Macrocytic means “large cell” in Greek and macrocytic anemia refers to RBCs with an MCV>100. To form mature RBCs, RBC precursors divide multiple times, and they get smaller with each division. Without the proper building blocks for DNA, such as adequate levels of folate, the RBC precursors divide fewer times resulting in larger red blood cells.
Megaloblastic anemia refers to anemia due to impaired DNA synthesis leading to changes in cell morphology. These changes include large RBCs (macrocytic) and large and hypersegmented neutrophils. Folate deficiency and vitamin B12 deficiency are the most common causes of megaloblastic anemia. In a patient with megaloblastic anemia, vitamin B12 deficiency must be ruled out prior to treating a patient with folate as folate supplementation in a patient with vitamin B12 deficiency can worsen neurologic symptoms.
Folate is absorbed in the proximal jejunum and ileum. Damage in these areas, such as transmural inflammation due to Crohn’s Disease, can lead to malabsorption of folate and thus folate deficiency.
Inadequate intake of folate, which is primarily found in fresh green leafy vegetables and liver, can lead to folate deficiency. Folate is heat sensitive and thus is lacking in cooked foods.
The “tea and toast” diet is a diet seen in the elderly where they subsist on food with little nutritious value. This diet is devoid of foods containing folate, such as green leafy vegetables, thus leading to folate deficiency. Body stores of folate can be depleted in 4-5 months.
Chronic alcoholics often have poor diets that can result in folate deficiency. Other reasons for folate deficiency in alcoholics include impaired enterohepatic cycling which can lead to malabsorption of folate. Alcoholics can deplete their body stores of folate in 5-10 weeks compared with nonalcoholics who’s stores take 4-5 months to be depleted
There are many medications that can antagonize the effect of folate and thus lead to folate deficiency.
MTX is a folic acid analog that binds and inhibits dihydrofolate reductase, preventing the formation of the biologically active form of folic acid, tetrahydrofolate. This results in a functional folate deficiency as thymidine synthesis does not occur.
TMP inhibits bacterial dihydrofolate reductase and has been found to exacerbate pre-existing folate deficiency.
Conditions such as hemolytic anemia and pregnancy that demand a greater amount of folate can result in a relative folate deficiency (folate levels are actually within the normal range).
In hemolytic anemia the body attempts to compensate for RBC hemolysis by synthesizing new RBCs which require DNA synthesis. This results in a greater requirement for folate and thus a relative folate deficiency.
There is rapid cell division in pregnancy resulting in a greater requirement for folate and thus a relative folate deficiency.
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