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Flashcards in Biochemistry Deck (70):

What is the normal range of platelets?

150,000 to 300,000 ul3


Where are platelets derived from?

thrombocytes -> megakaryocytes -> platelets


What vasoconstrictors do platelets contain?

granules contain serotonin (5-HT) and COX1 -> generates thromboxane A2


What can be found on platelet cell membranes?

glycoproteins/phospholipids (prevents them from sticking to each other); receptors for collagen/laminin (exposed when endothelial cells are damaged); receptor for released signal molecules


What controls platelet production?

thrombopoietin (TPO) which is produced by kidney and liver continuously


What happens to TPO in high platelet #s?

TPO bound to c-MPL receptor on platelets/megakaryocytes ->i internalized -> degraded


What happens to TPO in low platelet #s?

doesn't bind to c-MPL receptor; free TPO triggers platelet production


What is the difference between TPO and EPO?

EPO is selective to RBCs; TPO will increase all blood cell production


What is the purpose of vasospasm?

collapses vessel to disrupt blood flow and avoid further blood loss


What is the most important factor contributing to vasospasm?

myogenic response - smooth muscle cells respond to damage by releasing chemicals and and contracting (some reflex involved)


What other factors contribute to vasospasm?

platelet factors (5-HT, thromboxane A2) and neuronal reflex (not required)


What is von Willenbrand factor (vWF) and what is its function?

released from damaged vessel cells and initiates binding between collagen and platelets (used as an intermediate to bind between collagen and platelets)


What happens to platelets when activated?

they swell and retract to extend podocytes; retraction also releases granules of thromboxane A2, ADP, and 5-HT)


What is formed by the activation of platelets? How effective is it?

activated platelets stick to vessel wall and each other to form platelet plug; may be all that is needed to stop bleeding of small breaks (nosebleeds, cuts on skin)


Difference between primary and secondary hemostasis?

Primary = localized platelet plug as site of injury (temporary patch)

Secondary = enlarged platelet plug by adding fibrin via clotting cascade


What are the vitamin K dependent factors?

factor II, VII, IX, X, protein C, and protein S


What triggers the extrinsic pathway and what factors are involved?

activated by external trauma (cut on skin); involves the activation of factor VII through tissue factor (III) released from damaged cells


What triggers the intrinsic pathway and what factors are involved?

activated by trauma inside the vascular system and involves factors XII, XI, IX, and VIII


Describe the extrinsic pathway

tissue factor (III) comes into contact w/ factor VII and the 2 bind to Ca which makes a trimolecular complex that cleave factor X -> Xa


What factor starts off the intrinsic pathway and what is its cofactor in activation?

XII (hageman factor) -> XIIa through HMWK as cofactor


What converts prekallirein to kallirein and what is its purpose?

Factor XIIa helps in the conversion which accelerate conversion of XII -> XIIa through positive feedback


What factor does factor XIIa cleave?

factor XI -> XIa


What does factor XIa cleave in the intrinsic pathway?

cleaves factor IX (christmas factor) -> IXa (a protease)


What cleaves factor VIII to factor VIIIa?

thrombin (IIa)


What cleaves factor X -> Xa in the intrinsic pathway?

IXa, VIIIa, Ca and phospholipids (forms tenase)


What is the purpose of the common pathway and what factors are involved?

Common pathway results in a stable fibrin clot (secondary hemostasis); involves factors I, II, V, X, and XIII


What cleaves factor V to Va?

thrombin (IIa)


What makes up the prothrombin activator (prothrombinase) and what is the result?

Xa, Va, Ca, and phospholipids form prothrombinase; acts on prothrombin (II) to form thrombin (IIa)


Thrombin converts fibrinogen into what?

Fibrin which is then polymerized into fibrin fibers in the presence of Ca


What is needed to create cross-linked fibrin?

Thrombin and Ca help convert Factor XIII (fibrin stabilizing factor) to XIIIa which stabilizes fibrin into cross-linked "net"


Describe all the roles of thrombin (factor II)

Prothrombin -> thrombin
Factor V -> Va
Factor VIII -> VIIIa
activation of platelets
Fibrinogen -> fibrin
XIII (fibrin stabilizing factor) -> XIIIa -> cross-linked fibrin


What is used to activate Protein C?

Thrombin combines w/ thrombomodulin on endothelial cells to activate protein C


What does protein C do?

inactivates t-PA inhibitor that is floating in the blood


What is t-PA and where does it come from?

tissue plasminogen activator is released by damaged tissue; used to convert plasminogen to plasmin


Describe the steps to breaking down a clot

t-PA released by damaged tissues; thrombin binds to thrombomodulin on endothelial cells to activate protein C (instead of creating fibrin); activated protein C inhibits t-PA inhibitor floating in blood so that t-PA can activate plasminogen -> plasmin which then lysis the fibrin in the clot


Explain how atherosclerosis activates intrinsic pathway

plaque can rupture through endothelium and activate clotting cascade; clot can develop and occlude the rest of the artery (causing MI or stroke)


What does prothrombin time (PT) test?

tests extrinsic and common pathways


What is the normal range of PT and what could cause prolonged PT?

