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Hemoglobin Dissociation Curve Case Study

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Example 3: Modeling the Oxygenation Effects of P50 Changes at Altitude

It is well known that the oxyhemoglobin dissociation curve shifts in response to physiologic changes. Acidosis, hypercarbia, increased temperature, and increased levels of 2,3-diphosphoglycerate (2,3-DPG) all shift the curve to the right, reducing the affinity of hemoglobin for oxygen and thereby facilitating release of oxygen into tissues. Patients with chronic anemia, for example, have increased intraerythrocyte levels of 2,3-DPG and a right-shifted oxyhemoglobin curve.80 Teleologically, this would also appear to be an appropriate response to high-altitude hypoxemia, but in fact the opposite is true: Animals that have successfully adapted to high-altitude hypoxemia have left-shifted curves,81-83 as do Sherpas.82,84 In the example that follows, computer modeling is used to develop a possible explanation for this finding.

It can be theorized that a left-shifted curve is beneficial in high-altitude hypoxemia because it increases arterial oxygen content by virtue of increasing pulmonary end-capillary oxygen content. The shunt equation described earlier (Equation 57) can be rearranged as follows:

(61)

This shows that, with a constant pulmonary shunt and constant arteriovenous oxygen content difference, increases in pulmonary end-capillary oxygen content will increase the arterial oxygen content.

Now, the pulmonary end-capillary oxygen content, Cc′o2, consists of two terms, the oxygen bound to hemoglobin and the oxygen dissolved in plasma:

(62)

where

Hb = hemoglobin concentration (g/dL)

Sc′o2 = pulmonary end-capillary oxygen saturation

Pao2 = alveolar oxygen tension (mm Hg)

Pao2 is determined only by the alveolar gas equation and is independent of the position of the oxyhemoglobin curve.60 Therefore, the dissolved oxygen portion of Cc′o2 is also independent of the curve position. However, the Sc′o2 term does vary with curve position, increasing with a left-shifted curve. Therefore, Cc′o2 also increases with a left shift, taking on a maximum value of

(63)

This analysis demonstrates that a left-shifted curve increases arterial oxygen content by increasing pulmonary end-capillary oxygen content.

We now consider the effects of P50 changes in two situations.

1

In Situation A, a patient has high-altitude hypoxemia as a result of a Pao2 of 50 mm Hg. With a CO of 5 L/min, an Hb of 15 g/dL, oxygen consumption () of 250 mL/min, and a shunt fraction (Qs/Qt) of 0.1, it can be shown (Table 4-6) that Cao2 changes from 16.41 vol% with a P50 of 27 mm Hg to 18.44 vol% with a P50 of 18 mm Hg—a significant increase.

2

In Situation B, a patient has a large pulmonary shunt (Qs/Qt = 0.4), a normal Pao2 (100 mm Hg), and other parameters as in situation A. In this case, Cao2 goes from 16.47 vol% with a P50 of 27 mm Hg to 16.87 vol% with a P50 of 18 mm Hg—an insignificant change (see Table 4-6).

Figure 4-14 illustrates this concept in more detail, showing the two examples for P50 values ranging from 10 to 50 mm Hg. The data provided in situations A and B and in Figure 4-14 were obtained by using the preceding mathematical computer model of the oxyhemoglobin dissociation curve. Hill's equation relating saturation, tension, and P50 was used in conjunction with Doyle's equation for arterial oxygen tension and solved with the use of TK SOLVER.55,64

These two situations demonstrate that a leftward shift of the oxyhemoglobin dissociation curve significantly improves arterial oxygen content in the case of high-altitude hypoxemia but not in the case of a large shunt. This observation is consistent with the general finding of a right-shifted curve in patients, such as those with cyanotic heart disease, who have a right-to-left shunt.62 In these cases, a left-shifted curve is not beneficial because only a trivial improvement in Cc′o2 (and thus in PAo2) is obtained. Teleologically, it may be argued that in the presence of hypoxemia, at approximately equal arterial oxygen contents, the body prefers higher oxygen tensions (i.e., right shift), but if arterial oxygen content can be significantly improved, despite a decrease in oxygen tension, a left shift is preferred.

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