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30 Cards in this Set

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Deficiencies in folate and B12 result in a _____ MCV.
larger (megaloblastic anemia)
What happens to the nucleus in megaloblastic anemia?
nuclear maturation is arrested, instead of shrinking normally, the nucleus stays large b/c of defective DNA synthesis
A result of megaloblastic anemia is _____ hemolysis resulting in increased ____.
intramedullary

LDH
Folate is heat ____.
B12 is heat ____.
labile
stable
What allows for rapid absorption of folate from serum into the tissues?
folate binding proteins
Folate reserves are ___ leading to a ____ developed deficiency.

B12 reserves are ___ leading to a ____ developed deficiency.
small, quickly

large, slowly
What is probably a more accurate assessment of the body's folate levels?
folate in RBC is more stable that serum folate levels
Which one is found in plants: folate or B12?
folate
Explain absorption of B12.
R complexes found in food and saliva bind to B12 in stomach (after pepsin cleaves off attached proteins to B12). R-B12 travels to duodenum where proteases free B12, which then binds to intrinsic factor (IF). IF has receptors on ileum. Ileal cells split B12 and IF and B12 joins transcobalamin (TC II)
What cells produce IF?
parietal cells
Why is B12 the greatest in the DISTAL ileum?
b/c the number of IF receptors increases as you go further distally in the ileum
What is the main serum transport protein of b12?
transcobalamin (TC II)
Four causes of B12 deficiency:
1) achlorhydria - acid facilitates binding/unbinding
2) Decreased IF - pernicious anemia
3) Decreased pancreatic proteases
4) TCII deficiency (rare)
What is the pathophysiology behind pernicious anemia?
antibodies are produced against parietal cell and/or IF decreased absorption of B12
dUMP becomes dTMP by gaining ___ and ____, this requires the enzyme ____.
methyl group and hydroxyl group

5,10-methylene H4PteGlu
Where does B12 fit in this process (forming TMP)?
B12 takes a methyl group from methyl-THF and gives it to homocysteine (forming methionine). This forms THF which forms THF polyglutamate which forms 5,10 methylene H4PTeGlu
Where does folate fit in this process (forming TMP)?
needed for formation of methyl-THF
Deficiencies in folate or B12 result in an excess of ____.
homocysteine
Manifestations of B12/folate deficiency:
1)pancytopenia
2)GI mucosal atrophy and erosion
3)skin pigmentation
4)infertility
5)cardiac failure
6)NEUROLOGIC MANIFESTATIONS ONLY SEEN WITH B12 DEFICIENCY - subacute combined degeneration (posterior and lat. white matter of SC degenerates resulting in spasticity and neuropathies)
Two additional changes seen in blood smear of folate/B12 deficient patient:
1) oval macrocytes
2) hypersegmented PMNs
Besides the obvious, what else can cause a FOLATE deficiency?
1) drugs - anticonvulsants
2) liver disease - folate stored in liver
3) increased utilization - pregnancy
Besidse the obvious, what else can cause of B12 deficiency?
1) TCII deficiency
2) Leisch-Nyhan
3) nitrous oxide anesthesia
Clinical findings in megaloblastic anemia?
1) insidious onset
2) weakness
3) fever
4) glossitis
5) angular stomitis
6) CHF
7) neurological symptoms w/ B12
What is anisocytosis?
variable size of RBCs
What is poikilocytosis?
variable shape of RBCs
What is the appearance of the BM in megaloblastic anemia?
very cellular w/ megaloblasts and abnormal megakaryocyte morphology
Why is there increased methylmalonate in B12 deficiency?
B12 converts methylmalonate to succinate. W/o B12 there is high methylmalonate.
What will the Du Suppression test tell you if there is B12 or folate deficiency?
If someone is having trouble making their own thymidine, then the radioactive thymidine will be higher in the leukocyte DNA.
____ folate levels can be low in B12 deficiency, therefore look at ____ folate levels to distinguish between B12 and folate deficiencies.
RBC, serum
If folic acid or B12 are missing then FIGlu will be ___ . Why
increased, b/c FIGlu to glutamic acid