Blood Coagulation & Wound Repair

Question 1

Enzymatic cascade

Answer 1

Series of rxns where substrate becomes catalyst of the next rxn

Question 2

Zymogen

Answer 2

Inactive precursor form of enzyme

Question 3

Vitamin K

Answer 3

fat soluble vitamin in which factors II, VII, IX, and X are dependent upon.

Question 4

Serum

Answer 4

Liquid phase of clotted blood after spinning out clot

Question 5

Plasma

Answer 5

Liquid phase of unclotted (anti-coagulated) blood (still contains clotting proteins). Cells have been centrifuged away.

Question 6

Hemophilia A

Answer 6

Classic hemophilia. X-linked recessive disorder caused by missing or defective factor VIII (clotting factor)

Question 7

Blood thinners

Answer 7

inhibit coagulation, prolong bleeding time, can complicate dental surgery

Question 8

Warfarin

Answer 8

Decreases blood clotting by blocking an enzyme called vitamin K epoxide reductase which acts to activate vitamin K. Reduction in vitamin k = reduction in synthesis of clotting factors

Question 9

Thromboxane A2 or TXA2

Answer 9

vasoconstrictor that also increases platelet aggregation through increasing expression of the GPIIb/IIIa protein complex on platelet membranes.

Question 10

ADP

Answer 10

stored in dense bodies inside blood platelets and is released upon platelet activation. ADP causes platelet activation/aggregation.

Question 11

Gamma-carboxyglutamic acid

Answer 11

Requires vitamin k, post-translational modification that adds a calcium binding site to coagulation proteins

Question 12

Where is vitamin k metabolized?

Answer 12

gut bacteria

Question 13

Platelets (thrombocytes)

Answer 13

anuclear cell bodies derived from megakaryocytes which circulate in the vasculature.

Question 14

Factor XIII (Transglutaminase)

Answer 14

activated by thrombin in presence of Ca, catalyzes cross linking of fibrin

Question 15

Serotonin

Answer 15

Released upon degranulation of platelets at site of injury. Functions as a smooth muscle constrictor to immediately act to limit the loss of blood volume.

Question 16

Process of coagulation

Answer 16

• blood flow to injury site reduced (vasoconstriction)
• Platelets stick to injury site
• Platelet plug forms
• Platelets & damaged tissue release factor VIII
• Fibrin formed, works as mesh to stop bleeding

Question 17

Primary hemostasis

Answer 17

Vasoconstriction and platelet response

Question 18

Secondary hemostasis

Answer 18

clotting cascase

Question 19

What molecule releases important signaling molecules upon binding to collagen immediately after injury?

Answer 19

Platelets

Question 20

What is secreted by platelets upon initial binding to collagen at site of injury?

Answer 20

ADP, thromboxane A2, serotonin

Question 21

What molecules trigger the formation the platelet plug?

Answer 21

ADP, thromboxane A2

Question 22

What molecules stimulate vasoconstriction upon injury?

Answer 22

Serotonin, thromboxane A2

Question 23

What is required for fibrinogen to bind platelets?

Answer 23

GPIIb/IIIa must undergo conformational change to expose binding site for vWF or fibrinogen

Question 24

Extrinsic pathway

Answer 24

• Activated by external trauma that causes blood to escape from the vascular system
• involves factor VII
• slower than intrinsic but less important

Question 25

Intrinsic pathway

Answer 25

- activated by trauma inside the vascular system - activated by platelets, exposed endothelium, chemicals, collagen - Involves factors XII, XI, IX, VII

Question 26

Common pathway

Answer 26

- Where both pathways meet and finish clot production - Involves factos I, II, V, X

Question 27

Factor I (Fibrinogen)

Answer 27

Cleaved by thrombin to become fibrin and forms mesh that reinforces and strengthens platelet plug

Question 28

Factor II (Prothrombin)

Answer 28

Activated on surface of activated platelets by prothrombinase complex

Question 29

von willebrand factor

Answer 29

Associated with subendothelial connective tissue, served as a bridge between platelet, glycoprotein GPIb/IX and collagen

Question 30

Thrombomodulin

Answer 30

Protein on surface of endothelial cells; binds thrombin which then activates protein C

Question 31

Phases of wound healing

Answer 31

1. Hemostasis 2. inflammatory 3. proliferative 4. remodeling

Question 32

Hemostasis

Answer 32

Within minutes after injury platelets aggregate to form a fibrin clot which controls bleeding

Question 33

Inflammatory phase

Answer 33

Bacteria and debris are phagocytosed and removed from injury (macrophage/neutrophil), factors are released that cause migration and division of cells involved in proliferative phase

Question 34

Proliferative phase

Answer 34

Angiogenesis, collagen deposition, granulation tissue formation, epithelialization, wound contraction

Question 35

Remodeling phase

Answer 35

Collagen remodeled/realigned and cells no longer needed undergo apoptosis

Question 36

Fibronectin

Answer 36

- plasma form secreted by hepatocytes and cellular form secreted by cells as part of ECM - Regulates platelet function

Question 37

What is ACD anticoagulant used for? What does it do?

Answer 37

Centrifugation; Reduces the amount of calcium so there will be no regulation of binding and cascade cannot begin

Question 38

Prothrombin time (PT)

Answer 38

test used to help detect and diagnose bleeding/clotting disorder

Question 39

International Normalized Ratio (INR)

Answer 39

- used to monitor how well warfarin is working to prevent blood coagulation - Effective range is 2.0 to 3.0 (lower = fast clotting, higher = slower clotting)

Question 40

Hemophilia B

Answer 40

- X-linked recessive, due to decreased synthesis of factor IX - Inbreeding in Europe