Megaloblastic and Non-Megaloblastic Macrocytic Anemias

Macrocytic anemias can be divided into two major categories: megaloblastic and non-megaloblastic. These categories are based on the root cause of the faulty cell development.

Megaloblast means "big blast," or large precursor cell. As mentioned on the previous page, these anemias are caused by faulty red cell production known as ineffective erythropoiesis. The defective mechanism in megaloblastic anemias is the formation of the nucleus. In normal red cell formation (erythropoiesis), the nucleus divides, and as the division continues, the nucleus condenses and gets smaller. Eventually, the nucleus is very small and completely incapable of division. It will then be extruded from the maturing erythrocyte. In megaloblastic anemias, the nuclear maturation process does not proceed normally; the nucleus cannot replicate properly and does not condense properly, leading to a larger-than-normal cell. These abnormal precursor cells often die in the bone marrow through a process known as apoptosis or programmed cell death. To review normal red cell development stages, see the image to the right.

Since impairment of nuclear development is involved, other cells in the body will also be developing abnormally, so symptoms go beyond just anemia. More information on this subject will be given later in this course.

Non-megaloblastic macrocytic anemias, on the other hand, are not caused by faulty nuclear development but by other mechanisms not involving the nucleus. One example is the toxic effects on red cell development caused by too much alcohol consumption. This can cause vacuole formation in the developing cytoplasm, which will create a slightly larger RBC.

The following sections will elaborate on the physiological mechanisms of both categories of macrocytic anemias.