10-13 seconds; may be prolonged w/ vitamin K deficiency, Coumadin (warfarin) therapy, DIC, or liver disease (would have normal PTT)


What does partial thromboplastin time (PTT) test?

intrinsic and common pathways


What is the normal range of PTT and what could cause prolonged PTT?

25-35 seconds; may be prolonged w/ heparin therapy or overdose, DIC, or hemophilia


What is the function of vitamin K?

allows factors (II, VII, IX, X, protein C and S) to bind to phospholipid membranes through y-glutamyl carboxilation; puts factors in a place where they can be activated


How is vitamin K activated?

must be reduced from quinone -> quinoa form in liver through 2,3 epoxide reductase and quinone reductase


What is the MOA of Coumadin (Warfarin)?

inhibits the enzyme epoxide reductase and prevents activation of vitamin K -> prevents activation of dependent factors in cascade


Which form of warfarin is more pharmacologically active?

S-warfarin; must be free floating and not bound to anything


What are the half-lives for the vitamin K dependent factors?

II = 60 hrs
VII = 4-6 hrs
IX = 24 hrs
X = 40-60 hrs


What happens w/ protein C deficiency?

significant risk for venous thrombosis b/c thrombin is not activating protein C and is still activating Va and VIIIa in the clotting cascade


What factor is deficient in hemophilia A? What factor do you test for?

factor VIII; they will lack factor Xa so test for that


Describe the 3 basic structures of lipids

monoacyglycerol (MAG) - 1 fatty acid attached
diacylglycerol (DAG) - 2 fatty acids attached
triacylglycerol (TAG) - 3 fatty acids attached


What is the source of TAG synthesis in intestinal cells?

dietary TAGs digested in small intestine by pancreatic lipases


What lipoprotein is made in intestinal cells? Where is it released?

chylomicron - largest and least dense lipoprotein; released into lymphatics and enters blood through lymphatic duct


What is the source of TAG synthesis in the liver?

glucose or glycerol (promoted by excess carbohydrates)


What enzyme is specific to the liver and what does it do?

glycerol kinase -> used to transform glycerol into glycerol 3-P


What is the source of fatty acids in the liver?

acetyl CoA (forms new fatty acids in hepatocytes)


What lipoprotein is made in the liver? What does it hold besides TAGs?

VLDL - very low density lipoprotein; holds TAGs and cholesterol


What is source of TAG synthesis in adipocytes?

glucose (promoted by excess carbohydrates and fats)


What is the fatty acid source in adipocytes? How do they enter adipocytes?

chylomicrons and VLDL; broken down in capillaries by capillary lipoprotein lipase (CLPL) and fatty acids enter adipocytes


What is the major enzyme involved in breaking down TAGs in adipocytes? What activates and inhibits the enzyme?

hormone sensitive lipase (HSL)
activated by glucagon, Epi, and NE (hunger, exercise)
inhibited by insulin (fed status)


How do broken down fatty acids leave adipocytes?

short chain (< 6C) are released into blood; long chain fatty acids are combined w/ albumin (carrier) before entering blood


What is perilipin and how is it regulated?

protein that coats lipid droplets (prevents access by HSL); regulated by PKA (phosphorylation allows association w/ HSL)


What is the function of lipoproteins?

serve as vehicles for transporting hydrophobic substances through vessels and serve as ligands to help internalize lipoproteins


What are the 5 types of lipoproteins?

chylomicrons - intestinal cells; least dense; largest
VLDL - hepatocytes
LDL - "bad cholesterol"; majority is cholesterol
HDL - "good cholesterol"; smallest; most dense (majority is proteins)


Describe the functions for each of the following apolipoproteins: ApoB-48, ApoC-II, ApoE, ApoB-100

ApoB-48 - facilitates transport
ApoC-II - activates CLPL
ApoE - facilitates uptake into liver
ApoB-100 - facilitates uptake into cells


On what lipoproteins would you find ApoB-48?



On what lipoproteins would you find ApoC-II?

chylomicrons and VLDL (sources of fatty acids for adipocytes) and HDL


On what lipoproteins would you find ApoE?

chylomicrons, VLDL, IDL, and HDL


On what lipoproteins would you find ApoB-100?



What is the function of ApoA-1 and where would you find it?

found on HDL; activates LCAT enzyme that converts cholesterol to cholesterol ester


What is Type I Hperlipoproteinemia and how would you dx?

inability to hydrolyze TAGs in chylomicrons and VLDL either due to deficiency in CLPL (infancy) or ApoC-II (post-adolescence); plasma TAG levels > 1000 mg/dL


What is Type II Hyperlipoproteinemia and how would you dx?

defects in uptake of LDL and impaired ability to recognized ApoB-100
Normal cholesterol - 130-200 mg/dL
Heterozygous – 300-500 mg/dL
Homozygous - >800 mg/dL


How does high LDL cause atherosclerosis?

High LDL influx in arterial wall causes it to be converted to oxidized version by ROS; unregulated uptake by macrophages that become foam cells and burst (cause platelet adhesion)