Pathophysiology of Sleep Apnea

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.

Effects of orofacial myofunctional therapy on the symptoms and physiological parameters of sleep breathing disorders in adults: a systematic review

“…The activity of dilating pharynx muscles, especially the genioglossus and tensor palatini muscles oppose to the tendency of the pharynx to collapse as a protective mechanism. Changes in such mechanism are associated with the syndrome of obstructive sleep apnea disorder 7 . In that sense, OMT applied to OSA has the objective of strengthening the nasopharynx and oropharynx musculature contributing to reduce collapse of the airway during sleep [1][2][3][4] .…”

Increased arterial stiffness in obstructive sleep apnea: a systematic review

“…[2][3][4][5][6][7] OSA patients are often excessively sleepy during the daytime causing traffic crashes and work injuries, and they commonly have an increased number and severity of cardiovascular risk factors, such as hypertension, obesity, atherosclerosis, insulin resistance, the presence of increased inflammatory markers and endothelial dysfunction. 8 Although OSA patients commonly demonstrate one or more established cardiovascular risk factors, there is now a considerable body of evidence indicating that OSA itself is an independent cardiovascular risk factor. 3,[9][10][11][12][13][14][15][16] Arterial stiffness determines how quickly the pulse wave generated by the contracting heart travels to the periphery and is reflected back.…”

A resource of potential drug targets and strategic decision‐making for obstructive sleep apnoea pharmacotherapy

“…However, the key elements to OSA pathogenesis in Patient A may be an anatomical predisposition to upper airway obstructions plus diminished pharyngeal dilator muscle compensatory reflexes that are insufficient to reopen the airspace once closed. In contrast, the key predisposing factors causing OSA in Patient B may be enhanced loop gain and heightened arousal responses, both of which destabilize breathing and can precipitate recurrent apneas 9–13 . Treatment with nCPAP would be beneficial to both patients but if they are non-compliant what is the alternative?…”

“…The main predisposing factors to the manifestation of OSA include: (i) an anatomical predisposition to upper airway obstructions; (ii) diminished effectiveness of the upper airway neural compensatory mechanisms that are either already present to prevent an obstruction, or are recruited to reopen the airspace; (iii) enhanced loop gain that predisposes to respiratory control instability and sleep apnea; (iv) arousals from sleep that also destabilize breathing and can precipitate further sleep apnea after an initial event has occurred; (v) decreased functional residual capacity that occurs in sleep, and is exacerbated by obesity, that increases upper airway collapsibility; and/or (vi) rostral fluid shifts when adopting the supine position that may also increase upper airway collapsibility 9–13, 15 .…”