Surfactant

The low surface tension when the alveoli are small is due to the presence in the fluid lining the alveoli of surfactant, a lipid surface-tension-lowering agent. Surfactant is a mixture of dipalmitoylphosphatidylcholine (DPPC), other lipids, and proteins (. If the surface tension is not kept low when the alveoli become smaller during expiration, they collapse in accordance with the law of Laplace. In spherical structures like the alveoli, the distending pressure equals 2 times the tension divided by the radius (P = 2T/r); if T is not reduced as r is reduced, the tension overcomes the distending pressure. Surfactant also helps to prevent pulmonary edema. It has been calculated that if it were not present, the unopposed surface tension in the alveoli would produce a 20 mm Hg force favoring transudation of fluid from the blood into the alveoli.

Phospholipids, which have a hydrophilic "head" and two parallel hydrophobic fatty acids "tails" , line up in the alveoli with their tails facing the alveolar lumen , and surface tension is inversely proportionate to their concentration per unit area. They move farther apart as the alveoli enlarge during inspiration, and surface tension increases, whereas it decreases when they move closer together during expiration.

Surfactant is produced by type II alveolar epithelial cells . Typical lamellar bodies, membrane-bound organelles containing whorls of phospholipid, are formed in these cells and secreted into the alveolar lumen by exocytosis. Tubes of lipid called tubular myelin form from the extruded bodies, and the tubular myelin in turn forms the phospholipid film. Some of the protein-lipid complexes in surfactant are taken up by endocytosis in type II alveolar cells and recycled.

Formation of the phospholipid film is greatly facilitated by the proteins in surfactant. This material contains four unique proteins, SP-A, SP-B, SP-C, and SP-D. SP-A is a large glycoprotein and has a collagen-like domain within its structure. It probably has multiple functions, including regulation of the feedback uptake of surfactant by the type II alveolar epithelial cells that secrete it. SP-B and SP-C are smaller proteins, which facilitate formation of the monomolecular film of phospholipid. A mutation of the gene for SP-C has been reported to be associated with familial interstitial lung disease. Like SP-A, SP-D is a glycoprotein. Its function is uncertain. However, SP-A and SP-D are members of the collectin family of proteins that are involved in innate immunity in other parts of the body.

Surfactant is important at birth. The fetus makes respiratory movements in utero, but the lungs remain collapsed until birth. After birth, the infant makes several strong inspiratory movements and the lungs expand. Surfactant keeps them from collapsing again. Surfactant deficiency is an important cause of infant respiratory distress syndrome (IRDS; hyaline membrane disease), the serious pulmonary disease that develops in infants born before their surfactant system is functional. Surface tension in the lungs of these infants is high, and there are many areas in which the alveoli are collapsed (atelectasis). An additional factor in IRDS is retention of fluid in the lungs. During fetal life, Cl^- is secreted with fluid by the pulmonary epithelial cells. At birth, there is a shift to Na⁺ absorption by these cells via the epithelial Na⁺ channels (ENaCs), and fluid is absorbed with the Na⁺. Prolonged immaturity of the ENaCs contributes to the pulmonary abnormalities in IRDS.

Administration of phospholipid alone by inhalation has little value in the treatment of IRDS. However, a synthetic surfactant and a surfactant preparation derived from bovine lungs are available for use by inhalation. Used prophylactically at birth and as replacement therapy, they decrease the severity of IRDS and the severity but not the incidence of chronic lung disease in survivors.

Maturation of surfactant in the lungs is accelerated by glucocorticoid hormones. There is an increase in fetal and maternal cortisol near term, and the lungs are rich in glucocorticoid receptors.

Patchy atelectasis is also associated with surfactant deficiency in patients who have undergone cardiac surgery involving use of a pump oxygenator and interruption of the pulmonary circulation. In addition, surfactant deficiency may play a role in some of the abnormalities that develop following occlusion of a main bronchus, occlusion of one pulmonary artery, or long-term inhalation of 100% O₂. There is a decrease in surfactant in the lungs of cigarette smokers.

An interesting recent finding is the presence of excess surfactant lipids and proteins in mice with the GM-CSF gene knocked out. The role of GM-CSF in hematopoiesis is discussed. The pathologic findings in the lungs of the knockout mice resemble those in the lungs of humans with pulmonary alveolar proteinosis.