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Causes of and Compensations for Hypoxemia and Hypercapnia

John B. West

10.1002/cphy.c091007

Source: Volume 1, Issue 3, July 2011

Published online: July 2011

Full Article on Wiley Online Library



Abstract

By far the commonest cause of impaired gas exchange in patients with lung disease is ventilation‐perfusion inequality. This is a complicated topic and much can be learned from computer models. Ventilation‐perfusion inequality always causes hypoxemia, that is, an abnormally low Po2 in arterial blood. However, it is also the commonest cause of an increased arterial Pco2, or hypercapnia, in patients with chronic obstructive pulmonary disease (COPD). There is often confusion in this area with some people attributing the CO2 retention to “hypoventilation” when in fact these patients are usually moving much more air into their lungs than normal subjects. A patient with COPD can often return the arterial Pco2 to normal by increasing the ventilation. However, this does not return the arterial Po2 to normal because of the different shapes of the oxygen and carbon dioxide dissociation curves. Increasing pulmonary blood flow in the presence of ventilation‐perfusion inequality usually raises the arterial Po2 but much less than increasing ventilation. Raising the inspired oxygen concentration is typically very effective in increasing the arterial Po2. Ventilation‐perfusion inequality interferes with the transfer of all gases by the lung including the anesthetic gases. The gas exchange behavior of a lung depends greatly on the pattern of ventilation‐perfusion inequality. It is theoretically possible to find a distribution that improves the transfer of some gases but this requires bizarre conditions that can never occur in practice. © 2011 American Physiological Society. Compr Physiol 1:1541‐1553, 2011.

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Figure 1. Figure 1.

A log‐normal distribution of (A) ventilation per unit volume and (B) blood flow per unit volume with less dispersion and (C) how these are combined to give a log‐normal distribution of ventilation‐perfusion ratios. From Reference 20.
Figure 2. Figure 2.

Typical example of a log‐normal distribution of ventilation‐perfusion ratio as used in this analysis. In this case, the log standard deviation of ventilation (or blood flow) per unit volume is equal to 1.5. From References 17 and 18.
Figure 3. Figure 3.

Acute effect of imposing ventilation‐perfusion inequality on a homogeneous lung. All variables were held constant except the oxygen uptake and carbon dioxide output. Note that the reduction of carbon dioxide transfer is almost as great as that of oxygen. From Reference 17 and 18.
Figure 4. Figure 4.

Effects of increasing ventilation‐perfusion ratio inequality on gas exchange in a lung model in which oxygen uptake and carbon dioxide output are maintained at 300 and 240 ml·min−1, respectively (steady‐state conditions). Note the rapid fall in the Po2 of arterial and mixed venous blood and the corresponding increases in Pco2. From References 17 and 18.
Figure 5. Figure 5.

(A) The effects of increasing total ventilation on the Po2 and Pco2 of arterial blood for different degrees of ventilation‐perfusion inequality. The log standard deviation of the distribution is shown on each line. (B) The results for Po2 and Pco2 of mixed venous blood. From References 17 and 18. The normal ventilation is shown by the arrow.
Figure 6. Figure 6.

(A) The effects of increasing total blood flow on the Po2 and Pco2 of arterial blood. (B) The changes in the Po2 and Pco2 of mixed venous blood. From References 17 and 18.
Figure 7. Figure 7.

(A) The effects of increasing the inspired Po2 on the arterial Po2. Note that the arterial Po2 remains very low even for high inspired oxygen concentrations when the degree of ventilation‐perfusion inequality is severe. (B) The alveolar‐arterial Po2 difference plotted against the alveolar Po2 for different degrees of ventilation‐perfusion inequality. At the relatively moderate standard deviation of 0.8, the alveolar‐arterial difference is still very high when the alveolar Po2 is 600 mmHg. From References 17 and 18.
Figure 8. Figure 8.

Gas exchange behavior of a bimodal distribution of ventilation‐perfusion ratios where the abnormal mode is centered on a very high ventilation‐perfusion ratio (type A). See text for details.
Figure 9. Figure 9.

Same as Figure 8 except that the abnormal mode is centered on a very low ventilation‐perfusion ratio (type B). Both Figures 8 and 9 are from Wagner (personal communication).
Figure 10. Figure 10.

Conceptual stages in the changes of pulmonary gas exchange that occur after imposing ventilation‐perfusion inequality on a homogeneous lung. See text for details. From Reference 19.
Figure 11. Figure 11.

Diagram showing why the very nonlinear oxygen dissociation curve interferes with the uptake of oxygen in a lung with ventilation‐perfusion inequality. From Reference 21.
Figure 12. Figure 12.

