Impaired Lung Growth After Injury in Preterm Lung

Introduction

Infants born as early as 22 weeks estimated gestational age may survive if supported by neonatal intensive care, which includes the routine use of antenatal steroids, postnatal surfactant-replacement therapy, and respiratory support. These and other therapies are required because the gas-exchange regions of the lungs of prematurely born infants are structurally and functionally immature, with limited capacity to support extrauterine life. However, some approaches used for respiratory support are known to adversely affect ongoing lung development and contribute to lung injury, both acute and chronic. The goal of this chapter is to describe the impact of preterm birth and respiratory support on lung growth and development, with emphasis on impairment of alveolar formation.

Architectural Organization of the Mature Lung

Before birth, fetal respiratory gas exchange is subserved by the placenta, the interface between the maternal and fetal circulations. At earlier gestational ages with more extreme fetal immaturity, the morphology of the human fetal lung is too immature to provide efficient exchange of oxygen (O ₂ ) and carbon dioxide (CO ₂ ). To emphasize the structural immaturity of the lung, this section provides context regarding architectural organization of the mature lung related to its respiratory gas-exchange function.

Exchange of O ₂ and CO ₂ in the mature lung occurs in relatively large units that are referred to as terminal respiratory units (TRUs). TRUs are defined anatomically as a terminal respiratory bronchiole and all its alveolar ducts, together with their accompanying alveoli. In the adult human lung, each TRU contains approximately 100 alveolar ducts and 2000 anatomic alveoli. At functional residual capacity, TRUs are approximately 5 mm in diameter and have a volume of roughly 0.02 mL. Together, the two lungs of the adult human contain approximately 150,000 TRUs. Physiologically, diffusion of O ₂ and CO ₂ in the gas phase is so rapid that the partial pressures of each gas are uniform throughout a TRU. Because O ₂ from incoming air has a higher O ₂ partial pressure than the alveolar gas, O ₂ diffuses across the gradient into all associated alveoli of the TRU. Subsequently, O ₂ diffuses across the alveolar-capillary membrane and into the red blood cells, where O ₂ combines with hemoglobin for transport and delivery to body tissues. CO ₂ diffuses in the opposite direction.

In the normal adult human lung, the alveolar-capillary membrane is exceedingly thin, which facilitates gas diffusion through the barrier. The average width of the alveolar-capillary membrane is approximately 1.5 μm. ^, In the context of O ₂ diffusion, the alveolar-capillary membrane’s structural components are, in order, alveolar epithelium and its subjacent basal lamina, alveolar wall interstitium, basal lamina of the capillary endothelium and the capillary endothelium, plasma, the membrane of red blood cells, and, finally, hemoglobin molecules. For CO ₂ transfer, the obstacles to diffusion are encountered in the opposite sequence.