Chapter 5, cont… (Page 4)

Oxygen transfer

V/Q IMBALANCE IN PATIENTS - VARIABLE EFFECT ON OXYGEN AND CARBON DIOXIDE

Fig. 5­12 demonstrates that increasing degrees of V/Q imbalance should cause both low PaO₂ and elevated PaCO₂. Clinically, however, most patients who are hypoxemic from V/Q imbalance have low PaO₂ but also low or normal PaCO₂. Why this apparent contradiction?

The reason is not, as some often think, the greater diffusibility of carbon dioxide as compared to oxygen. (Diffusion impairment is not a limiting factor for transfer of carbon dioxide or oxygen, at least with the patient at rest.) The main reason is the physiologic difference between the oxygen and carbon dioxide dissociation curves ( Fig. 5­13).

Fig. 5­13. V/Q imbalance and the dissociation curves for carbon dioxide and oxygen. v/Q represents low V/Q units and V/Q represents high V/Q units. See text for discussion.

The different shape and position of the two curves allows increased alveolar ventilation to lower partial pressure of carbon dioxide PCO₂), but not raise partial pressure of oxygen PO₂).

With V/Q imbalance, some alveolar­capillary units are relatively overventilated and others relatively underventilated. Blood leaving the various units mixes in the pulmonary veins. As already pointed out, hyperventilation of some units does not add enough oxygen to balance the low oxygen contents from low V/Q areas.

Fig. 5­13 shows the oxygen and carbon dioxide dissociation curves plotted on the same scale. The upper curve is for carbon dioxide; note that it is diagonal in the physiologic range. The lower curve is for oxygen; it is almost flat in the physiologic range. (This is the same oxygen dissociation curve shown in Fig. 5­11.) On the abscissa is the partial pressure of either oxygen or carbon dioxide; on the ordinate is the content of either oxygen or carbon dioxide. Point a on each curve is the normal arterial point for content and partial pressure.

To the right of the graph are two lung units, one representing low V/Q and one high V/Q. The content of oxygen and carbon dioxide in the blood from each type of unit is represented on the dissociation curves.

Note that the effect of low V/Q units is to lower PO₂ and raise PCO₂; the shape of the dissociation curves dictates that the respective contents will also change in the same direction. The effect of high V/Q units is to raise Po, and lower Pco.; the shape of the dissociation curves dictates that this high V/Q unit can reverse the high PCO₂ but not the low PO₂. Thus any elevation in PCO₂ from low V/Q units can be compensated for by PCO₂ reduction in high V/Q units. These high V/Q units cannot compensate for the reduction in oxygen content since the oxygen dissociation curve is nearly flat in the range of high PO₂ values.

The final carbon dioxide content in Fig. 5­13 is point a on the carbon dioxide dissociation curve, arrived at by averaging the high and low V/Q points on the carbon dioxide curve. The final oxygen content is point x, arrived at by averaging the high and low V/Q points on the oxygen curve. Point x is between the low V/Q and arterial points on the oxygen curve and represents a PO₂ considerably reduced from normal.

Fig. 5­14. Changes in PaO₂ and PaCO₂ from V/Q imbalance. All values are mm Hg. See text for discussion.

The important point is that hyperventilation in some units can compensate for the tendency of hypoventilated units to increase the PCO₂. Thus if PCO₂ is increased in the blood draining the hypoventilated units, hyperventilation of other units can compensate because the carbon dioxide dissociation curve (carbon dioxide content vs. PCO₂) is almost linear and diagonal in the range of physiologic PCO₂ values. To take advantage of this mechanism, the patient has to augment his minute ventilation and alveolar ventilation (Fig. 5­14). Patients who are able to increase their minute ventilation in the face of V/Q imbalance will usually manifest hypoxemia along with normal or low PaCO₂.

Although the majority of patients with V/Q imbalance do not manifest hypercapnia, some do, particularly when V/Q imbalance is severe and chronic. Such patients are unable to sustain the necessary increase in minute ventilation. The most common example clinically is the patient with severe chronic obstructive pulmonary disease whose V/Q imbalance has resulted in large amounts of alveolar dead space. Such a patient must maintain an increased minute ventilation to maintain a normal PaCO₂. However, if the work of breathing that is required to keep a high minute ventilation is too great, the patient will opt for less work and hence an elevated PaCO₂; this occurs in many patients with severe chronic lung disease. Even so, in such cases the basic cause of hypercapnia is increased dead space from V/Q imbalance. V/Q imbalance is the most common cause, not only of reduced PaO₂, but, by the mechanism just explained, also of elevated PaCO₂.

SUMMARY

The physiologic process of oxygenation involves (I) delivering oxygen from the atmosphere to the lungs where it is taken up by the pulmonary capillaries, and (2) transporting oxygen from the pulmonary circulation to all the body's tissues. Understanding the basic physiology of these two steps helps answer two important clinical questions: (I) Are the lungs properly transferring oxygen into the blood? and (2) is the patient adequately oxygenated?

The first question can be answered yes or no by determining the alveolar­arterial oxygen pressure difference (P(A­a)O₂), also referred to as the "A-a gradient." The P(A­a)O₂ is determined by subtracting the measured arterial partial pressure of oxygen PaO₂) from the calculated alveolar partial pressure of oxygen (PAO₂), with the latter obtained from the equation PAO₂ = PIO₂ ­ (1.2 x PaCO₂). For a patient breathing room air, normal P(A­a)O₂ is age­dependent, ranging from approximately 5 to 30 mm Hg. Normal P(A­a)O₂ increases as the fraction of inspired oxygen FIO₂) increases and can go up to approximately 100 mm Hg on 100% oxygen. If P(A­a)O₂ is elevated above normal, the lungs are not transferring oxygen properly. An elevated P(A­a)O₂ represents a parenchymal lung problem and is almost always caused by ventilation­perfusion (V/Q) imbalance.

