The Gas Exchanger: Matching Ventilation and Perfusion

Alveolar Ventilation and Carbon Dioxide Elimination

Components of Ventilation: Dead Space and Alveolar Ventilation ↑

Alveolar ventilation () is a term used to characterize the volume of air per minute that enters or exits the alveoli of the lung. This gas is potentially able to participate in gas exchange, assuming that the alveoli are being supplied by blood (perfused). Dead space ventilation (), in contrast, is the term used to characterize the volume of air per minute that enters or exits the parts of the lung that do not participate in gas exchange. Dead space is comprised of the volume of the conducting (non–gas-exchanging) areas of the lung (anatomic dead space) as well as the volume of the alveoli that are not being perfused (alveolar dead space) (Fig. 5-1).

Total ventilation (usually represented as with the E standing for expired gas because we usually measure ventilation by collecting the volume of expired gas over a fixed period of time) is the sum of alveolar ventilation and dead space ventilation:

Anatomic dead space can be estimated in the average person as equal to 1 mL per pound of body weight. For the average person weighing 150 pounds, anatomic dead space would be 150 mL. Alveolar dead space in normal individuals is quite small, approximately 20 to 50 mL. This volume represents alveoli, typically in the apex of the lung in an upright person, that do not receive blood flow (more on the physiology of this phenomenon later in the chapter).

One of the ways to assess dead space and its likely impact on gas exchange is to express it as a proportion of the normal breath or tidal volume (). A normal tidal volume in a person at rest is approximately 450 to 500 mL. If total dead space, sometimes called physiological dead space, is the sum of anatomic and alveolar dead space and these two elements add up to roughly 175 mL, then the dead space to tidal volume ratio () is 175/500, or approximately one third.

Measurement of Dead Space

Diseases of the lung often interfere with gas exchange. Our ability to characterize the severity of the disease relies, therefore, on the methods available to assess these derangements. The measurements of dead space and the ratio of dead space to tidal volume are used clinically for this purpose. For example, one definition of respiratory failure, the inability of the respiratory system to sustain the metabolic needs of the body, is a ratio that is greater than or equal to 0.6.

Anatomic Dead Space. As noted previously, anatomic dead space can be estimated from the size of the individual and is usually assumed to be equal to 1 mL/lb of body weight. Initial work on actually measuring anatomic dead space used the physiologic principles of gas exchange to develop appropriate methodologies.

Because the gas in the anatomic dead space at the end of an inhalation does not participate in gas exchange, it exits the mouth during exhalation with the same composition as it entered. The gas exiting the mouth after the anatomic dead space has been emptied represents gas from the alveoli. In normal individuals, most alveoli are perfused, but a small number are not; these nonperfused alveoli represent alveolar dead space. The gas breathed from the atmosphere contains approximately 79% nitrogen and 21% oxygen, with tiny amounts of carbon dioxide and other molecules. The gas exiting a perfused alveolus contains nitrogen (which is physiologically inert in the lung), oxygen from the atmosphere (not all of which is taken into the blood), and carbon dioxide. The carbon dioxide arrives at the alveolus carried by the blood returning from the body. It is displaced from hemoglobin by oxygen coming into the blood from the alveolus and then travels down a diffusion gradient into the alveolus, the lung space.

Imagine now that you want to mark the gas coming from the anatomic or alveolar space, based on your knowledge of gas exchange, in order to measure the anatomic dead space. You could assess the concentration of carbon dioxide during an exhalation and plot the partial pressure of carbon dioxide as a function of the volume of exhaled gas (Fig. 5-2). Three phases can be observed. The initial gas exiting the mouth contains almost no carbon dioxide; this gas represents air coming from the anatomic dead space (where there is no gas exchange and hence almost no carbon dioxide). One then begins to see an increase in the carbon dioxicde level. The gas now exiting the mouth is derived from a combination of the anatomic dead space and alveoli. Finally, the exhaled partial pressure of CO₂ reaches a plateau. This gas is assumed to be exiting solely from alveoli. By measuring the amount of gas exhaled that has essentially a PCO₂ of 0 mm Hg, one can estimate the anatomic dead space. A slightly more accurate estimate is achieved by measuring the volume of exhaled gas at the midpoint of the “transition zone,” the portion of the graph when the PCO₂ is increasing, because this is a mixture of anatomic dead space gas and alveolar gas, as mentioned.

Physiological Dead Space. Physiological dead space, as defined previously, is the sum of anatomic and alveolar dead space. It can be measured using the Bohr method, which is based on the following principle. If you collect exhaled gas in a bag from a person over several minutes, you have within the bag a combination of gas coming from perfused alveoli, nonperfused alveoli (alveolar dead space), and anatomic dead space. This type of collection is called mixed expired gas. If we measure the fraction of CO₂ in the gas, we can make the following assumption:

To state it simply, the fractional amount of CO₂ expired (which is equal to the partial pressure of the carbon dioxide divided by the barometric pressure, or F_ECO₂ = PCO₂ / P_tot) multiplied by the exhaled volume (V_T) equals the amount of carbon dioxide leaving the lung. This amount must be equal to what is inhaled from the atmosphere and is sitting in the parts of the lung that are dead space and unaffected by gas exchange, added to the amount of carbon dioxide coming from alveoli that are perfused and are collecting carbon dioxide from the blood.

