Hereditary Diseases

Question 1

Molecular abnormality associated with hereditary spherocytosis

Answer 1

Ankyrin gene mutation causes a decrease in Spectrin assembly on membrane
Causes spontaneous loss of red blood cell membrane w/ decrease in surface:volume ratio

Question 2

Pathogenesis of hereditary spherocytosis

Answer 2

1. Spherocytes cannot pass through cords of Billroth in the spleen. Circulation stagnates.
2. Accumulation of lactic acid results in impairment of glycolysis, low ATP –> No Sodium Pump
3. Osmotic Injury to Cells

Question 3

What is G-6-PD deficiency

Answer 3

Abnormalities in hexose monophosphate shunt of glutathione metabolism result in susceptability to oxidate injury and subsequent hemolysis

Question 4

Genetic linkage of G6PD

Answer 4

X linked

Question 5

What causes the actual hemolytic crises of G6PD deficiency

Answer 5

Oxidant Damage

H2O2 accumulates and oxidizes sulfhydryl groups of hemoglobin chains, causing precipitation of Hb

Question 6

Common triggers of oxidant damage in G6PD deficiency?

Answer 6

Antimalarials (Primaquine, Quinacrine)
Sulfonamides, Nitrofurans
Infections

Question 7

What are Hb precipitates called

Answer 7

Heinz Bodies

Question 8

Effect of Heinz bodies on RBCs in G6PD deficiency

Answer 8

They attach to the cell membrane, decreasing deformability
Macrophages remove pieces –> Bite Cells
Spherocyte Formation + Splenic Sequestration
(Can also damage cytoskele, lipids, membrane leading to intravasc)

Question 9

What is PNH?

Answer 9

Abnormalities of pluripotent stem cells result in blood cells suusceptible to endogenous complement-mediated lysis

Question 10

What are the abnormalities that render cells more vulnerable to complement?

Answer 10

Abnormalities of Glycosyl Phosphatidyl Inositol (GPI) Anchor

Question 11

PNH can evolve into…

Answer 11

AA or AL

Question 12

How do PNH patients tend to die?

Answer 12

Venous thromboses (hepatic, portal, cerebral)

Question 13

Pathology of Sideroblastic Anemia

Answer 13

Sideroblastic Rings in the Marrow (Iron laden mito)
Hypochromic RBCs, siderotic granules
Hyperferremia, Near total transf. saturation

Question 14

What is sideroblastic anemia

Answer 14

Abnormalities in the formation of protoporphyrin ring synthesis leads to a mismatch between iton delivery to mito and incorporation into heme.

Question 15

What is Basophilic Stipling?

Answer 15

Non-specific finding w/ accumulation f ribosomes and r-RNA attached to RBC membrane.
Classically associated with lead poisoning.