Q. What is the pathophysiology of microcytes in iron-deficiency anemia (IDA)? I mean I understand that hypochromasia is due to low hemoglobin content, but what makes the cells smaller? Is it something like first there is hypochromasia and then the cells shrink??? Aren’t hypochromatic cells normocytic? Why don’t red cells keep shrinking as they become hypochromatic?  Please help. The question is bothering me a lot. 🙂

A. You’re right: in IDA, the red cells do get smaller. Since the bulk of the red cell is composed of hemoglobin, the less hemoglobin there is in the cell, the smaller the cell volume, and the smaller the cell overall. So in iron-deficiency anemia, there is less iron around, and therefore less hemoglobin – so the cells are smaller than normal. Same thing happens in thalassemia: less hemoglobin around (though not because of iron, but because of a genetic defect in a hemoglobin chain), so the red cells are smaller.

Just to clarify: chromasia just refers to the amount of hemoglobin in the cell. Cells can be normochromic (as they are in normal blood), or hypochromic (as they are in IDA). The size of the red cell is measured separately from the chromasia. Normally-sized red cells are called normocytic, small ones are called microcytic, and large ones are called macrocytic.

You asked if hypochromic cells are normocytic – and for the reason stated above, the answer is no, they usually aren’t. They are usually microcytic, because there’s less hemoglobin in the cell, so the cell gets smaller.

Finally, to answer your last question, in iron-deficiency anemia, the red cells do keep shrinking as they become more and more hypochromic! Assuming the iron deficiency is a continuing problem, as each new wave of red cells is produced, there will be less and less iron around – and the cells will get smaller and smaller.

So when you look at a blood smear from a patient with IDA (like the one above), you’ll see some cells that are a little bigger (these are older red cells that were made when there was still a fair amount of iron around), and some that are a little smaller (these are newer red cells, made when the iron level had dropped). Check out the two cells in the center of the image: both are hypochromic, but the one in the center is about twice as big as the one to its left.

This is why you can use the RDW to help differentiate between IDA and mild-moderate thalassemia!