Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
69 Cards in this Set
- Front
- Back
|
define: physiological process of blood clotting and bleeding, repair of tissue
|
hemostasis
|
|
|
4 major events in hemostasis following loss of vascular integrity
|
vascular constriction, platelet activation, formation of fibrin clot, clot lysis and wound healing
|
|
|
what protein is primarily responsible for stimualting platelet clumping
|
fibrinogen
|
|
|
what do platelets release upon activation?
|
ADP, tXA2(thromboxane), serotonin, platelet factor 3, lipoproteins(coagulation cascade)
|
|
|
define: platelet plug that contains only platelets
|
white thrombus
|
|
|
define: platelet plug that has red blood cells
|
red thrombus
|
|
|
what protein is present in dissolution of the clot
|
plasmin
|
|
|
what cells make platelets? Where?
|
megakaryocytes in marrow in venous sinuses
|
|
|
stages in thrombopoiesis
|
megakaryoblast, megakaryocyte, platelet
|
|
|
life span of platelet
|
10 days
|
|
|
define: humoral factor produced when platelet levels drop
|
thrombopoietin (tpo)
|
|
|
fcn of thrombopoietin (tpo)
|
stimulates maturation of megakaryocyctes and production of platelets
|
|
|
what granules do platelets have
|
dense granules, alpha granules, lamba granules
|
|
|
what do dense granules contain
|
serotonin(vasoconstrictor), Ca, ADP, ATP
|
|
|
what do alpha granules contain
|
fibrinogen, growth factors
|
|
|
what are lamba granules similar to
|
lysosomes
|
|
|
what is required of platelets in order for hemostasis to occur
|
adhere to exposed collagen, release contents of granules, aggregate
|
|
|
what mediates adhesion of platelets to collagen and stabilizes coagualtion factor VIII
|
von Willebrand factor (vWF)
|
|
|
define; complex multimeric glycoprotein produced by megakaryocytes and endothelial cells
|
von Willebrand factor (vWF)
|
|
|
where are von Willebrand factors stored
|
alpha granules of platelets, Weibel-Palade bodies in endothelial cells
|
|
|
platelets are rich in receptors for
|
ADP, thrombin, epinephrine, serotonin, collagen
|
|
|
what does release of ADP by platelets stimulate?
|
inc overall cascation cascade, modifies platelet membrane to adhere glycoproteins
|
|
|
what does initiation of signal transduction cascade entail
|
induction by specific receptors on surface of platelets, adherance to collagen and release of intracellular Ca leads to activation of PLA2
|
|
|
what exactly happens when thrombin receptor is inducted on surface of platelets? (cascade…_
|
thrombin receptor coupled to G protein→act PLC-γ→hydrolyzes PIP2→forms IP3, DAG→release of intracellular Ca, act protein kinase C
|
|
|
what happens in initiation of signal transduction cascade after release of Ca→PLA2?
|
PLA2→hydrolyze membrane phospholipids→liberation of arachidonic acid→inc release of thromboxane(TXA2)
|
|
|
3 general steps of signal transduction cascade
|
induction of specific receptors, changes in platelet morphology during activation, granule contents released/activating more platelets
|
|
|
how exactly is platelet morphology changed?
|
release of Ca→myosin light chain kinase(MLCK)→phosphorylates light chain of myosin and actin→altered platelet morphology→platelets interact to form clot
|
|
|
what granuel contents are released in signal transduction cascade
|
platelet factor 3,4, fibrinogen, Ca, K, catecholamines
|
|
|
what allows control of coagulation by positive and negative regulators thru different synthetase enzymes
|
thromboxane(platelets) vs prostaglanding I2(endothelial cells)
|
|
|
what is the inhibitory pathway for platelet aggregation? Upregulation of adenylate cyclase cuases….
|
inc in cAMP→turns on cAMP dep kinases→phosphorylates proteins→down regulates platelet fcns
|
|
|
what is important in the activation of coagulation cascade besides activaiton of platelets?
|
activated platelet surface phospholipids
|
|
|
what is the goal of clotting cascade
|
convert fibrinogen from soluble plasma protein to insoluble matric of cross linked fibrin
|
|
|
what is the result of the intrinsic pathway
|
formaiton of red thrombus/clot in response ot abnormal vessel wall. NO tissue injury
|
|
|
result of extrinsic pathway
|
fibrin clot formaiton in response to TISSUE injury
|
|
|
what are the coagulation components specific ot intrinsic pathway
|
prekallikrein, kininogen proteins, clotting factors VIII, IX, XI, XII
|
|
|
when does initiation of intrinsic pathway occur?
