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  • Iron deficiency: serum ferritin is < 12 ng/mL (27 pmol/L) or < 30 ng/mL (67 pmol/L) if also anemic.

  • Caused by bleeding unless proved otherwise.

  • Responds to iron therapy.


Iron deficiency is the most common cause of anemia worldwide. The causes are listed in Table 13–3. Aside from circulating red blood cells, the major location of iron in the body is the storage pool as ferritin or as hemosiderin in macrophages.

Table 13–3.Causes of iron deficiency.

The average American diet contains 10–15 mg of iron per day. About 10% of this amount is absorbed in the stomach, duodenum, and upper jejunum under acidic conditions. Dietary iron present as heme is efficiently absorbed (10–20%) but nonheme iron less so (1–5%), largely because of interference by phosphates, tannins, and other food constituents. The major iron transporter from the diet across the intestinal lumen is ferroportin, which also facilitates the transport of iron to apotransferrin in macrophages for delivery to erythroid progenitor cells in the bone marrow prepared to synthesize hemoglobin. Hepcidin, which is increasingly produced during inflammation, negatively regulates iron transport by promoting the degradation of ferroportin. Small amounts of iron—approximately 1 mg/day—are normally lost through exfoliation of skin and gastrointestinal mucosal cells.

With hemorrhage, there is decreased oxygen delivery to the kidneys resulting in stabilization of a hypoxia-inducible factor in the kidneys and increased erythropoietin generation in the kidneys and liver. Erythropoietin stimulates erythropoiesis via an increased synthesis of erythroferrone. In turn, erythroferrone suppresses hepcidin synthesis leading to ferroportin stability and enhanced iron transport across the gastrointestinal lumen.

Menstrual blood loss plays a major role in iron metabolism. The average monthly menstrual blood loss is approximately 50 mL but may be five times greater in some individuals. Women with heavy menstrual losses must absorb 3–4 mg of iron from the diet each day to maintain adequate iron stores, which is not commonly achieved. Women with menorrhagia of this degree will almost always become iron deficient without iron supplementation.

In general, iron metabolism is balanced between absorption of 1 mg/day and loss of 1 mg/day. Pregnancy and lactation upset the iron balance, since requirements increase to 2–5 mg of iron per day. Normal dietary iron cannot supply these requirements, and medicinal iron is needed during pregnancy and lactation. Decreased iron absorption can also cause iron deficiency, such as in people affected by celiac disease (gluten enteropathy), and it also commonly occurs after gastric resection or jejunal bypass surgery.

The most important cause of iron deficiency ...

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