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World J Gastroenterol. Oct 7, 2009; 15(37): 4617-4626
Published online Oct 7, 2009. doi: 10.3748/wjg.15.4617
An update on iron physiology
Manuel Muñoz, Isabel Villar, José Antonio García-Erce
Manuel Muñoz, Transfusion Medicine, School of Medicine, University of Málaga, Málaga 29071, Spain
Isabel Villar, Department of Hospital Pharmacy, University Hospital Miguel Servet, Zaragoza 50009, Spain
José Antonio García-Erce, Hematology and Hemotherapy, University Hospital Miguel Servet, Zaragoza 50009, Spain
Author contributions: Muñoz M, Villar I and García-Erce JA contributed equally to this work.
Correspondence to: Manuel Muñoz, Professor, Transfusion Medicine, School of Medicine, University of Málaga, Málaga 29071, Spain. mmunoz@uma.es
Telephone: +34-952-131540 Fax: +34-952-131534
Received: July 23, 2009
Revised: September 8, 2009
Accepted: September 15, 2009
Published online: October 7, 2009
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.

Keywords: Iron metabolism; Iron deficiency; Functional iron deficiency; Hepcidin; Anemia of chronic disease