Macrocytic Anemia Flashcards
(24 cards)
Vitamin B12 and folate are involved in the synthesis of DNA, what nucleotide do they help to form?
Deoxythymidine monophosphate (dTMP)
An individual has vitamin B12 or folate deficiency; what effect does this have on nuclei?
Large nuclei in all cells- nucleus does not mature because cells are not making DNA
What is another name for vitamin B12?
Cobalamin
What is the circulating form of folate?
Methyl-tetrahydrofolate
What is the purpose of cobalamin (regarding DNA synthesis and homocysteine)?
Acts as a cofactor for methionine synthase (homocysteine methyltransferase) to generate methionine from homocysteine and folate from methyl-tetrahydrofolate
What AA is used for 1 carbon transfer reactions?
Methionine
What is the homocysteine level in a patient with vitamin B12/folate deficiency?
High
Elevated homocysteine levels predisposes individuals to what vascular event?
Thrombosis
What is the most common cause of an elevated homocysteine level in the US?
Folate deficiency
Thymidylate synthase and dihydrofolate reductase are enzymes that help make dTMP, both can be inhibited. What drugs inhibit these enzymes?
Thymidylate synthase- 5-fluorouracil
Dihydrofolate reductase- methotrexate, trimethoprim
In a patient with a macrocytic megaloblastic anemia, why are neurologic problems unique to vitamin B12 deficiency?
Vitamin B12 is involved in odd-chain fatty acid metabolism
Detail the pathogenesis of the neurologic symptoms of vitamin B12 deficiency.
Increased propionyl CoA replaces acetyl CoA in neuronal membranes which leads to demyelination
What test can distinguish vitamin B12 deficiency from folate deficiency?
Methylmalonic acid
What is the most sensitive test for vitamin B12 deficiency?
Methylmalonic acid
What is the most common cause of vitamin B12 deficiency?
Prenicious anemia
How do you classify causes of vitamin B12 deficiency?
Decreased intake
Impaired absorption
What are common causes of decreased intake of vitamin B12 ?
Vegan diet
Malnutrition
Breast fed infants of pure vegans
What are common causes of impaired absorption of vitamin B12 ?
Decreased IF
Decreased gastric acid
Decreased terminal ileum absorption
What is the effect of prenicious anemia on gastrin levels?
Increased- type 2 hypersensitivity destroys parietal cells resulting in achlorhydria
What are clinical findings associated with all causes of vitamin B12 deficiency?
Glossitis Neurologic disease (demyelination)
Detail the neurologic disease that you would expect to see in a patient with vitamin B12 deficiency.
Peripheral neuropathy Demyelination of spinal cord: posterior column- problems with proprioception/vibration sense lateral corticospinal tract- spasticity dorsal spinocerebellar tract- ataxia Dementia
Decreased maternal intake of folic acid increases the risk of what developmental defect?
Neural tube defects
Contrast nonmegaloblastic macrocytosis with megaloblastic macrocytic anemia.
Cells are round
No hypersegmented neutrophils
Leukocytes and platelets are quantitatively normal
Glossitis and neuropathy are absent
What is the most common cause for all types of macrocytosis?
EtOH
