Alveolar ventilation and pulmonary blood flow:the V˙A

Enrico Calzia

Peter Radermacher

Alveolar ventilation and pulmonary blood flow:

the V˙ _A /Q˙ concept

Given a stable cardiac output (CO) and inspiratory oxy- gen concentration (F_IO2), any gas exchange abnormality leading to hypoxia or hypercapnia may be explained solely on the basis of an altered distribution of the venti- lation 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 ex- change 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 cap- illaries (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 compart- ments (i.e., shunt), the gas composition in each alveolus will determine the arterial blood gas values in direct de- pendence on both ventilation and perfusion. In lung re- gions 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 compo- sition 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 compo- sition of each alveolus will approach that of inspired gas, at lower V˙

A/Q˙ ratios that of mixed venous blood. In reali- ty, the V˙

A/Q˙ ratio is slightly less than unity, because the respiratory quotient, which is the ratio of O₂absorbed to CO₂excreted, is usually less than unity.

2. Graphic analysis of pulmonary gas exchange:

the P

_O2

-P

_CO2

diagram

The effects of a ventilation–perfusion mismatch on gas exchange are graphically described by the P_O2–P_CO2dia- gram first introduced by Rahn and Farhi (Fig. 1) [3].

Since the P_O2and P_CO2in each alveolus is determined by the V˙

A/Q˙ ratio, a line through all P_O2–P_CO2 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 per- fused but not ventilated alveoli, thus corresponding to shunt areas) to ∞ (representing ventilated but not per- fused alveoli, thus corresponding to dead space). Theo- retically, the most efficient gas exchange should be ex- pected 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 inhomo-

geneous distribution of the V˙

A/Q˙ values, mainly as a re- sult 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 al- veolar-to-arterial P_O2or P_CO2differences reflect inhomo- geneous 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” sim- plification is attractive because it allows one to quantify gas exchange abnormalities by the proportion of gas ex- change units in each compartment.

Although “ideal” alveolar zones contribute to mini- mizing alveolar-to-arterial differences, blood from shunt perfusion zones joins blood coming from alveolar re- gions with gas values identical to mixed venous ones, thus increasing both alveolar-to-arterial O₂ differences and arterial CO₂ levels. An unappreciated result of in- creased shunt fraction is the increase in arterial P_CO2 as mixed venous CO₂passes 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

(1)

where Q_s/Q_t=shunt fraction or venous admixture, Ca_O2=arterial blood O₂ content, Cc_O2=end-capillary O₂ content, and Cv_O2=mixed venous blood O₂content.

Since capillary O₂content cannot be measured direct- ly, it is assumed to equal ideal alveolar O₂ content (C_AIO2), which is estimated by the ideal alveolar O₂par- tial pressure (P_AIO2) obtained by the simplified alveolar gas equation

(2) where P_AIO2=“ideal” alveolar O₂ partial pressure, P_IO2=inspired O₂ partial pressure, Pa_CO2=arterial blood CO₂partial pressure, and RQ=respiratory quotient.

The accuracy of these formulas is limited by mainly three factors. First, the calculation of Cc_O2 from P_AIO2 assumes equilibration of alveolar and end-capillary gas and ignores the impact that changes in pH and P_CO2may have on gas exchange. Second, although Pa_CO2 is pre- sumed to equal P_AICO2, this assumption is incorrect when shunt causes P_CO2to increase more than P_AICO2. And fi- nally, 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, allow- ing 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 ex- clusion of inspired gas from gas exchange. Thus, expired gas partial pressures are maintained closer to the inspired ones. Commonly, the dead space fraction is calculated by the Bohr equation

(3) where V_D/V_T=dead space fraction, Pa_CO2=arterial blood CO₂partial pressure, and P_ECO2=mid-expired CO₂partial 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 any- where from 0 to ∞, and not just 0, 1, and ∞. 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 re- ality, because most alveolar regions are characterized by V˙

A/Q˙ -values between 1 and 0.8, or very near 0 and ∞ re- spectively. Experimentally, one may measure the exact V˙

A/Q˙ distribution of the entire lung using the multiple in- ert gas technique. However, the utility of this approach to bedside assessment of gas exchange abnormalities is low because of its impracticality.

