Physiology

Question 1

Blood Groups

Answer 1

• A: A antigen on RBC surface and anti-B antibody in plasma.
• B: B antigen on RBC surface and anti-A antibody in plasma.
• AB: A and B antigens on RBC surface; no antibodies in plasma; “universal recipient” of RBCs, “universal donor” of plasma.
• O: Neither A nor B antigen on RBC surface; both antibodies in plasma; “universal donor” of RBCs, “universal recipient” of plasma.
• Incompatible blood transfusions can cause immunologic response, hemolysis, renal failure, shock, and death.
• Note: anti-A and anti-B antibodies—IgM (do not cross placenta); anti-Rh—IgG (cross placenta).

Question 2

Rh Factor

Answer 2

• Rh antigen on RBC surface.
• Rh− mothers exposed to fetal Rh+ blood (often during delivery) may make anti-Rh IgG.
• In subsequent pregnancies, anti-Rh IgG crosses the placenta, causing hemolytic disease of the newborn (erythroblastosis fetalis) in the next fetus that is Rh+.
• Treatment: Rho(D) immune globulin for mother during every pregnancy to prevent initial sensitization of Rh− mother to Rh antigen.

Question 3

Coagulation, complement, and kinin pathways

Answer 3

Question 4

Procoagulation cascade

Answer 4

• Warfarin inhibits the enzyme vitamin K epoxide reductase.
• Neonates lack enteric bacteria, which produce vitamin K.
• Vitamin K deficiency: decr synthesis of factors II, VII, IX, X, protein C, protein S.
• vWF carries/protects VIII.

Question 5

Anticoagulation cascade

Answer 5

• Antithrombin inhibits activated forms of factors II, VII, IX, X, XI, XII.
• Heparin enhances the activity of antithrombin.
• Principal targets of antithrombin: thrombin and factor Xa.
• Factor V Leiden mutation produces a factor V resistant to inhibition by activated protein C.
• tPA is used clinically as a thrombolytic.

Question 6

Platlet plug formation (primary hemostasis)

Answer 6

1. Injury: vWF binds to exposed collagen upon endothelial damage
2. Adhesion: Platelets bind vWF via GpIb receptor at the site of injury only (specific) –> Platelets release ADP and Ca2+ (necessary for coagulation cascade) –> ADP helps platelets adhere to endothelium.
3. Activation: ADP binding to receptor induces GpIIb/IIIa expression at platelet surface.
4. Aggregation: Fibrinogen binds GpIIb/IIIa receptors and links platelets. Balance between: -Pro-aggregation factors: TXA2 (released by platelets), ↓ blood flow, ↑ platelet aggregation -Anti-aggregation factors: PGI2 and NO (released by endothelial cells), ↑ blood flow, ↓ platelet aggregation Temporary plug stops bleeding

Question 7

Thrombogenesis

Answer 7

• Formation of insoluble fibrin mesh.
• Aspirin inhibits cyclooxygenase (TXA2 synthesis).
• Ticlopidine and clopidogrel inhibit ADPinduced expression of GpIIb/IIIa.
• Abciximab inhibits GpIIb/IIIa directly.
• Ristocetin activates vWF to bind to GpIb.
• Useful for diagnosis: normal platelet aggregation response is not seen in von Willebrand disease.

Question 8

Erythrocyte sedimentation rate

Answer 8

• Acute-phase reactants in plasma (e.g., fibrinogen) can cause RBC aggregation, thereby incr RBC sedimentation rate (RBC aggregates have a higher density than plasma).
• Incr ESR–> infections, autoimmune diseases (e.g., SLE, rheumatoid arthritis, temporal arteritis), malignant neoplasms, GI disease (ulcerative colitis), pregnancy.
• Decr ESR–> polycythemia, sickle cell anemia, CHF, microcytosis, hypofibrinogenemia.