V/Q imbalance is an imbalance of the normal distribution of ventilation to perfusion among the millions of alveolar capillary units. Gas exchange (the transfer of oxygen and carbon dioxide between the alveolar air and the pulmonary capillary blood) is always disturbed in the presence of V/Q imbalance. Hypoxemia results when areas of the lung are relatively overperfused (or underventilated), a common occurrence in parenchymal lung diseases.

Graphic representation of V/Q relationships helps explain the pattern of gas exchange abnormality seen clinically. For example, patients with predominant chronic bronchitis are hypoxemic because they have relatively large areas of underventilated (overperfused) lung. Patients with predominant emphysema have large areas of overventilated (underperfused) lung representing extra dead space that they must ventilate with each breath; as long as they can augment their total ventilation to satisfy the extra dead space, hypoxemia does not occur.

REVIEW QUESTIONS

State whether each of the following is true or false.

1. The most common physiologic cause of hypoxemia is diffusion barrier.

2. An increase in the alveolar­arterial PO₂ difference most commonly arises from a ventilation/perfusion imbalance within the lungs.

3. Thebesian vessels supply the myocardium and drain the venous blood directly into the ventricles.

4. Alveolar PO₂ is a function of, among other factors, PCO₂, respiratory quotient, and altitude.

5. The alveolar­arterial PO₂ difference may normally be as high as 50 mm Hg when breathing 100% oxygen.

6. Both the PaO₂ and PaCO₂ are age­dependent, the former decreasing and the latter slightly increasing with age.

7. The reason why patients with ventilation/perfusion imbalance commonly manifest hypoxemia but not hypercapnia is the greater diffusibility of carbon dioxide compared to oxygen.

8. While breathing 100% oxygen, a patient's respiratory quotient becomes unity.

9. Hemodialysis can lead to hypoxemia by reducing alveolar ventilation.

10. Alveolar units that receive ventilation but no perfusion have a ventilation­perfusion ratio of infinity.

References

Aurigemma, N.M., Feldman, N., Gottlieb, M., et al.: Arterial oxygenation during hemodialysis, N. Engl. J. Med. 297:871,1977.

Gibson, G.J.: Clinical tests of respiratory function, New York, 1984, Raven Press.

Gilbert, R., Keighley, J .F.: The arterial/alveolar oxygen tension ratio: an index of gas exchange applicable to varying inspired oxygen concentrations, Am. Rev. Respir. Dis. 109:142, 1974.

Harris, E.A., Kenyon, A.M., Nisbet, H.D., et al.: The normal alveolar­arterial oxygen­tension gradient in man, Clin. Sci. Mol. Med. 46:89. 1974.

Hess, D., and Maxwell, C.: Which is the best index of oxygenation­­P(A­a)O₂, PaO₂/PAO₂, or PaO₂/FIO₂? Respir. Care 30:961,1985.

Hunt, J.M., Chappell, T.R., Henrich, W.L., et al.: Gas exchange during dialysis: contrasting mechanisms contributing to comparable alterations with acetate and bicarbonate buffers, Am. J. Med. 77:255, 1984.

Martin, L.: Abbreviating the alveolar gas equation: an argument for simplicity, Respir. Care 31:40, 1986.

Martin, L.: Hypoventilation without CO₂ retention, Chest 77:720, 1980.

Quebbman, E.J., Maierhofer, W.J., and Pienng, W.F.: Mechanisms producing hypoxemia during hemodialysis, Crit. Care Med. 12:359, 1984.

Remolina, C., Khan, A.U., Santiago, T.V., et al.: Positional hypoxemia in unilateral lung disease, N. Engl. J. Med. 304:523,1981.

Sorbini, C.A., Grassi, V., Solinas, E., et al.: Arterial oxygen tension in relation to age in healthy subjects, Respiration 25:3, 1968.

West, J.B.: Ventilation­perfusion inequality and overall gas exchange in computer models of the lung, Respir. Physiol. 7:88, 1969.

West, J.B.: Causes of carbon dioxide retention in lung disease, N. Engl. J. Med. 284:1232, 1971.

West, J.B.: Ventilation/blood flow and gas exchange, Oxford, 1980, Blackwell Scientific Publications, Ltd.

West, J.B., and Wagner, P.D.: Bioengineering aspects of the lung, New York, 1977, Marcel Dekker, Inc.

West, J.B., Hackett, P.H., Maret, K.H., et al.: Pulmonary gas exchange on the summit of Mt. Everest, J. Appl. Physiol. 55:678,1983.

Suggested readings

Begin, R., and Renzetti, A.D.: Alveolar­arterial oxygen pressure gradient. I. Comparison between an assumed and actual respiratory quotient in stable chronic pulmonary disease. II. Relationship to aging and closing volume in normal subjects, Respir. Care 22(5):491, 1977.

Burrows, B., Fletcher, C.M., Heard, B.E., et al.: The emphysematous and bronchial types of chronic airways obstruction: a clinicopathological study of patients in London and Chicago, Lancet 1:830, 1966.

Huet, Y., Lemaire, F., Brun­Buisson, C., et al.: Hypoxemia in acute pulmonary embolism, Chest 88:829, 1985.

Mellemgaard, K.: The alveolar­arterial oxygen difference: its size and components in normal man, Acta. Physiol. Scand. 67:10,1966.

Wagner, P.D., Saltzman, H.A., and West, J.B.: Measurement of continuous distributions of ventilation­perfusion ratios: theory, J. Appl. Physiol. 36(5):588, 1974.

West, J.: Ventilation­perfusion relationships, Am. Rev. Resp. Dis. 116:919, 1977.

See also General References (Physiology) in Appendix G.

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