Mutations in the amino acid sequence or spatial arrangement of the globin polypeptide chains can lead to abnormalities in the Hgb molecule, such as sickle cell disease. These abnormalities result in a change in function. Compounds like CO, nitrites (nitric oxide), and cyanides have the ability to oxidize the iron molecule in the heme group of Hgb, converting it from the reduced ferrous state (Fe++) to the ferric state (Fe+++). This oxidation reduces the ability of Hgb to bind with O2.

In the alveoli, the majority of O2 in plasma quickly diffuses into red blood cells and chemically binds to Hgb. This binding process is reversible, allowing Hgb to release O2 to tissues through passive diffusion. As a result, the concentration of O2 in Hgb decreases. The relationship between the partial pressure of O2 (PO2) in blood and the number of O2 molecules bound to Hgb is illustrated by the oxyhemoglobin dissociation curve. This curve (Fig. 24.4) demonstrates the dependence of Hgb saturation on PO2, especially at partial pressures below 60 mm Hg. The flat portion of the curve (above 60 mm Hg) indicates that a decrease in PO2 within a wide range (100 to 60 mm Hg) has minimal impact on Hgb saturation, which remains at a sufficient level of 90% to 100% for normal O2 transport and delivery. The steep portion of the curve (below 60 mm Hg) shows that a small change in PO2 results in the release of a large amount of O2 from Hgb, facilitating its diffusion into tissues. The point on the curve where Hgb is 50% saturated with O2 is referred to as the P50, which is 27 mm Hg in healthy adults.

The oxyhemoglobin dissociation curve can be influenced by various physiological factors, causing it to shift either to the right or to the left (Fig. 24.5). Factors that decrease the affinity of Hgb for O2, such as temperature, PCO2, 2,3-diphosphoglycerate (2,3-DPG), and pH, shift the curve to the right, resulting in increased P50. Conversely, factors that increase the affinity of Hgb for O2, such as temperature, PCO2, 2,3-DPG, and pH, shift the curve to the left, leading to a decreased P50.
Abnormalities of the Hgb molecule occur with mutations in the amino acid sequence (i.e., sickle cell disease) or in the spatial arrangement of the globin polypeptide chains and result in abnormal function. Compounds such as CO, nitrites (nitric oxide), and cyanides can oxidize the •Fig. 24.4 Oxyhemoglobin Dissociation Curve Showing the Relationship Between the Partial Pressure of Oxygen (Po2) in Blood and the Percentage of Hemoglobin (Hgb) Binding Sites That Are Occupied by Oxygen Molecules (Percentage Saturation). Adulthemoglobin(HgbA)isabout50%saturatedwithoxygenataPO2of27mmHg,90%saturatedat60mmHg,andabout98%saturatedat100mmHg.TheP50isthepartialpressureatwhichHgbis50%saturatedwithO2.WhentheO2dissociationcurveshiftstotheright,P50increases.Whenthecurveshiftstotheleft,P50decreases.
iron molecule in the heme group and change it from the reduced ferrous state (Fe++) to the ferric state (Fe+++), which reduces the ability of O2 to bind to Hgb.
In the alveoli, the majority of O2 in plasma quickly diffuses into red blood cells and chemically binds to Hgb. This process is reversible, so that Hgb quickly gives up its O2 to tissue through passive diffusion (the concentration of O2 in Hgb decreases). The oxyhemoglobin dissociation curve illustrates the relationship between PO2 in blood and the number of O2 molecules bound to
Hgb (Fig. 24.4 ). The S shape of the curve demonstrates the dependence of Hgb saturation on PO2, especially at partial pressures lower than 60 mm Hg. The clinical significance of the flat portion of the oxyhemoglobin dissociation curve (>60 mm Hg) is that a drop in PO2 over a wide range of partial pressures (100 to 60 mm Hg) has a minimal effect on Hgb saturation, which remains at 90% to 100%, a level sufficient for normal O2 transport and delivery. The clinical significance of the steep portion (<60 mm Hg) of the curve is that a large amount of O2 is released from Hgb with only a small change in PO2, which facilitates the release and diffusion of O2 into tissue. The point on the curve at which Hgb is 50% saturated with O2 is called the P50, and it is 27 mm Hg in normal adults.
˜˜˜˜°°°°Temperature PCO2 2,3-DPG pH Decreased P50 (increased affinity) Temperature PCO2 2,3-DPG pH Increased P50 (decreased affinity) •Fig. 24.5 Factorsthatshifttheoxyhemoglobindissociationcurvetotheright(decreasedaffinityofHgbforO2)ortotheleft(increasedaffinity).2,3-DPG,2,3-diphosphoglycerate;PCO2,partialpressureofcarbondioxide.
Physiological Factors That Shift the Oxyhemoglobin Dissociation Curve
The oxyhemoglobin dissociation curve can shift in numerous clinical conditions, either to the right or to the left (
Fig.
24.5 ). The curve is shifted to the right when the affinity of