Chapter 20: Development of Lungs, Thorax & Diaphragm

The respiratory system originates from the foregut's ventral outgrowth, the respiratory diverticulum, starting at stage 12 (around 30–31 days postfertilization). The specialized respiratory epithelium is endoderm-derived, while supporting structures arise from the investing splanchnopleuric mesenchyme, which critically regulates the branching morphogenesis of the airways. Development is characterized by five histological phases: the embryonic phase (0–7 weeks) sees the lung buds growing dorsally into the pericardioperitoneal canals and establishing primary bronchi; the pseudoglandular phase (5–17 weeks) involves the laying down of virtually all conducting airway generations (about 20), differentiation of cell types like ciliated cells and mucous glands, and condensation of mesenchyme into cartilage; the canalicular phase (17–27 weeks) is when the blood–gas barrier thins as the cuboidal epithelium differentiates into Type I and Type II pneumocytes; and the saccular/alveolar phases (28 weeks through childhood) involve the formation of terminal saccules, development of secondary crests, and maturation of surfactant production by Type II cells, which is vital for preventing neonatal respiratory distress syndrome (NRDS). Normal lung maturation depends on mechanical factors, specifically fetal breathing movements and adequate lung distension provided by lung fluid regulated by amniotic fluid volume; hence, conditions like congenital diaphragmatic hernia (CDH), most often the posterolateral Bochdalek’s hernia, or oligohydramnios are strongly associated with pulmonary hypoplasia. The thorax and diaphragm also develop concurrently; the pleural cavities form from the pericardioperitoneal canals, which are separated from the pericardial and peritoneal cavities by the pleuropericardial and pleuroperitoneal membranes. The respiratory diaphragm itself is a composite structure formed mainly by the septum transversum mesenchyme, receiving its motor innervation from the phrenic nerve (C3, C4, C5) as it migrates caudally. At birth, the lungs must immediately transition from fluid secretion to absorption, and pulmonary vascular resistance drops sharply, driven by mechanical expansion and oxygenation. In neonates, especially preterm infants, the highly compliant chest wall is easily deformable, increasing the work of breathing and vulnerability to lung injury from ventilation, potentially leading to bronchopulmonary dysplasia. Congenital anomalies include disorders of the proximal airways (e.g., tracheo-oesophageal fistulae, tracheomalacia) and distal airways (e.g., bronchial atresia resulting in a bronchocele, or multicystic abnormalities). Postnatal lung development and alveogenesis continue throughout childhood, highlighting the extended period of vulnerability to environmental insults like maternal smoking.