Advances in gas-exchange physiology and pathophysiology

Summary Although respiratory gas exchange is a mature field, recent research brings new insights and techniques for patient evaluation. While some gases suffer pulmonary diffusion limitation, others do not, explained by comparing their solubility in the alveolar wall to their solubility (dissociation curve slope) in blood. Well-established concepts of shunt and deadspace are revisited with new computerized analyses and measurement approaches showing that in COVID-19, abnormal gas exchange reflects not just shunts but also alveolar deadspace suggesting vascular obstruction (sometimes persisting for months). So-called “silent hypoxia” in COVID-19 likely reflects normal variation in hypoxic ventilatory responsiveness; in most patients, arterial PCO2 is normal or reduced. Evidence that COVID-19 impairs neurological pathways of breathing control is not strong. Finally, we review O2 transport from air to mitochondria as an interactive system (lungs, heart, blood, tissues) where all components function in ways that affect each other. This systems approach enables separation and quantification of central and peripheral contributions to impaired O2 transport.