ABSTRACT
This chapter details the composition and activity of pulmonary surfactant,
and the mechanisms by which it becomes dysfunctional during lung injury.
Pulmonary surfactant has physiologically essential actions in decreasing
the work of breathing, stabilizing alveolar inflation-deflation, and reducing
the hydrostatic driving force for edema formation. These actions depend
on the ability of lung surfactant to lower and vary surface tension effec-
tively within the alveolar network. Surfactant dysfunction occurs when
surface activity is disrupted by chemical or physical processes during injury, leading to deficits in pressure-volume mechanics and gas exchange.
Surfactant metabolism can also be compromised during lung injury by
alterations in type II pneumocytes, and the host defense activities of sur-
factant proteins (SP)-A and SP-D can be impaired. Surfactant dysfunction
is an important contributor to the pathophysiology of clinical acute lung
injury (ALI) and the acute respiratory distress syndrome (ARDS). This
chapter discusses mechanisms and characteristics of surfactant dysfunction from biophysical interactions with plasma proteins, cell membrane
lipids, and other inhibitors in edema. Activity detriments from chemical
interactions between lung surfactant components and inflammatory phos-
pholipases, proteases, and reactive oxidants are also detailed, along with
decreased surface activity from depletion or alteration of large surfactant
aggregates. Mechanistic understanding of the biophysics and physiology of
lung surfactant activity and dysfunction is crucial for developing effective
surfactant-based therapies for clinical ALI=ARDS and related pulmonary diseases as discussed in Chapter 15.
