A 62-year-old woman comes to the clinic for a routine follow-up. She has a 10-year history of rheumatoid arthritis that has been poorly controlled due to medication nonadherence. She reports feeling increasingly tired over the past several months but denies black stools, blood in her urine, or heavy menses. Vital signs are within normal limits. Physical examination reveals swelling and tenderness in the metacarpophalangeal joints of both hands. Laboratory studies show the following:
| Test | Result |
|---|---|
| Hemoglobin | 10.0 g/dL |
| Mean corpuscular volume | 86 fL |
| Platelet count | 250,000/mm³ |
| Leukocyte count | 7,500/mm³ |
| Serum iron | 35 µg/dL |
| Total iron-binding capacity | 220 µg/dL |
| Serum ferritin | 540 ng/mL |
Which of the following best describes the primary pathophysiology of this patient's hematologic findings?
- ADepletion of total body iron stores
- BAutoantibody-mediated red blood cell destruction
- Increased production of hepcidin leading to iron sequestrationCevap
- DImpaired erythrocyte DNA synthesis
- EInherited defect in globin chain synthesis
Cevap
Increased production of hepcidin leading to iron sequestration
The correct answer correctly identifies hepcidin as the primary mediator of anemia of chronic disease. In conditions of chronic inflammation, such as poorly controlled rheumatoid arthritis, inflammatory cytokines (especially IL-6) stimulate the liver to synthesize hepcidin. Hepcidin binds to and degrades ferroportin, the iron efflux channel on enterocytes and macrophages. This traps iron within macrophages (leading to high serum ferritin) and prevents its transfer to transferrin (leading to low serum iron and low TIBC), ultimately restricting iron availability for red blood cell production in the bone marrow.
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Anahtar Kavram
Anemia of chronic disease is characterized by low serum iron, low total iron-binding capacity (TIBC), and normal or elevated ferritin due to hepcidin-mediated iron sequestration in the setting of chronic inflammation.