250. Megaloblastic Anemia Flashcards

1
Q

Megaloblastosis

  • main cause
  • consequences in blood and bone marrow
  • two key types
A

Cause: Defective DNA synthesis
Bone Marrow: Ineffective erythropoiesis
- hypercellular marrow, low peripheral blood counts
- asynchrony in nuclear/cytoplasmic maturation
- destruction of bone marrow precursors: release of contents = high bilirubin, high LDH, low haptoglobin (binds freed Hb)
Blood: macro-ovalocytes, neutrophil hypersegmentation

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2
Q

Vitamin B12 Deficiency

  • normal fx
  • cause of deficiency
  • CP
  • Dx
  • Tx
A

Normal Fx:

  • DNA precursor synthesis - in methyl transfer step (takes methyl group from methylTHF to methylate homocysteine to methionine, to make THF for purine/pyrimidine synthesis)
  • cofactor in H transfer, to make succinyl coA from methylmalonyl coA
  • Absorption: Meat, Eggs, Dairy; gastric acid liberates it from binding proteins, binds salivary haptocorin, pancreas frees B12 to bind IF from gastric parietal cells, absorbed in ILEUM, 2-4 years storage in LIVER

Cause: MALABSORPTION&raquo_space; diet, Gastric Disease (acid poor enviro, pernicious anemia, pancreatic disease, IBD)

CP: Pernicious Anemia: auto-Ab destroy gastric parietal cells (low HCl production) or bind IF (increased malignancy risk) = pancytopenia, hemolysis, macroovalocytes, hypersegmentation neutrophils, SUBACUTE COMBINED DEGENERATION (brain and CNs cause dementia, personality change, loss of vibration and proprioception, paresthesias)

Dx: low B12, increased Methylmalonic acid, increased homocysteine, Auto-ABs against parietal cells or IF if pernicious anemia

Tx: B12 supplement (IM first to repletion, oral effective even with malabsorption), tx underlying cause

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3
Q

Folate (B9) Deficiency

  • normal fx
  • causes
  • CP
  • dx
  • tx
A

Normal Fx: Player in methyl transfer step of DNA precursor synthesis
Absorption: from leafy green veggies taken up by small intestine (minimal body stores - MONTHS)

Causes:

  • DIET DEFICIENCY: poor diet, CHRONIC ALCOHOLISM
  • increased requirements: pregnancy, hemolytic anemia
  • Malabsorption of small intestine: Celiac, IBD
  • Drugs blocking B9 utilization: MTX, TMP, phenytoin
  • loss through hemolysis

CP: megaloblastic anemia, NO neuro sx, malnutrition sx, NTDs in pregnancy

Dx: low serum folic acid levels (sensitive to recent meals), Red Cell Folate Levels (chronic folate status), elevated serum homocysteine only

Tx: Oral Folic Acid (easily absorbed even in malabsorption), prophylactically in high demand pts, must EXCLUDE B12 deficiency

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