Because the fraction of carbon dioxide in inhaled gas (and hence, in the dead space) is essentially 0, the equation can be rewritten as follows:

Using the relationship that alveolar volume is the same as tidal volume minus dead space volume, the equation can be further transformed:

If we now transform fractional CO₂ into partial pressures by using the FCO₂ = PCO₂ / P_tot equation, we have:

(We have simply abbreviated V_DCO₂ as V_D in the above equation.) Rearranging:

Thus, the ratio of dead space to tidal volume is equal to the partial pressure of carbon dioxide in alveolar gas minus the partial pressure of carbon dioxide in mixed expired gas, divided by the partial pressure of carbon dioxide in alveolar gas. We can measure the partial pressure of CO₂ in mixed expired gas by collecting the expired gas, as previously noted.

In a normal person, the partial pressure of CO₂ in alveolar gas can be approximated by the PCO₂ at the very end of exhalation, called the end-tidal CO₂ (recall Figure 5-2 in our discussion of the measurement of anatomic dead space). In patients with significant lung disease, however, one does not always get a nice plateau in the expired CO₂ concentration because of abnormalities in the ventilation and perfusion of alveoli, and the measurement of end-tidal CO₂ can be misleading as a marker for alveolar CO₂. However, the blood in the capillaries that perfuse the alveoli quickly comes into equilibrium with the alveolar gas as CO₂ diffuses from pulmonary arterial blood into the air sacs of the blood surrounds. Therefore, one may replace the P_ACO₂ with arterial partial pressure carbon dioxide (P_aCO₂) as a reasonable approximation of the alveolar carbon dioxide. The P_aCO₂ level in a healthy person at rest is generally between 38 and 42 mm Hg. It is a common convention to use an uppercase A as the subscript indicating alveolar quantities and a lowercase a as the subscript indicating arterial quantities, and we follow this notation here.

Carbon Dioxide Elimination: The Lung As An Excretory Organ ↑

Carbon dioxide is a byproduct of metabolism and, in high concentrations in the body, can produce a number of toxic effects, including dyspnea (shortness of breath), acidosis, and altered levels of consciousness. The body's primary means of eliminating carbon dioxide is through the lungs via the alveoli. The excretory function of the lung with respect to carbon dioxide can be summarized by the following relationship (note: K is a constant):

Let us examine the implications of this relationship. Alveolar ventilation, the amount of air going into and out of perfused alveoli, is directly proportional to carbon dioxide production (); the greater the amount of carbon dioxide produced by the body, the greater the alveolar ventilation must be to maintain a constant partial pressure of carbon dioxide in the blood (P_aCO₂). If CO₂ production were to increase, for example, as seen with fever, and alveolar ventilation did not increase, the P_aCO₂ would increase. Viewed from a different angle, if there were a problem with the ventilatory pump, such as a weakened diaphragm from an acute polio infection, that caused alveolar ventilation to be reduced while carbon dioxide production remained constant, then the P_aCO₂ would increase.

The relationship between , alveolar ventilation, and the partial pressure of carbon dioxide in the arterial blood, as embodied by the equation above, may be considered the clearance equation for the lung. This relationship is analogous to the clearance equation used to describe kidney function in renal physiology (Table 5-1).

Determinants of Distribution of Ventilation ↑

In the upright posture, ventilation is directed preferentially to the bases of the lungs. This is the consequence largely of the varying pleural pressures from the bases to the apices of the lungs. In an upright person, because of the impact of gravity on the lung and the mechanical interactions between the lungs and chest wall, pleural pressure is less negative at the base than at the apex of the lungs. For example, in a typical individual, pleural pressure at the base at functional residual capacity (FRC) is -3 cm H₂O, and -8 cm H₂O at the apex. Consequently, at FRC, the alveoli at the apex are more distended than at the base. To understand this, recall the compliance relationship from Chapter 3: C = ΔV/ΔP. At FRC, the greater transmural pressure at the apex leads to larger alveoli there, assuming the compliance of the alveoli are the same throughout the lung (in other words, assuming all have the same compliance curve).

At this greater alveolar volume at FRC, the alveolus at the apex may now be on a flatter or less compliant portion of the pressure–volume curve than the alveolus at the base (Fig. 5-3). Thus, to get more air into this apical alveolus on the next inhalation (i.e., to expand it further) requires a greater change in pressure; the alveolus at the apex is less compliant than the alveolus at the base at FRC. Therefore, for a given change in pleural pressure resulting from activity of the inspiratory muscles, air will go preferentially to the more compliant alveoli at the bases.