- Lange Pulmonary Physiology > Chapter 6. Diffusion of Gases >
- Oxygen then diffuses through the alveolar-capillary interface. It must first, therefore, move from the gas phase to the liquid phase, according to Henry's law, which states that the amount of a gas absorbed by a liquid with which it does not combine chemically is directly proportional to the partial pressure of the gas to which the liquid is exposed and the solubility of the gas in the liquid
- Oxygen must dissolve in and diffuse through the thin layer of pulmonary surfactant, the alveolar epithelium, the interstitium, and the capillary endothelium, as was shown in Figure 1–4 (step 2, near the arrow). It must then diffuse through the plasma (step 3), where some remains dissolved and the majority enters the erythrocyte and combines with hemoglobin (step 4). The blood then carries the oxygen out of the lung by bulk flow and distributes it to the other tissues of the body
- The factors that determine the rate of diffusion of gas through the alveolar-capillary barrier are described by Fick's law for diffusion,
where gas = volume of gas diffusing through the tissue barrier per time, mL/min
A = surface area of the barrier available for diffusion
D = diffusion coefficient, or diffusivity, of the particular gas in the barrier
T = thickness of the barrier or the diffusion distance
P1 – P2 = partial pressure difference of the gas across the barrier
- The surface area of the blood-gas barrier is believed to be at least 70 m2 in a healthy average-sized adult at rest. That is, about 70 m2 of the potential surface area is both ventilated and perfused at rest.
- If more capillaries are recruited, as in exercise, the surface area available for diffusion increases; if venous return falls, for example, because of hemorrhage, or if alveolar pressure is raised by positive- pressure ventilation, then capillaries may be derecruited and the surface area available for diffusion may decrease.
- The thickness of the alveolar-capillary diffusion barrier is only about 0.2 to 0.5 mm.
- Diffusion probably increases at higher lung volumes because as alveoli are stretched, the diffusion distance decreases slightly (and also because small airways subject to closure may be open at higher lung volumes).
- The diffusivity, or diffusion constant, for a gas is directly proportional to the solubility of the gas in the diffusion barrier and is inversely proportional to the square root of the molecular weight (MW) of the gas
- The diffusivity is inversely proportional to the square root of the molecular weight of the gas because different gases with equal numbers of molecules in equal volumes have the same molecular energy if they are at the same temperature
- Therefore, light molecules travel faster, have more frequent collisions, and diffuse more rapidly. Thus, Graham's law states that the relative rates of diffusion of two gases are inversely proportional to the square roots of their molecular weights, if all else is equal.
- oxygen is less dense than carbon dioxide, it should diffuse 1.2 times as fast as carbon dioxide (which it does as it moves through the alveoli). In the alveolar-capillary barrier, however, the relative solubilities of oxygen and carbon dioxide must also be considered. The solubility of carbon dioxide in the liquid phase is about 24 times that of oxygen, and so carbon dioxide diffuses about 0.85 x 24, or about 20 times, more rapidly through the alveolar-capillary barrier than does oxygen. For this reason, patients develop problems in oxygen diffusion through the alveolar-capillary barrier before carbon dioxide retention due to diffusion impairment occurs.
- The factors that limit the movement of a gas through the alveolar-capillary barrier, as described by Fick 's law for diffusion, can be arbitrarily divided into three components: the diffusion coefficient, the surface area and thickness of the alveolar-capillary membrane, and the partial pressure gradient across the barrier for each particular gas.
- The diffusion coefficient, as discussed in the previous section, is dependent on the physical properties of the gases and the alveolar-capillary membrane. The surface area and thickness of the membrane are physical properties of the barrier, but they can be altered by changes in the pulmonary capillary blood volume, the cardiac output or the pulmonary artery pressure, or by changes in lung volume. The partial pressure gradient of a gas (across the barrier) is the final major determinant of its rate of diffusion. The partial pressure of a gas in the mixed venous blood and in the pulmonary capillaries is just as important a factor as its alveolar partial pressure in determining its rate of diffusion. This will be demonstrated in the next section.
- Diffusion Limitation
- An erythrocyte and its attendant plasma spend an average of about 0.75 to 1.2 seconds inside the pulmonary capillaries at resting cardiac outputs
- if the content of carbon monoxide (in milliliters of carbon monoxide per milliliter of blood) were measured simultaneously, it would be rising very rapidly. The reason for this rapid rise is that carbon monoxide combines chemically with the hemoglobin in the erythrocytes. Indeed, the affinity of carbon monoxide for hemoglobin is about 210 times that of oxygen for hemoglobin. The carbon monoxide that is chemically combined with hemoglobin does not contribute to the partial pressure of carbon monoxide in the blood because it is no longer physically dissolved in it. Therefore, the partial pressure of carbon monoxide in the pulmonary capillary blood does not come close to the partial pressure of carbon monoxide in the alveoli during the time that the blood is exposed to the alveolar carbon monoxide. The partial pressure gradient across the alveolar-capillary barrier for carbon monoxide is thus well maintained for the entire time the blood spends in the pulmonary capillary, and the diffusion of carbon monoxide is limited only by its diffusivity in the barrier and by the surface area and thickness of the barrier. Carbon monoxide transfer from the alveolus to the pulmonary capillary blood is referred to as diffusion-limited rather than perfusion-limited.
