Review of Medical Physiology - William F. Ganong 2002

Respiration
Pulmonary Functions
Gas Exchange in the Lungs

Sampling of Alveolar Air

Theoretically, all gas except for the initial 150 mL exhaled with each breath originates from the alveoli (alveolar air); however, some gas mixing occurs at the interface between the dead space and the alveolar air (see Fig. 34-17). Therefore, the final portion of the expired air is typically collected for analysis. Modern equipment featuring a custom automated valve allows for the collection of the last 10 mL of gas exhaled during resting ventilation. Figure 34-18 compares the composition of alveolar gas with that of inspired and expired air.

The alveolar gas equation can also be used to calculate PA_O2:

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where Fi_O2 is the fractional concentration of dry gas; Pi_O2 is the fractional concentration in inspired air; and R is the respiratory exchange ratio (see Chapter 17).

Composition of Alveolar Air

Oxygen continuously diffuses from the alveolar gas into the bloodstream, while CO₂ diffuses from the Blood into the alveoli. At equilibrium, the inspired air mixes with the alveolar gas, replenishing the O₂ taken up by the blood and diluting the CO₂ added from the alveoli. A portion of this mixture is then exhaled. Consequently, the O₂ content in alveolar gas decreases while the CO₂ content increases until the next breath. Given that the alveolar gas volume is approximately 2 L at the end of expiration (functional residual capacity, see Fig. 34-7), each 350 mL increment of inspired or expired air has a relatively minor effect on P_O2 and P_CO2. Furthermore, the composition of alveolar gas remains remarkably stable even outside of resting conditions.

Fig. 34-18. Partial pressures of gases (mmHg) in various Regions of the Respiratory system and Circulation.

Diffusion Across the Alveolocapillary Membrane

Gases diffuse between the alveoli and the pulmonary capillary blood in both directions across the ultrathin alveolocapillary membrane, which consists of the pulmonary epithelium, capillary endothelium, and their fused basement membranes (see Fig. 34-3). Solutes pass from the alveoli into the capillary blood, reaching equilibrium within 0.75 s—the typical transit time of blood through pulmonary capillaries at rest—though this also depends on the chemical reaction rates of the solutes with blood components. For instance, nitrous oxide (used as an anesthetic gas) does not bind to blood constituents, and N₂O reaches equilibrium within 0.1 s (Fig. 34-19). In this case, N₂O uptake is not diffusion-limited, but rather perfusion-limited (dependent entirely on pulmonary capillary blood flow). Conversely, erythrocyte Hemoglobin takes up carbon monoxide so avidly that the partial pressure of CO in the capillaries remains extremely low, preventing equilibrium from being reached within the 0.75 s capillary transit time. Therefore, CO transfer is not perfusion-limited at rest, but is strictly diffusion-limited. Oxygen lies intermediate between N₂O and CO; it is bound by hemoglobin but has a lower affinity than CO, reaching equilibrium with capillary blood in approximately 0.3 s. Consequently, its uptake is also perfusion-limited.

Fig. 34-19. Uptake of various gases during their transit through pulmonary capillaries (over 0.75 s); N₂O does not bind in the blood, so its partial pressure rises rapidly to match alveolar levels. In contrast, CO is rapidly sequestered by erythrocytes, keeping its partial pressure well below that in the alveoli. Values for O₂ fall intermediately.

The diffusing capacity of the Lungs for an inspired gas is directly proportional to the surface area of the alveolocapillary membrane and inversely proportional to its thickness. Diffusing capacity for CO (D_LCO) is commonly measured as an index of overall pulmonary diffusing capacity because its uptake is diffusion-limited. The value of D_LCO is proportional to The rate of CO uptake into the blood (V_CO) divided by the partial pressure of CO in the blood entering the pulmonary capillaries. An exception applies to chronic smokers: their back-pressure of CO is nearly zero and thus negligible, simplifying the equation to:

The normal resting value for D_LCO is 25 mL/min/mmHg. It increases approximately threefold during physical exertion due to capillary dilatation and the recruitment of additional perfused capillaries. In normal alveolar gas, P_O2 is typically 100 mmHg (see Fig. 34-18), whereas the P_O2 of mixed venous blood entering the capillaries is 40 mmHg. The diffusing capacity for O₂ at rest, comparable to that of CO, is 25 mL/min/mmHg, raising capillary blood P_O2 to 97 mmHg—slightly below the alveolar P_O2. A further drop in aortic P_O2 to 95 mmHg results from normal physiological shunting (see below). The value of D_LO2 increases to 65 mL/min/mmHg or higher during exercise and declines in conditions such as sarcoidosis and berylliosis, which cause alveolar wall fibrosis. Another cause of pulmonary fibrosis is overexpression of PDGF (see Chapter 27) by alveolar macrophages, which ultimately stimulates neighboring mesenchymal Cells.

Mixed venous P_CO2 is 46 mmHg, whereas alveolar P_CO2 is 40 mmHg; thus, CO₂ diffuses down its pressure gradient from the blood into the alveoli. The P_CO2 of blood leaving the lungs drops to 40 mmHg. Because CO₂ diffuses freely across Introduction/36.html">Biological Membranes, the diffusing capacity of the lungs for CO₂ is significantly greater than that for O₂. Consequently, CO₂ retention is rarely a clinical issue in patients with alveolar fibrosis, whereas impaired O₂ diffusing capacity presents a major physiological challenge.