Role of the Cardiovascular System in Coupling the External Environment to Cellular Respiration

Cardiovascular Function and Pulmonary Gas Exchange

Cardiac function is of importance to oxygen exchange in the lungs in a number of ways. First, total pulmonary blood flow (normally equal to cardiac output) affects partial pressure of oxygen (P o ₂ ) of venous blood entering the lungs. Although in health this is of little significance, it is of major importance in disease. Second, the relationship between total pulmonary blood flow and the volume of blood in the pulmonary capillaries determines red cell exposure (or transit) time in the lungs. In resting normal humans, transit time is greatly in excess of what is needed. This may not be the case during exercise or in disease. Third, the distribution of pulmonary blood flow among the ~500 million alveoli cannot be perfectly matched to their ventilation. This causes ventilation/perfusion (V̇ a /Q̇) mismatch that interferes with arterial oxygenation. Once again, this is of little consequence in health but is of major importance in disease of the cardiopulmonary system. Fourth, dysfunction of the left ventricle from any cause that raises diastolic filling pressure has the potential for causing pulmonary edema, especially if there has been pulmonary capillary damage from disease. Pressures are sufficiently low in health that edema does not occur at rest. On heavy exercise, mild interstitial edema can occur but the effects are subtle. Importance of left ventricular dysfunction increases dramatically when filling pressures exceed 20 to 25 mm Hg. Pulmonary microvessels may even undergo a degree of physical disruption at very high vascular pressures. Fifth, right ventricular hypertrophy from pulmonary diseases may impair left ventricular function, effectively decreasing left ventricular compliance through mechanical interdependence of the heart chambers.

Total Pulmonary Blood Flow and Oxygen Exchange

Pulmonary oxygen exchange under steady-state conditions obeys mass balance principles. Corresponding equations can be written to describe oxygen uptake from respired air and into the pulmonary circulation. These are, respectively,

V̇ o ₂ is whole body oxygen consumption; V̇ i and V̇ a are inspired and expired alveolar ventilation, respectively; F io ₂ and F ao ₂ are inspired and expired alveolar oxygen fractional concentrations, respectively; Q̇ is total pulmonary blood flow and Ca o ₂ and are arterial and pulmonary arterial (mixed venous) oxygen concentrations, respectively. These two equations embody the principle of taking the difference between the oxygen flow rate into and out of the lungs, expressed for ventilation ( Eq 1 ) or blood flow ( Eq 2 ). While not completely correct, it is reasonable for clinical purposes to assume that V̇ i equals V̇ a , to simplify Eq 1 . Strictly, V̇ a = V̇ i – V̇ o ₂ + V̇ co ₂ (where V̇ co ₂ is CO ₂ output by the lungs). If the respiratory quotient (R) equals 1.0, V̇ o ₂ = V̇ co ₂ and V̇ a = V̇ i . Normally, V̇ o ₂ exceeds V̇ co ₂ so that R is 0.8, on average. Under these conditions, V̇ a is about 1% less than V̇ i , an unimportant difference.

In healthy lungs, alveolar P o ₂ (proportional to FA o ₂ , Eq 1 ) is tightly related to Ca o ₂ ( Eq 2 ) by the O ₂ -Hb dissociation curve. Thus Ca o ₂ can be directly computed using alveolar P o ₂ and the O ₂ -Hb dissociation curve. This is not true in lung disease, in which for Eq 1 , FA o ₂ is mean alveolar [O ₂ ] averaged over the ~500 million alveoli (weighted by the ventilation of each) and Ca o ₂ is arterial [O ₂ ], similarly averaged but weighted by blood flow to each of the alveoli. When ventilation and/or blood flow is distributed in a nonhomogeneous manner in lung disease, the P o ₂ corresponding to mean alveolar gas is often much higher than that of arterial blood (corresponding to Ca o ₂ ). Ca o ₂ cannot then be accurately calculated from FA o ₂ and the O ₂ -Hb dissociation curve.

