Most often the number of vessels is normal, but their luminal
diameters are decreased, either by acute vasoconstriction or by
organic changes of the arterial wall that may be permanent. Vasoconstriction
can be caused by many biologically active agents (eg, serotonin,
norepinephrine, endothelin-1), but by far the most important cause
is alveolar hypoxia, especially potentiated by
metabolic acidemia. The mechanisms underlying the vasoconstriction are
complex, but they are thought to involve interactions among endothelial
responses, mitochondrial oxygen sensors, and K+-activated
calcium channels.6-8 Some of the major causes of
hypoxia in children are upper airway obstruction; sleep apnea; central
nervous system depression from many causes, including prematurity;
thoracic cage impairment by obesity (Pickwickian syndrome); neuromuscular
diseases; kyphoscoliosis; congenitally small thoracic cage (achondroplasia,
Jeune syndrome); large diaphragmatic hernia; extensive parenchymal
or small airway disease (meconium aspiration, severe bronchiolitis,
cystic fibrosis, infections); and high altitude.9,10 Most
of these factors cause multiple changes of acid-base balance and
blood gases, but the likelihood of pulmonary arterial hypertension and
even right-sided congestive heart failure must be considered, too.