By HARINATH SHEELA, MD, with IVANA OKOR
Iron is a key element for survival; it is essential for oxygen transport, infection resistance and generation of energy via enzyme-catalyzed reactions. It is strictly conserved and recycled in humans such that minor changes in iron content can lead to disease states. Iron exists in two stable oxidation states, as ferrous iron Fe2+and ferric iron Fe3+, which makes its use in the body very versatile. Iron is found in the body mainly in the form of hemoglobin and myoglobin (80%), iron containing proteins, plasma transferrin-bound iron and stored iron (20)(ferritin or hemosiderin).
Iron homeostasis involves the interaction of different proteins and hormones on both systemic and cellular levels. The body doesn't have an effective physiologic mechanism of iron excretion hence it relies solely on absorption mechanism for iron homeostasis.
The normal iron content in an adult male is 3-4g and the body can function effectively by absorbing 1-2mg of iron daily. Approximately 1mg of iron is lost daily via sweat, urine, sloughing of gastrointestinal cells and shedding of skin cells. Premenopausal women may lose up to 2mg of iron daily during menstruation, without increased iron absorption they predisposed to iron deficiency anemia.
Iron absorption is a specialized process that actively involves the gastrointestinal tract. A daily diet contains approximately 15mg of iron; this exists in form of heme and non-Heme (inorganic) iron. Approximately 30 percent of Heme iron and only about 10 percent of the non-heme iron is absorbed. The mechanism and pathway for absorption of Heme iron and Non Heme iron differ; heme iron is believed to be absorbed directly via a heme carrier protein located on apical membrane of duodenal enterocytes, while non-heme iron absorption is more influenced by dietary factors. Dietary heme iron is derived from hemoglobin and myoglobin from animal sources such as meat, poultry and fish; non-heme iron is derived from both meat and plant products.
The rate of iron absorption depends on the physiological state of the body; decreased iron stores, ineffective erythropoiesis, and hypoxia all lead to an increased rate of iron absorption. Dietary iron absorption is enhanced by Ascorbic acid (Vitamin C), citrate and gastric acids; it is inhibited by phytates found in cereals, polyphenols in teas, dietary calcium, soy protein, tannins, soil clay and casein in milk. The use of proton pump inhibitors also decreases non-heme iron absorption.
In addition, iron absorption may also be reduced due to pathological conditions. Diseases that lead to a reduced absorptive surface area such as celiac disease and inflammatory bowel disease lead decreased iron absorption. Impaired iron absorption may also be seen in patients with chronic liver disease, anemia of chronic disease and iron-loading anemia.
Mechanism of Iron Absorption
Non-heme iron exists primarily in the oxidized Fe3+ (ferric) but Fe2+ (ferrous) iron is more easily transported across the basolateral membrane. Gastric acid in the stomach recreates the acidic environment needed by duodenal enzymes to reduce Fe3+ to Fe2+. In the duodenum, Cytochrome b as well as ferric reductase enzyme reduces Fe3+ to Fe2+, which can then be taken up by the duodenal iron transporter.
The duodenal iron transporter is a divalent metal transporter protein (DMT1), which takes up iron from the intestinal lumen. Mutations in the SLC11A2 gene coding for DMT1 have been shown to cause severe iron deficiency. This transporter also takes up other divalent metals such as lead, zinc, cobalt, manganese and copper; therefore, they serve as potential competitive inhibitors for the iron uptake. After luminal uptake, iron is either stored in ferritin or transported out of the cell.
An iron exporter known as Ferroportin transports iron across the basolateral membrane of the duodenal enterocyte, it facilitates the transfer of iron from enterocytes to circulation. It can also be found on macrophages and hepatocytes where it plays an important role in iron circulation.
Ferroportin is under the physiologic control of the peptide hormone hepcidin. Hepcidin is produced by liver hepatocytes in response to increased iron stores and acute inflammation; its main role is to decrease iron absorption and transfer to plasma by down regulating and internalizing ferroportin. Hepcindin also regulates the release of iron from macrophages. Production of hepcidin is inhibited by iron deficiency, hypoxia, and ineffective erythropoiesis. Due to the role hepcindin plays in iron absorption, certain iron over load disorders especially hemochromatosis have now been linked to low hepcidin production.
After iron leaves the enterocyte, it is reoxidized to Fe3+ by a ferroxidase known as hephaestin. The ferric iron is then bound to transferrin, a carrier protein that transports iron to tissues.
Dr. Harinath Sheela finished his fellowship in Gastroenterology at Yale University School of Medicine. His interests include (IBD), (IBS), Hepatitis B, Hepatitis C, Metabolic and other liver disorders. He is board certified in both Internal Medicine and Gastroenterology. He is the chairman at Florida Hospital's Department of Gastroenterology and an active member of the Orange County Medical Society. In addition to being an Assistant Professor at the University of Central Florida School of Medicine, he is a teaching attending physician at both the Florida Hospital Internal Medicine Residency and Family Practice Residence (MD and DO) programs.
Ivana Okor is a 3rd year medical student at NSUCOM. She has an MPH in Epidemiology and a dual Bachelors in Chemistry and Psychology. She intends to be an internal medicine physician.