Nonpulmonary influences on gas exchange.

There are several determinants governing arterial and mixed venous blood PO2 and PCO2. Ventilation-perfusion imbalance, increased intrapulmonary shunt, and diffusion limitation to oxygen encompass the pulmonary factors. Alternatively, inspired oxygen concentration, overall ventilation, cardiac output, and oxygen consumption (uptake) are contemplated as the four most influential nonpulmonary determinants. All three pulmonary factors plus oxygen uptake cannot be directly modulated, but all the other remaining nonpulmonary determinants are. Inspired oxygen concentration, the amount and pattern of total ventilation, and cardiac output may be, at least in part, relatively well clinically controlled. Arterial PO2 (PaO2) may fall if inspired PO2, overall ventilation, and/or cardiac output decrease, and/or oxygen consumption increases, even though the pulmonary factors remain unchanged. Conversely, if inspired oxygen fraction, ventilation, and/or cardiac output increase, and/or oxygen consumption decreases, PaO2 may improve regardless of the changes operated at the level of the pulmonary determinants. Several pathophysiologic features deserve to be underlined. First, the importance of understanding the role played by mixed venous PO2 as a vital nonpulmonary determinant governing PaO2. Second, the response to 100% oxygen breathing repeatedly exhibits a consistent amount of agreement in the main findings. Third, there is always an interactive interplay between pulmonary and nonpulmonary determinants of PaO2 and arterial PCO2 (PaCO2) in any respiratory disease state following the use of pharmacologic or nonpharmacologic approaches. All in all both PaO2 and PaCO2 become the end-point outcomes of the complex interaction of pulmonary and nonpulmonary factors modulating pulmonary gas exchange. This needs to be unraveled to improve the understanding and management of most acute and chronic respiratory disease states.