Physiology

Question 1

Vitamin K Pathway in Coagulation Cascade

Answer 1

1. oxidized vitamin K is reduced by epoxide reductase
2. Reduced vitamin K activates factors (2, 7, 9, 10, C, S)

Warfarin inhibits epoxide reductase

Neonates lack enteric bacteria (makes vitamin K)

Question 2

Protein C pathway

Answer 2

1. protein C activated by thrombomodulin (endothelial cells)
2. Activated Protein C (with Protein S) cleaves and inactivates Va and VIIIa

Factor V Leiden: mutated factor V resistant to cleavage by protein C

Question 3

Plasminogen pathway

Answer 3

1. Plasminogen converted to plasmin by tPA
   2) plasmin cleaves fibrin to become breakdown products

tPA clinically used as thrombolytic

Question 4

Antithrombin

Answer 4

Inhibits factors 2, 7, 9, 10, 11, 12

Activated by heparin

Question 5

Steps for Platelet Plug Formation

Answer 5

Step 1: Transient vasoconstriction of damaged vessels
- reflex neural stimulation, endothelin release from endothelial cells

Step 2: Platelet adhesion

• vWF (from Weibel-Palade bodies of endothelial cells and alpha granules of platelets) binds to exposed subendothelial collagen
• platelet bind to vWF by GP1b receptor

Step 3: Platelet degranulation

• adhesion induces shape change and degranulation (ADP, Ca2+, TXA2, serotonin)
• ADP released and binding to receptors promote exposure of GPIIb/IIIa receptors on platelets
• TXA2 synthesized by platelet COX released to promote platelet aggregation
• serotonin increases vasodilation and vascular permeability

Step 4: Platelet aggregation
- fibrinogen binds GPIIb/IIIa receptors as linking molecule resulting in platelet plug

Question 6

Pro and Anti aggregation factors for platelets

Answer 6

Pro:
TXA2, decreased blood flow, increased platelet aggregation

Anti:
PGI2 (Prostacyclin), increased blood flow, decreased platelet aggregation

Question 7

Erythrocyte sedimentation rate

Answer 7

Acute-phase reactants in plasma (e.g. fibrinogen) can cause RBC aggregation, increasing sedimentation rate (RBC aggregates have higher density than plasma)

Increased ESR rate: infections, autoimmune (SLE, RA, temporal arteritis), malignant neoplasms, GI disease (UC), pregnancy

Decreased ESR rate: polycythemia, sickle cell anemia, congestive heart failure, microcytosis, hypofibrinogenemia