Pathophysiology of obstructive sleep apnea in adults
- M Safwan Badr, MD
M Safwan Badr, MD
- Section Editor — Sleep Related Breathing Disorders
- Professor and Chief, Pulmonary Critical Care and Sleep Medicine
- Wayne State University School of Medicine
Obstructive sleep apnea (OSA) is a fairly common disorder with significant adverse health consequences [1-4]. OSA is characterized by recurrent obstruction of the pharyngeal airway during sleep, with resultant hypoxia and sleep fragmentation. The pathogenesis of OSA is due to the interaction between unfavorable anatomic upper airway (UA) susceptibility and sleep-related changes in UA function . However, the mechanisms linking sleep-related physiologic changes to UA obstruction in some individuals are not fully understood. In addition, the majority of studies investigating UA obstruction during sleep have been conducted during nonrapid eye movement (NREM) sleep, given the difficulty in achieving rapid eye movement (REM) during invasive studies in the laboratory environment.
This topic will review the effects of sleep on respiratory mechanics, the determinants of UA patency, and the pathophysiology of UA obstruction during sleep. The pathophysiology of OSA in children and the clinical features, diagnosis, and treatment of OSA in children and adults are reviewed separately. (See "Mechanisms and predisposing factors for sleep-related breathing disorders in children" and "Overview of obstructive sleep apnea in adults" and "Clinical presentation and diagnosis of obstructive sleep apnea in adults" and "Management of obstructive sleep apnea in adults" and "Management of obstructive sleep apnea in children".)
EFFECT OF SLEEP ON RESPIRATORY MECHANICS
Sleep is accompanied by multiple physiologic changes relevant to ventilation and respiration (algorithm 1). Sleep is viewed as a quiet resting period, judging by the limited movement, decreased responsiveness, and the passive appearance of a sleeping individual. Sleep is associated with a decreased metabolic rate, loss of the wakefulness drive to breathe , and a subsequent decrease in ventilatory motor output to respiratory muscles, including upper airway (UA) muscle. Furthermore, the loss of the wakefulness drive to breathe renders respiration during sleep critically dependent on the level of chemoreceptor and mechanoreceptor stimuli , and hence susceptible to central apnea and to upper airway obstruction. The pathogenesis of central apnea is discussed separately. (See "Central sleep apnea: Pathogenesis".)
Upper airway mechanics
Decreased muscle activity — Reduced UA muscle activity during sleep is a physiologic phenomenon of little consequence in healthy individuals, but it may promote UA narrowing in susceptible individuals.
Decreased ventilatory motor output is associated with decreased UA muscle activity, particularly in muscles that display tonic activity (independent of the phase of respiration). For example, the tensor palatini demonstrates immediate decrease in activity with sleep onset, with associated reduction in inspiratory flow [7,8]. Studies investigating respiratory muscle activity at sleep onset demonstrate that the activity of respiratory pump muscles and UA-dilating muscles changes less when the dominant electroencephalogram (EEG) waveform is theta (light sleep) versus alpha (wakefulness) .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Young T, Palta M, Dempsey J, et al. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 328:1230.
- Bixler EO, Vgontzas AN, Ten Have T, et al. Effects of age on sleep apnea in men: I. Prevalence and severity. Am J Respir Crit Care Med 1998; 157:144.
- Bixler EO, Vgontzas AN, Lin HM, et al. Association of hypertension and sleep-disordered breathing. Arch Intern Med 2000; 160:2289.
- Bixler EO, Vgontzas AN, Lin HM, et al. Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Crit Care Med 2001; 163:608.
- Dempsey JA, Veasey SC, Morgan BJ, O'Donnell CP. Pathophysiology of sleep apnea. Physiol Rev 2010; 90:47.
- Skatrud JB, Dempsey JA. Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation. J Appl Physiol Respir Environ Exerc Physiol 1983; 55:813.
- Tangel DJ, Mezzanotte WS, White DP. Influence of sleep on tensor palatini EMG and upper airway resistance in normal men. J Appl Physiol (1985) 1991; 70:2574.
- Tangel DJ, Mezzanotte WS, Sandberg EJ, White DP. Influences of NREM sleep on the activity of tonic vs. inspiratory phasic muscles in normal men. J Appl Physiol (1985) 1992; 73:1058.
- Worsnop C, Kay A, Pierce R, et al. Activity of respiratory pump and upper airway muscles during sleep onset. J Appl Physiol (1985) 1998; 85:908.
