Iron Storage and Recycling

Iron Storage - Iron Vaults Unlocked

Iron is stored intracellularly, preventing toxicity. Key forms ensure availability.

• Storage Proteins:

  Feature	Ferritin	Hemosiderin
  Composition	Apoferritin shell + $Fe^{3+}$ core (micelles)	Aggregates of denatured ferritin, iron, lipids
  Solubility	Soluble	Insoluble
  Iron Availability	Readily available	Slowly available
  Abundance	Primary store; reflects body iron	Increases in iron overload
  Visualization	Electron microscopy	Light microscopy (Perls' Prussian blue stain)

• Major Storage Sites:

  • Liver (hepatocytes, Kupffer cells)
  • Bone marrow (macrophages)
  • Spleen (macrophages)

📌 Mnemonic: "Ferritin is Friendly & Fast (soluble, available); Hemosiderin is Hard & Held-up (insoluble, less available)."

⭐ Serum ferritin is an acute phase reactant; its levels can be ↑ in inflammation, independent of iron status. Normal range: Men 20-250 ng/mL, Women 10-120 ng/mL.

Iron Transport & Regulation - Iron Express Lane

• Key Transporters:
  • Transferrin (Tf): Primary plasma $Fe^{3+}$ carrier; delivers iron to cells via transferrin receptors (TfR1). Normal saturation: 20-50%.
  • Ferroportin (FPN1): Sole iron exporter from cells (enterocytes, macrophages, hepatocytes) to plasma-bound transferrin.
  • Haptoglobin & Hemopexin: Bind free Hb & heme respectively, salvaging iron.
• Master Regulator: Hepcidin
  • Peptide hormone synthesized mainly in the liver.
  • 📌 Hepcidin 'hides' iron: Binds ferroportin → internalization & degradation → ↓ iron absorption & ↓ release from macrophages.

  ⭐ Hepcidin is the master iron regulatory hormone, primarily synthesized in the liver.

• Hepcidin Regulation & Action Flowchart:

• Regulation Summary:
  • Hepcidin ↑ by: Iron overload, inflammation (IL-6).
  • Hepcidin ↓ by: Iron deficiency, hypoxia, increased erythropoiesis.

Iron Recycling - Recycle, Reuse, Re-Iron!

The body efficiently reclaims iron from aged red blood cells (RBCs), meeting most daily needs.

• Sites & Source:
  • Macrophages (RES): Spleen, liver, bone marrow.
  • Senescent RBCs (~120 days): Primary source.
• Mechanism:
  • Macrophages phagocytose old RBCs.
  • Heme oxygenase: Heme $\rightarrow$ Fe$^{2+}$ + Biliverdin + CO.
  • Iron (Fe$^{2+}$) exported by ferroportin (FPN1).
  • Hepcidin: Degrades FPN1 $\rightarrow$ ↓ iron release.
  • Transport: Fe$^{3+}$ (oxidized) + transferrin $\rightarrow$ bone marrow (erythropoiesis) or liver (ferritin storage).

⭐ The majority of daily iron needs (approx. 20-25 mg/day) are met through recycling of iron from senescent red blood cells by macrophages.

Clinical Correlates - Iron Imbalance Issues

Key differences in iron storage and recycling disorders:

⭐ Mutations in the HFE gene are the most common cause of hereditary hemochromatosis.

High‑Yield Points - ⚡ Biggest Takeaways

• Ferritin: Primary soluble iron storage protein; serum levels reflect body iron stores.
• Hemosiderin: Insoluble iron aggregate, seen in iron overload; stains Prussian blue positive.
• Transferrin: Plasma protein that transports two Fe3+ ions to erythroid precursors.
• RES Macrophages: Phagocytose old RBCs, releasing iron via heme oxygenase for recycling.
• Hepcidin: Liver-derived peptide hormone; master iron regulator, blocks ferroportin.
• Iron Recycling: Efficiently conserves iron, with most daily iron needs met by recycled iron from senescent RBCs.