Normal adult HbA has a P50 of approximately 26 mmHg, while myoglobin has a P50 of approximately 1 mmHg. A newly characterized hemoglobin variant is found to have a P50 of 42 mmHg. The most likely clinical consequence in a homozygous individual is:
- A Tissue hypoxia with compensatory erythrocytosis despite adequate arterial PO2 ✓
- B Congenital erythrocytosis due to enhanced tissue oxygen delivery
- C Cyanosis from birth with normal arterial PO2 due to methemoglobin accumulation
- D No physiological abnormality, since P50 variation within this range is clinically silent
Correct answer: A. Tissue hypoxia with compensatory erythrocytosis despite adequate arterial PO2
Explanation
P50 is the PO2 at which hemoglobin is half saturated; a higher P50 means lower oxygen affinity and a right-shifted curve. At a P50 of 42 mmHg, hemoglobin releases oxygen too readily in the lungs and loads poorly, causing tissue hypoxia. Erythropoietin-driven erythrocytosis follows. Low-affinity variants cause cyanosis only when deoxyhemoglobin exceeds about 5 g/dL, and methemoglobin is a separate entity with iron in the ferric state.
Reference: Harper's Illustrated Biochemistry, 31st ed.
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