Macrocytic anemia (B12 and folate deficiency) Flashcards

1
Q

What is the role of folate in nucleotide synthesis?

A

Folate is converted to dihydrofolate (DHF) and then tetrahydrofolate (THF), which is essential for DNA synthesis.

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2
Q

What is the role of B12 in the folate cycle?

A

B12 is required for methionine synthase to convert homocysteine to methionine and regenerate THF from methyl-THF.

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3
Q

Which metabolic reaction is unique to B12 and not folate?

A

B12 is required for methylmalonyl-CoA mutase to convert methylmalonyl-CoA to succinyl-CoA, preventing methylmalonic acid (MMA) buildup.

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4
Q

What accumulates in B12 deficiency that does not accumulate in folate deficiency?

A

Both homocysteine and methylmalonic acid accumulate in B12 deficiency, while only homocysteine accumulates in folate deficiency.

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5
Q

How does B12 deficiency affect homocysteine and MMA levels?

A

Both homocysteine and methylmalonic acid (MMA) are elevated.

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6
Q

How does folate deficiency affect homocysteine and MMA levels?

A

Only homocysteine is elevated, MMA is normal.

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7
Q

What are common dietary sources of folate?

A

Leafy green vegetables, liver, fortified grains.

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8
Q

Where is folate absorbed in the GI tract?

A

Jejunum.

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9
Q

What conditions impair folate absorption?

A

Celiac disease, small bowel resection, jejunal bypass surgery.

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10
Q

What are common causes of folate deficiency?

A

Alcoholism, elderly patients, poor diet, malabsorption (celiac, Crohn’s), pregnancy, increased demand (hemolysis, malignancy).

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11
Q

What drugs can cause folate deficiency?

A

Methotrexate, trimethoprim (TMP), phenytoin.

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12
Q

What can be used to prevent methotrexate-induced folate deficiency?

A

Leucovorin (folinic acid), which bypasses dihydrofolate reductase inhibition.

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13
Q

What are common dietary sources of B12?

A

Animal products: meat, eggs, dairy.

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14
Q

Describe the steps of B12 absorption.

A
  1. B12 is bound to proteins in food. 2. Haptocorrin (from saliva) binds B12 in the stomach. 3. Pancreatic proteases release B12 in the duodenum. 4. Intrinsic factor (from parietal cells) binds B12. 5. B12-IF complex is absorbed in the ileum.
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15
Q

What conditions impair B12 absorption?

A

Pernicious anemia (autoantibodies against parietal cells), Crohn’s disease (ileal involvement), ileal resection, bariatric surgery, Diphyllobothrium latum (fish tapeworm).

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16
Q

Why does dietary B12 deficiency take years to develop?

A

The liver stores years’ worth of B12, so deficiency is slow to manifest unless absorption is impaired.

17
Q

What are the general symptoms of megaloblastic anemia?

A

Fatigue, pallor, weakness, glossitis (beefy red tongue), diarrhea, anorexia.

18
Q

What neurological symptoms are unique to B12 deficiency?

A

Subacute combined degeneration (SCD) affecting dorsal columns and lateral corticospinal tracts, leading to ataxia, paresthesias, and weakness.

19
Q

What psychiatric symptoms can occur with B12 deficiency?

A

Irritability, dementia, depression, cognitive impairment.

20
Q

What is the triad of subacute combined degeneration (SCD)?

A
  1. Dorsal column dysfunction (loss of proprioception, vibration). 2. Lateral corticospinal tract dysfunction (spastic paresis). 3. Spinocerebellar tract dysfunction (ataxia).
21
Q

What are the classic lab findings in megaloblastic anemia?

A
  • MCV >100 fL
  • Hypersegmented neutrophils (>5 lobes)
  • Low reticulocyte count
22
Q

What serum markers differentiate B12 from folate deficiency?

A

Both have elevated homocysteine, but only B12 deficiency has elevated methylmalonic acid (MMA).

23
Q

What B12 level is considered diagnostic for deficiency?

A

B12 <200 pg/mL.

24
Q

What folate level is considered diagnostic for deficiency?

A

Folate <4 ng/mL.

25
Q

How is folate deficiency treated?

A

Oral folate supplementation (1 mg/day).

26
Q

What is the treatment for severe B12 deficiency with neurologic symptoms?

A

Intramuscular (IM) B12 injections.

27
Q

What happens if folate is given to a patient with unrecognized B12 deficiency?

A

Anemia improves, but neurological symptoms worsen due to uncorrected methylmalonic acid toxicity.

28
Q

What are the key differences between folate and B12 deficiency?

A

Both cause megaloblastic anemia, but B12 deficiency causes neurological symptoms and elevated methylmalonic acid, while folate deficiency does not.