question and answer
Why does alcoholism swell red blood cells?
February 2006
A. BUCKRIDAN, MD, of Toronto, ON, asks, "How does alcoholism raise the mean corpuscular volume (MCV)? Are there other causes of high MCV?"
The mechanism by which alcoholism causes microcytosis, or high MCV, isn't known. Ethanol inhibits the action of some enzymes involved in folate metabolism — subjects on a diet deficient in this nutrient develop folate deficiency faster if they continue to consume alcohol. Yet impaired folate metabolism isn't the only factor causing macrocytosis. The condition persists in alcoholics even when they take large doses of folic acid.

There's some evidence that macrocytosis may in part be due to high levels of blood acetaldehyde, the first metabolite of ethanol. Studies in experimental animals and in human alcoholics have shown that acetaldehyde can bind to proteins and cellular constituents forming stable adducts — in fact, elevated adduct levels have been isolated from the erythrocytes of ethanol abusers. These high adduct concentrations may also be associated with ethanol-induced effects in hematopoiesis and adverse consequences in cellular functions. MCV is higher in Japanese heavy drinkers with inactive aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH2*1/2*2 than among those with active ALDH2 encoded by ALDH2*1/2*1. Inactive ALDH2 dramatically increases blood acetaldehyde levels after alcohol intake. At the present, it's believed that the macrocytosis of alcoholics is due to a poorly defined direct effect of alcohol on the bone marrow.

There are numerous causes for high MCV in addition to alcoholism. In general, these are divided into two categories — associated with megaloblastic changes in the bone marrow, or not. The first group includes vitamin B12 deficiency, folate deficiency, most cancer chemotherapy or immunosuppressive therapy, and some inborn errors of metabolism. In the second category we find chronic alcoholism, liver disease, obstructive jaundice, any condition associated with high reticulocyte count (hemolytic anemia, acute blood loss, etc.), aplastic anemia or bone marrow suppression (due to chemotherapy or marrow infiltration), myelodysplastic syndromes, hypothyroidism, absence of spleen, Down's syndrome, chronic obstructive pulmonary disease, erythropoietin therapy, selenium deficiency, multiple sclerosis, familial macrocytosis and hereditary hydrocytosis. MS
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