Fetal haemoglobin (HbF) has a higher oxygen affinity than adult HbA. The primary reason for this difference is:

• A HbF has a lower haem iron content, reducing cooperativity and increasing O2 affinity
• B HbF is exposed to lower PO2 in the umbilical arteries, causing allosteric adaptation to bind O2 more tightly
• C HbF contains gamma chains instead of beta chains; gamma chains bind 2,3-DPG less avidly, shifting the O2-dissociation curve left ✓
• D Fetal blood has a higher pH due to alkaline amniotic fluid, directly increasing HbF affinity via the Bohr effect

Explanation

HbF consists of two alpha (α) and two gamma (γ) chains (α2γ2). The γ chains have reduced affinity for 2,3-bisphosphoglycerate (2,3-DPG) compared to β chains of HbA because the critical histidine residue at position 143 of the β chain (which forms an ionic bond with 2,3-DPG) is replaced by serine in the γ chain. Since 2,3-DPG stabilises the deoxy (T) state and reduces O2 affinity, its reduced binding to HbF results in a leftward shift of the oxygen-haemoglobin dissociation curve. This allows HbF to extract oxygen from maternal HbA at the placenta (fetal PO2 ~35 mmHg, where HbF is more saturated than HbA). The other options are incorrect mechanisms.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.