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39 Cards in this Set
- Front
- Back
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________ activation is the process initiating clot formation and clot lysis as well as producing the _________ bradykinin
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Zymogen
vasodilator |
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Hemostasis (cessation of bleeding) involves: vasoconstriction
________ aggregation _____ _____ (fibrin) formation |
platelet
blood clot |
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Disc-shaped cells lacking nuclei but containing mitochondria. arise from megakaryocytes in bone marrow, half life __ days.
1/20 the number of RBC's |
platelets
10 |
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Surface of platelets have glycoprotein receptors:
GpIa function GpIb function GpIIb/IIIa function |
binds tightly to collagen (damaged blood vessels exposes subendothelial collagen)
Binds fibrinogen which helps aggregation of platelets binds tightly to Von Willebrand factor (vWF) |
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thromboxane A2 (from arachidonic acid) and serotonin (from granules) functions in blood coagulation
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vasoconstrictors
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Platelets contain _______ with several blood clotting __________:
Fibrinogen, ADP, vasoconstrictors |
granules
zymogens |
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Platelets contain _____ and _________ to help shape change in response to ADP and thrombin (discs, spheres)
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actin
microfilaments |
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thromboxane A2 is involved in 2 major steps of coagulation, what are they?
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Vasoconstriction
Platelet aggregation (formation of platelet plug during primary hemostasis) |
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ADP and thromboxane A2 are both involved in what function?
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Primary hemostasis - Platelet aggregation
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Thromboxane A2 is formed through what Eiconsanoid pathway?
_________ exactly imposes the action of Thromboxane, yet they are both formed through the same intermediate (PGH2) |
cyclo-oxygenase
Prostacyclin |
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Aspirin and all NSAIDS prevent blood clots by targeting what?
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cyclooxygenase
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2 things opposing platelet aggregation and vasoconstriction
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Prostacyclin (PGI2) also from arachidonic acid (membrane)
Nitric oxide from arginine |
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surface protein which binds thrombin and this complex activates protein C and protein S (critical steps in control of clotting)
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Thrombomodulin
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vWf forms a noncovalent complex with antihemophilic factor (VIII). This complex _________ clotting
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accelerates
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Glycoprotein involved in platelet plug formation by enhancing binding of platelets to collagen via GpIb. Mobilized to surface when endothelium is injured.
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von Willebrand factor (vWf)
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Making thrombin (IIa) is the key of clotting - strong catalyst so once you make thrombin it just goes from there. To get Prothrombin to thrombin you need:
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Xa (from intrinsic and extrinsic, serine endopeptidase)
Va (accelerating factor) Ca2+ Phospholipid micelles (surface area = platelets) |
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One way to prevent clotting would be a _______ binding agent, since this molecule is a catalyst in taking:
Prothrombin (II) to Thrombin (IIa) and Fibrin (Ia) to clot fibrin polymer (crosslinked) |
Ca2+
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_______ (a serine endopeptidase) removes acidic fibrinopeptides A and B (glu, asp, tyrosine sulfate residues) from Aalpha and Bbeta chains near the disulfide knot on fibrinogen.
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Thrombin
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After fibrinogen has been cleaved, it forma a three-dimensional lattice with a half-staggered array because the central and terminal globular units are now attracted to one another. This requires ______ and _______. This is the soft clot.
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Thrombin - for cleavage
Calcium - for 3-D structure |
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In order to make the soft clot hard, there must be cross-linking of interchain glutamine and lysine residues forming an amide (peptide) bond. This is catalyzed by factor ___
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XIIIa
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Prothrombin contains gamma-carboxyglutamic acid (gla) residues. Gla residues are important for binding ___. They are made posttranslationally in a reaction that depends on _________.
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Ca2+
vitamin K |
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Factors VII, IX, X and Protein C also contain ___ residues and thus depend on Ca2+ for activation
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gla
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Which factors does thrombin, the key hydrolytic catalyst, onvert to their active forms?
Also fibrinogen to fibrin |
V, VII, VIII, XI, XIII
and Fibrinogen to Fibrin |
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The extrinsic pathway of converting X to Xa requires what elements?
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Tissue factor (factor III)
VIIa (always a little present, upregulated when thrombin present) IXa - accelerating factor Ca2+ |
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Components of the intrinsic pathway:
3 endopeptidases: Factors ___, ___, and ___ a modifier protein (___/___) platelet phospholipids ___ (element) |
XIIa, XIa, IXa
VIII/vWf ->VIIIa (via thrombin) Ca2+ |
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What are serpins?
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Serine protease inhibitors, make up the majority of the 10% of plasma proteins that are inhibitors
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_______ (more abundant than prothrombin) inactivates by binding to thrombin (IIa)
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Antithrombin III
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Reactivity of Antithrombin III (anti-clotting factor) is greatly enhanced by ________ which is sulfated heteropolysaccharide released from Mast cells and on surface of endothelial cells
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heparin
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Protein C forms a complex with Protein S that inactivates __ and ___ by hydrolysis
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Va
VIIIa |
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_____ inhibits the extrinsic pathway by binding to both Xa and VIIa.
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TFP-I (tissue factor pathway inhibitor)
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Found on endothelial cells, alters thrombin so that protein C is activated, binding of thrombin caused by this receptor limits clotting activity
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Thrombomodulin
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At the same time you start making clotting factors you also start clot lysis because they both involve which factor?
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Factor XII
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Critical step in clot lysis?
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Plasminogen to plasmin (breaks up fibrin clot)
Need TPA and kallikrein |
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Functions of ?
-Blood clotting Factors II, VII, IX, X, protein C, and protein S -Osteocalcin or bone gla protein (mobilization of Ca2+ from bone) -Nephrocalcin (Ca2+ resorption, perhaps) -Gas6 – cellular growth regulation |
Vitamin K
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2 situations where you get Vit K deficiency:
______ – chronic diarrhea, fat in the stool, etc… Long term use of ________. What we derive from digestive tract is made by bacterial flora (make Vit K1) |
Fat malabsorption
antibiotics |
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Why are newborns given vitamin K,?
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no stores or intestinal flora
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green leafy vegetables, peas, tomatoes, cauliflower, cereals
Sources of ?? |
Vitamin K
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Vitamin K deficiency causes what symptoms?
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prolonged blood clotting time, bruise easily
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2 antagonists of Vitamin K whose functions are:
Prevent reduction of epoxide to vitamin Used to prevent blood clots |
Dicoumarol
Warfarin (rodenticide) |