An update on iron physiology

Abstract

Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron (1-2 mg/d) is regulated tightly, it is just balanced with losses. Therefore, internal turnover of iron is essential to meet the requirements for erythropoiesis (20-30 mg/d). Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron-deficiency anemia. Hepcidin, which is made primarily in hepatocytes in response to liver iron levels, inflammation, hypoxia and anemia, is the main iron regulatory hormone. Once secreted into the circulation, hepcidin binds ferroportin on enterocytes and macrophages, which triggers its internalization and lysosomal degradation. Thus, in chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, which results in hypoferremia and iron-restricted erythropoiesis, despite normal iron stores (functional ID), and anemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD + ID). In contrast, low hepcidin expression may lead to iron overload, and vice versa. Laboratory tests provide evidence of iron depletion in the body, or reflect iron-deficient red cell production. The appropriate combination of these laboratory tests help to establish a correct diagnosis of ID status and anemia.

The role of lysosomes in iron metabolism and recycling

“…The total body iron of a healthy human is typically about 50 mg/kg, most of which is in hemoglobin and myoglobin within erythrocytes and muscle cells, respectively (Munoz et al, 2009). Since humans lack an effective iron-excreting mechanism (McCance and Widdowson, 1938), body iron has to be tightly regulated by strictly controlled uptake from the food, which in turn requires effective reutilization following degradation of iron-containing macromolecules.…”

Effectiveness of oral iron to manage anemia in long-term hemodialysis patients with the use of ultrapure dialysate

“…Chronic inflammation is now believed to decrease iron absorption from the gut through increased hepcidin synthesis (13). hepcidin, a serum protein, is produced by the liver and is a key regulator of iron mobilization.…”

The significance of soluble transferrin receptors in diagnosing iron deficiency anemia

“…Recent works also contain the recommendation to use this parameter in diagnosing MH with the associated iron deficit, which entails sTfR and ferritin in the serum [28]. They have also been recommended as the latest standard for determining the iron status among healthy persons [29].…”