Hemoglobin Chesapeake is a high-affinity hemoglobin variant (increased oxygen affinity) caused by alpha-Arg92Leu substitution at the alpha1-beta2 interface. The compensatory erythropoietic response in an affected individual would be:
- A Anemia due to increased RBC destruction
- B Polycythemia due to chronic tissue hypoxia stimulating EPO ✓
- C Normal hemoglobin level with decreased 2,3-BPG
- D Methemoglobinemia due to oxidation of the variant Hb
Correct answer: B. Polycythemia due to chronic tissue hypoxia stimulating EPO
Explanation
High-affinity hemoglobin variants (like Hb Chesapeake) bind oxygen tightly but release it poorly to tissues, resulting in chronic tissue hypoxia despite normal or even elevated hemoglobin. This triggers increased EPO secretion from the kidney, driving erythropoiesis and producing polycythemia (erythrocytosis). P50 is reduced (leftward shifted ODA curve). This is a benign, compensatory polycythemia — the diagnostic clue is elevated Hb + normal EPO + no JAK2 mutation, distinguishing it from polycythemia vera.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.