Megaloblastic vs nonmeg macrocytic anemia

[anbuitachi]

Does anyone know why folate deficiency cause megaloblastic anemia? Because apparently inhibiting pyrimidine synthesis only causes macrocytic, not necc megaloblastic. So what is so special about folate that it causes megaloblastic?

B/c in pathoma it says folate causes megaloblastic, and also see things like hypersegmented neutrophils, and megaloblastic changes in other cells. but in drugs like 5 FU, you only see macrocytic anemia, w/o the other stuff.... so how does folate do this?

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[MLT2MT2DO]

Does anyone know why folate deficiency cause megaloblastic anemia? Because apparently inhibiting pyrimidine synthesis only causes macrocytic, not necc megaloblastic. So what is so special about folate that it causes megaloblastic?

B/c in pathoma it says folate causes megaloblastic, and also see things like hypersegmented neutrophils, and megaloblastic changes in other cells. but in drugs like 5 FU, you only see macrocytic anemia, w/o the other stuff.... so how does folate do this?

Definition of Megaloblastic anemia: megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis,

Know that B12/Folate deficiency is the cause Megaloblastic anemia and others are just macrocytic anemia, outside of this I'm guessing you're playing with 260+ concepts.

 

[dbeast]

Definition of Megaloblastic anemia: megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis,

Know that B12/Folate deficiency is the cause Megaloblastic anemia and others are just macrocytic anemia, outside of this I'm guessing you're playing with 260+ concepts.

The bolded is the first time I've read that definition of megaloblastic anemia (go figure), but I think it just led me to an a-ha moment. Because B12 and Folate are together responsible for the dUMP to dTMP reaction, you have plenty of uracil for RNA but no Thymine for DNA. I'm sure that's like day 1 biochem but I just figured this out. Is this why?

 

[preDoGuy24]

Does anyone know why folate deficiency cause megaloblastic anemia? Because apparently inhibiting pyrimidine synthesis only causes macrocytic, not necc megaloblastic. So what is so special about folate that it causes megaloblastic?

B/c in pathoma it says folate causes megaloblastic, and also see things like hypersegmented neutrophils, and megaloblastic changes in other cells. but in drugs like 5 FU, you only see macrocytic anemia, w/o the other stuff.... so how does folate do this?

Sounds to me like it's more of a dosing concept. With 5fu/methotrexate you probably aren't going to dose to the point of creating megaloblastic anemia, plus I would think these drugs are going to preferentially inhibit rapidly dividing tumor cells over the normally, but still quickly dividing gi/blood cells. You can also use the always fun leucovorin rescue that usmlerx loves, to cut down on the damage to the normal cells, though that's b12 but still in the megaloblastic neighborhood.

Just my guess../ two cents, and agree with above this is probably out of step 1 territory, I haven't come across a practice question on this concept yet in school/board prep

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[Sanzy]

Does anyone know why folate deficiency cause megaloblastic anemia? Because apparently inhibiting pyrimidine synthesis only causes macrocytic, not necc megaloblastic. So what is so special about folate that it causes megaloblastic?

B/c in pathoma it says folate causes megaloblastic, and also see things like hypersegmented neutrophils, and megaloblastic changes in other cells. but in drugs like 5 FU, you only see macrocytic anemia, w/o the other stuff.... so how does folate do this?

Why/where did you get the idea that poor pyrimidine synthesis doesn't cause megaloblastic anemia? Orortic aciduria, a problem with pyrimidine synthesis, causes a megaloblastic anemia that is refractory to both folate and B12. Cytarabine is a pyrimdine analogue that can cause megaloblastic anemia.

Unfortunately, I don't know why specifically 5-FU causes a nonmegaloblastic macrocytic anemia.

 

[blaqmamba]

http://forums.studentdoctor.net/showthread.php?t=941757

read the argument for yourselves!

Still no conclusion, I assume