Composition of Air

Inspiration brings ambient air to the alveoli, where O₂ is taken up and CO₂ is excreted. Alveolar ventilation thus begins with ambient air. Ambient air is a gas mixture composed of N₂ and O₂, with minute quantities of CO₂, argon, and inert gases. The composition of a gas mixture can be described in terms of either gas fractions or the corresponding partial pressure. Because ambient air is a gas, it obeys the gas laws.

When these gas laws are applied to ambient air, two important principles arise. The first is that when the components are viewed in terms of gas fractions (F), the sum of the individual gas fractions must equal one.

Equation 22-2

It follows, then, that the sum of the partial pressures (in mm Hg) or the tensions (in torr) of a gas must be equal to the total pressure. Thus, at sea level, where atmospheric pressure is 760 mm Hg, the partial pressures of the gases in air (also known as barometric pressure (P_b) are

Equation 22-3

The second important principle is that the partial pressure of a gas (P_gas) is equal to the fraction of that gas in the gas mixture (F_gas) times the total or ambient (barometric) pressure.

Equation 22-4

Ambient air is composed of approximately 21% O₂ and 79% N₂. Therefore, the partial pressure of O₂ in ambient air (PO₂) is

Equation 22-5

This is the O₂ tension (i.e., the partial pressure of O₂) of ambient air at the mouth at the start of inspiration. The O₂ tension at the mouth can be altered in one of two ways—by changing the fraction of O₂ or by changing barometric (atmospheric) pressure. Thus, ambient O₂ tension can be increased through the administration of supplemental O₂ and is decreased at high altitude.

As inspiration begins, the ambient air is brought into the airways, where it becomes warmed to body temperature and humidified. Inspired gases become saturated with water vapor, which exerts a partial pressure and dilutes the total pressure of the other gases. Water vapor pressure at body temperature is 47 mm Hg. To calculate the partial pressure of a gas in a humidified mixture, the water vapor partial pressure must be subtracted from the total barometric pressure. Thus, in the conducting airways the partial pressure of O₂ is

Equation 22-6

Equation 22-7

Note that the total pressure has remained 760 mm Hg (150 + 563 + 47 mm Hg). Water vapor pressure, however, has reduced the partial pressures of O₂ and N₂. The conducting airways do not participate in gas exchange. Therefore, the partial pressures of O₂, N₂, and water vapor remain unchanged in the airways until the gas reaches the alveolus.

Alveolar Gas Composition

When the inspired gas reaches the alveolus, O₂ is transported across the alveolar membrane, and CO₂ moves from the capillary bed into the alveolus. The process by which this occurs is described in Chapter 23. At the end of inspiration and with the glottis open, the total pressure in the alveolus is atmospheric; thus, the partial pressures of the gases in the alveolus must equal the total pressure, which in this case is atmospheric. The composition of the gas mixture, however, is changed and can be described as

Equation 22-8

N₂ and argon are inert gases, and therefore the fraction of these gases in the alveolus does not change over time. The fraction of water vapor also does not change because the gas is already fully saturated with water vapor and is at body temperature by the time that it reaches the trachea. As a consequence of gas exchange, the fraction of O₂ in the alveolus decreases and the fraction of CO₂ in the alveolus increases. Because of changes in the fractions of O₂ and CO₂, the partial pressure exerted by these gases also changes. The partial pressure of O₂ in the alveolus (PAO₂) is given by the alveolar gas equation, which is also called the ideal alveolar oxygen equation:

Equation 22-9

The partial pressures of O₂, CO₂, and N₂ from ambient air to the alveolus are shown in Table 22-1.

Table 22-1 Total and Partial Pressures of Respiratory Gases in Ideal Alveolar Gas and Blood at Sea Level (760 mmHg)

The fraction of CO₂ in the alveolus is a function of the rate of CO₂ production by the cells during metabolism and the rate at which the CO₂ is eliminated from the alveolus. This process of elimination of CO₂ is known as alveolar ventilation. The relationship between CO₂ production and alveolar ventilation is defined by the alveolar carbon dioxide equation,

Equation 22-10

where _CO2 is the rate of CO₂ production by the body, A is alveolar ventilation, and FACO₂ is the fraction of CO₂ in dry alveolar gas. This relationship demonstrates that the rate of elimination of CO₂ from the alveolus is related to alveolar ventilation and to the fraction of CO₂ in the alveolus. Alveolar PACO₂ is defined by the following:

Equation 22-11

Hence, we can substitute in the previous equation and demonstrate the following relationship:

Equation 22-12

This equation demonstrates several important relationships. First, there is an inverse relationship between the partial pressure of CO₂ in the alveolus (PACO₂) and alveolar ventilation (A), irrespective of the exhaled CO₂. Specifically, if ventilation is doubled, PACO₂ will decrease by 50%. Conversely, if ventilation is decreased by half, the partial pressure of CO₂ in the alveolus will double. Second, at a constant alveolar ventilation (A), doubling of the metabolic production of CO₂ (CO₂) will double the partial pressure of CO₂ in the alveolus. The relationship between alveolar ventilation and alveolar PCO₂ is shown in Figure 22-1.