Fig. 1 The PO₂-PCO₂diagram of Rahn and Farhi graphically ex- plains the theoretical concepts of ventilation/perfusion distribution and pulmonary gas exchange. (From [13], with permission) 22

4. Hypoxia and hypercapnia are caused by severe V˙

_A

/Q˙ mismatching

Both oxygenation and CO₂homeostasis may be consider- ably impaired by V˙_A/Q˙ mismatch, although usually only hypoxia is referred to as the result of increased venous ad- mixture, while hypercapnia is generally considered the re- sult of increased dead space ventilation or hypoventilation.

However, if minute ventilation is fixed, 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 chemoreceptor feedback 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 O₂saturation, blood O₂content cannot be increased by hy- perventilation, and is therefore more susceptible to be de- creased by increasing venous admixture. Obviously, how- ever, substantial hypercapnia will also result from hugely increased venous admixture exceeding the limits of com- pensation, especially if venous admixture is almost com- pletely caused by true shunt (e.g., atelectatic regions).

5. Clinical implications

Beneficial effects of different recommended recruitment and ventilation strategies for patients receiving mechani- cal ventilation are generally explained by their impact of ventilation to perfusion matching [5], even though the precise interplay between lung mechanics, hemodynam- ics, and V˙

A/Q˙ distribution is complex. Preventing alveo- lar collapse by the use of continuous positive airway pressure (CPAP) and positive end-expiratory pressure (PEEP) minimizes shunt, as do recruitment maneuvers, whereas vasodilator therapy, including aerosolized bron- chodilator therapy, by increasing blood flow to potential- ly underventilated lung units increases shunt and arterial desaturation. This is the cause of hypoxemia following bronchodilator therapy in severe asthmatics. Pressure- limited ventilation and smaller tidal volume ventilation

with attention paid to avoiding dynamic hyperinflation minimize dead space [6]. Prone positioning of the patient and interspacing spontaneous ventilatory efforts by caus- ing 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 extra- pulmonary factors, such as changes in cardiac output, sys- temic oxygen uptake, and mixed venous O₂saturation, can directly alter arterial oxygenation and CO₂ content inde- pendent of changes in V˙

A/Q˙ . For example, although intra- venous vasodilators usually increase intrapulmonary shunt in patients with adult respiratory distress syndrome or car- diogenic pulmonary edema, the associated increase in car- diac output, especially in the heart failure group, may off- set the increased shunt by increasing mixed venous O₂sat- uration [7]. Thus, the resultant change in arterial oxygen- ation cannot be predicted ahead of time [8]. Furthermore, some intravenous vasodilators may affect CO₂elimination through several mechanisms. They may impair CO₂elimi- nation by increasing shunt fraction or increasing blood flow and CO₂delivery to the lungs; also, if cardiac output does not increase in response of the intravenous adminis- tration of vasodilators, the intrathoracic blood volume may decrease, thus increasing the amount of hypoperfused areas especially in apical lung zones [9]. Giving vasodilators by inhalation should minimize shunt because only ventilated lung units will receive the vasodilating agent. Thus, inhala- tional vasodilating therapy should improve V˙

A/Q˙ matching.

This has been shown to occur in patients with gas ex- change abnormalities when treated with nitric oxide (NO) inhalation or aerosolized prostacyclin [10, 11]. The under- lying pathology seems to be crucially important in regard to the effects on arterial oxygenation. While patients with adult respiratory distress syndrome or right heart failure improve their gas exchange, inhaled vasodilators may worsen arterial oxygenation by inhibiting hypoxic vaso- constriction in patients with chronic obstructive pulmonary disease, since V˙

A/Q˙ mismatch in hypoventilated areas rath- er than true shunt is the predominant cause of arterial hyp- oxemia in such cases [12].

References

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