Iron deficiency anemia etiology

Iron deficiency is approximately twice as common in breastfed infants up to 30 percent have iron deficiency anemia, and more than 60 percent of the anemic infants are also iron deficient at 12 months of age (Pisacane et al., 1995), although the etiology is unclear. The iron content of human milk is low 0.5 mg/L compared with 10 to 12 mg/L in supplemented cow-milk formulas. The absorption rate, however, is considerably higher. Breastfed infants absorb up to 50 percent of consumed iron, compared with a 7- to 12-percent absorption rate for formula-fed infants (Fomon et al., 1993). The risk of iron deficiency increases after 4 months of age since most full-term infants are born with adequate iron stores to support hemoglobin synthesis through the first 4 months after birth. 

Anemia is defined by abnormally low circulating hemoglobin concentrations. A variety of etiologies exist for anemia, including dietary deficiencies of folate or vitamin B12 (pernicious or macrocytic anemia), infections and inflammatory states (anemia of chronic disease), and conditions that result in insufficient production of red blood cells (aplastic anemia) or excessive destruction of red blood cells (hemolytic anemia). However, worldwide, the most prevalent form of anemia is that of iron deficiency, which causes anemia characterized by hypochromic and normo- or microcytic red blood cells. Iron deficiency anemia remains a health problem in both the developed and the developing world. This article discusses the metabolism of iron the assessment of iron deficiency iron requirements across the life span and the consequences, prevention, and treatment of iron deficiency and iron deficiency anemia. 

Iron deficiency anemia has been implicated in adverse pregnancy outcomes, maternal and infant mortality, cognitive dysfunction and developmental delays in infants and children, and compromised physical capacity in children and adults. However, data to support causal relationships with some of these outcomes is limited, and the extent to which outcomes are associated with iron deficiency specifically or more generally with anemia regardless of the etiology is the subject of debate. 

Anemias are classified by RBC size as macrocytic, normocytic, or microcytic. Vitamin B12 deficiency and folic acid deficiency are both macrocytic anemias. An example of a microcytic anemia is iron deficiency, whereas a normocytic anemia may be the result of recent blood loss or chronic disease. In many patients more than one anemia and etiology may occur at the same time. Inclusion of the underlying cause of the anemia makes diagnostic terminology easier to understand (e.g., microcytic anemia secondary to iron deficiency). 

Anemia has frequently, but not consistently, been reported in association with scurvy in clinical cases, both in adults and infants, and in experimental scurvy in guinea pigs and monkeys. The extensive literature has been cited (M18, L19, V2). The anemias were not constant in type or severity, although all were reheved when ascorbic acid was reintroduced to tbe diet. In contrast, no anemia or abnormality of the blood picture was ever seen in experimental human scurvy. The therapeutic effect of ascorbic acid on the anemia cannot be accepted as proof of its etiology, since associated deficiencies would also be made good with the return of normal appetite. It is well recognized that the clinical cases of scurvy usually have associated deficiencies. Often, there is iron deficiency in the milk-fed infants, and folic acid or vitamin B12 deficiency in the malnourished adult. ... 

The etiology of microcytic hypochromic anemias as a class can be ascribed to decreased hemoglobin synthesis. Al has been shown to inhibit hemoglobin synthesis in Friend erythroleukemia cells (Abreo et al. 1990) and in bone marrow cells (Zamen et al. 1992), where it also accumulates. In vitro studies evaluating incorporation of Fe " into heme have identified heme, rather than globin, synthesis as the inhibited pathway in uremia (Moriyama et al. 1975). The most common cause of a fault in heme synthesis leading to microcytic anemia is iron deficiency or lack of availability. Although Al-related anemia is refractory to Fe, the anemia could be caused by an interaction between Al and Fe metabolism. 

Because geohelminths such as hookworm also contribute to iron deficiency, programs that increase iron intakes but do not address this major source of iron loss are unlikely to be effective at improving iron status. Other infections and inflammation also cause anemia, as does malaria, and the safety of iron supplementation during infection or malaria has been debated. Where malaria and iron deficiency coexist, the current view is that iron supplementation is sufficiently beneficial to support its use. Ideally, however, where multiple etiologies of anemia coexist, these etiologies need to be recognized and simultaneously addressed. 

The underlying cause of anemia (e.g., blood loss iron, folic acid, or vitamin B12 deficiency or chronic disease) must be determined and used to guide therapy. As discussed previously, patients should be evaluated initially based on laboratory parameters to determine the etiology of the anemia (see Fig. 63-3). Subsequently, the appropriate pharmacologic treatment should be initiated based on the cause of anemia. 

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