Invited Review: pulmonary alveoli: formation, the "call for oxygen," and other regulators.

The lung's only known essential function is to provide sufficient alveolar surface to meet the organism's need for oxygen and elimination of CO(2). The importance of the magnitude of alveolar surface area (Sa) to O(2) uptake (VO(2)) is supported by the presence among mammals of a direct linear relationship between Sa and VO(2). This match has been achieved, despite the higher body mass-specific VO(2) of 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 VO(2) suggests 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 VO(2), the neural regulation of breathing, and lung architecture, composition, and mechanics.