Pulmonary Physiology of
Tzong-Jin Wu, MD,* and
Waldemar A. Carlo, MD†
After completing this article, readers should be able to:
1. Describe the physiology of production and clearance of lung liquid.
2. Compare and contrast the initial breath in spontaneously breathing and asphyxiated
3. Delineate themajor respiratory reﬂexes involved in resuscitation.
4. List changes in pulmonary circulation at birth.
5. List possible deleterious effects of hyperoxia.
The most important part of the transition from intrauterine to extrauterine life is the
establishment of effective pulmonary gas exchange. Currently used techniques of resuscitation, although usually successful, are based onfew physiologic studies and have come
under critical review recently. This article reviews current understanding of pulmonary
physiology during transition and resuscitation, based primarily on experimental animal
studies, and relates it to clinical practices in neonatal resuscitation.
Lung Liquid in Neonatal Transition
The switch from placental to pulmonary gas exchange at birth requiresrapid removal of
lung liquid from the potential air space (Fig. 1)□. This process is much more complex than
simple mechanical compression of the chest at delivery that results in oral drainage of lung
liquid, and it is controlled primarily by ion transport across the airway and pulmonary
During fetal life, the lungs are ﬁlled with liquid, and normal growth of the lungs
depends inpart on the balance between production and drainage of this ﬂuid. The
pulmonary epithelium actively transports chloride into the lung lumen, generating an
osmotic gradient that causes liquid to ﬂow from the microcirculation through the
interstitium into potential air spaces. In fetal lambs, the hourly production of lung liquid
increases from 2 mL/kg at midgestation to 5 mL/kg at term, and thetotal volume
increases from 4 to 6 mL/kg at midgestation to more than 20 mL/kg near term.
Secretion of lung liquid begins to decrease 2 to 3 days before spontaneous term or
preterm labor, resulting in a 15 mL/kg reduction in lung water. Labor decreases
extravascular lung water by 45%, with a further 38% reduction 6 hours after birth. At birth,
several factors drive ﬂuid from the lung lumeninto the interstitium. First, the lung
epithelium switches from a predominantly chloride-secreting membrane before birth to a
predominantly sodium-absorbing membrane after birth. The expression and function of
the epithelial sodium channels at the apical membrane and Na , K -ATPase at the
basolateral membrane increase at birth. The causes of these
changes are not clear but may be linked toalterations in the
hormonal milieu associated with delivery. Second, the lung
liquid contains almost no protein compared with 30 mg/mL
of protein in the interstitial ﬂuid, resulting in an osmotic
eNOS: endothelial nitric oxide synthase
pressure gradient. Third, inﬂation of the lungs with air
FRC: functional residual capacity
establishes transpulmonary pressure, decreaseshydrostatic
PVR: pulmonary vascular resistance
pressure in the pulmonary circulation, and increases pulmo*Fellow Instructor.
Professor, Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
NeoReviews Vol.2 No.2 February 2001 e45
neonatal resuscitation pulmonary physiology
nary blood ﬂow, which in turn increases effective vascular
surfacearea for ﬂuid uptake. Under normal conditions,
transepithelial liquid clearance requires 2 to 3 hours, and
drainage from the interstitium into the circulation is
complete by 6 hours. Most of the luminal ﬂuid enters the
pulmonary microcirculation, but about 10% exits the
lungs through lymphatics. The process may be slower
with preterm birth, delivery by cesarean section without