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Introduction

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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. 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 or inactivation 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, TITF1, and CSF2RA 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 macrophage 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. Suggested reviews of these topics are provided in the References section.15

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Physical Forces at the Air–Liquid Interface

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In 1929, Van Neergard recognized the critical role of surface tension as a “retractile force” in the lung, observing the marked difference in inflation 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 idiopathic respiratory distress syndrome with alveolar collapse and respiratory failure.6 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 dynes/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 surfactant film throughout life. Pulmonary surfactant lipids and proteins are synthesized and secreted by alveolar type II epithelial cells into the alveoli, where they form multilayered lipid-rich films that reduce surface tension to maintain ventilation (Figs. 5-1 and 5-2).

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Figure 5-1

Pulmonary alveolar ultrastructure. The air–blood barrier is comprised of the capillary endothelium (above the dotted orange line) and the closely apposed type I epithelial cell (below the dotted orange line). The dotted blue line delineates the interstitial space between endothelial cells and type II epithelial cells with their specialized secretory lipid organelles (lamellar ...

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