The lecture will address in a comprehensive manner the steps modulating gas exchange from lung to mitochondria and the matching between O₂ transport and bioenergetics at tissue level. Particular attention will be devoted to mechanisms of pulmonary gas exchange, including measurements of ventilation-perfusion (V_A/Q) distributions. The interplay between intrapulmonary and extra-pulmonary factors governing arterial blood gases in different circumstances (health and disease) will be also examined.

Potential perturbations of the main determinants of systemic oxygen flow in respiratory diseases including abnormal cardio-pulmonary interactions will be pictured. We will analyze both causes and consequences of low muscle O₂ conductance (including functional QO₂-VO₂ mismatching at tissue level) and alterations of mitochondrial O₂ utilization in severe disease stages. Relationships between peripheral gas exchange abnormalities and systemic effects of chronic diseases will be explored. It has been recently suggested that nitroso-redox imbalance in the cardiovascular system may play a central role in different chronic disorders (congestive heart failure, COPD, diabetes) triggering tissue hypoxia due to mismatching between O₂ flow-O₂ demand. Further research, however, is still needed to elucidate the mechanisms by which red blood cells act as oxygen-responsive transducers of nitric oxide bioactivity, as well as to identify the clinical impact of this pathway.