Figure 22-1 Alveolar PCO₂ as a function of alveolar ventilation in the lung. Each line corresponds to a given metabolic rate associated with a constant production of CO₂ (V.CO₂ isometabolic line). Normally, alveolar ventilation is controlled to maintain an alveolar PCO₂ of about 40 torr. Thus, at rest, when V.CO₂ is approximately 250 mL/min, alveolar ventilation of 5 L/min will result in an alveolar PCO₂ of 40 mm Hg. A 50% decrease in ventilation at rest (i.e., from 5 to 2.5 L/min) results in doubling of alveolar PCO₂. During exercise, CO₂ production is increased (V.CO₂ = 750 mL/min), and to maintain a normal PCO₂, ventilation must increase (in this case to 15 L/min). Again, however, a 50% reduction in ventilation (15 to 7.5 L/min) will result in doubling of PCO₂.

Arterial Gas Composition

In normal individuals, arterial PCO₂ is tightly regulated and maintained at about 40 mm Hg. Increases or decreases in arterial PCO₂, particularly when associated with changes in arterial pH, have profound effects on cell function, including enzyme and transport protein activity. Specialized chemoreceptors monitor PCO₂ in arterial blood and in the brainstem (Chapter 24), and minute ventilation varies in accordance with the level of PCO₂.

An increase in arterial PCO₂ results in respiratory acidosis (pH <7.35), whereas a decrease in arterial PCO₂ results in respiratory alkalosis (pH >7.45). Hypercapnia is defined as an elevation in arterial PCO₂, and it is secondary to inadequate alveolar ventilation (hypoventilation) relative to CO₂ production. Conversely, hyperventilation occurs when alveolar ventilation exceeds CO₂ production, and it decreases arterial PCO₂ (hypocapnia).

Distribution of Ventilation

Ventilation is not uniformly distributed in the lung, in large part because of the effects of gravity. In the upright position, alveoli near the apex of the lung are more expanded than alveoli at the base. Gravity pulls the lung downward and away from the chest wall. As a result, pleural pressure is less at the apex than at the base of the lung, and static translung pressure (P_L = P_A − P_pl) is increased; this results in an increase in alveolar volume at the apex. Because of the difference in alveolar volume at the apex and at the base of the lung (Fig. 22-2), alveoli at the lung base are located along the steep portion of the pressure-volume curve, and they receive more of the ventilation (i.e., they have greater compliance). In contrast, the alveoli at the apex are closer to the top of the pressure-volume curve. They have lower compliance and thus receive proportionately less of the tidal volume. The effect of gravity is less pronounced when one is supine rather than upright, and it is less when one is supine rather than prone. This is because the diaphragm is pushed cephalad when one is supine, and it affects the size of all of the alveoli.

Figure 22-2 Regional distribution of lung volume, including alveolar size and location on the pressure-volume curve of the lung at different lung volumes. Because of suspension of the lung in the upright position, the pleural pressure (P_pl) and translung pressure (P_L) of units at the apex will be greater than those at the base. These lung units will be larger at any lung volume than units at the base. The effect is greatest at residual volume (RV), is less at functional residual capacity (FRC), and disappears at total lung capacity (TLC). Note also that because of their location on the pressure-volume curve, inspired air will be differentially distributed to these lung units; the lung units at the apex are less compliant and will receive a smaller proportion of the inspired air than the lung units at the base, which are more compliant (i.e., reside at a steeper part of the pressure-volume curve).

In addition to gravitational effects on the distribution of ventilation, ventilation in the terminal respiratory units is not uniform. This is caused by variable airway resistance (R) or compliance (C), and it may be described quantitatively by the time constant (τ):

Equation 22-12

Alveolar units with long time constants fill and empty slowly. Thus, an alveolar unit with increased airway resistance or increased compliance will take longer to fill and longer to empty. In normal adults, the respiratory rate is about 12 breaths per minute, the inspiratory time is about 2 seconds, and the expiratory time is about 3 seconds. In normal individuals this time is sufficient to approach equilibrium (Fig. 22-3). In the presence of increased resistance or increased compliance, however, equilibrium is not reached.

