Hematology and Oncology- Physiology

Question 1

Hematopoiesis- organs

Answer 1

“Young Liver Synthesizes Blood”

Yolk Sac
Liver
Spleen
Bone Marrow

Question 2

Hemoglobin development

Answer 2

“Always Alpha, Gamma Goes, Becomes Beta”

gamma-epsilon (Embryonic- yolk sac)
alpha2-gamma2 (HbF- fetus)
alpha2-beta2 (HbA1- adult)
alpha2-delta2 (HbA2- adult)

Question 3

Characteristics of HbF

Answer 3

Less 2,3- BPG affinity (makes sense because it is shifting the curve left, to increase O2 affinity/ O2 binding- to extract from mom’s HbA1 and HbA2)

Question 4

ABO classification

Answer 4

A- Has A surface antigens, make IgM Abs to B
B- Has B surface antigens, makes IgM Abs to A
AB- has both A and B surface antigens; makes no Abs
O- has no surface antigens; makes IgM Abs to both A and B

Question 5

Rh classification

Answer 5

Rh+ –> has D surface antigens; does not make antibodies
Rh- –> has no D surface antigens; makes IgG Abs to D

Clinically important when mom is Rh- and kid is Rh+ (mom makes Abs to kids blood, that can potentially kill kid)

Therefore, give mom RhoGam (Anti-D IgG; to clear fetuses RBCs and prevent her from making her own anti-D IgG)

Gets worse during subsequent pregnancies, if not treated during the first one (because pre-formed Anti-D IgG are in mom’s circulation)

Question 6

Erythroblastosis fetalis- S&S

Answer 6

Hemolytic disease of the newborn

Neonates present with purpura, HSM, anemia, edema, ascites (placenta is pale, thick and enlarged)

Question 7

ABO hemolytic disease of the newborn

Answer 7

Most common

Don’t hear about as often, because antibodies to A or B antigens that are not present on the cell is generally IgM (which does not cross the placenta)

Occasionally (most common in a Type O mom) with a A or B fetus, IgG is produced that then reacts with kids RBCs

This generally does not worsen with subsequent pregnancies, and kid presents with mild jaundice that is corrected with phototherapy/ exchange transfusion when baby is delivered

Question 8

Hemoglobin electrophoresis

Answer 8

“A Fat Santa Claus”

Anode (+)

HbA
HbF
HbS (glutamic acid (-) is replaced with valine (neutral))
HbC (glutamic acid (-) is replaced with lysine (+))

Cathode (-)

Question 9

Intrinsic pathway

Answer 9

12, 11, 9, 8

Question 10

Extrinsic pathway

Answer 10

7

Question 11

Combined pathway

Answer 11

10, 5, 2, 1, 13 (stabilizes 1)

Question 12

Procoagulation

Answer 12

Oxidized Vitamin K (enzyme: epoxide reductase- inhibited by Warfarin) –> Reduced Vitamin K –> activates 2, 7, 9, 10, C, S (via gamma glutamyl transferase)

Question 13

Anticoagulation- Protein C

Answer 13

Protein C (via thrombin-thrombomodulin complex) –> activated Protein C (via protein S) –> cleaves and inactivates Va and VIIIa

Therefore Protein C plays a role in anticoagulation

Question 14

Anticoagulation- Plasminogen

Answer 14

Plasminogen (via tPA) –> Plasmin –> Fibrinolysis (1. cleaves fibrin mesh, 2. destruction of coagulation factors)

Question 15

Anticoagulation- Antithrombin

Answer 15

Main targets of antithrombin: thrombin and Xa

Inhibits activated form of factors II, VII, IX, X, XI, XII

Heparin enhances the activity of antithrombin

Question 16

Factor V Leiden mutation

Answer 16

Produces a factor V that is resistant to being inactivated by Protein C –> thereby makes individual in a hypercoagulable state

Question 17

tPA

Answer 17

Activates Plasminogen to Plasmin

Used clinically as a thrombolytic

Question 18

Platelet pathway (primary hemostasis)

Answer 18

Injury –> Exposure –> Adhesion –> Activation –> Aggregation

Question 19

Injury

Answer 19

Endothelial damage

Question 20

Exposure

Answer 20

vWF binds to exposed collagen

vWF is in endothelial cells and platelet granules

Question 21

Adhesion

Answer 21

Platelets bind vWF via GpIb receptors –> Platelets undergo a conformational change –> Platelets release ADP and Ca2+ –> ADP helps platelet adheres to endothelium

Question 22

Activation

Answer 22

ADP binding to receptor induces GpIIb/IIIa expression at platelet surface

Question 23

Aggregation

Answer 23

Fibrinogen binds GpIIb/IIIa receptors and links platelets

Question 24

Pro-aggregation factors

Answer 24

TXA2 (released by platelets)
Decrease blood flow
Increase platelet aggregation

Question 25

Anti-aggregation factors

Answer 25

PGI2 and NO (released by endothelial cells)
Increase blood flow
Decrease platelet aggregation

Question 26

Aspirin

Answer 26

Irreversibly inhibits COX (TXA2 synthesis)

Question 27

Clopidogrel

Answer 27

Inhibits ADP-induced expression of GpIIb/IIIa

Question 28

Abciximab

Answer 28

Inhibit GpIIb/IIIa directly

Question 29

Ristocetin

Answer 29

Activates vWF to bind to GpIb

Failure of agglutination indicates von Willibrand disease and Bernard Soulier syndrome (GpIb deficiency)

Question 30

Glanzmann throbastehenia

Answer 30

Deficiency of GpIIb/IIIa