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VMP824 Physiology/Microanatomy 2 > Lecture 5 1/24/24 > Flashcards

Lecture 5 1/24/24 Flashcards

1
Q

What is the definition of hemostasis?

A

interruption of blood flow through an injured vessel

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2
Q

What are the goals of hemostasis?

A

-form clot quickly
-confine clot to where needed
-limit propagation
-dissolve clot when no longer needed

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3
Q

What are the three main processes of hemostasis?

A

-formation of platelet plug (primary)
-formation of fibrin through coagulation cascade (secondary)
-formation of plasmin for clot breakdown (fibrinolysis)

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4
Q

How do the processes of hemostasis occur, in relation to each other?

A

-primary and secondary hemostasis occur about the same time
-fibrinolysis occurs in quick succession to primary and secondary hemostasis

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5
Q

What are the antithrombotic properties associated with “at rest” blood vessels?

A

-blood flow
-bioactive molecules

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6
Q

How do bioactive molecules prevent thrombus formation?

A

-vasodilation
-inhibition of platelet function/aggregation
-inhibition of coagulation
-fibrinolysis

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7
Q

What are the prothrombotic properties associated with “activated” blood vessels?

A

-exposure of subendothelial cells/activation of coagulation cascade
-turbulent blood flow
-bioactive molecules

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8
Q

What is tissue factor?

A

protein found in the collagenous extracellular matrix that is the beginning of secondary hemostasis/coagulation

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9
Q

How do bioactive molecules promote thrombus formation?

A

-vasoconstriction
-inhibition of fibrinolysis

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10
Q

How do platelets morphologically differ when at rest compared to activated?

A

-discoid/plate-shaped at rest
-spherical with multiple projections when activated

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11
Q

What are the components of platelet structure?

A

-cytoskeleton
-open canalicular system to increase surface area
-dense tubular system of ER

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12
Q

What are the alpha granules associated with the platelets?

A

-vWF
-fibrinogen
-factors 5, 7, 8, 11, 13
-PAI

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13
Q

What are the dense granules associated with the platelets?

A

-serotonin
-ADP
-Ca++

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14
Q

What is the role of the platelets’ alpha and dense granules?

A

pro-coagulation

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15
Q

What is the function of GpVI and Alpha2Beta1 proteins on the platelet surface?

A

-binds to collagen
-part of primary hemostasis
-backup plan if vWF is absent/not functioning

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16
Q

What is the function of Gp1b?

A

-vWF receptor
-part of primary hemostasis

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17
Q

What is the role of GpIIb-IIIa?

A

-fibrinogen receptor
-involved in primary and secondary hemostasis

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18
Q

How do Gp1b and GpIIb-IIIa differ structurally?

A

-Gp1b is always active and ready to bind
-GpIIb-IIIa is not active when platelet is at rest

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19
Q

What is the goal of primary hemostasis?

A

formation of the primary platelet plug

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20
Q

Which “players” are involved in primary hemostasis?

A

-platelets
-Von Willebrand factor (vWF)
-vessel wall

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21
Q

What are the three phases of primary hemostasis?

A

-platelet adhesion
-platelet activation
-platelet aggregation

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22
Q

What are the characteristics of vWF?

A

-synthesized by endothelial cells
-circulates in blood in zymogen form
-undergoes a conformational change after binding to collagen that allows for interaction with Gp1b

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23
Q

What is important about the Gp1b-vWF bond?

A

it provides stabilization against sheer forces and is difficult to disrupt

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24
Q

What occurs during the platelet activation stage, once the platelets are attached to collagen?

A

-shape change
-granule secretion
-conformational changes in surface proteins (GpIIb-IIIa)

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25
Q

What compounds are released by activated platelets?

A

-thromboxane
-ADP
-PAF
-vWF
-serotonin
-FV
-fibrinogen
-Ca++

26
Q

What are the overall effects of platelet activation?

A

-further activation
-platelet aggregation

27
Q

How do platelets aggregate?

A

fibrinogen molecules bind to GpIIb-IIIa on two different platelets, linking them together

28
Q

What marks the end of primary hemostasis?

A

the formation of the primary platelet plug with fibrinogen acting as the “glue”

29
Q

What is flippase?