Returning to the normal lung setting and Eq 1 and Eq 2 , it is clear from Eq 1 that alveolar [O ₂ ], FA o ₂ , is a direct function of V̇ o ₂ , F io ₂ , and alveolar ventilation only. Thus so too is arterial [O ₂ ], Ca o ₂ . The important conclusion is that changes in cardiac output, Q̇, will have no influence on arterial [O ₂ ] or P o ₂ in normal lungs, that is so long as Ca o ₂ is a direct function of FA o ₂ . For example, an increase in cardiac output per se with anxiety or fever would not affect arterial P o ₂ in a normal lung (if V̇ o ₂ , F io ₂ , and ventilation remained unchanged). A fall in cardiac output from dehydration, blood loss, or myocardial infarct would also not affect arterial P o ₂ under the same assumptions in a normal lung.

Eq 2 shows that the sole influence of cardiac output on gas exchange in a normal lung is to affect mixed venous [O ₂ ] and P o ₂ . As cardiac output falls so too will and as cardiac output rises, so too will . While as stated this does not affect arterial [O ₂ ] or P o ₂ in the normal lung, this is not the case in diseases of the lungs associated with ventilation/blood flow mismatch or right to left shunting. In such diseases, it is still true that must rise and fall with cardiac output just as in health (other influences staying constant). However, since arterial blood is the mixture of blood from all lung regions, a shunt (or areas of low V̇ a /Q̇ ratio) will mix blood from regions having lower [O ₂ ] than normal, reducing mixed arterial [O ₂ ] and P o ₂ . As cardiac output falls, the [O ₂ ] and P o ₂ of such shunts or low V̇ a /Q̇ regions will fall because such pathways essentially fail to oxygenate flowing blood above mixed venous levels. Thus the contribution of such regions to arterial blood, being tightly coupled to mixed venous [O ₂ ], is in turn closely dependent on cardiac output. The end result is more severe arterial hypoxemia as cardiac output falls and less severe hypoxemia as cardiac output rises. This is illustrated in Fig. 4.1 , in which a normal lung and a lung containing as an example of disease—a 25% right-to-left shunt—are compared as cardiac output changes. Arterial oxygen saturation, a better reflection of the oxygen concentration of the blood, follows changes in P o ₂ ( Fig. 4.2 ). Mixed venous P o ₂ ( Fig. 4.3 ) changes similarly in both cases (according to Eq 2 ) but only in the abnormal lung do arterial P o ₂ and oxygen saturation vary with cardiac output. The clinical message is clear: the degree of arterial hypoxemia in a given patient depends not only on how much shunt (or V̇ a /Q̇ mismatch) is present but also on cardiac output. Therefore, if arterial P o ₂ were to fall in such a patient, changes in cardiac output should be excluded if the arterial P o ₂ change is to be interpreted as a change in health of the lung. Application of the classical shunt (or venous admixture) equation illustrates this dramatically:

Here Q̇ va /Q̇ t is venous admixture as a percentage of the cardiac output and Ci o ₂ is essentially the [O ₂ ] of normal end capillary blood in nonshunted, normal V̇ a /Q̇ regions of the lung. As Q̇ va /Q̇ t is computed over the range of cardiac output values and for the examples in Fig. 4.1 , but assuming staying constant ( constant at the normal value of 40 Torr for Q̇ t = 6 L ⋅ min ^–1 in each case, rather than the actual associated with each cardiac output), it can be seen ( Fig. 4.4 ) how badly Q̇ va /Q̇ t is overestimated when actual cardiac output is low and underestimated when cardiac output is high. Neither of the extremes of cardiac output in Fig. 4.4 , that is, 3 and 12 L ⋅ min ^–1 , is beyond the range of common experience in the intensive care setting. Apparent shunt (Q̇ va /Q̇ t ) would be about twice the actual value when cardiac output is 50% reduced and half the real value when cardiac output is doubled if venous [O ₂ ] is assumed to be at normal levels.