Lecture 13

Question 1

What is the sympathetic response to injury

Answer 1

for blood vessels to constrict in order to slow down blood loss

Question 2

Stopping the bleeding steps (4)

Answer 2

• injury damages vascular endothelium and exposes sub-endothelial collagen
• vWF cements platelets to collagen to form a cellular ring
• fibrin deposits on platelet plug and later contracts by covalent crosslinking
• plasmin digests fibrin clot and endothelium regenerates

Question 3

Hemostatic events to tissue injury(5)

Answer 3

• Vasoconstriction (neural)
• platelet activation-adhesion and aggregation
• coagulation-blood clot-thrombin generation-fibrin polymerization
• fibrinolysis-blood clot dissolution
• vascular patency restored

Question 4

What are platelets(4)

Answer 4

shed from megakaryocytes
store secretory products in granules
increased [ ] of actin and myosin to facilitate the formation of a solid platelet plug via contraction
Binding of platelets to collagen mediated by vWF with high avidity (strength)

Question 5

Platelets can be activated in response to…(3)

Answer 5

collagen, vWF, and tissue factor (bigger injury)

Question 6

Platelet aggregation end point

Answer 6

rise in cystolic Ca which induces platelet activation/aggregation

Question 7

Sequence of events leading to formation of a platelet plug and vasoconstriction of a blood vessel wall (6)

Answer 7

• vessel damage->
• altered endothelial surface (collagen exposed)->
• platelet activation/aggregation->
• discharge of mediators and synthesis of TXA2->platelet plug
• chemical mediators and TXA2-> blood vessels contraction of VSM cells
• > vasoconstriction

Question 8

Coagulation what does it do?

Answer 8

provides strength and support to the platelet plug

ultimately=fibrinogen+thrombin= fibrin

Question 9

What strengthens the clot

Answer 9

crosslinking-transglutaminase

Question 10

Activation of platelets causes(2)

Answer 10

expression of negatively charges phospholipids (on cell surface(->attachment of Ca+2))
Clotting factors (2,7,9,10) attach to Ca+2 ions

Question 11

Intrinsic pathway(within damaged blood vessel)

Answer 11

• 7 steps set off by factor 12 (hageman factor)
• occurs simultaneously with platelet plug formation
• Platelets secrete PF3: essential for clotting cascade and enhanced platelet aggregation

Question 12

Phospholipid PF3

• expressed by…
• Acceleration of coagulation cascade by:(3)

Answer 12

activated platelets

• promotes platelet recruitment
• aggregation
• fibrin formation

Question 13

Extrinsic pathway(3)

Answer 13

4 steps- happens quicker than intrinsic
requires contact with tissue factor
thromboplastin directly activates factor 10

Question 14

Actions of thrombin-pro coagulant

Answer 14

cleaves fibrinogen to fibrin
activates clotting factors 5, 8, 11, 13
Stimulate platelet activation

Question 15

Actions of thrombin- anticoagulant

Answer 15

activates protein C which inactivates clotting factors 5, 8

Question 16

Thrombin is critical to

Answer 16

coagulation

Question 17

Cross linking of fibrin

Answer 17

initial soft plug characterized by H bonding
covalent cross linking provides strength
mediated by transglutaminase (factor 8)

Question 18

what limits clot formation to the site of injury?(3)

anticoagulant mechanisms(3)

Answer 18

labile clotting factors-slow blood down to interact more often

• diluted by blood flow
• removed by liver

tissue factor pathway inhibitor (TFPI)
thrombomodulin
Anti thrombin 3(enhanced by heparin

Question 19

Thrombomodulin- how is it anticoagulant

Answer 19

forms complex with thrombin->activation of protein C->inactivation of factors 5 and 8 through proteolytic cleavage

Question 20

Anticlotting roles of Endothelial cells

-normally provide an intact barrier between blood and subendothelial collagen

Answer 20

platelet aggregation and formation of tissue factor 8 not triggered

Question 21

Anti clotting roles of EC

-synthesize and release PGI2 and NO

Answer 21

inhibit platelet activation and aggregation

Question 22

Anti clotting roles of EC

-Secrete tissue plasminogen activator

Answer 22

catalyzes the formation of plasmin which dissolves clots

Question 23

Fibrinolysis

Answer 23

Plasmin degrades fibrin into peptides dissolving the blood clot
Plasminogen is activated by tissue plasminogen activator (tPA) ONLY when bound to fibrin
Thus fibrin promotes its own breakdown