Lung Diffusing Capacities (D_L) for Nitric Oxide (NO) and Carbon Monoxide (CO): The Evolving Story

Nitric oxide and carbon monoxide diffusing capacities (D_LNO and D_LCO) obey Fick's First Law of Diffusion and the basic principles of chemical kinetic theory. NO gas transfer is dominated by membrane diffusion (D_M), whereas CO transfer is limited by diffusion plus chemical reaction within the red cell. Marie Krogh, who pioneered the single-breath measurement of D_LCO in 1915, believed that the combination of CO with red cell hemoglobin (Hb) was instantaneous. Roughton and colleagues subsequently showed, in vitro, that the reaction rate was finite, and prolonged in the presence of high $P_{{\mathrm{O}}_2}$. Roughton and Forster (R-F) proposed that the resistance to transfer (1/D_L) was the sum of the membrane resistance (1/D_M) and (1/θVc), the red cell resistance (θ being the CO or NO conductance for blood uptake and Vc the capillary volume). From this R-F equation, D_M for CO and Vc can be solved with simultaneous NO and CO inhalation. At near maximum exercise, D_MCO and Vc for normal subjects were 88% and 79%, respectively, of morphometric values. The validity of these calculations depends on the values chosen for θ for CO and NO, and on the diffusivity of NO versus CO. Recent mathematical modeling suggests that θ for NO is “effectively” infinite because NO reacts only with Hb in the outer 0.1 μM of the red cell. An “infinite θ_NO” recalculation reduced D_MCO to 53% and increased Vc to 95% of morphometric values. © 2020 American Physiological Society. Compr Physiol 10:73-97, 2020.