Iron Metabolism: Hepcidin Regulation and Disorders

The NP must understand iron metabolism as a tightly regulated system governed by the hepcidin-ferroportin axis. Total body iron in adults is approximately 3-4 grams: 65% in hemoglobin, 10% in myoglobin, 20-30% in storage forms (ferritin and hemosiderin in hepatocytes and macrophages), and less than 1% in enzymes and plasma transferrin. Daily iron losses are approximately 1-2 mg through desquamation of intestinal and skin epithelial cells and trace losses in urine and bile; there is no regulated excretion pathway, making absorption control essential. Dietary iron is absorbed in the duodenum: non-heme iron (Fe3+) is reduced to Fe2+ by duodenal cytochrome b (DcytB) on the apical brush border, then transported into the enterocyte via divalent metal transporter 1 (DMT1). Heme iron is absorbed intact by the heme carrier protein (HCP1) and liberated intracellularly by heme oxygenase. Inside the enterocyte, iron is either stored as ferritin (if body stores are replete) or exported across the basolateral membrane by ferroportin (the ONLY cellular iron exporter). HEPCIDIN, a 25-amino-acid peptide hormone synthesized by hepatocytes, is the master regulator of systemic iron homeostasis. Hepcidin binds...