Pathophysiology of Sleep Apnea

Jerome A. Dempsey; Sigrid C. Veasey; Barbara J. Morgan; Christopher P. O'Donnell

doi:10.1152/physrev.00043.2008

journal article Jan 01, 2010

Pathophysiology of Sleep Apnea

Jerome A. Dempsey Sigrid C. Veasey Barbara J. Morgan Christopher P. O'Donnell

Physiological Reviews Vol. 90 No. 1 pp. 47-112 · American Physiological Society

View at Publisher Save 10.1152/physrev.00043.2008

Abstract

Sleep-induced apnea and disordered breathing refers to intermittent, cyclical cessations or reductions of airflow, with or without obstructions of the upper airway (OSA). In the presence of an anatomically compromised, collapsible airway, the sleep-induced loss of compensatory tonic input to the upper airway dilator muscle motor neurons leads to collapse of the pharyngeal airway. In turn, the ability of the sleeping subject to compensate for this airway obstruction will determine the degree of cycling of these events. Several of the classic neurotransmitters and a growing list of neuromodulators have now been identified that contribute to neurochemical regulation of pharyngeal motor neuron activity and airway patency. Limited progress has been made in developing pharmacotherapies with acceptable specificity for the treatment of sleep-induced airway obstruction. We review three types of major long-term sequelae to severe OSA that have been assessed in humans through use of continuous positive airway pressure (CPAP) treatment and in animal models via long-term intermittent hypoxemia (IH): 1) cardiovascular. The evidence is strongest to support daytime systemic hypertension as a consequence of severe OSA, with less conclusive effects on pulmonary hypertension, stroke, coronary artery disease, and cardiac arrhythmias. The underlying mechanisms mediating hypertension include enhanced chemoreceptor sensitivity causing excessive daytime sympathetic vasoconstrictor activity, combined with overproduction of superoxide ion and inflammatory effects on resistance vessels. 2) Insulin sensitivity and homeostasis of glucose regulation are negatively impacted by both intermittent hypoxemia and sleep disruption, but whether these influences of OSA are sufficient, independent of obesity, to contribute significantly to the “metabolic syndrome” remains unsettled. 3) Neurocognitive effects include daytime sleepiness and impaired memory and concentration. These effects reflect hypoxic-induced “neural injury.” We discuss future research into understanding the pathophysiology of sleep apnea as a basis for uncovering newer forms of treatment of both the ventilatory disorder and its multiple sequelae.

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Details

Published: Jan 01, 2010
Vol/Issue: 90(1)
Pages: 47-112

Authors

J

Jerome A. Dempsey

The John Rankin Laboratory of Pulmonary Medicine, Departments of Population Health Sciences and of Orthopedics and Rehabilitation, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; Center for Sleep and Respiratory Neurobiology and Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia; and Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

S

Sigrid C. Veasey

The John Rankin Laboratory of Pulmonary Medicine, Departments of Population Health Sciences and of Orthopedics and Rehabilitation, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; Center for Sleep and Respiratory Neurobiology and Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia; and Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

B

Barbara J. Morgan

The John Rankin Laboratory of Pulmonary Medicine, Departments of Population Health Sciences and of Orthopedics and Rehabilitation, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; Center for Sleep and Respiratory Neurobiology and Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia; and Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

C

Christopher P. O'Donnell

The John Rankin Laboratory of Pulmonary Medicine, Departments of Population Health Sciences and of Orthopedics and Rehabilitation, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; Center for Sleep and Respiratory Neurobiology and Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia; and Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Cite This Article

Jerome A. Dempsey, Sigrid C. Veasey, Barbara J. Morgan, et al. (2010). Pathophysiology of Sleep Apnea. Physiological Reviews, 90(1), 47-112. https://doi.org/10.1152/physrev.00043.2008

Pathophysiology of Sleep Apnea

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