Hepcidin is the master regulator of systemic iron homeostasis. In anemia of chronic disease (ACD), hepcidin levels are typically:

• A Suppressed, causing iron deficiency by reduced intestinal absorption
• B Normal, with iron deficiency occurring due to dietary insufficiency
• C Absent, as inflammation destroys liver hepatocytes that produce hepcidin
• D Elevated due to IL-6-driven BMP-SMAD signaling, sequestering iron in macrophages and hepatocytes ✓

Explanation

In inflammation, IL-6 (secreted by macrophages) acts on hepatocytes via JAK2/STAT3 signaling to increase hepcidin (HAMP gene) transcription. Additionally, BMP6 (produced in response to iron stores) activates SMAD1/5/8 → SMAD4 pathway, also increasing hepcidin. Elevated hepcidin binds and induces degradation of ferroportin (FPN1) on enterocytes (blocking intestinal absorption) and macrophages (blocking iron recycling from senescent erythrocytes). This sequesters iron in macrophages/hepatocytes — a bacteriostatic defense — but causes functional iron-restricted erythropoiesis (ACD).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.