Causes
Vitamin B12 deficiency:
Achlorhydria-induced malabsorption
Deficient intake
Deficient intrinsic factor, a molecule produced by cells in the stomach that is required for B12 absorption (pernicious anemia or gastrectomy)
Coeliac disease
Biological competition for vitamin B12 by diverticulosis, fistula, intestinal anastomosis, or infection by the marine parasite Diphyllobothrium latum (fish tapeworm)
Selective vitamin B12 malabsorption (congenital—juvenile megaloblastic anemia 1—and drug-induced)
Chronic pancreatitis
Ileal resection and bypass
Nitrous oxide anesthesia (usually requires repeated instances). Folate deficiency:
Alcoholism
Deficient intake
Increased needs: pregnancy, infant, rapid cellular proliferation, and cirrhosis
Malabsorption (congenital and drug-induced)
Intestinal and jejunal resection
(indirect) Deficient thiamine and factors (e.g., enzymes) responsible for abnormal folate metabolism. Combined Deficiency: vitamin B12 & folate. Inherited Pyrimidine Synthesis Disorders: Orotic aciduria
Inherited DNA Synthesis Disorders
Toxins and Drugs:
Folic acid antagonists (methotrexate)
Purine synthesis antagonists (6-mercaptopurine, azathioprine)
Pyrimidine antagonists (cytarabine)
Phenytoin
Nitrous Oxide
Erythroleukemia
Inborn genetic mutations of the Methionine synthase gene
Di Guglielmos syndrome
Congenital dyserythropoietic anemia
Copper deficiency resulting from an excess of zinc from unusually high oral consumption of zinc-containing denture-fixation creams has been found to be a cause. Pathophysiology
There is a defect in DNA synthesis in the rapidly dividing cells and to a lesser extent, RNA and protein synthesis are also impaired. Therefore, unbalanced cell proliferation and impaired cell division occur as a result of arrested nuclear maturation so the cells show nuclear-cytoplasmic asynchrony. In the bone marrow, most megaloblasts are destroyed prior to entering the peripheral blood (intramedullary hemolysis). Some can escape the bone marrow (macrocytes) to peripheral blood but they are destroyed by the reticulo-endothelial system (extramedullary hemolysis). Diagnosis
The gold standard for the diagnosis of Vitamin B12 deficiency is a low blood level of Vitamin B12.
Nevus anemicus is a congenital disorder characterized by macules of varying size and shape that are paler than the surrounding skin and cannot be made red by trauma, cold, or heat. The paler area is due to the blood vessels within the area which are more sensitive to the body’s normal vasoconstricting chemicals. Signs and symptoms
This benign patch appears on the skin at birth or in early childhood. In most people these are under 10 centimeters (3.9 in) in size. If there is doubt about the diagnosis, rubbing the area causes the skin around the lesion to become red while the lesion itself does not change in color. Often the patches are difficult to see against the background color of the patient’s skin, but if sunburn develops, then the white area stands out prominently. The involved area is lighter than the normal skin, not because of a loss of pigment occurs, but because blood vessels are constricted, producing a permanent blanching of the area. This blanching is a functional rather than a structural abnormality, presumed to be caused by local increased sensitivity to catecholamines. Although the cutaneous vasculature appears normal histologically, the blood vessels within the nevus do not respond to injection of vasodilators. It has been postulated that the persistent pallor may represent a sustained localized adrenergic vasoconstriction. Results of a skin biopsy would be interpreted as normal and only physiological testing can reveal the nevus in contrast to normal skin. Stroking the patch elicits no red flare.