A carbon monoxide cycle drives carbon monoxide uptake and poisoning

An understanding of the physiology of acute carbon monoxide (CO) poisoning remains incomplete. This study describes a novel approach-considering a CO cycle driven by CO inhalation which includes: alveolar CO uptake → the transport to peripheral tissues → an increase in the P_CO and [COHb] in peripheral capillary blood → and a return of COHb to the lungs. Unlike earlier models, this model allows evaluation of how [COHb] changes will affect physiological events at different sites in this cycle. We calculated increases in the P_CO and the [COHb] at these sites during constant breathing of different CO concentrations, using an approach that emphasizes the importance of the rate of the replacement reaction (CO + oxyhemoglobin (O₂Hb) ↔ COHb + oxygen (O₂)) in the physiology of CO poisoning. Key findings include: (i) how interactions between inhaled CO, COHb recirculating back to alveolar capillaries, and alveolar capillary P_CO back-pressure regulate pulmonary CO uptake; (ii) how a decrease in the arterial [O₂Hb] evokes an amplification of the P_CO in blood entering peripheral tissues; (iii) that hemoglobin's R-to-T allosteric shifts influence CO delivery to peripheral tissues; and (iv) a clearer characterization of how tissue P_CO is increased during CO exposures.