Problems Associated with Insufficient Iron

As in the case of hyperferremia, there are two basic categories of hypoferremia (or low circulating-iron levels) based on their etiology. Most common are the acquired anemias, including iron deficiency, drug-induced anemia, and anemia of chronic disease/inflammation. Less common are hereditary anemias, such as sickle-cell anemia and congenital sideroblastic anemia. Some, such as sickle-cell anemia, are classified in a clinical setting by the morphological shape of the hemoglobin (Table fVB.3.4).

Macrocytic anemia can be induced by diet, resulting from malabsorption, or it can be caused by an inherited disorder. Because Vitamin B12 (cobalamin) and folic acid (folate) are required for normal red blood cell nuclear growth and synthesis, deficiencies of these nutrients can cause anemia (Simmons 1989: 12-14). Vitamin B12 deficiency from dietary causes is very rare and occurs only in strict vegetarians who exclude all meat, eggs, and milk. However, this deficiency can also arise from a number of disorders, including impaired absorption of B12 or folate such as in pernicious anemia; malabsorption that can result from certain drugs, such as those used to treat sprue and celiac diseases, and gastrectomy; competition from parasites such as the fish tapeworm; hereditary impairment of absorption capabilities; increased requirements of the vitamin due to pregnancy, tumors, and hyperthyroidism; or impaired utilization of the vitamin, as in red cell enzymopathy, abnormal binding proteins, absence of transport protein, or nitrous oxide administration (Simmons 1989: 40).

Folate deficiencies can result from the following: a lack of green vegetables in a diet; alcoholism; impaired absorption due to sprue and celiac diseases; drugs used to treat malignant diseases; malaria and bacterial infections; increased requirements stemming from pregnancy; conditions such as hyperthyroidism; or impaired utilization as occurs with drugs like phenytoin (Simmons 1989:40-1).

Table IV. B.3.4. Morphological clarification of anemia

Two types of hypochromic microcytic anemia are most prevalent. One is caused by blood loss that is not counterbalanced by a sufficient dietary intake. The second, less common cause results from unmet nutritional demands even without blood loss. In men, bleeding from the gastrointestinal tract is the most frequent cause, and although this condition may occur in women as well, menorrhagia (excessive menstrual flow) is more often responsible. The other principal cause of this variety of anemia is chronic disease, in which iron deficiency appears to form a nonspecific defense mechanism against disease.

Less common is sideroblastic anemia, which can be acquired or congenital. Acquired sideroblastic anemia can be drug - or toxin-induced from cancer chemotherapy, antituberculous drugs, and ethanol, or it can be idiopathic, such as preleukemic or dys-myelopoietic syndromes (Beissner and Trowbridge 1986). Patients with sideroblastic anemia tend to accumulate excess iron in the tissues and therefore are vulnerable to many of the problems associated with iron overload. Lead poisoning can also cause hypochromic microcytic anemia.

Some anemias are associated with specific geographical regions. For example, thalassemias are a varied group of inherited disorders characterized by one or more defects in the synthesis of the normal alpha or beta globin chains of hemoglobin. They can occur in homozygous or heterozygous states and include thalassemia major, thalassemia intermedia, thalassemia minor, and thalassemia minima (Simmons 1989: 55). The geographical distribution of thalassemia is primarily in the Mediterranean region, although it is also found in Southeast Asia, the Middle East, and the Orient and among immigrants from those areas. There is much variation in the clinical manifestations of these genetic disorders. The defect in hemoglobin chains causes a reduction in hemoglobin in afflicted individuals. Ironically, and as discussed earlier, thalassemia can also result in iron overload of some organs because intestinal iron absorption is increased due to the hemolytic anemia and ineffective production of red blood cells. In the heterozygous form, however, thalassemia has been postulated to be a deterrent to malaria infections, perhaps by causing a reduction in the amount of circulating iron.

A normocytic normochromic anemia that involves the premature destruction of red blood cells is sicklecell anemia, an inherited autosomal dominant disorder. Sickle-cell anemia is lethal in the homozygous form, but it can also become symptomatic in heterozygotes in situations of oxygen deprivation such as at high altitudes. Geographically, sickle-cell anemia is most common in equatorial Africa but is also found to a lesser extent in the Mediterranean region and India. This distribution has been attributed to the improved immunity individuals who are heterozygous for the sickle-cell trait have from malaria parasites (e. g., Plasmodium falciparum). Approximately 8.5 percent of

American blacks are heterozygous for the sickle-cell trait and are relatively symptom-free; in contrast, homozygous individuals suffer from hemoglobin levels between 5 and 9 g per decaliter (dl), leg ulcers, hematuria, and other afflictions (Simmons 1989:68-70).

Common autosomal dominant normocytic normochromic anemias that represent a defect in the red cell membrane include hereditary spherocytosis, found primarily in people of northern European descent, and hereditary elliptocytosis, found worldwide (Simmons 1989: 62-4). Spherocytic (congenital and acquired) anemia involves a deficiency in the Glucose-6-phosphate dehydrogenase enzyme (abbreviated G6PD) that is sex-linked with full expression in affected males and partial expression in females (Simmons 1989: 65). Its geographic distribution is worldwide, with the highest frequency in African populations, although it is also found in Italian, Greek, Asian, and Jewish populations.

Congenital nonspherocytic hemolytic anemia results from deficiency in several red cell enzymes, including glucose 6-phosphate dehydrogenase (G6PD). This condition is found in Asian, European, and Mediterranean populations, as well as in other populations to a lesser extent (Simmons 1989). This anemia is also caused by ingestion or contact with the fava bean by Mediterranean peoples (even from just inhaling the pollen of the bean among some sensitive males, usually under the age of 12). It can also be triggered by the use of antimalarial and other drugs in African and Mediterranean populations. A third cause can result from infection with viral or bacterial pathogens worldwide in persons with G6PD deficiency - pathogens include Escherichia coli, Salmonella, Streptococcus, Rickettsiae, viral hepatitis, pneumococcal pneumonia, malaria, and rheumatoid arthritis (Simmons 1989:65).

A variety of anemias are associated with immunological disorders, including transfusion reactions, ABO or Rh blood-group incompatibility between fetus and mother, and autoimmune hemolytic anemia, a condition in which antibodies or lymphocytes attack cells of the person who produced them. The most common type of autoimmune hemolytic anemia is termed warm-antibody because the autoantibody reacts most efficiently with red cells at 37° Celsius (C) and occurs especially in systemic lupus erythematosus and lymphomas. Less common is cold-antibody type, in which the antibodies are optimally reactive at temperatures less than 37° C, including cold hemagglutinin disease and paroxysmal cold hemoglobinuria (Simmons 1989:78-81).