265b congenital anemia

Question 1

RBC membrane proteins that are important - integral and peripheral?

Answer 1

integral - band 3

peripheral - spectrin and ankyrin

Question 2

ankyrin fxn

Answer 2

link spectrin t0 band 3

Question 3

spectrin

Answer 3

a and b subunits that self associate - supports lipid bilayer as a scaffold

Question 4

band 3

Answer 4

Cl and HCO3 exchange in bilayer

Question 5

hereditary spherocytosis (HS) - cause?

Answer 5

Defect in proteins interacting with RBC membrane skeleton and plasma membrane (e.g., ankyrin, band 3, protein 4.2, spectrin).

Question 6

hereditary spherocytosis (HS) - findings?

Answer 6

hemolysis –> anemia, jaundice
Splenomegaly
aplastic crisis (parvovirus B19 infection).

Question 7

hereditary spherocytosis (HS) - labs?

Answer 7

osmotic fragility test+.

Eosin-5-maleimide binding test useful for screening.

^MCHC, reticulocytosis, ^RCDW

Normal to decreased MCV with abundance of cells; masks microcytia.

Question 8

hereditary spherocytosis (HS) - Rx?

Answer 8

splenectomy, transfusions

Question 9

hereditary spherocytosis (HS) - RBC appearance?

Answer 9

Less membrane causes small and round RBCs with no central pallor (^ MCHC, ^ red cell distribution width) –> premature removal of RBCs by spleen. (AKA spherocytes)

Question 10

hereditary spherocytosis (HS) - findings?

Answer 10

hemolysis –> anemia, jaundice
Splenomegaly
aplastic crisis (parvovirus B19 infection).

Question 11

RBC metabolism

Answer 11

no nuclei/mito

uses 2 pathways

1) pentose phosphate pathway to make NADPH using G6PD
2) Glycolysis to make ATP - pyruvate kinase is major rate limiting step

Question 12

hereditary spherocytosis (HS) - Rx?

Answer 12

splenectomy

Question 13

glycolysis in RBCs

Answer 13

Glucose –> G6P via hexokinase then F6P

F6P –> F1,6P via PFK I then to PEP

PEP –> pyruvate via PK (generates ATP)

pyruvate –> lactate

Question 14

Hereditary elliptocytosis - rbc appearance? cause?

Answer 14

elliptocyte due to spectrin deficiency

Question 15

RBC metabolism

Answer 15

no nuclei/mito

uses 2
1) pentose phosphate pathway to make NADPH using G6PD

2) Glycolysis to make ATP - pyruvate kinase is major rate limiting step

Question 16

G6PD deficiency - findings? RBC smear appearance?

Answer 16

abdominal/back pain, hemoglobinuria a few days after oxidant stress –> coca-cola urine + jaundice, fever

Labs: blood smear shows RBCs with Heinz bodies (Hg is denatured and precipitates in RBCs) and bite cells.

“Stress makes me eat bites of fava beans with Heinz ketchup.”

Question 17

glycolysis in RBCs

Answer 17

Glucose –> G6P via hexokinase then F6P

F6P –> F1,6P via PFK I then to PEP

PEP –> pyruvate via PK (generates ATP)

pyruvate –> lactate

Question 18

G6PD deficiency - inheritance?

Answer 18

X-linked recessive

Question 19

G6PD deficiency - pathogenesis?

Answer 19

Defect in G6PD –> reduced glutathione –> ^ RBC susceptibility to oxidant stress.

Hemolytic anemia following oxidant stress (classic causes: sulfa drugs, antimalarials, infections, fava beans).

Question 20

G6PD deficiency - findings?

Answer 20

Back pain, hemoglobinuria a few days after oxidant stress.

Labs: blood smear shows RBCs with Heinz bodies and bite cells.

“Stress makes me eat bites of fava beans with Heinz ketchup.”

Question 21

pyruvate kinase deficiency - genetics?

Answer 21

AR

Question 22

pyruvate kinase deficiency - pathogenesis?

Answer 22

Defect in pyruvate kinase–> decreased ATP –> rigid RBCs.

Question 23

pyruvate kinase deficiency - findings?

Answer 23

hemolytic anemia in a newborn –> hyperbilirubinemia

anemia, jaundice (but no increase in hemolysis?)

increased 2,3 DPG –> right shift of O2 curve