The lung originates as an outpouching from the endodermal tube that gives rise to the gastrointestinal tract. The epithelial lung bud grows anteriorly into mesenchymal tissue, the forerunner of the interstitium and blood vessels of the lung. As the respiratory tract divides and branches, interstitial tissue and blood vessels surround the developing airways. At approximately 28 weeks’ gestation in humans, alveolar formation begins. Although this process is active during fetal life, the major increase in the number of alveoli occurs after birth. Approximately 1 million alveoli are present at birth, about 100 million at 1 year, and about 300 million at 6 years, after which the number appears to stabilize. Thus, the capacity of the lung to generate new alveoli continues for a considerable time after birth.

Lung growth itself is regulated, in part, by physical factors. It appears to be stimulated by the distending force of lung fluid in the airways and to be inhibited by the absence of this fluid, as occurs in oligohydramnios. Growth also can be inhibited by external compression, as occurs in diaphragmatic hernia, in which the bowel in the chest compresses the lung. Current research indicates that transcription factors, regulatory genes, and hormones pay a major role in controlling lung growth and budding.

Because respiratory distress syndrome of the newborn is the result of immaturity of the lung, considerable interest has been expressed in the maturation of the fetal lung and the regulation of this process. During late fetal life, the development of the lung is characterized by an increase in the number and size of the alveoli and by the thinning of the connective tissue septa between them. This development reduces the distance between the alveolar lumen and red blood cells in capillaries in the interstitium, thus facilitating gas exchange. The alveolar lining cells also become flatter in late gestation, further reducing the barrier to gas exchange.

The cuboidal type II alveolar cells are the sites of the synthesis and secretion of pulmonary surfactant, the phospholipid-protein mixture that lines the alveoli of the lung and prevents alveolar collapse due to surface forces. After synthesis, surfactant is stored in the lamellar bodies, which then are secreted onto the surface of the type II cell by a process of exocytosis. In the alveolar lumen, the lamellar body unravels to form a structure known as tubular myelin and, ultimately, surfactant lines the surface of the alveolar cells. The onset of the functional maturation of the lung is marked by the appearance of lamellar bodies in the alveolar type II cells.