How does fetal hemoglobin differ from adult hemoglobin, and how does this difference enable the transfer of oxygen in the placenta?

Fetal hemoglobin (HbF) differs from adult hemoglobin (HbA) in several key ways, particularly in its structure and oxygen-binding affinity. These differences are crucial for effective oxygen transfer from the mother to the fetus through the placenta. Here’s a detailed explanation of how these differences enable oxygen transfer:

Differences Between Fetal Hemoglobin and Adult Hemoglobin

1. Composition:
   • Fetal Hemoglobin (HbF): HbF is composed of two alpha (α) and two gamma (γ) subunits, resulting in the structure α2γ2.
   • Adult Hemoglobin (HbA): In contrast, HbA consists of two alpha (α) and two beta (β) subunits, forming the structure α2β2.
2. Oxygen Affinity:
   • HbF has a higher affinity for oxygen compared to HbA. This means that HbF can bind oxygen more tightly, which is essential for extracting oxygen from maternal blood. The P50 value (the partial pressure of oxygen at which hemoglobin is 50% saturated) for HbF is about 19 mmHg, while for HbA, it is around 27 mmHg. This leftward shift in the oxygen dissociation curve for HbF allows it to effectively capture oxygen even at lower pO2 levels typical in the placenta .
3. Reduced Affinity for 2,3-Bisphosphoglycerate (2,3-BPG):
   • HbF exhibits a decreased affinity for 2,3-BPG, a metabolite that normally decreases hemoglobin’s affinity for oxygen when bound. This lower affinity allows HbF to retain its higher affinity for O2, further enhancing its ability to extract oxygen from maternal blood .

Oxygen Transfer in the Placenta

1. Placental Structure:
   • The placenta serves as the interface between maternal and fetal blood circulations. Maternal blood flows through the intervillous space of the placenta, where it comes into close proximity with fetal blood vessels without mixing.
2. Oxygen Diffusion:
   • Oxygen from maternal blood diffuses across the placental membrane into fetal blood. Given that maternal hemoglobin (HbA) has a lower affinity for oxygen than fetal hemoglobin (HbF), as maternal blood releases O2 due to increased CO2 levels and decreased pH (the Bohr effect), more O2 is available to be taken up by HbF.
3. Efficient Oxygen Extraction:
   • The higher affinity of HbF for oxygen allows it to effectively “pull” oxygen from maternal hemoglobin even when maternal blood is not fully saturated with oxygen. This is critical because the fetus relies entirely on maternal circulation for its oxygen supply during gestation.
4. Countercurrent Exchange Mechanism:
   • The placental structure facilitates a countercurrent exchange mechanism, where maternal and fetal blood flow in opposite directions. This arrangement maximizes the gradient for oxygen transfer, allowing efficient diffusion of O2 into fetal circulation while simultaneously facilitating CO2 removal from fetal blood back into maternal circulation.