Hemostasis

Question 1

What occurs immediately after blood vessel damage?

Answer 1

Myogenic contraction (vasoconstriction)

Question 2

What occurs after a severe injury to a blood vessel?

Answer 2

Neurogenic vasospasm - increased sympathetic nerve firing + vasoconstriction via a spinal (pain) reflex

Question 3

How long do myogenic and neurogenic contractions last?

Answer 3

20-30 min

Question 4

What types of humoral responses cause vasoconstriction?

Answer 4

Serotonin Thromboxane A2 Prostaglandins (PGFs)

Question 5

How long does humorally-triggered vasoconstriction last?

Answer 5

Several hours

Question 6

What happens when subendothelial connective tissue is exposed to blood during injury?

Answer 6

Platelet adhesion to subendothelial collagen

Question 7

What is Von Willebrand Factor (VWF)?

Answer 7

A plasma protein factor synthesized by endothelial cells that promotes platelet adhesion and clotting factor VIII. Missing/non-functioning VWF = Hereditary Von Willebrand disease.

Question 8

What is platelet release reaction?

Answer 8

Alterations in shape and release of granules mediated by binding of VWF or thrombin to platelet membrane receptors. Causes release of calcium, serotonin, and ADP.

Question 9

What is the relationship between ADP levels and clotting?

Answer 9

ADP levels must be above a critical concentration for platelets to maintain clumping. Release of additional ADP from storage sites accelerates clumping.

Question 10

In addition to ADP, what is another potent aggregating agent?

Answer 10

Thromboxane A2

Question 11

What prevents platelets from spreading?

Answer 11

Nearby cells secrete a powerful inhibitor, prostacyclin (PGI3).

Question 12

What effect does aspirin have on clotting?

Answer 12

Reduces clotting by inhibiting cyclo-oxygenase which is needed to form thromboxane A2.

Question 13

What is primary hemostasis?

Answer 13

Vasoconstriction + platelet plug formation

Question 14

What is secondary hemostasis?

Answer 14

Blood coagulation

Question 15

What is fibrinogen?

Answer 15

Circulating precursor to fibrin

Question 16

What is prothrombin?

Answer 16

Circulating precursor to thrombin

Question 17

What is thrombin?

Answer 17

Proteolytic enzyme that converts fibrinogen to fibrin.

Question 18

What is thromboplastic activity?

Answer 18

Factors released from injured tissue that causes conversion of prothrombin to thrombin (in the presence of calcium)

Question 19

What is the genetic cause of hemophilia?

Answer 19

Sex-linked congenital deficiency of factor VIII.

Question 20

What are the proteins of the intrinsic pathway?

Answer 20

1. Prekallikrein 2. HMW kininogen 3. Factor XI

Question 21

What is the first step to activate the intrinsic clotting pathway?

Answer 21

Binding of clotting factor XII to the subendothelial connective tissues exposed by blood vessel injury.

Question 22

What other factors convert factor X to factor Xa?

Answer 22

VIII, IXa, Ca2+, platelet phospholipid

Question 23

How is prothrombin II activated to IIa?

Answer 23

Factor V is cleaved by factor Xa in the presence of calcium.

Question 24

How are fibrin networks formed?

Answer 24

Factor XIIIa helps form covalent bonds among fibrin strands

Question 25

What is the first factor in the extrinsic clotting pathway?

Answer 25

Exposure of "tissue factor" (factor III/CD142) on the surface of subendothelial cells.

Question 26

Does thrombin act as a positive feedback mechanism on the intrinsic pathway? What does it do to extrinsic?

Answer 26

Yes Shuts down extrinsic

Question 27

How quickly does the extrinsic pathway take to activate? Intrinsic?

Answer 27

Extrinsic: 10-15 seconds Intrinsic: 1-3 minutes

Question 28

How do many anticoagulants work?

Answer 28

Chelate calcium ions to prevent clotting.

Question 29

What clotting factors use calcium?

Answer 29

II, VII, IX, X

Question 30

What residues bind calcium and what substance aids their carboxylation/formation?

Answer 30

gamma-carboxygltuamic acid residues carboxylated by Vitamin K.

Question 31

What is coumarin?

Answer 31

Anticoagulation drug that acts by blocking carboxylation.

Question 32

What causes clot retraction?

Answer 32

Platelet actomyosin

Question 33

What circulating plasma protein is the major inhibitor of thrombin? What drug enhances it?

Answer 33

Antithrombin III activity increased by heparin

Question 34

Although thrombin has a positive feedback system, it also has a negative feedback system carried out via proteins ____ and \_\_\_.

Answer 34

C and S Blocks factors VIII and V

Question 35

What proteolytic enzyme digests fibrin and fibrinogen and what activates it?

Answer 35

Plasmin made from plasminogen in response to tPA

Question 36

How is tPA used therapeutically?

Answer 36

Can be used to restore blood flow to inappropriately ischemic tissues.

Question 37

What effect does serotonin have on blood vessels?

Answer 37

Vasoconstriction

Question 38

What effect does histamine have on blood vessels?

Answer 38

Increases vessel leakiness after injury to prevent infection.

Question 39

What lesions form in people lacking primary hemostasis?

Answer 39

Petechiae (small) Purpura (medium) Ecchymoses (large)