Hepcidin is the master regulator of iron homeostasis. In a patient with anemia of chronic disease (ACD), the MECHANISM by which elevated hepcidin sequesters iron is:

• A Hepcidin cleaves transferrin, preventing iron delivery to erythroid precursors
• B Hepcidin activates ferritin transcription, storing iron in macrophages away from circulation
• C Hepcidin binds ferroportin on macrophages, enterocytes, and hepatocytes, inducing its internalisation and degradation ✓
• D Hepcidin inhibits HIF-2alpha in duodenal enterocytes, reducing DMT1 expression

Explanation

Hepcidin is a hepatic antimicrobial peptide regulated by IL-6 (in inflammation), iron load, and erythropoietic demand. It binds ferroportin (FPN1/SLC40A1) — the sole cellular iron exporter — on macrophages (recycling RBC iron), duodenal enterocytes (dietary iron absorption), and hepatocytes, causing ferroportin internalisation and lysosomal degradation. Cells then retain iron, lowering serum iron and transferrin saturation while ferritin rises — the biochemical signature of ACD.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.