Harrison - Megaloblastic Anemias

Question 1

Causes of megaloblastic anemias:

Answer 1

Usually a deficiency of either cobalamin (B12) or folate, but megaloblastic anemia may occur because of genetic or acquired abnormalities that affect the metabolism of these vitamins or because of defects in DNA synthesis not related to cobalamin or folate.

Question 2

Form of B12 in mt:

Answer 2

2-deoxyadenosyl (ado) form –> Cofactor for the enzyme methylmalonyl coenzyme A (CoA) mutase.

Question 3

Form of B12 in plasma and cytoplasm:

Answer 3

Methylcobalamin –> Cofactor for methionine synthase.

Question 4

Cobalamin is synthesized solely by?

Answer 4

Microorganisms.

Question 5

The only source of cobalamin for humans is:

Answer 5

Food of animal origin.

Vegetables, fruits etc are free from cobalamin unless they are contaminated by bacteria.

Question 6

Absorption of B12:

Answer 6

2 mechanisms - Passive and active.

Question 7

Passive absorption of B12:

Answer 7

Inefficient <1% of B12 - Occuring through buccal, duodenal, and ileal mucosa.

Question 8

Dietary B12 is released from protein complexes by enzymes in the stomach, duodenum, and jejunum. It combines rapidly with?

Answer 8

A SALIVARY protein –> Family of cobalamin-binding proteins known as HAPTOCORRINS (HCs).

Question 9

Haptocorrin fate in the intestine:

Answer 9

Haptocorrin is digested by pancreatic trypsin and the cobalamin is transferred to IF.

Question 10

IF gene:

Answer 10

11q13 coding for 9 exons.

Question 11

B12 deficiency develops more rapidly in those with malabsorption or in vegans?

Answer 11

Those with malabsorption - Because of the appreciable amount of B12 undergoing enterohepatic circulation.

Question 12

Marrow in megaloblastic anemias?

Answer 12

Usually cellular.