Figure 61-1 Proposed pathway of synthesis, transport, secretion, and reuptake of surfactant in the type II alveolar cell. Phospholipids are synthesized in the smooth endoplasmic reticulum (ER). The glucose/ glycerol precursor may be derived from lung glycogen or circulating glucose. Phospholipids and surfactant proteins are packaged in the Golgi apparatus (GZ), emerge as small lamellar bodies (SLB), coalesce to mature lamellar bodies (MLB), migrate to the apical membrane, and are released by exocytosis into the liquid hypophase below the air-liquid interface. The tightly coiled lamellar body unravels to form the lattice (tubular) myelin figure (LMF), the immediate precursor to the phospholipid monolayer at the alveolar surface. Reuptake by endocytosis forms multivesicular bodies (MVB) that recycle surfactant. The enzymes, receptors, transporters, and surfactant proteins are controlled by regulatory processes at the transcriptional level in the nucleus (N). Corticosteroid and thyroid hormones are regulatory ligands that may accelerate surfactant synthesis. (From Hansen T, Corbet A: Lung development and function. In Taeusch HW, Ballard R, Avery ME, editors: Diseases of the Newborn, ed 6, Philadelphia, 1991, Saunders, p 465.) lecithin in amniotic fluid indicates fetal pulmonary maturity. Because the amount of lecithin is difficult to quantify, the ratio of lecithin (which increases with maturity) to sphingomyelin (which remains constant during gestation) (L/S ratio) is determined. An L/S ratio of 2:1 usually indicates pulmonary maturity. The presence of minor phospholipids, such as phosphatidylglycerol, also is indicative of fetal lung maturity and may be useful in situations in which the L/S ratio is borderline or possibly affected by maternal diabetes, which reduces lung maturity. The absence of phosphatidylglycerol suggests that surfactant might not be mature.
A deficiency of pulmonary surfactant (most often due to prematurity) results in atelectasis, decreased functional residual capacity, arterial hypoxemia, and respiratory distress. Surfactant synthesis may also be reduced as a result of hypovolemia, hypothermia, acidosis, hypoxemia, and rare genetic disorders of surfactant synthesis. These factors also produce pulmonary artery vasospasm, which may contribute to RDS in larger premature infants who have developed sufficient pulmonary arteriole smooth muscle to produce vasoconstriction. Surfactant deficiency–induced atelectasis causes alveoli to be perfused but not ventilated, which results in a pulmonary shunt and hypoxemia. As atelectasis increases, the lungs become increasingly difficult to expand, and lung compliance decreases. Because the chest wall of the premature infant is very compliant, the infant attempts to overcome decreased lung compliance with increasing inspiratory pressures, resulting in retractions of the chest wall. The sequence of decreased lung compliance and chest wall retractions leads to poor air exchange, an increased physiologic dead space, alveolar hypoventilation, and hypercapnia. A cycle of hypoxia, hypercapnia, and acidosis acts on type II cells to reduce surfactant synthesis and, in some infants, on the pulmonary arterioles to produce pulmonary hypertension.
Infants at greatest risk for RDS are premature and have an immature L/S ratio. The incidence of RDS increases with decreasing gestational age. RDS develops in 30% to 60% of infants between 28 and 32 weeks of gestation. Other risk factors include delivery of a previous preterm infant with RDS, maternal diabetes, hypothermia, fetal distress, asphyxia, male sex, white race, being the second-born of twins, and delivery by cesarean section without labor.