|
when prekallikrein, kininogen factor XI, XII exposed to - charged surface:contact phase
|
|
|
what is the primary stimulus for contact phase
|
exposure of collagen in wall of vessel to coagulation proteins in plasma
|
|
|
what does assembly of contact phase components result in
|
prekallikrein→kallikrein→act factors XII→factor XIIa→release of bradykinin(vasodilator), factor XI→Xia
|
|
|
what does the presence of Ca allow factor XI to activate in intrinsic clotting cascade
|
factor XI activates factor IX to IXa
|
|
|
fcn of factor Ixa
|
component of complex(tenase) that activates factor Xa
|
|
|
what is a cofactor in clotting cascade
|
factor VIIIa
|
|
|
what limits extene of tenase complex formation/down regulates coagualtion cascade?
|
thrombin-inactivates factor VIIIa
|
|
|
where do intrinsic and extrinsic coagulation cascades converge?
|
activated factor Xa
|
|
|
how is extrinsic pathway initiated?
|
site of injury in response to release of tissue factor (III) from damaged cells(thromboplastin)
|
|
|
where does inhibition of extrinsic pathway occur?
|
tissue factor-factor VIIa--Ca+2--Xa complex
|
|
|
what is activated in the common pathway?
|
prothrombin→(factor Xa, Va,Ca, PI,PS)→thrombin→converts fibrinogen→fibrin
|
|
|
how are extrinsic and intrinsic pathways linked
|
ability of enzymes to cross talk-factor Xa to factor VII, tissue factor and factor VIIa→IX
|
|
|
what do factors II, VII, IX, X require to undergo essentail modification in ER
|
vitamin K dependendt
|
|
|
what posttranslational modificaiton do factors II, VII, IX, X undergo?
|
add y-carboxyglutamic acid
|
|
|
what does thrombin convert when it binds with thrombomodulin?
|
protein C→protein Ca.
|
|
|
fcn of protein S, Ca?
|
degrade factors Va, VIIIa--neg feedback by thrombin
|
|
|
what controls clotting activity
|
feedback mechanisms, protease inhibitors
|
|
|
ex of specific protease inhibitors
|
antithrombin, α2-macroglobulin, heparin cofactor II, a1-antitrypsin
|
|
|
define: serine protease that hydrolyses fibrinogen at 4 arg-gly bonds b/w fibrinopeptide and A/B portions of protein
|
active thrombin
|
|
|
fcn of plasmin
|
degradation of fibrin clots
|
|
|
what serine proteases convert plasminogen to plasmin?
|
tissue plasminogen activator (tPA) and urokinase
|
|
|
what is deficient in hemophilia A
|
factor VIII-key component in coagulation cascade
|
|
|
deficiency in hemophilia B? treatment?
|
factor IX. Human plasma, recomb DNA technology
|
|
|
patietns with what have elevated plasma fibrinogen levels
|
coronary artery disease, diabetes, hypertension, hyperlipoproteinemia
|
|
|
what leads to inc plasma fibrinogen levels?
|
pregnancy, menopause, hypercholesterolemia, oral contraceptives, smoking
|
|
|
defective platelet adhesion is a result of what deficiency
|
vWF deficiency, which results in factor VIII deficiecny
|
|
|
what are some drugs used in bleeding?
|
heparin, coumarin, tPA, aspirin, platelet receptor agonists
|
|
|
what does heparin bind to to stop bleeding?
|
activates antithrombin III--inhibits serine proteases of coagulation cascade
|
|
|
how does coumarin inhibit coagulation?
|
inhibits vitamin K dep y-carboxylation rxns necessary to fcn of thrombin, VII, IX, X, protein C,S
|
|
|
is coumarin used for long term or short term purposes?
|
long term
|
|
|
what bleeding treatment is highly selective for degradation of fibrin in clots?
|
tPA
|
|
|
when is tPA given?
|
heart attack, restoring patency of coronary arteries after thrombosis
|
|
|
what drug is an important inhibitor of platelet activaiton
|
aspirin
|
|
|
what does aspirin do
|
inhibit activity cyclooxygenase, red production of tXA2, reduce PGI2
|
