Megaloblastic Anemia (b)

B12 or Folic acid deficiency

The morphologic hallmark of megaloblastic anemias is an enlargement of erythroid precursors (megaloblasts), which gives rise to abnormally large red cells (macrocytes

granulocyte precursors are enlarged (giant metamyelocytes) and yield highly characteristic hypersegmented neutrophils

impairment of DNA synthesis, which results in a delay in nuclear maturation and cell division. Because the synthesis of RNA and cytoplasmic elements proceeds at a normal rate and thus outpaces that of the nucleus, the hematopoietic precursors show nuclear-cytoplasmic asynchrony

undergo apoptosis in the marrow (ineffective hematopoiesis

pancytopenia (anemia, thrombocytopenia, and granulocytopenia

Morphology in megaloblastic anemia:

The bone marrow is markedly hypercellular, as a result of increased numbers of megaloblasts. These cells are larger than normoblasts and have a delicate, finely reticulated nuclear chromatin (suggestive of nuclear immaturity) and an abundant, strikingly basophilic cytoplasm

As the megaloblasts differentiate and begin to acquire hemoglobin, the nucleus retains its finely distributed chromatin and fails to undergo the chromatin clumping typical of an orthochromatic normoblast

Similarly, the granulocytic precursors also demonstrate nuclear-cytoplasmic asynchrony, yielding giant metamyelocytes. Megakaryocytes, too, may be abnormally large and have bizarre multilobed nuclei.

Normally, neutrophils have three or four nuclear lobes, but in megaloblastic anemias neutrophils often have five or more.

The red cells typically include large, egg-shaped macro-ovalocytes; the MCV is often greater than 110 fL

Causes of Megaloblastic Anemia Vitamin B12 Deficiency:

Decreased intake

Inadequate diet, vegetarianism

Impaired absorption

Intrinsic factor deficiency

Pernicious anemia

Gastrectomy

Malabsorption states

Diffuse intestinal disease, e.g., lymphoma, systemic sclerosis

Ileal resection, ileitis

Competitive parasitic uptake

Fish tapeworm infestation

Bacterial overgrowth in blind loops and diverticula of bowel

Increased requirement

Pregnancy, hyperthyroidism, disseminated cancer.