Macrocytic Anemia

Question 1

Vitamin B12 and folate are involved in the synthesis of DNA, what nucleotide do they help to form?

Answer 1

Deoxythymidine monophosphate (dTMP)

Question 2

An individual has vitamin B12 or folate deficiency; what effect does this have on nuclei?

Answer 2

Large nuclei in all cells- nucleus does not mature because cells are not making DNA

Question 3

What is another name for vitamin B12?

Answer 3

Cobalamin

Question 4

What is the circulating form of folate?

Answer 4

Methyl-tetrahydrofolate

Question 5

What is the purpose of cobalamin (regarding DNA synthesis and homocysteine)?

Answer 5

Acts as a cofactor for methionine synthase (homocysteine methyltransferase) to generate methionine from homocysteine and folate from methyl-tetrahydrofolate

Question 6

What AA is used for 1 carbon transfer reactions?

Answer 6

Methionine

Question 7

What is the homocysteine level in a patient with vitamin B12/folate deficiency?

Answer 7

High

Question 8

Elevated homocysteine levels predisposes individuals to what vascular event?

Answer 8

Thrombosis

Question 9

What is the most common cause of an elevated homocysteine level in the US?

Answer 9

Folate deficiency

Question 10

Thymidylate synthase and dihydrofolate reductase are enzymes that help make dTMP, both can be inhibited. What drugs inhibit these enzymes?

Answer 10

Thymidylate synthase- 5-fluorouracil

Dihydrofolate reductase- methotrexate, trimethoprim

Question 11

In a patient with a macrocytic megaloblastic anemia, why are neurologic problems unique to vitamin B12 deficiency?

Answer 11

Vitamin B12 is involved in odd-chain fatty acid metabolism

Question 12

Detail the pathogenesis of the neurologic symptoms of vitamin B12 deficiency.

Answer 12

Increased propionyl CoA replaces acetyl CoA in neuronal membranes which leads to demyelination

Question 13

What test can distinguish vitamin B12 deficiency from folate deficiency?

Answer 13

Methylmalonic acid

Question 14

What is the most sensitive test for vitamin B12 deficiency?

Answer 14

Methylmalonic acid

Question 15

What is the most common cause of vitamin B12 deficiency?

Answer 15

Prenicious anemia

Question 16

How do you classify causes of vitamin B12 deficiency?

Answer 16

Decreased intake

Impaired absorption

Question 17

What are common causes of decreased intake of vitamin B12 ?

Answer 17

Vegan diet
Malnutrition
Breast fed infants of pure vegans

Question 18

What are common causes of impaired absorption of vitamin B12 ?

Answer 18

Decreased IF
Decreased gastric acid
Decreased terminal ileum absorption

Question 19

What is the effect of prenicious anemia on gastrin levels?

Answer 19

Increased- type 2 hypersensitivity destroys parietal cells resulting in achlorhydria

Question 20

What are clinical findings associated with all causes of vitamin B12 deficiency?

Answer 20

Glossitis
Neurologic disease (demyelination)

Question 21

Detail the neurologic disease that you would expect to see in a patient with vitamin B12 deficiency.

Answer 21

Peripheral neuropathy
Demyelination of spinal cord:
posterior column- problems with proprioception/vibration sense
lateral corticospinal tract- spasticity
dorsal spinocerebellar tract- ataxia
Dementia

Question 22

Decreased maternal intake of folic acid increases the risk of what developmental defect?

Answer 22

Neural tube defects

Question 23

Contrast nonmegaloblastic macrocytosis with megaloblastic macrocytic anemia.

Answer 23

Cells are round
No hypersegmented neutrophils
Leukocytes and platelets are quantitatively normal
Glossitis and neuropathy are absent

Question 24

What is the most common cause for all types of macrocytosis?

Answer 24

EtOH