Invited Review: Pulmonary alveoli: formation, the “call for oxygen,” and other regulators

Abstract

The lung's only known essential function is to provide sufficient alveolar surface to meet the organism's need for oxygen and elimination of CO2. The importance of the magnitude of alveolar surface area (Sa) to O2uptake (V˙o2) is supported by the presence among mammals of a direct linear relationship between Sa and V˙o2. This match has been achieved, despite the higher body mass-specific V˙o2of small organisms compared with large, by a greater subdivision of alveolar surface, not by a larger relative lung volume in small organisms. This highly conserved relationship between alveolar architecture and V˙o2suggests the presence of similarly conserved mechanisms that control the onset, rate, and cessation of alveolus formation and alveolar size, which are also influenced by retinoids and thyroid and corticosteroid hormones. Furthermore, the “call for oxygen” is met at a breathing rate and tidal volume at which the work of breathing is lowest. Thus there is a complex, fascinating, but poorly understood, signaling relationship among V˙o2, the neural regulation of breathing, and lung architecture, composition, and mechanics.