Figure 22-3 Examples of local regulation of ventilation as a result of variation in the resistance (R) or compliance (C) of individual lung units. In the upper schema are shown the individual resistance and compliance of three different lung units. In the lower graph are shown the volume of these three lung units as a function of time. In the upper schema, the normal lung has a time constant (τ) of 0.56 second. This unit reaches 97% of final equilibrium in 2 seconds, the normal inspiratory time, as shown in the lower graph. The unit at the right has a twofold increase in resistance; hence its time constant is doubled. That unit fills more slowly and reaches only 80% equilibrium during a normal breath (graph). The unit is underventilated. The unit on the left has reduced compliance (stiff), which acts to reduce its time constant. This unit fills faster than the normal unit but receives only half the ventilation of a normal unit.

Single-Breath Nitrogen Test

The single-breath N₂ test can be used to assess the uniformity of ventilation. The subject takes a single maximal inspiration of 100% O₂. During the subsequent exhalation, [N₂] in the exhaled air is measured. Air (100% O₂, 0% N₂) initially exits from the conducting airways; then [N₂] begins to rise as alveolar emptying occurs. Finally, there is a plateau [N₂] as only the alveoli that contain N₂ empty (Fig. 22-4).

Figure 22-4 The single-breath N₂ washout curve is a simple useful pulmonary function test of the regional distribution of ventilation. It clearly shows that not all lung units have equal /. The well-ventilated units (short time constant) empty faster than less well ventilated units (long time constant). The portion of the curve up to the first vertical dashed line represents the washout of dead space air mixed with alveolar gas. The long alveolar plateau rises slowly (<2%) if the distribution of ventilation is relatively uniform, as shown here. The final phase, after the second vertical line, shows very late, slowly emptying alveoli. This phase is accentuated with age.

Physiological Dead Space Ventilation

The second type of dead space is physiological dead space. Alveoli that are perfused but not ventilated are often found in diseased lungs. The total volume of gas in each breath that does not participate in gas exchange is called the physiological dead space ventilation. This volume includes the anatomic dead space and the dead space secondary to the ventilated but not perfused alveoli. The physiological dead space is always at least as large as the anatomic dead space, and in the presence of disease it may be considerably larger.

The Pulmonary Circulation

The pulmonary circulation begins with the right atrium. Deoxygenated blood from the right atrium enters the right ventricle via the tricuspid valve, and it is then pumped under low pressure (9 to 24 mm Hg) into the pulmonary artery through the pulmonic valve. The pulmonary artery (pulmonary trunk), which is about 3 cm in diameter, branches quickly (5 cm from the right ventricle) into the right and left main pulmonary arteries, which supply blood to the right and left lungs, respectively. The arteries of the pulmonary circulation are the only arteries in the body that carry deoxygenated blood. The deoxygenated blood in the pulmonary arteries passes through a progressively smaller series of branching vessels (vessel diameters: arteries, >500 μm; arterioles, 10 to 200 μm; capillaries, <10 μm) that end in a complex meshlike network of capillaries (see Chapter 20, Fig. 20-7). The sequential branching pattern of the pulmonary arteries follows the pattern of airway branching. The functions of the pulmonary circulatory system are to (1) reoxygenate the blood and dispense with CO₂, (2) aid in fluid balance in the lung, and (3) distribute metabolic products to and from the lung. Oxygenation of red blood cells occurs in the capillaries that surround the alveoli, where the pulmonary capillary bed and the alveoli come together in the alveolar wall in a unique configuration for optimal gas exchange (Fig. 22-5). Gas exchange occurs through this alveolar-capillary network.

Figure 22-5 Cross section of an alveolar wall showing the path for diffusion of O₂ and CO₂. The thin side of the alveolar wall barrier (short double arrow) consists of type I epithelium (I), interstitium (*) formed by the fused basal laminae of the epithelial and endothelial cells, capillary endothelium (E), plasma in the alveolar capillary (C), and finally the cytoplasm of the red blood cell (R). The thick side of the gas exchange barrier (long double arrow) has an accumulation of elastin (EL), collagen (COL), and matrix that jointly separate the alveolar epithelium from the alveolar capillary endothelium. As long as the red blood cells are flowing, O₂ and CO₂ diffusion probably occurs across both sides of the air-blood barrier. A, alveolus; Nu, nucleus of the capillary endothelial cell.