Pernicious Anemia As A Subset Of Megaloblastic Anemias

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Intrinsic factor is the single most important ingredient to the absorption of vitamin B12 and subsequent delivery of vitamin B12 to the circulation. When problems with intrinsic factor develop, the condition is called pernicious anemia. Drs. George Minot and William Murphy of Boston were awarded the Nobel Prize in 1934 for their discovery that ingestion of liver successfully treated patients with pernicious anemia. Several factors may account for the lack of intrinsic factor in the stomach, including physical factors such as partial or whole gastrectomy, or genetic and immune factors. Whatever the cause, either intrinsic factor is not being secreted or it is being blocked or neutralized in some fashion. Atrophic gastritis may occur in which gastric secretions are diminished and therefore intrinsic factor fails to be secreted. The reasons for this remain unclear but age may play a role.5 Immune factors may arise that cause antibodies to be produced against intrinsic factor, thyroid tissue, and parietal cells, all of which will decrease the production of intrinsic factor. Antibodies to intrinsic factor are present in 56% of patients with pernicious anemia, with 90% of patients showing parietal cell antibodies, and this suggests a strong autoimmune component to this disorder. Additionally, there is a higher frequency of pernicious anemias in individuals with diabetes, thyroid conditions, and other autoimmune processes.6 Pernicious anemia may occur genetically as an autosomal recessive trait in children before the age of 2. Cubilin, a receptor for vitamin B12 and intrinsic factor, has been identified since 1998, but its role in juvenile-onset pernicious anemia is still being researched.7 Adult forms of congenital pernicious anemia do occur and are associated with achlorhydria or malabsorption in relatives.

Pernicious anemia is more common in individuals with Irish and Scandinavian ethnicity. Pernicious anemia patients will experience all of the symptoms of a patient with megaloblastic anemia, but they have a higher tendency for neurological involvement including those already mentioned as well as degeneration of peripheral nerves and the spinal column. Neurological symptoms may be slow to develop but include a vast array of symptomatology. Patients may experience paresthesias in the limbs, an abnormal or clumsy walking pattern or stiffness in the limbs. Treatment will usually reverse these symptoms.


Dietary deficiencies are rarely the cause of vitamin B12 deficiency, except for individuals who are strictly vegetarians or infants nursed by vegetarian mothers who are not supplementing their diets. Other potential sources of a deficiency in vitamin B12 are the malabsorption syndromes, which include any condition that affects B12 absorption. Lack of intrinsic factor may occur if a gas-trectomy or partial gastrectomy has occurred, and the parietal cells that secrete IF would invariably be affected, thereby affecting vitamin B12 absorption. Added to this is a condition called blind loop syndrome, in which there is an overgrowth of bacteria in a small pocket of malformed intestine. The microorganisms take up the vitamin B12, and it is not available to be absorbed. Although unusual, the fish tapeworm Diphyllobothrium latum may compete for vitamin B12 when it attaches to the intestine. Individuals who have this parasite exhibit signs of megaloblastic anemia, which can be corrected once the parasite is discovered and destroyed.

Dietary deficiency is a serious consideration in folic acid deficiency and may occur in pregnancy or infancy because of increased requirement or in the

90 Part II • Red Cell Disorders elderly or alcoholic persons because of lack of availability. Folic acid is depleted from body stores within 3 to 6 months, and in vulnerable populations, folic acid deficiency continues to be one of the most common vitamin deficiencies in the United States. Tropical spue is one of the most common malabsorption syndromes that contributes to folic acid deficiency. This syndrome is usually seen in individuals from tropical or subtropical climates like Haiti, Cuba, and Puerto Rico. Although rare, this condition affects overall digestion and is thought to be a result of infection, overgrowth of bacteria, or poor nutrition. Normally, the villi that line the digestive tract are fingerlike projections whose job is to promote absorption from ingested food. The villi from individuals with tropical sprue are flattened, leading to poor absorption activity. Individuals with sprue will manifest this disease with diarrhea, indigestion, and weight loss. Last, folic acid deficiency may be expected in individuals taking methotrexate or other chemotherapy drugs, because many of these directly affect DNA synthesis of dividing cells, normal and abnormal.

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