8) Macrocytic anemias Flashcards
asynchronous maturation of any nucleated cell type
megaloblastic
establishment of megaloblastic anemia requires…
BM exam
causes of nonmegaloblastic macrocytic anemias (5)
- increased retics
- hypothyroidism
- alcoholic liver disease
- nonalcoholic liver disease
- aplastic anemia/refractory anemia
causes of megaloblastic anemias (4)
- B12 deficiency
- folate deficiency
- chemotherapy with drugs that inhibit DNA synth
- CDA
other name for B12
cobalamin
only vitamin exclusively synthesized by microorganisms
B12
2 functions of B12
- synthesis of methionine from homocysteine, central reaction in DNA synth
- coenzyme to make succinyl CoA from methylmalonic acid (MMA)
buildup of both homocysteine and MMA
B12 deficiency
buildup of homocysteine, but not MMA
folate deficiency
folate trap
B12 deficiency causes folate to leak out of cells
traps folate in methylated form
required for absorption of B12
intrinsic factor
carries B12 in plasma
transcobalamin I, II, or III
why is dietary B12 deficiency so rare?
body stores 2-5 mg which will last for several years
4 general causes of B12 deficiency
- pernicious anemia (PA)
- inadequate intake
- other malabsorption syndromes
- microbiological utilization
GI system effects related to B12 deficiency
gastric atrophy
atrophic gastritis
intrinsic factor decreased
abd pain, constipation, diarrhea
CNS effects related to B12 deficiency
decreased myelination
tingling, numbness, weakness of extremities
“megaloblastic madness”, irritability, memory loss
B12 deficiency on PB
macro-ovalocytes
hypersegmented neutros
decreased platelets
normal retics
Howell Jolly bodies
Cabot rings
BM effects related to B12 deficiency
megaloblastic erythroid hyperplasia
giant metamyelocytes
bands
karyhorrhexis
why do signs of hemolysis (LD, bilirubin, haptoglobin) occur in B12 deficiency?
abnormal cells lyse in BM (intravascular hemolysis)
diagnosis of pernicious anemia (5)
- megaloblastic BM
- achlorhydria (low gastric acid)
- decreased B12
- Schilling test (determines lack of IF)
- Serum Ab tests for autoAb against IF, parietal cells
pernicious anemia tx
IV or IM B12
folic acid (causes remission of sx, but does not reverse neuro sx)
buck blind loop syndrome
cause of B12 deficiency where, post surgery, there is overgrowth of bacteria in SI, which utilize B12 before it can be absorbed
infestation with this tapeworm can cause B12 deficiency
Diphyllobothrium latum
active form of folate
tetrahydrofolate (THF)
plays vital role in metabolism of nucleotides and amino acids
folate
sources of folate
romaine, spinach, okra, broccoli
beans
brewer’s yeast
boiling destroys…
folate
4 causes of folate deficiency
- inadequate intake
- increased demand (pregnancy)
- inadequate absorption
- drugs (OC, anticoags, phenobarb, primidione, phenytoin, alcohol)
good indicator of folate status over last 4 months
not affected by recent diet
RBC folate level
signs of B12 deficiency absent in folate deficiency
CNS sx
pancytopenia
diagnosis of folate deficiency
- decreased serum folate
- decreased RBC folate
- FIGLU excretion following histidine administration (not done much anymore)
how does B12 affect folate?
required to keep conjugated folate in the cells
deficiency may cause ↓ RBC folate and ↑ serum folate
B12, serum folate and RBC folate all decreased
B12 + folate deficiency
