Which of the following is associated with an increase in P50?

An increase in P50, which refers to the partial pressure of oxygen (pO2) at which hemoglobin is 50% saturated, indicates a decreased affinity of hemoglobin for oxygen. This concept is critical in understanding how hemoglobin functions in transporting oxygen throughout the body.

Sickle cell disease is associated with an alteration in the structure of hemoglobin (HbS) that affects its oxygen-binding characteristics. The presence of sickle-shaped red blood cells and the reduced affinity for oxygen cause the P50 value to increase. As hemoglobin’s affinity for oxygen decreases, it is more likely to release oxygen to the tissues, which is a relevant adaptation in certain contexts.

In contrast, decreased H+ ions, fetal hemoglobin, and decreased temperature would each lower P50 by increasing hemoglobin's affinity for oxygen. Decreased H+ ions signify a more alkaline environment, which stabilizes the R state of hemoglobin and promotes tighter binding of oxygen. Fetal hemoglobin, which has a different structure than adult hemoglobin, also binds oxygen more tightly, resulting in a lower P50. Finally, decreased temperature generally results in enhanced oxygen affinity, further promoting a lower P50.

Thus, the association of sickle cell with an increased P50 is