- Perfusion Limitation
- he partial pressure of nitrous oxide in the pulmonary capillary blood equilibrates very rapidly with the partial pressure of nitrous oxide in the alveolus because nitrous oxide moves through the alveolar-capillary barrier very easily and because it does not combine chemically with the hemoglobin in the erythrocytes. After only about 0.1 of a second of exposure of the pulmonary capillary blood to the alveolar nitrous oxide, the partial pressure gradient across the alveolar-capillary barrier has been abolished.
- nitrous oxide can diffuse into the blood at the arterial end. The transfer of nitrous oxide is therefore perfusion-limited
- Diffusion of Oxygen
- The partial pressure of oxygen rises fairly rapidly (note that it starts at the Po2 of the mixed venous blood, about 40 mm Hg, rather than at zero), and equilibration with the alveolar Po2 of about 100 mm Hg occurs within about 0.25 of a second
- the time course for oxygen transfer falls between those for carbon monoxide and nitrous oxide.
- e chemical combination of oxygen and hemoglobin, however, occurs rapidly (within hundredths of a second), and at the normal alveolar partial pressure of oxygen, the hemoglobin becomes nearly saturated with oxygen very quickly, as will be discussed in the next chapter. As this happens, the partial pressure of oxygen in the blood rises rapidly to that in the alveolus, and from that point, no further oxygen transfer from the alveolus to the equilibrated blood can occur. Therefore, under the conditions of normal alveolar Po2 and a normal resting cardiac output, oxygen transfer from alveolus to pulmonary capillary is perfusion-limited.
- Diffusion of Carbon Dioxide
- The time course of carbon dioxide transfer from the pulmonary capillary blood to the alveolus is shown in Figure 6–3. In a normal person with a mixed venous partial pressure of carbon dioxide of 45 mm Hg and an alveolar partial pressure of carbon dioxide of 40 mm Hg, an equilibrium is reached in about 0.25 of a second, or about the same time as that for oxygen. This fact may seem surprising, considering that the diffusivity of carbon dioxide is about 20 times that of oxygen, but the partial pressure gradient is normally only about 5 mm Hg for carbon dioxide, whereas it is about 60 mm Hg for oxygen. Carbon dioxide transfer is therefore normally perfusion-limited, although it may be diffusion-limited in a person with an abnormal alveolar-capillary barrier, as shown in the figure.
- Measurement of Diffusing Capacity
- The diffusing capacity (or transfer factor) is the rate at which oxygen or carbon monoxide is absorbed from the alveolar gas into the pulmonary capillaries (in milliliters per minute) per unit of partial pressure gradient (in millimeters of mercury). The diffusing capacity of the lung (for gas x), DLx, is therefore equal to the uptake of gas x, x, divided by the difference between the alveolar partial pressure of gas x, PAx, and the mean capillary partial pressure of gas x, Px:
- This is really just a rearrangement of the Fick equation given at the beginning of this chapter. The terms for area, diffusivity, and thickness have been combined into DLx and the equation has been rearranged:
Table 6–1. Conditions that Decrease the Diffusing Capacity
Thickening of the barrier Interstitial or alveolar edema Interstitial or alveolar fibrosis Sarcoidosis Scleroderma Decreased surface area Emphysema Tumors Low cardiac output Low pulmonary capillary blood volume Decreased uptake by erythrocytes Anemia Low pulmonary capillary blood volume Ventilation-perfusion mismatch
How would each of the following conditions or circumstances be expected to affect the diffusing capacity (DL) of the lungs? Explain your answers.
- a. Changing from the supine to the upright position
- b. Exercise
- c. Valsalva maneuver
- d. Anemia
- e. Low cardiac output due to blood loss
- f. Diffuse interstitial fibrosis of the lungs
- g. Emphysema
6–2. If the pulmonary capillary partial pressure of a gas equilibrates with that in the alveolus before the blood leaves the capillary (assume the gas is diffusing from the alveolus to the pulmonary capillary):
- a. its transfer is said to be perfusion limited.
- b. its transfer is said to be diffusion limited.
- c. increasing the cardiac output will not increase the amount of the gas diffusing across the alveolar-capillary barrier.
- d. increasing the alveolar partial pressure of the gas will not increase the amount of the gas diffusing across the alveolar-capillary barrier.
- e. recruiting additional pulmonary capillaries will not increase the amount of the gas diffusing across the alveolar capillary barrier.
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