exudation? | Margination, adhesion, emigration, chemotaxis
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| Describe the selectin family. | Ca-dependent lectins; expressed on the surface of endothelium; mediate rolling of leukocytes at site of inflammation
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| What is P-selectin? | stored in weibel-Palade bodies and alpha-platelet granules; stimulated of TNF or IL-1
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| What is E-selectin? | synthesized de novo; later recruitment of leukocytes; stimuled by TNF or IL-1
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| What is L-selectin? | Lymphocyte binding to lymph node venules
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| What is ICAM-1? | intercellular adhesion molecule; surface of cytokine stimulated endothelium
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| What is VCAM-1? | vascular cell adhesion molecule; receptor for lymphocytes, monocytes, eosinophils, basophils
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| What is PECAM-1? | platelet endothelial cell adhesion molecule; CD-31; important in diapedesis
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| What are integrins? | adhesion molecules; transmembrane in structure; heterodimers
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| What is the most notable Beta-1 integrin? | VLA-4; expressed on leukocytes; bind to VCAM-1
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| What are beta-2 integrins? | localization of phagocytes to injury; LFA-1 and Mac-1, and CR3/4 are examples
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| What are the 3 pathways for killing/degradation via phagocytosis? | oxygen-dependent (h2o2); h202-myeloperoxidase-halide system; oxygen-independent (leukocyte granules)
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| What are the effects of histamine and serotonin? | arteriorlar dilation; constriction of large arteries; increased permeability of postcapillary venules; immediate and transient
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| What types of cells store histamine and serotonin? | mast cells, basophils, platelets
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| What is the critical step in activation of complement? | cleavage of C3
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| What are the 3 pathways of complement? | classic (c1), alternate (c3's), lectin (c1-mannose)
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| Which complement fragments are anaphylatoxins? What is their role? | C3a,C4a,C5a; stimulate histamine release
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| What complement serves as chemotaxis? | C5a
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| What complement serves helps to opsonize foreign bodies? | C3b
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| What is Hageman Factor? | Factor XII of clotting system; triggers kinin and clotting
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| What is the first step in the kinin system? | prekallikrein to kallikrein by activated Hageman
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| What does kallikrein do? | forms bradykinin; amplifies Hageman; breaks C5 up; converts plasmin
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| What does bradykinin do? | short-lived vasoactive peptide; increases vascular permeability; dilates blood vessels; contracts smooth muscle; causes pain
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| What is the primary peptide in bee stings? | bradykinin
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| What role does thrombin play? | cleaves fibrinogen into insoluble fibrin clots; link between coagulation system and inflammation
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| What is plasmin's primary role? | lyses fibrin clots
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| What role does plasmin play in inflammation? | activated Hageman; cleaves C3; increase vascular permeability
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| What are the two pathways for arachidonic acid? | Cyclooxygenase and Lipoxygenase
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| What is Thromboxane A2? | potent platelet aggregator and vasoconstrictor
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| What is Prostacyclin PGI2? | vasodilator and inhibitor of platelet aggregation
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| What is PGE2? | sensitizes skin to painful stimuli; cytokine induced fever
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| What is PGD2, PGE2, PGF2? | causes vasodilation and potentiate edema
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| What is the lipooxygenase pathway? | converts arachidonic acid to HPETE, to HETE, to leukotrienes
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| Describe Leukotriene B4. | potent chemotactant, neutrophil aggregation, stimulate ROS and lysosomes
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| Describe Leukotrien C4,D4,E4. | intense vasoconstriction, bronchospasm, vascular permeability
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| Describe Lipoxins A4,B4. | negative regulators for leukotrienes, inhibit leukocyte action
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| How is lipoxin formed? | transcellular biosynthetic mechanism; neutrophillic stimulation of platelets
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| What are some actions of PAF? | Platelet activating factor; vasoconstriction, bronchoconstriction, leukocyte chemotaxis, PG and LkTr synthesis
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| What are the two KEY cytokines of inflammation? | Interleukin-1 and Tumor Necrosis Factor
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| What mainly produces IL-1 and TNF-alpha? | macrophages
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| What is the role of chemokines? | stimulate leukocyte recruitment in inflammation
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| Describe CXC or alpha chemokines. | act on neutrophils; IL-8
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| Describe CC or beta-chemokines. | act on mono, eosinophils, basophils, lymphcytes; MCP-2
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| Describe C or gamma-chemokines. | act of lymphocytes; lymphotactin
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| Describe CX,C chemokines. | monocytes and T-cells; fractaline
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| What types of cells produce NO? | macrophages and endothelium
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| What are the effects of NO release? | vasodilation; reduce platelet aggregation and inflammatory response; microbicidal actions
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| What are the effects of extracellular release of ROS? | endothelial cell damage; inactivation of antiproteases; injury to cells
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| What are some neuropeptides involved in acute inflammation? | substance P and Neurokinin A
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| What are some biologica fxns of Substance P? | pain signals, regulate BP, stimulate secretions, increase vascular permeability
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| What are the most likely mediators of vasodilation? | prostaglandins, NO
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| What are the most likely mediators of vascular permeability? | histamine, C5a, bradykinin, Leukotrienes, PAF, Substance P
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| What are mediators of Chemotaxis? | C5a, Leukotriene B4, Chemokines
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| What are mediators of fever? | IL-1, IL-6, TNF, Prostaglandins
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| What are mediators of pain? | prostaglandins, bradykinin
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| what are mediators of tissue damage? | lysosomal enzymes, ROS, NO
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