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Coagulation and Hemostasis I

Includes:
I. Hemostasis
II. Endothelial Cells
III. platelets
IV. Coagulation Cascade
V. Vit K
VI. Natural Inhibitors of Coag.
VII. Fibrinolytic System

AB
the local stoppage of blood flow involves *1. vascular wall w/ lining endothelium 2. platelets 3. coagulation protiens
primary hemostasisassd with platelets and blood vessels
secondary hemostasisassd with coagulation protiens
normal hemostases (events)1. vasoconstriction (arterioles) 2. exp of subendo CT 3. coag sequence activated 4. perm hemostatic plug
function of endothelial cellmodulate aspects of hemostasis-coagulation system; both anti/prothrombotic properties
prostacyclin (PGI2)inhibits platelet aggregation and adhesion; antiplatelet effect of ECs
thrombomodulinbinds thrombin ->anticoag. effect of ECs ;capable of activating protein C
plateletscell fragments from megakaryocyte
alpha granulesin platelets; membranes contain P-selectin
products found in alpha granulesfibrinogen, fibronectin, factors V and VII, platelet factor 4, growth factor
types of granules found in plateletsalpha and electron dense
electron dense bodiesstorage sites for nonmetabolic pool of ADP/ATP, Ca++, histamine, serotonin, epinephrine
von Willebrand's factormolecular bridge between platelets and collagen, acts thru glycoprotein receptors
platelet attatchment needsexposed subendothelial collagen, vWF
substance exposed on the platelet surface when the platelet bcms activatedphospholipin complex
purpose of phospholipin complexprovide site on platelet surf. where coag. factors and Ca++ can bind
what happens when Ca++ and coag.factors bind to plateletsintrinsic pathway is activated
three imp. stimuli for platelet aggregationADP, thomboxane A2, thrombin
reversibleprimary hemostatic plug
irreversiblesecondary hemostatic plug
ADP + thromboxane A2 + thrombin -> ?increased platelet aggreg., secondary plug (->platelet contracture (consolidation, viscous metamorphosis)
ADP + thromboxane A2 -> ?platelet aggregation and primary plug
prothrombic property of platelets can be induced bycytokines (IL-1, TNF), bacterial endotoxins
ptothrombic binding sites on platelets are for ***activated forme os IX and X
prothrombotic substance secreted by plateletsinhibitor for tissue plasminogen activator
what binds to platelet glycoprotien receptors and enhances aggregationfibrinogen
intrinsic pathwaysurface contact, exp of subEC collagen, prekallikrein, HMW kininogen
extrinsic pathwaytissue damage
what starts the final common pathway?factor X
final common pathwayconvergence of intrincic and extrinsic pathway
soluble proenzymes -> activated enzymes -> thrombin prod. -> soluble fibrinogen -> insoluble fibrincoagulation cascade
needed for liver to convert glutamyl residues to gammacarboxyglutamatesvit K
vit K dep clotting factorsII, VII, IV, X
inhibitor of vit K activityWarfarin (coumadin)
factors that naturally inhibit fibrin clot formation naturallyantithrombinIII(AT III), protein C, protein S
required by antithrombinIII to produce effective anticoag.heparin or heparin-like protiens
AT-III forms a 1:1 complex with *thrombin
AT III has inhib. activity against ****Xa, XIIa, XIa, and IX
factors that decrease AT III levelspreg., oral contraceptives, ext. malignancy, septicemia, after major surgery, autosomal domin. disorder
factors inactivated by protien CV, VIII
Protein C circulates asinactive zymogen
protein C is activated by ***thrombin n the presence of thrombomodulin
vit K dep cofactor for protein Cprotein S
protein D increases production of ***tissue plasminogen activator (t-PA)
breaks down fibrin and reduces fibrin polymerizationfibrinolytic system
substances capable of converting plasminogen to plasminstreptokinase and urokinase, t-PA, factor XIIa, kallikrein, HMW kinninogen
interfere with polymerization of fibrin monomerfibrin split products
polymerization of fibrin monomercauses clotting
attacks fibrin clot and forms fibrin split productsplasmin


Suzanne M. Clous

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