Iron absorption: dietary Fe3+ reduced to Fe2+ at the duodenal brush border (DCYTB) → imported by DMT1 → exported to plasma by ferroportin (FPN). Plasma iron binds transferrin → delivered to erythroblasts (transferrin-R) + stored in ferritin in liver / macrophages / enterocytes. HEPCIDIN (hepatic peptide hormone) is the master regulator: high hepcidin internalizes + degrades ferroportin → blocks export from enterocytes + macrophages → plasma iron falls. Hepcidin is upregulated by iron load + inflammation (IL-6 — explains anemia of chronic inflammation), downregulated by erythropoietic drive (erythroferrone from erythroblasts). Hereditary hemochromatosis = HFE mutations → low hepcidin → unrestricted absorption.
Organ Systems
immune-hematologic
digestive
endocrine
Pathway Steps
dietary-iron → enterocyte-iron — via DCYTB reductase + DMT1 importer (apical). At the apical enterocyte, DCYTB reduces ferric to ferrous iron for the DMT1 importer; heme iron uses a separate, more efficient route. Vitamin C aids non-heme absorption while phytates, tannins, and calcium inhibit it.
enterocyte-iron → plasma-iron — via ferroportin (FPN) — HEPCIDIN-controlled. Ferroportin is the only cellular iron exporter and the master control point: the hepatic hormone hepcidin (raised by iron load and inflammation) degrades it, trapping iron in cells — the basis of anemia of chronic disease, while hepcidin deficiency causes hemochromatosis.
plasma-iron → erythroblast-iron — via transferrin → transferrin-R endocytosis → ferritin storage or heme synthesis. Plasma iron rides transferrin to receptor-mediated endocytosis, then is stored in ferritin or used for heme. There is no regulated route to excrete iron — loss is only via bleeding/cell shedding — so absorption is the sole control, which is why overload is hard to clear.