(A) The effects of increasing ventilation on the arterial Po2 and Pco2 when the oxygen dissociation curve is made linear (cf. Figure 5). This emphasizes how the normal nonlinear dissociation curve prevents the return of the arterial Po2 to normal in the presence of ventilation‐perfusion inequality even when the ventilation is greatly raised. (B) The effects on the Po2 and Pco2 of mixed venous blood. From References 17 and 18.
Figure 13. Figure 13.

Example of a distribution of ventilation‐perfusion ratios in a young, normal subject as measured with the multiple inert gas infusion technique 16. Note that the distribution appears to be log normal with a small dispersion. The log standard deviation is about 0.3. From Reference 15.
Figure 14. Figure 14.

An example of the distribution of ventilation‐perfusion ratios in a patient with chronic obstructive pulmonary disease with type A presentation. Note the bimodal distribution and the large amount of ventilation going to lung units with an abnormally high ventilation‐perfusion ratio. From Reference 16.
Figure 15. Figure 15.

An example of the distribution of ventilation‐perfusion ratios in a patient with chronic obstructive pulmonary disease with type B presentation. Note again the bimodal distribution, but this time, there is a large amount of blood flow going to lung units with an abnormally low ventilation‐perfusion ratio. From Reference 16.


Figure 1.

A log‐normal distribution of (A) ventilation per unit volume and (B) blood flow per unit volume with less dispersion and (C) how these are combined to give a log‐normal distribution of ventilation‐perfusion ratios. From Reference 20.



Figure 2.

Typical example of a log‐normal distribution of ventilation‐perfusion ratio as used in this analysis. In this case, the log standard deviation of ventilation (or blood flow) per unit volume is equal to 1.5. From References 17 and 18.



Figure 3.

Acute effect of imposing ventilation‐perfusion inequality on a homogeneous lung. All variables were held constant except the oxygen uptake and carbon dioxide output. Note that the reduction of carbon dioxide transfer is almost as great as that of oxygen. From Reference 17 and 18.



Figure 4.

Effects of increasing ventilation‐perfusion ratio inequality on gas exchange in a lung model in which oxygen uptake and carbon dioxide output are maintained at 300 and 240 ml·min−1, respectively (steady‐state conditions). Note the rapid fall in the Po2 of arterial and mixed venous blood and the corresponding increases in Pco2. From References 17 and 18.



Figure 5.

(A) The effects of increasing total ventilation on the Po2 and Pco2 of arterial blood for different degrees of ventilation‐perfusion inequality. The log standard deviation of the distribution is shown on each line. (B) The results for Po2 and Pco2 of mixed venous blood. From References 17 and 18. The normal ventilation is shown by the arrow.



Figure 6.

(A) The effects of increasing total blood flow on the Po2 and Pco2 of arterial blood. (B) The changes in the Po2 and Pco2 of mixed venous blood. From References 17 and 18.



Figure 7.

(A) The effects of increasing the inspired Po2 on the arterial Po2. Note that the arterial Po2 remains very low even for high inspired oxygen concentrations when the degree of ventilation‐perfusion inequality is severe. (B) The alveolar‐arterial Po2 difference plotted against the alveolar Po2 for different degrees of ventilation‐perfusion inequality. At the relatively moderate standard deviation of 0.8, the alveolar‐arterial difference is still very high when the alveolar Po2 is 600 mmHg. From References 17 and 18.



Figure 8.

Gas exchange behavior of a bimodal distribution of ventilation‐perfusion ratios where the abnormal mode is centered on a very high ventilation‐perfusion ratio (type A). See text for details.



Figure 9.

Same as Figure 8 except that the abnormal mode is centered on a very low ventilation‐perfusion ratio (type B). Both Figures 8 and 9 are from Wagner (personal communication).



Figure 10.

Conceptual stages in the changes of pulmonary gas exchange that occur after imposing ventilation‐perfusion inequality on a homogeneous lung. See text for details. From Reference 19.



Figure 11.

Diagram showing why the very nonlinear oxygen dissociation curve interferes with the uptake of oxygen in a lung with ventilation‐perfusion inequality. From Reference 21.



Figure 12.

(A) The effects of increasing ventilation on the arterial Po2 and Pco2 when the oxygen dissociation curve is made linear (cf. Figure 5). This emphasizes how the normal nonlinear dissociation curve prevents the return of the arterial Po2 to normal in the presence of ventilation‐perfusion inequality even when the ventilation is greatly raised. (B) The effects on the Po2 and Pco2 of mixed venous blood. From References 17 and 18.



