The oxyhemoglobin dissociation curve is influenced by changes in blood pH, particularly the concentration of hydrogen ions (H+). When tissues produce and release more CO2 into the blood, it generates H+ ions, resulting in a decrease in pH. This shift in pH causes the dissociation curve to move to the right, which is beneficial because it helps release oxygen (O2) from hemoglobin (Hgb) for diffusion into tissues. The curve shift is caused by both the decrease in pH and the direct effect of CO2 on Hgb. On the other hand, as blood passes through the lungs, CO2 is exhaled, increasing the pH. This increase in pH causes the dissociation curve to shift to the left, a phenomenon known as the Bohr effect. The Bohr effect enhances O2 uptake in the lungs and the delivery of O2 to tissues. An increase in body temperature, such as during exercise, shifts the dissociation curve to the right, facilitating the release of more O2 to meet the increased demand. Conversely, during cold weather, especially in the extremities, a decrease in body temperature shifts the O2 dissociation curve to the left, resulting in higher Hgb affinity. In this case, the partial pressure of O2 (PaO2) may be normal, but the release of O2 in the extremities is not facilitated. 
2,3-Diphosphoglycerate (2,3-DPG) is a metabolic intermediary formed in red blood cells during glycolysis. As 2,3-DPG levels increase, the affinity of Hgb for O2 decreases, causing the oxyhemoglobin dissociation curve to shift to the right. Although 2,3-DPG and O2 bind to different sites on the Hgb molecule, the binding of 2,3-DPG inhibits the binding of O2 through an allosteric effect. Conditions such as hypoxia, decreased Hgb, and increased pH can increase 2,3-DPG levels. Stored blood samples have decreased levels of 2,3-DPG, which can pose a problem for transfusion recipients due to the increased Hgb affinity for O2, inhibiting the unloading of O2 to tissues. As mentioned earlier, fetal hemoglobin (HgbF) has a greater affinity for O2 than adult Hgb, causing the oxyhemoglobin dissociation curve to shift to the left. 
When carbon monoxide (CO) binds to the heme group of the Hgb molecule, it forms carboxyhemoglobin (HgbCO). The oxyhemoglobin and carboxyhemoglobin dissociation curves illustrate the significant difference in CO's affinity for Hgb compared to O2. CO has approximately 200 times greater affinity for Hgb than O2.
Changes in blood hydrogen ion concentration (pH) shift the oxyhemoglobin dissociation curve. An increase in CO2 production by tissue and its release into blood results in the generation of hydrogen ions (H+) and a decrease in pH. This shifts the dissociation curve to the right, which has a beneficial effect by aiding in the release of O2 from Hgb for diffusion into tissues. The shift to the right in the dissociation curve is due to the decrease in pH and to a direct effect of CO2 on Hgb. Conversely, as blood passes through the lungs, CO2 is exhaled, which results in an increase in pH, which in turn causes the oxyhemoglobin dissociation curve to shift to the left. This effect of CO2 on the affinity of Hgb for O2 is known as the Bohr effect, and it serves to enhance O2 uptake in the lungs and delivery of O2 to tissues. An increase in body temperature, as occurs during exercise, shifts the oxyhemoglobin dissociation curve to the right and enables more O2 to be released to tissues, where it is needed because the demand increases. During cold weather, a decrease in body temperature, especially in the extremities (lips, fingers, toes, and ears), shifts the O2 dissociation curve to the left (higher Hgb affinity). In this instance, PaO2 may be normal, but release of O2 in these extremities is not facilitated.
2,3-Diphosphoglycerate
Mature red blood cells do not have mitochondria, and therefore they depend on anaerobic glycolysis. Large quantities of a metabolic intermediary, 2,3-DPG, are formed in red blood cells during glycolysis, and the affinity of Hgb for O2 decreases as 2,3-DPG levels increase. Thus the oxyhemoglobin dissociation curve shifts to the right. Although the binding sites of 2,3-DPG and O2 differ on the Hgb molecule, binding of 2,3-DPG creates an allosteric effect that inhibits the binding of O2. Conditions that increase 2,3-DPG include hypoxia, decreased Hgb, and increased pH. Decreased levels of 2,3-DPG are observed in stored blood samples and thus may present a problem to transfusion recipients because of the greater affinity of Hgb for O2, which inhibits the unloading of O2 to tissues.
As discussed previously, HgbF has a greater affinity for O2 than does adult Hgb, and the oxyhemoglobin dissociation curve thus shifts to the left.
•Fig. 24.6 Theoxyhemoglobinandcarboxyhemoglobindissociationcurvesclearlyillustratetheincreasedaffinitythatcarbonmonoxide(CO)hasforHgb,incomparisonwithO2.100 80 60 40 20 0 0 20 40 60 PO2 (mm Hg) Hemoglobin saturation (%) 80 100 O2 + hemoglobin CO + hemoglobin
CO binds to the heme group of the Hgb molecule at the same site as O2 and forms carboxyhemoglobin (HgbCO). A major difference between the ability of CO and that of O2 to bind to Hgb is illustrated by a comparison of the oxyhemoglobin and carboxyhemoglobin dissociation curves. The affinity of CO for Hgb is about 200 times greater than it is for O2 (