Development and Growth of the Lung

The lung is designed to provide a large internal surface area in which the inspired air and capillary blood get in intimate contact to each other and thus allow for an efficient exchange of gases. This goal is achieved by a sequence of distinct but overlapping developmental processes (Fig. 5-1; Table 5-1). Organogenesis (embryonic stage) starts with a ventral outpouching of the foregut giving rise to the left and right lung buds. The following development of the airways and gas exchange structures is based on two different mechanisms. Starting from the lung buds, a continuous process of branching and growth into the surrounding mesenchyme preforms the whole conducting airway tree and probably also parts of the respiratory airways (branching morphogenesis). Most of this process takes place during the pseudoglandular stage. The tremendous increase of the gas exchange surface area in late fetal and postnatal lung development is brought about by a process of repetitive airspace septation leading to the formation of alveoli (stage of alveolarization). The canalicular and saccular stages may be considered as intermediate stages between both developmental principles. In the canalicular stage the first air-blood barriers are formed and surfactant production starts. During the saccular stage the switch from branching to septation occurs. Following bulk alveolarization, which in humans occurs mainly after birth, the interalveolar septa and their capillary networks are remodeled to optimize gas exchange during the stage of microvascular maturation. At this point lung development is viewed as finished; it is followed by normal growth of the organ. However, we assume today that some form of late alveolarization at a slow rate may exist. Relative to lung development, the time point of birth varies greatly among mammalian species. In humans, birth occurs early in the alveolar stage. The staging of lung development as described traditionally is highly descriptive. It is based on light microscopical observations of morphologic changes in the developing lung (Figs. 5-1 and 5-2). Large overlaps exist between subsequent stages for two reasons. First, lung development proceeds metachrotically from the proximal to the peripheral portions of the airway tree. Second, some developmental steps and maturation processes defining the stages may run in parallel in neighboring areas. The beginning of pulmonary development is relatively well defined by the first appearance of the future trachea and the lung buds in the region of the foregut. There is no such clear limit, however, as to when it ends during childhood. Thus, lung development slowly blends into lung growth and it boils down to a question of sophisticated definitions when development ends and growth starts.