Alveolar ventilation and pulmonary blood flow: the V.A/Q. concept

Enrico Calzia
Peter Radermacher
Given a stable cardiac output (CO) and inspiratory oxygen concentration (FIO2), any gas exchange abnormality leading to hypoxia or hypercapnia may be explained solely on the basis of an altered distribution of the ventilation and perfusion (V.A/Q. ) regardless of the underlying disease [1]. 1. The alveolus is the functional unit of the lung The alveolus and the surrounding capillaries represent the functional lung gas exchange unit. Diffusive gas transport across the alveolar–capillary membrane is very rapid [2]. Even under pathologic conditions gas exchange at the alveolar level is not limited by diffusion across the gas–blood barrier, but mainly by the interplay between gas transport to (and from) the alveolar space (ventilation, V.A) and blood flow across the alveolar capillaries
(perfusion, Q. ). End-capillary gas partial pressures exactly reflect alveolar gas composition. Therefore, since arterial blood is the sum of the blood from each alveolar
region and the blood that bypasses the alveolar compartments (i.e., shunt), the gas composition in each alveolus will determine the arterial blood gasvalues in direct dependence on both ventilation and perfusion. In lung regions where ventilation exceeds perfusion, the alveolar gas partial pressures will approach the inspired ones. In contrast, if perfusion exceeds ventilation, the alveolar gas composition will more closely resemble the composition of mixed venous blood. Consequently, at a V.A/Q. ratio near unity, O2 and CO2 gas exchange is optimally balanced. Since alveoli with such an optimal V.A/Q. ratio are the main contributors to the achievement of “normal” arterial blood gas values they are called “ideal” alveoli. At V.A/Q. ratios exceeding the ideal value the gas composition of each alveolus will approach that of inspired gas, at lower V.A/Q. ratios that of mixed venous blood. In reality, the V.A/Q. ratio is slightly less than unity, because the respiratory quotient, which is the ratio of O2 absorbed to CO2 excreted, is usually less than unity. 2. Graphic analysis of pulmonary gas exchange:
the PO2-PCO2 diagram The effects of a ventilation–perfusion mismatch on gas
exchange are graphically described by the PO2–PCO2 diagram first introduced by Rahn and Farhi (Fig. 1) [3]. Since the PO2 and PCO2 in each alveolus is determined by the V.A/Q. ratio, a line through all PO2–PCO2 value pairs can be drawn connecting two endpoints of mixed venous blood and inspired gas composition. Each point on this
line represents V.A/Q. values from 0 (representing perfused but not ventilated alveoli, thus corresponding to shunt areas) to 8 (representing ventilated but not perfused alveoli, thus corresponding to dead space). Theoretically, the most efficient gas exchange should be expected in a perfectly homogeneous lung,with an overall V. A/Q. value near unity. However, even in healthy subjects a limitation in gas exchange is imposed by the inhomogeneous distribution of the V.A/Q. values, mainly as a result of gravitational forces. In normal physiologic states, however, this inhomogeneity is fairly moderate, but it substantially increases with disease. 3. V.A/Q. mismatch is quantified by the three-compartment model of ideal alveoli, shunt, and dead space
Assuming a perfectly homogeneous V.A/Q. distribution and no shunt, alveolar (=end capillary) and arterial gas partial pressures should be equal. Consequently, any alveolar-to-arterial PO2 or PCO2 differences reflect inhomogeneous V.A/Q. distribution and are used to quantify the V. A/Q. mismatch. Conceptually, as suggested by Riley and Cournand [4], alveolar gas exchange can be simplified to
occurring within three types of alveoli: those with matched V.A/Q. (ideal), those with no Q. (dead space), and those with no V.A (shunt). This “three-compartment” simplification is attractive because it allows one to quantify gas exchange abnormalities by theproportion of gas exchange units in each compartment. Although “ideal” alveolar zones contribute to minimizing alveolar-to-arterial differences, blood from shunt perfusion zones joins blood coming from alveolar regions
with gas values identical to mixed venous ones, thus increasing both alveolar-to-arterialO2 differences and arterial CO2 levels. An unappreciated result of increased shunt fraction is the increase in arterial PCO2 as mixed venous CO2 passes the alveoli and mixes with the arterial blood. Based on these considerations, the amount of right-to-left shunt can be derived from the calculated gas content in capillary, arterial, and mixed venous blood using the equation where Qs/Qt=shunt fraction or venous admixture,
CaO2=arterial blood O2 content, CcO2=end-capillary O2 content, and CvO2=mixed venous blood O2 content. Since capillary O2 content cannot be measured directly, it is assumed to equal ideal alveolar O2 content (CAIO2), which is estimated by the ideal alveolar O2 partial pressure (PAIO2) obtained by the simplified alveolar gas equation
(2) where PAIO2=“ideal” alveolar O2 partial pressure, PIO2=inspired O2 partial pressure, PaCO2=arterial blood CO2 partial pressure, and RQ=respiratory quotient. The accuracy of these formulas is limited by mainly three factors. First, the calculation of CcO2 from PAIO2 assumes equilibration of alveolar and end-capillary gas and ignores the impact that changes in pH and PCO2 may have on gas exchange. Second, although PaCO2 is presumed to equal PAICO2, this assumption is incorrect when shunt causes PCO2 to increase morethan PAICO2. And finally, the respiratory exchange ratio (RQ) is assumed to be 0.8, but may actually vary between 1.0 and 0.7 based on metabolic activity and diet. Despite these limitations, however, these formulae are remarkably accurate, allowing the estimation of right-to-left shunt in the clinical setting. In contrast to shunts, gas exchange abnormalities due to increased dead space ventilation result in partial exclusion of inspired gas from gasexchange. Thus, expired gas partial pressures are maintained closer to the inspired ones. Commonly, the dead space fraction is calculated by the Bohr equation where VD/VT=dead space fraction, PaCO2=arterial blood
CO2 partial pressure, and PECO2=mid-expired CO2 partial pressure. Although this three-compartment model is useful in calculating shunt and dead space, clearly, gas exchange units can have local ventilation to perfusion ratios anywhere
from 0 to 8, and not just 0, 1, and 8. However, the three-compartment model forces parts of the lung to be in one of these three compartments. Under normal resting conditions, this assumption is not so far off of reality, because most alveolar regions are characterized by V. A/Q. -values between 1 and 0.8, or very near 0 and 8 respectively.
