Megaloblastic anemia with hypersegmented neutrophil

Q. I’m confused how in megablastic anemia, cells become macrocytic due to immature nuclei when RBCs don’t have nuclei! Is it referring to the erythroblast precursors before the nuclei are lost?

A. Great question. In megaloblastic anemia, cells have a hard time making DNA (because there’s a lack of B12 and/or folate) – but RNA production proceeds normally. So you end up with cells that have normally maturing cytoplasm, but slowly-maturing nuclei. This means that the cell grows pretty large before the nucleus gets mature enough to signal division (so the cells end up being larger than normal). Also, when you look at the nucleus, it looks more immature than the cytoplasm (hence the term “nuclear-cytoplasmic asynchrony). You’re right: these changes are easiest to see when you look at erythroblast precursors (which have nuclei). You can also see the same changes in neutrophil precursors (you’d have to look at the marrow to see both of these types of precursor cells).

When you look at the blood, you can’t see these precursors. But you do see macrocytes (larger-than-normal mature red blood cells) and hypersegmented neutrophils. The reason the mature red cells are bigger than usual has to do with the fact that the red cell precursors get bigger than normal before each cell division, as described above…and that translates into bigger-than-normal mature (non-nucleated) red blood cells. The reason for the hypersegmented neutrophils is less clear; it has something to do with the abnormal, asynchronous maturation going on in the neutrophil series – but how the mature neutrophil winds up with a nucleus with more lobes (or segments) than normal is kind of a mystery.