Theoretical analysis of the determinants of lung oxygen diffusing capacity

The process of pulmonary oxygen uptake is analyzed to obtain an explicit equation for lung oxygen diffusing capacity in terms of hematocrit and pulmonary capillary diameter. An axisymmetric model with discrete cylindrical erythrocytes is used to represent radial diffusion of oxygen from alveoli through the alveolar-capillary membrane into pulmonary capillaries, through the plasma, and into erythrocytes. Analysis of unsteady diffusion due to the passage of the erythrocytes shows that transport of oxygen through the alveolar-capillary membrane occurs mainly in the regions adjacent to erythrocytes, and that oxygen transport through regions adjacent to plasma gaps can be neglected. The model leads to an explicit formula for diffusing capacity as a function of geometric and oxygen transport parameters. For normal hematocrit and a capillary diameter of 6.75μm, the predicted diffusing capacity is 102mlO₂min^-1mmHg^-1. This value is 30-40% lower than values estimated previously by the morphometric method, which considers the total membrane area and the specific uptake rate of erythrocytes. Diffusing capacity is shown to increase with increasing hematocrit and decrease with increasing capillary diameter and increasing thickness of the membrane. Simulations of pulmonary oxygen uptake in humans under conditions of exercise or hypoxia based show closer agreement with experimental data than previous models, but still overestimate oxygen uptake. The remaining discrepancy may reflect effects of heterogeneity of perfusion and ventilation in the lung.