Primal diseases of bone marrow - megaloblastic and pernicious anemias. Etiology, pathogenesis & pathomorphological characteristics of target organs.
Megaloblastic anemias simply mean that the bone marrow is hypercellular with larger than normal erythroid progenitors. There are two principal mechanisms: folate deficiency and B12 deficiency. Both vitamins are required for DNA synthesis, reduced amounts means we can produce fewer RBCs, and the RBCs it does produce are abnormally large, because nuclear maturation lags behind the cytoplasm. In the peripheral blood the earliest changes are appearance of hypersegmented neutrophils (appear before fully fledged anemia). Let's now look at the two types of megaloblastic anemia:
Blood smear in megaloblastic anaemia: a hypersegmented neutrophil (six or more nuclear lobes; normal is 3–5) among large oval red cells (macro-ovalocytes).
Image: “Hyperlobated Neutrophil (8612790151)” by Ed Uthman from Houston, TX, USA, CC BY 2.0, via Wikimedia Commons.
- Folate (folic acid) deficiency
- Not common, risk in those with poor diet, present in all foods but destroyed with cooking
- Absorbed in proximal ⅓ of intestines
- Clinical onset is gradual with nonspecific symptoms include weakness, fatigability etc. Unlike B12 anemia (below) there are no neurological symptoms
- Vitamin B12 (pernicious anemia) deficiency
- Low B12 (cobalamin) results in a morphologically identical anemia to folate deficiency
- Many causes, but the lack of intrinsic factor (which absorbs B12) is key
- Technically pernicious anemia is an autoimmune condition against parietal cells and intrinsic factor, the loss of intrinsic factor means B12 cannot be absorbed. However, as this is by far the most common cause of B12 deficiency, the terms are often used interchangeably.
- Main clinical symptoms beyond anemia are demyelination of posterior and lateral columns of the spinal cord, causing possibly severe neurologic deficits
Remember: the blood picture of B12 and folate deficiency is the same; they are told apart by neurological signs (subacute combined degeneration – B12 only) and by serum methylmalonic acid, raised only in B12 deficiency (homocysteine rises in both). Folate alone given in B12 deficiency corrects the anaemia but lets the nerve damage progress.