A Lung Model Describing Uptake of Organic Solvents and Roles of Mucosal Blood Flow and Metabolism in the Bronchioles

Abstract

A simple lung model (mucosal blood flow and metabolism model, MBM model) was developed to describe the uptake of organic solvents and investigate the role of mucosal blood flow and metabolism. The model separates the lung into four compartments, the peripheral bronchial tract (gas phase), the mucus layer lining the wall surface of the tract, the alveolar space (gas phase), and the alveolar blood. Solvent molecules are absorbed in the mucus layer during inhalation and released during exhalation. The deposited solvent diffuses radially into the mucosal tissue of the respiratory tract and transfers to the mucosal blood flow. To describe this behavior, a hypothetical mucosal blood flow throughout the mucus layer was used. The solvent in the mucosal tissue may be also metabolized, and a hypothetical metabolism in the mucus layer was used. The rate of the hypothetical mucosal blood flow was determined to be 5.2 ml/min based on the best fitting of previously obtained data for seven polar organic solvents. The MBM model predicts that as the blood-air partition coefficient (lambda(B)) increases from 0.1 to 20, the relative end-exhalation (E(end)) will decrease from 0.89 to 0.07, and as lambda(B) increases to 500, E(end) will increase to 0.33. After lambda(B) = 500, E(end) is predicted to decrease again, and at lambda(B) = 10000, E(end) is 0.09. The model also predicts that as lambda(B) increases from 0.1 to 10, the relative uptake (U) increases from 0.08 to 0.61, and as lambda(B) increases to 150, U decreases to 0.50. After lambda(B) = 150, U increases again, and at lambda(B) = 10,000, U is 0.8. The predictions show good agreement with values observed in human experimental studies. The MBM model predicts that uptake by the mucosal blood (U(Al)) would be equal to uptake by the alveolar blood (U(Mu)) at lambda(B) of 1000 and U(Al) is more than 90% of total uptake at lambda(B) > 10,000. The model also shows that U is significantly increased by the mucosal metabolism at lambda(B) between 50 and 5000. Especially, U in the case of CL(Mu) = 100 ml/min is higher by 0.3 than that in the nonmucosal metabolism.

Isoprene and acetone concentration profiles during exercise on an ergometer

“…Nonetheless, the previous relation is one of the pillars for investigating observed behavior of many trace gases found in exhaled breath. First, bearing in mind that during rest on average it holds that r ∼ 1 [32,68], we immediately see that breath concentrations of low-soluble trace gases such as isoprene (λ isoprene ∼ 0.75 (mol l −1 /mol l −1 = dimensionless) at body temperature [31]) are very sensitive to sudden changes in ventilation or perfusion, whereas breath concentrations of compounds with high Henry constants such as acetone (λ acetone ∼ 200 (mol l −1 /mol l −1 = dimensionless) at body temperature [50,69]) tend to show a rather damped reaction to such disturbances. Moreover, it is evident that, while other factors are equal, increasing/decreasing alveolar ventilation will decrease/increase exhaled breath concentrations (due to increased/decreased dilution), whereas the relationship between breath concentration and cardiac output is monotonic and reflects dependence on supply.…”

A modeling-based evaluation of isothermal rebreathing for breath gas analyses of highly soluble volatile organic compounds

“…Some major breath VOCs have already been investigated in this form, e.g. during rest and exercise conditions or exposure scenarios [4][5][6][7][8][9][10][11][12]. Such mechanistic descriptions of the observable exhalation kinetics give valuable insights into the relevance of the measured breath concentrations with respect to the endogenous situation and hence are mandatory to fully exploit the diagnostic potential of breath VOCs.…”

Review of Urban Bicyclists' Intake and Uptake of Traffic-Related Air Pollution

“…As blood concentrations approach equilibrium with inspired air, the uptake rate will fall to the steady-state rate of metabolic clearance (Csanády & Filser, 2001;Wallace, Pellizzari, & Gordon, 1993). Although exercise increases ventilation and perfusion, it also can decrease the rate at which pollutants are metabolized by reducing blood flow to the liverreducing the steady-state uptake rate while simultaneously increasing blood concentrations (Astrand, 1985;Csanády & Filser, 2001;Kumagai & Matsunaga, 2000;Nadeau et al, 2006). Detailed uptake models allow estimation of different locations/tissues of pollutant uptake, which is relevant because of varying susceptibility to negative health effects from air pollution uptake by different tissues.…”