Disorders of Iron Metabolism

Iron Homeostasis & Dysregulation - Iron's Balancing Act

• Core Principle: Iron balance maintained by regulating absorption, storage, transport.
• Key Players & Regulation:
  • Hepcidin: Master regulator (liver hormone); blocks ferroportin.
  • Ferroportin: Iron efflux channel (enterocytes, macrophages).
  • Transferrin: Transports iron.
  • Ferritin: Stores iron.
• Dysregulation Pathways:
  • ↑ Hepcidin (e.g., inflammation, Anemia of Chronic Disease - ACD) → ↓ iron absorption/release → ↓ serum iron.
  • ↓ Hepcidin (e.g., hemochromatosis, iron deficiency) → ↑ iron absorption/release → ↑ serum iron.

⭐ Hepcidin is the master regulator of iron homeostasis, and its dysregulation is key to many iron disorders (e.g., increased in ACD, decreased in hemochromatosis).

Iron Deficiency Anemia - Running on Empty

Most common global nutritional deficiency.

• Etiology: ↓ intake, ↓ absorption (celiac, gastrectomy, PPIs), ↑ loss (GI bleed, menses), ↑ demand (pregnancy, growth).
• Clinical: Fatigue, pallor, koilonychia (spoon nails), pica, glossitis, angular stomatitis.
  • 
• Labs:
  • Microcytic hypochromic (↓ Hb, MCV, MCH, MCHC). ↑ RDW (early).
  • ↓ Serum Fe, ↓ Ferritin (<15-30 ng/mL), ↑ TIBC.
  • ↓ Transferrin Saturation (<16%).
  • PS: Anisopoikilocytosis, pencil cells.
• Rx: Treat cause. Oral iron (ferrous sulfate). Parenteral if severe/malabsorption.

⭐ Plummer-Vinson syndrome (triad: dysphagia, iron-deficiency anemia, esophageal webs) is a classic association with chronic IDA.

Anemia of Chronic Disease - Inflammatory Lock-Up

• Patho: Chronic inflammation → ↑IL-6 → liver ↑hepcidin.
• Hepcidin: Blocks gut iron absorption; traps iron in macrophages → functional iron deficiency despite normal/↑ stores.
• Labs: ↓ Serum Fe, ↓ TIBC, Normal/↑ Ferritin. Normocytic (later microcytic). ↑ESR/CRP.
• Rx: Treat primary disease. ESAs for severe cases. Iron only if true IDA coexists.

⭐ Anemia of Chronic Disease (ACD) is characterized by low serum iron, low TIBC, and normal/high ferritin due to hepcidin-mediated iron sequestration in macrophages.

Iron Overload & Sideroblastic Anemia - Metal & Misfire

• Hereditary Hemochromatosis (HH):
  • HFE gene (C282Y, H63D) → ↑ Fe absorption. Fe deposition: liver, pancreas, heart.
  • "Bronze diabetes", cirrhosis, cardiomyopathy.
  • Labs: ↑ Ferritin (>1000 ng/mL), ↑ Serum Fe, ↑ Transferrin Saturation (>45%), ↓ TIBC.
  • Rx: Phlebotomy, iron chelators.

  ⭐ Hereditary Hemochromatosis is most commonly due to HFE gene mutations (C282Y, H63D) leading to increased iron absorption and deposition in organs like liver, pancreas, and heart (causing 'bronze diabetes').

• Sideroblastic Anemia: Defective heme synthesis → mitochondrial Fe accumulation.
  • Types: Congenital (X-linked ALAS2), Acquired (MDS, alcohol, lead, isoniazid).
  • Labs: ↑ Serum Fe, ↑ Ferritin. Anemia (often dimorphic). Basophilic stippling (lead).
  • BM: Ring sideroblasts (>15%).
  • Rx: Pyridoxine (B6), treat cause.

Diagnostic Iron Panel - Unmasking Disorders

Diagnostic iron panel reveals patterns for specific disorders:

Transferrin saturation, calculated as $Serum\ Iron / TIBC \times 100%$, is a key diagnostic marker.

⭐ It typically shows <15% in IDA and >45-50% in iron overload, aiding differentiation.

High‑Yield Points - ⚡ Biggest Takeaways

• Iron Deficiency Anemia (IDA): Most common; microcytic hypochromic; ↓ ferritin, ↓ serum Fe, ↑ TIBC.
• Anemia of Chronic Disease (ACD): ↑ Hepcidin blocks iron release; ↓ serum Fe, ↓ TIBC, normal/↑ ferritin.
• Hereditary Hemochromatosis: HFE gene defect; ↑ iron absorption; bronze diabetes, cirrhosis. ↑ Ferritin, ↑ transferrin saturation.
• Sideroblastic Anemia: Defective heme synthesis; ring sideroblasts. Key causes: lead poisoning, INH.
• Plummer-Vinson Syndrome: Triad: IDA, esophageal webs, dysphagia.