Figure 13.

Example of a distribution of ventilation‐perfusion ratios in a young, normal subject as measured with the multiple inert gas infusion technique 16. Note that the distribution appears to be log normal with a small dispersion. The log standard deviation is about 0.3. From Reference 15.



Figure 14.

An example of the distribution of ventilation‐perfusion ratios in a patient with chronic obstructive pulmonary disease with type A presentation. Note the bimodal distribution and the large amount of ventilation going to lung units with an abnormally high ventilation‐perfusion ratio. From Reference 16.



Figure 15.

An example of the distribution of ventilation‐perfusion ratios in a patient with chronic obstructive pulmonary disease with type B presentation. Note again the bimodal distribution, but this time, there is a large amount of blood flow going to lung units with an abnormally low ventilation‐perfusion ratio. From Reference 16.

References
 1. Dantzker DR, Wagner PD, West JB. Instability of lung units with low VA/Q ratios during O2 breathing. J Appl Physiol 38: 886‐895, 1975.
 2. Evans JW. Mathematical analysis of compartmental lung models. In: West JB, editor. Pulmonary Gas Exchange. New York, Academic Press, 1980, p. 307‐334.
 3. Evans JW, Wagner PD, West JB. Conditions for reduction of pulmonary gas transfer by ventilation‐perfusion inequality. J Appl Physiol 36: 533‐537, 1974.
 4. Farhi LE, Rahn H. A theoretical analysis of the alveolar‐arterial O2 difference with special reference to the distribution effect. J Appl Physiol 7: 699‐703, 1955.
 5. Haldane JS. Respiration. New Haven, CT: Yale University Press, 1922, p. 137.
 6. Kelman GR. Digital computer subroutine for the conversion of oxygen tension into saturation. J Appl Physiol 21: 1375‐1376, 1966.
 7. Kelman GR. Calculation of certain indices of cardiopulmonary function using a digital computer. Respir Physiol 1: 335‐343, 1966.
 8. Kelman GR. Digital computer procedure for the conversion of Pco2 into blood CO2 content. Respir Physiol 3: 111‐115, 1967.
 9. Kelman GR. Computer program for the production of O2‐CO2 diagrams. Respir Physiol 4: 260‐269, 1968.
 10. Olszowka AJ, Farhi LE. A system of digital computer subroutines for blood gas calculations. Respir Physiol 4: 270‐280, 1968.
 11. Prime FJ, Westlake EK. The respiratory response to CO2 in emphysema. Clin Sci (Lond). 3: 321‐32, 1954.
 12. Rahn H. A concept of mean alveolar air and the ventilation‐blood flow relationships during pulmonary gas exchange. Am J Physiol 158: 21‐30, 1949.
 13. Suskind M, Rahn H. Relationship between cardiac output and ventilation and gas transport, with particular reference to anesthesia. J Appl Physiol 7: 59‐65, 1954.
 14. Wagner PD, Dantzker DR, Dueck R, Clausen JL, West JB. Ventilation‐perfusion inequality in chronic obstructive pulmonary disease. J Clin Invest 59: 203‐216, 1977.
 15. Wagner PD, Laravuso RB, Uhl RR, West JB. Continuous distributions of ventilation‐perfusion ratios in normal subjects breathing air and 100% O2. J Clin Invest 54: 54‐68, 1974.
 16. Wagner PD, Saltzman HA, West JB. Measurement of continuous distributions of ventilation‐perfusion ratios: theory. J Appl Physiol 36: 588‐599, 1974.
 17. West JB. Ventilation‐perfusion inequality and overall gas exchange in computer models of the lung. Respir Physiol 7: 88‐110, 1969.
 18. West JB. Effect of slope and shape of dissociation curve on pulmonary gas exchange. Respir Physiol 8: 66‐85, 1969.
 19. West JB. State of the art: Ventilation‐perfusion relationships. Am Rev Respir Dis 116: 919‐943, 1977.
 20. West JB, Wagner PD. Pulmonary gas exchange. In: West JB, editor. Bioengineering Aspects of the Lung. New York: Marcel Dekker, 1977, p. 361‐457.
 21. West JB. Respiratory Physiology: The essentials. Philadelphia, PA: Lippincott Williams and Wilkins, 2008, p. 68.

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Article Title: Causes of and Compensations for Hypoxemia and Hypercapnia
 

How to Cite

John B. West. Causes of and Compensations for Hypoxemia and Hypercapnia. Compr Physiol 2011, 1: 1541-1553. doi: 10.1002/cphy.c091007