- Rowley JA, Zahn BR, Babcock MA, Badr MS. The effect of rapid eye movement (REM) sleep on upper airway mechanics in normal human subjects. J Physiol 1998; 510 ( Pt 3):963.
- Rowley JA, Sanders CS, Zahn BR, Badr MS. Gender differences in upper airway compliance during NREM sleep: role of neck circumference. J Appl Physiol (1985) 2002; 92:2535.
- Henke KG, Dempsey JA, Badr MS, et al. Effect of sleep-induced increases in upper airway resistance on respiratory muscle activity. J Appl Physiol (1985) 1991; 70:158.
- Gleadhill IC, Schwartz AR, Schubert N, et al. Upper airway collapsibility in snorers and in patients with obstructive hypopnea and apnea. Am Rev Respir Dis 1991; 143:1300.
- Badr MS, Skatrud JB, Dempsey JA, Begle RL. Effect of mechanical loading on expiratory and inspiratory muscle activity during NREM sleep. J Appl Physiol (1985) 1990; 68:1195.
- Pillar G, Malhotra A, Fogel R, et al. Airway mechanics and ventilation in response to resistive loading during sleep: influence of gender. Am J Respir Crit Care Med 2000; 162:1627.
- Pillar G, Schnall RP, Peled N, et al. Impaired respiratory response to resistive loading during sleep in healthy offspring of patients with obstructive sleep apnea. Am J Respir Crit Care Med 1997; 155:1602.
- Xi L, Smith CA, Saupe KW, et al. Effects of rapid-eye-movement sleep on the apneic threshold in dogs. J Appl Physiol (1985) 1993; 75:1129.
- Skatrud JB, Dempsey JA, Badr S, Begle RL. Effect of airway impedance on CO2 retention and respiratory muscle activity during NREM sleep. J Appl Physiol (1985) 1988; 65:1676.
- Sforza E, Bacon W, Weiss T, et al. Upper airway collapsibility and cephalometric variables in patients with obstructive sleep apnea. Am J Respir Crit Care Med 2000; 161:347.
- Dempsey JA, Skatrud JB, Jacques AJ, et al. Anatomic determinants of sleep-disordered breathing across the spectrum of clinical and nonclinical male subjects. Chest 2002; 122:840.
- Chi L, Comyn FL, Mitra N, et al. Identification of craniofacial risk factors for obstructive sleep apnoea using three-dimensional MRI. Eur Respir J 2011; 38:348.
- Kairaitis K, Stavrinou R, Parikh R, et al. Mandibular advancement decreases pressures in the tissues surrounding the upper airway in rabbits. J Appl Physiol (1985) 2006; 100:349.
- Okubo M, Suzuki M, Horiuchi A, et al. Morphologic analyses of mandible and upper airway soft tissue by MRI of patients with obstructive sleep apnea hypopnea syndrome. Sleep 2006; 29:909.
- Redline S, Tishler PV, Hans MG, et al. Racial differences in sleep-disordered breathing in African-Americans and Caucasians. Am J Respir Crit Care Med 1997; 155:186.
- Cakirer B, Hans MG, Graham G, et al. The relationship between craniofacial morphology and obstructive sleep apnea in whites and in African-Americans. Am J Respir Crit Care Med 2001; 163:947.
- Schwab RJ, Pasirstein M, Pierson R, et al. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. Am J Respir Crit Care Med 2003; 168:522.
- Redline S, Tishler PV, Tosteson TD, et al. The familial aggregation of obstructive sleep apnea. Am J Respir Crit Care Med 1995; 151:682.
- Schwab RJ. Properties of tissues surrounding the upper airway. Sleep 1996; 19:S170.
- Soultan Z, Wadowski S, Rao M, Kravath RE. Effect of treating obstructive sleep apnea by tonsillectomy and/or adenoidectomy on obesity in children. Arch Pediatr Adolesc Med 1999; 153:33.
- Gozal D, Kheirandish-Gozal L. Sleep apnea in children--treatment considerations. Paediatr Respir Rev 2006; 7 Suppl 1:S58.
- Marcus CL. Treatment of obstructive sleep apnea syndrome in children. In: Principles and Practice of Pediatric Sleep Medicine, Sheldon SH, Ferber R, Kryger MH (Eds), Elsevier Saunders, Philadelphia 2005. p.235.
