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Pathogenesis of Obstructive and Central Sleep Apnea

Division of Sleep Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to David P. White, M.D., Brigham and Women's Hospital Division of Sleep Medicine, Sleep Research at BI, 75 Francis Street, Boston, MA 02115. E-mail dpwhite{at}rics.bwh.harvard.edu

ABSTRACT

Considerable progress has been made over the last several decades in our understanding of the pathophysiology of both central and obstructive sleep apnea. Central sleep apnea, in its various forms, is generally the product of an unstable ventilatory control system (high loop gain) with increased controller gain (high hypercapnic responsiveness) generally being the cause. High plant gain can contribute under certain circumstances (hypercapnic patients). On the other hand, obstructive sleep apnea can develop as the result of a variety of physiologic characteristics. The combinations of these may vary considerably between patients. Most obstructive apnea patients have an anatomically small upper airway with augmented pharyngeal dilator muscle activation maintaining airway patency awake, but not asleep. However, individual variability in several phenotypic characteristics may ultimately determine who develops apnea and how severe the apnea will be. These include: (1) upper airway anatomy, (2) the ability of upper airway dilator muscles to respond to rising intrapharyngeal negative pressure and increasing Co₂ during sleep, (3) arousal threshold in response to respiratory stimulation, and (4) loop gain (ventilatory control instability). As a result, patients may respond to different therapeutic approaches based on the predominant abnormality leading to the sleep-disordered breathing.

Key Words: Apnea, sleep, pathogenesis • central sleep apnea • obstructive sleep apnea • upper airway

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