Pressure is caused by the constant impact of moving molecules against a surface. Therefore, the pressure of a gas acting on the surfaces of the respiratory passages and alveoli is proportional to the sum of the impaction forces of all the molecules striking the surface at any given instant. The important gases to consider in the lung are oxygen, nitrogen, and carbon dioxide. The rate of diffusion of each gas is directly proportional to its partial pressure.
The concentration of a gas in solution (e.g., blood) is determined not only by its partial pressure but also by the solubility coefficient of the gas. The solubility coefficients for the important respiratory gases at body temperature are oxygen, 0.024; carbon dioxide, 0.57; carbon monoxide, 0.018; and nitrogen, 0.012. Thus, carbon dioxide is more than 20 times as soluble as oxygen, and oxygen is twice as soluble as nitrogen. The solubilities help determine the quantity of gas dissolved in the fluids of the body, which is a major factor in determining the rate at which the gas can diffuse through tissues.
Major factors that affect the rate of gas diffusion in a fluid include (1) the partial pressure of the gas, (2) the solubility of the gas in the fluid, (3) the surface area available for diffusion, (4) the distance through which the gas must diffuse, (5) the molecular weight of the gas, and (6) the temperature of the fluid.
The greater the solubility of the gas and the greater the surface area for diffusion, the greater the number of molecules available to diffuse for any given pressure difference. On the other hand, the greater the distance the molecules must diffuse, the longer it takes for the diffusion to occur. Finally, the greater the velocity of the molecules, which at any given temperature is inversely proportional to the square root of the molecular weight, the greater the rate of diffusion of the gas. All these factors can be expressed in a single formula:
where D = diffusion rate
P = pressure difference between the two ends of the diffusion pathway A = cross-section area of the pathway S = solubility of the gas d = distance of diffusion MW= molecular weight of the gas
The characteristics of a gas determine its solubility and molecular weight, which determine the diffusion coefficient of the gas. The diffusion coefficient, which equals
' J"'- , determines the relative rates at which different gases at the same pressure will diffuse. If the diffusion coefficient of oxygen is 1.0, the relative diffusion coefficients of other gases of respiratory importance are carbon dioxide, 20.3; carbon monoxide, 0.81; nitrogen, 0.53; and helium, 0.95.
Oxygen, carbon dioxide, and nitrogen are all highly soluble in lipids and consequently are also highly soluble in cell membranes. The major limitation to the movement of these gases in tissues is the rate at which the gases can diffuse through the tissue water, an important consideration in pulmonary edema.
The respiratory unit is composed of a respiratory bronchiole, alveolar ducts, atria, and alveoli. The alveolar walls are extremely thin and closely applied to an almost continuous network of interconnecting capillaries. The membrane through which gaseous exchange between the alveolar air and the pulmonary blood occurs is known as the respiratory (pulmonary) membrane. For oxygen to get from the alveolus into the pulmonary capillary bed, it must pass through four separate layers, referred to collectively as the alveolar-capillary, or respiratory, membrane. These layers include (1) a layer of fluid, called alveolar fluid, lining the alveolus and containing surfactant that reduces its surface tension; (2) the alveolar epithelium, composed of very thin epithelial cells and a basement membrane; (3) a very thin interstitial space between the alveolar epithelium and the capillary membrane; and (4) the capillary endothelial membrane and its basement membrane, which fuses with the alveolar basement membrane in many places.
The average diameter of the pulmonary capillaries is less than 8 mm, which means that red blood cells must actually squeeze through them. Therefore, at least part of the red blood cell membrane touches the capillary wall. Where this occurs, oxygen does not have to pass through significant amounts of plasma as it diffuses from the alveolus to the red blood cell. This reduces the diffusion distance and thus increases the rapidity of diffusion of gases between the alveolus and the hemoglobin molecules.
The total diffusing surface area of the lung is enormous (160 m2) and very thin (averaging 0.63 mm). These characteristics, combined with the solubility of CO 2 and O2, make the lungs very efficient for maximizing gas exchange. The factors that determine how rapidly a gas passes through the respiratory membrane are (1) the thickness of the membrane, (2) the surface area of the membrane, (3) the diffusion coefficient of the gas in the water of the membrane, and (4) the pressure difference between the two sides of the membrane.
Thickness of the membrane is rarely a significant impediment to the transfer of CO 2, but O2, being 20 times less soluble than CO2, can be effected by processes that increase the diffusion distance. Two common clinical entities that increase the diffusion distance are pulmonary edema and pulmonary fibrosis, which explains the common finding of hypoxemia in patients with congestive heart failure. Another example of how the factors that determine gas diffusion can be applied clinically is the treatment of carbon monoxide poisoning with 100% oxygen, or hyperbaric oxygen, to increase the pressure difference between the two sides of the alveolar capillary membrane and thus facilitate oxygen loading.
The surface area of the respiratory membrane may be greatly decreased by a variety of conditions, such as atelectasis, resection of lung tissue, or emphysema. In emphysema, many of the alveoli coalesce, with dissolution of alveolar walls. The new alveolar chambers are much larger than the original alveoli, but the total surface area of the respiratory membrane available for gas diffusion is considerably decreased. When the total surface area of the lung is decreased to approximately one-third to one-fourth normal, exchange of gases through the membrane is impeded significantly, even under resting conditions. During strenuous exercise, even the slightest increase in dead space in patients with severe emphysema can seriously interfere with the exchange of gases.
The pressure difference across the respiratory membrane is the difference between the partial pressure of the gas in the alveoli and the partial pressure of the gas in the blood. In room air, the normal difference between the partial pressure of alveolar oxygen (PA o2) and the partial pressure of arterial oxygen (Pa o2), (PAo2 - PaO2), or [P(A - a)o2], is 2 to 10 mmHg. The normal difference between the partial pressure of alveolar carbon dioxide (PA co2) and the partial pressure of arterial carbon dioxide (Paco2), (PAco2 - Paco2), or [P(A - a)co2], is zero. An increase in the P(A - a)co2 is due to an increase in dead space. The dead-space air does not participate in gas exchange and thus dilutes the alveolar CO2.
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