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Uptake of oxygen and excretion of carbon dioxide require rapid, efficient exchange in the lung. The quantities of exchanged gases are staggering. For example, a 1800-calorie diet requires absorption of 375 L of oxygen per day, as well as excretion of a slightly smaller volume of carbon dioxide. Because blood remains in the pulmonary capillary bed for a limited time, the process of exchange must be accomplished in less than 0.75 second at rest and 0.5 second during exercise. This rapid, high-volume exchange occurs efficiently despite numerous interacting processes of diffusion and chemical reaction that occur in the lung. The rates of these processes are not only affected by intrinsic characteristics of blood but also determined by a host of other factors, including inspired oxygen fraction, alveolar gas tensions, cardiac output, and metabolic activity. The ease of exchange of respiratory gases belies the complexity of the overall process.


The concentration (C) of a gas dissolved in fluid depends upon its partial pressure (P) and solubility (α)


Gases diffuse from a higher to a lower partial pressure, not necessarily from a higher to a lower concentration. This fact is especially pertinent when a gas diffuses between two phases, as occurs when O2 and CO2 are exchanged between alveolar gas and blood. For example, dissolved CO2 diffuses down a partial pressure gradient from blood (46 mm Hg) into the alveolus (40 mm Hg), even though its actual concentration (millimoles of molecular CO2 per liter of gas or blood) is greater in alveolar gas (2.5) than it is in venous blood (1.4).

Influence of Physical Properties

The rate of a gas diffusing through an aqueous membrane such as that separating alveolar gas and capillary blood is influenced by five factors. The rate is directly proportional to the surface area of the membrane, but inversely proportional to the thickness of the membrane. The rate increases in direct proportion to the difference in gas pressure between alveolar gas and capillary blood, and the diffusion and solubility coefficients of the gas in the membrane.

The diffusion coefficient of a gas in the alveolar–capillary membrane is largely a function of the size of the gas molecule, which is inversely proportional to the square root of its molecular weight (MW). Oxygen (MW 32) has a slightly greater diffusion coefficient than carbon dioxide (MW 44) in the alveolar membrane. However, the solubility of CO2 in water, the major component of tissue composing the membrane, is much greater than the solubility of O2. This difference far outweighs the effect of the slightly smaller size of the oxygen molecule. Thus, the rate of CO2 transfer across the alveolar membrane is approximately 20 times greater than that of O2 when both gases diffuse under the same partial pressure gradient. As a result, a much ...

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