Disorders of Iron Metabolism

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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 metabolism in overload and deficiency

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.
    • Koilonychia (Spoon Nails) in Iron Deficiency Anemia
  • 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. Ring Sideroblast Formation in HSCB Deficiency

Diagnostic Iron Panel - Unmasking Disorders

Diagnostic iron panel reveals patterns for specific disorders:

ParameterIDAACDIron OverloadSideroblastic
Serum Fe↓↓↓/N↑↑↑/N
TIBC↑↑↓/N↓/NN/↓
Transferrin Sat.↓↓ (<15%)↓/N↑↑ (>45-50%)↑/N
Ferritin↓↓↑/N↑↑↑/N
sTfRN/↓NN

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.

Practice Questions: Disorders of Iron Metabolism

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All of the following decrease in iron deficiency anemia except:

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Flashcards: Disorders of Iron Metabolism

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Primary _____ is due to mutations in the HFE gene on chromosome 6, leading to increased expression of DMT1 and decreased synthesis of Hepcidin

TAP TO REVEAL ANSWER

Primary _____ is due to mutations in the HFE gene on chromosome 6, leading to increased expression of DMT1 and decreased synthesis of Hepcidin

hemochromatosis

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