Experimentally, one may measure the exact V. A/Q. distribution of the entire lung using the multiple inert gas technique. However, the utility of this approach to bedsideassessment of gas exchange abnormalities is low because of its impracticality. Fig. 1 The PO2-PCO2 diagram of Rahn and Farhi graphically explains the theoretical concepts of ventilation/perfusion distribution and pulmonary gas exchange. (From [13], with permission)
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4. Hypoxia and hypercapnia are caused by severe V.A/Q. mismatching
Both oxygenation and CO2 homeostasis may be considerably impaired by V.A/Q. mismatch, although usually only hypoxia is referred to as the result of increased venous admixture, while hypercapnia is generally considered the result of increased dead space ventilation or hypoventilation. However, if minute ventilation isfixed, as is the case during controlled ventilation, then increasing shunt fraction will cause hypercarbia. In the awake, spontaneously breathing subject, CO2 elimination may be sufficiently maintained through chemoreceptorfeedback even in the presence of low V.A/Q. alveoli, so that arterial CO2 remains normal. In contrast, due to the narrow limits imposed by hemoglobin O2 saturation, blood O2 content cannot be increased by hyperventilation,
and is therefore more susceptible to be decreased by increasing venous admixture. Obviously, however, substantial hypercapnia will also result from hugely increased venous admixtureexceeding the limits of compensation, especially if venous admixture is almost completely caused by true shunt (e.g., atelectatic regions).
5. Clinical implications Beneficial effects of different recommended recruitment and ventilation strategies for patients receiving mechanical ventilation are generally explained by their impact of ventilation to perfusion matching [5], even though the precise interplay between lung mechanics, hemodynamics, and V.A/Q. distribution is complex. Preventing alveolar collapse by the use of continuouspositive airway pressure (CPAP) and positive end-expiratory pressure (PEEP) minimizes shunt, as do recruitment maneuvers, whereas vasodilator therapy, including aerosolized bronchodilator therapy, by increasing blood flow to potentially underventilated lung units increases shunt and arterial desaturation. This is thecauseofhypoxemia following bronchodilator therapy in severe asthmatics. Pressurelimited ventilation and smallertidalvolume ventilation with attention paid to avoiding dynamic hyperinflation minimize dead space [6]. Prone positioning of the patient and interspacing spontaneousventilatory efforts by causing
diaphragmatic contraction improve V.A/Q. matching. When one takes into account the effects of systemic blood flow on gas exchange, the interactions become more complex again. The interactions between intra- and extrapulmonary factors, such as changes in cardiac output, systemic oxygen uptake, and mixed venous O2 saturation, can directly alter arterial oxygenationand CO2 content independent of changes in V.A/Q. . For example, although intravenous vasodilators usually increase intrapulmonary shunt
in patients with adult respiratory distress syndrome or cardiogenic pulmonary edema, the associated increase in cardiac output, especially in the heart failure group, may offset the increased shunt by increasing mixed venous O2 saturation [7]. Thus, the resultant change in arterial oxygenation cannot be predicted ahead of time [8]. Furthermore,
some intravenous vasodilators may affect CO2 elimination through several mechanisms. They may impair CO2 elimination by increasing shunt fraction or increasing blood
flow and CO2 delivery to the lungs; also, if cardiac output does not increase in response of the intravenous administration of vasodilators, the intrathoracic blood volume may decrease, thus increasing the amount of hypoperfused areas especially in apical lungzones [9]. Giving vasodilators by inhalation should minimize shunt because only ventilated lung units will receive the vasodilating agent. Thus, inhalational vasodilating therapy should improve V.A/Q. matching. This has been shown to occur in patients with gas exchange abnormalities when treated with nitric oxide (NO) inhalation or aerosolized prostacyclin [10, 11]. The underlying pathology seems to be crucially important in regard
to the effects on arterial oxygenation. While patients with dult respiratorydistresssyndrome or right heart failure improve their gas exchange, inhaled vasodilators may worsen arterial oxygenation by inhibiting hypoxic vasoconstriction in patients with chronic obstructive pulmonary disease, since V.A/Q. mismatch in hypoventilated areas rather than true shunt is the predominant cause of arterial hypoxemia in such cases [12].
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