Chapter 5: Pulmonary Surfactant and Disorders of Surfactant Homeostasis

INTRODUCTION

Pulmonary surfactant is a complex mixture of phospholipids and proteins that creates a unique interface separating alveolar gas and liquids at the alveolar cell surface, reducing surface tension, and maintaining lung volumes at end expiration. Reduction of the surface tension at the air-liquid interface is a requirement for respiratory function following birth and throughout life. Deficiency of pulmonary surfactant causes respiratory failure in premature infants, or infantile respiratory distress syndrome (IRDS). The adequacy of pulmonary surfactant is maintained by unique and highly regulated systems mediating the synthesis, secretion, reutilization, and catabolism of surfactant. Loss of pulmonary surfactant later in life occurs in the adult respiratory distress syndrome (ARDS), a significant cause of morbidity and mortality following infection, shock, or trauma. Mutations in genes regulating surfactant homeostasis, including SFTPA, SFTPB, SFTPC, ABCA3, NKX2-1, and CSF2RA/B cause acute and/or chronic lung disease in newborn infants, children, and adults. Disorders of GM-CSF signaling inhibit surfactant lipid and protein catabolism by alveolar macrophages causing pulmonary alveolar proteinosis (PAP). This chapter reviews the biology of the surfactant system and its implications for the pathogenesis, diagnosis, and treatment of respiratory disease in premature infants and adults. Reviews of these topics are suggested.^1–7

PHYSICAL FORCES AT THE AIR-LIQUID INTERFACE

In 1929, Van Neergard recognized the critical role of surface tension as a “retractile force” in the lung, observing the markedly increased pressures required to inflate the air- versus water-filled lung. Avery and Mead associated the lack of a lipid-rich material in the lungs of infants dying from IRDS with alveolar collapse and respiratory failure.⁸ In the absence of pulmonary surfactant, molecular forces at the air-liquid interface create a region of high surface tension because intermolecular forces between water molecules are unopposed at the air-liquid interface, and an area of high retractile force at the surface is created. Forces of 70 dyn/cm² are generated at the air-water interface; if unopposed in the alveolus, such forces lead to alveolar collapse and respiratory failure. A surface film composed of multilayered sheets of phospholipids creates a distinct phase separating air and liquid, reducing surface tension to nearly zero and maintaining residual lung volume at end expiration. Complex interactions between surfactant phospholipids and proteins are required to maintain the surfactant film throughout life. Pulmonary surfactant lipids and proteins are synthesized and secreted by alveolar type 2 (AT2) cells into the alveoli, where they form multilayered lipid rich films that reduce surface tension to maintain ventilation (Figs. 5-1 and 5-2).