A

molecule that moves negatively charged phospholipids to the inside of the cell membrane

30
Q

What is floppase?

A

molecule that moves neutral phospholipids to the outside of the cell membrane

31
Q

What is scrambase?

A

molecule that moves negatively charged phospholipids outside and neutral phospholipids inside

32
Q

What happens when a platelet is activated?

A

-flippase and floppase are deactivated
-scrambase is activated

33
Q

What is platelet factor 3?

A

the activated cell membrane of a platelet (neg. charged outer membrane)

34
Q

What is the overall function of platelet factor 3?

A

connect primary and secondary hemostasis

35
Q

Why is factor 10 able to bind to the negatively charged activated platelet, despite having a negative charge itself?

A

Ca2+ ions facilitate the binding of factor 10 to the platelet wall

36
Q

What is the main goal of secondary hemostasis?

A

activation of the coagulation cascade to form fibrin

37
Q

What are the “players” involved in secondary hemostasis?

A

-coagulation factors
-platelet factor 3
-calcium

38
Q

What are the coagulation factors?

A

-fibrinogen
-prothrombin
-tissue factor
-Ca2+
-factor 7
-factor 9 complexed with co-factor 8
-factor 10 complexed with co-factor 5
-factor 11
-factor 12
-factor 13

39
Q

What does the factor 10/co-factor 5 complex form?

A

prothrombinase

40
Q

What does the factor 9/co-factor 8 complex form?

A

tenase

41
Q

How do the soluble clotting factors circulate in plasma?

A

as pro-enzymes

42
Q

How does tissue factor differ from the other coagulation factors?

A

tissue factor is a membrane-bound protein typically found in the vascular space

43
Q

Which factors are involved in the extrinsic pathway of the coagulation cascade?

A

-tissue factor
-factor 7

44
Q

Which factors are involved in the intrinsic pathway of the coagulation cascade?

A

-factor 12
-factor 11
-factor 9
-factor 8

45
Q

Which factors are involved in the common pathway of the coagulation cascade?

A

-factor 10
-factor 5
-prothrombin
-fibrinogen

46
Q

What are the characteristics of coagulation cascade initiation?

A

-extrinsic pathway
-via tissue factor
-on the surface of fibroblasts
-small amount of thrombin production

47
Q

What are the characteristics of coagulation cascade amplification?

A

-intrinsic pathway
-via thrombin
-on the surface of platelets
-leads to more thrombin production

48
Q

What is the role of tissue factor and factor 7?

A

to activate the factor 10/co-factor 5 complex

49
Q

What is the role of the factor 10/co-factor 5 complex?

A

activate prothrombin into thrombin

50
Q

What is the role of factor 9/co-factor 8 complex?

A

activate more factor 10 during the amplification phase

51
Q

What is the role of thrombin?

A

to convert fibrinogen into fibrin

52
Q

What are the functions of factor 12?

A

-bradykinin generation
-stimulation of fibrinolysis

53
Q

What are the specific physiologic inhibitors of secondary hemostasis?

A

-tissue factor pathway inhibitor
-antithrombin
-thrombomodulin
-protein C
-protein S

54
Q

What are the non-specific physiologic inhibitors of secondary hemostasis?

A

-alpha-2-macroglobulin
-alpha-1antitrypsin

55
Q

What is the essential link between primary and secondary hemostasis?

A

-platelets provide negatively charged surface for coagulation factor assembly and release
-thrombin activates platelets

56
Q

What is the essential link between secondary hemostasis and fibrinolysis?

A

-thrombin inhibits fibrinolysis
-factor 12 promotes fibrinolysis

57
Q

What is the main goal of fibrinolysis?

A

formation of plasmin to break down the fibrin clot

58
Q

What are the “players” in fibrinolysis?

A

-plasminogen
-plasminogen activators (tPA)
-fibrin

59
Q

How does fibrinolysis work?

A

-plasminogen is an inactivated “bomb” within the fibrin clot
-activation of plasminogen into plasmin destroys the clot and releases fibrinogen

60
Q

What are the inhibitors of fibrinolysis?

A

-antiplasmin
-plasminogen activator inhibitor

VMP824 Physiology/Microanatomy 2 (50 decks)

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