- Wasicko MJ, Leiter JC, Erlichman JS, et al. Nasal and pharyngeal resistance after topical mucosal vasoconstriction in normal humans. Am Rev Respir Dis 1991; 144:1048.
- Wasicko MJ, Hutt DA, Parisi RA, et al. The role of vascular tone in the control of upper airway collapsibility. Am Rev Respir Dis 1990; 141:1569.
- Redolfi S, Yumino D, Ruttanaumpawan P, et al. Relationship between overnight rostral fluid shift and Obstructive Sleep Apnea in nonobese men. Am J Respir Crit Care Med 2009; 179:241.
- Kasai T, Bradley TD, Friedman O, Logan AG. Effect of intensified diuretic therapy on overnight rostral fluid shift and obstructive sleep apnoea in patients with uncontrolled hypertension. J Hypertens 2014; 32:673.
- Elias RM, Bradley TD, Kasai T, et al. Rostral overnight fluid shift in end-stage renal disease: relationship with obstructive sleep apnea. Nephrol Dial Transplant 2012; 27:1569.
- Yadollahi A, Gabriel JM, White LH, et al. A randomized, double crossover study to investigate the influence of saline infusion on sleep apnea severity in men. Sleep 2014; 37:1699.
- White LH, Lyons OD, Yadollahi A, et al. Effect of below-the-knee compression stockings on severity of obstructive sleep apnea. Sleep Med 2015; 16:258.
- Redolfi S, Arnulf I, Pottier M, et al. Attenuation of obstructive sleep apnea by compression stockings in subjects with venous insufficiency. Am J Respir Crit Care Med 2011; 184:1062.
- Redolfi S, Arnulf I, Pottier M, et al. Effects of venous compression of the legs on overnight rostral fluid shift and obstructive sleep apnea. Respir Physiol Neurobiol 2011; 175:390.
- van Lunteren E, Strohl KP. The muscles of the upper airways. Clin Chest Med 1986; 7:171.
- Wheatley JR, Mezzanotte WS, Tangel DJ, White DP. Influence of sleep on genioglossus muscle activation by negative pressure in normal men. Am Rev Respir Dis 1993; 148:597.
- Horner RL, Innes JA, Holden HB, Guz A. Afferent pathway(s) for pharyngeal dilator reflex to negative pressure in man: a study using upper airway anaesthesia. J Physiol 1991; 436:31.
- Fabbri LM, Luppi F, Beghé B, Rabe KF. Complex chronic comorbidities of COPD. Eur Respir J 2008; 31:204.
- Rowley JA, Sanders CS, Zahn BR, Badr MS. Effect of REM sleep on retroglossal cross-sectional area and compliance in normal subjects. J Appl Physiol (1985) 2001; 91:239.
- Stanchina ML, Malhotra A, Fogel RB, et al. The influence of lung volume on pharyngeal mechanics, collapsibility, and genioglossus muscle activation during sleep. Sleep 2003; 26:851.
- Begle RL, Badr S, Skatrud JB, Dempsey JA. Effect of lung inflation on pulmonary resistance during NREM sleep. Am Rev Respir Dis 1990; 141:854.
- Schwab RJ, Gefter WB, Hoffman EA, et al. Dynamic upper airway imaging during awake respiration in normal subjects and patients with sleep disordered breathing. Am Rev Respir Dis 1993; 148:1385.
- Schwab RJ, Gupta KB, Gefter WB, et al. Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Significance of the lateral pharyngeal walls. Am J Respir Crit Care Med 1995; 152:1673.
- Kairaitis K, Byth K, Parikh R, et al. Tracheal traction effects on upper airway patency in rabbits: the role of tissue pressure. Sleep 2007; 30:179.
- Roberts JL, Reed WR, Thach BT. Pharyngeal airway-stabilizing function of sternohyoid and sternothyroid muscles in the rabbit. J Appl Physiol Respir Environ Exerc Physiol 1984; 57:1790.
- Van de Graaff WB. Thoracic influence on upper airway patency. J Appl Physiol (1985) 1988; 65:2124.
- Remmers JE, deGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol Respir Environ Exerc Physiol 1978; 44:931.
- Onal E, Burrows DL, Hart RH, Lopata M. Induction of periodic breathing during sleep causes upper airway obstruction in humans. J Appl Physiol (1985) 1986; 61:1438.
- Warner G, Skatrud JB, Dempsey JA. Effect of hypoxia-induced periodic breathing on upper airway obstruction during sleep. J Appl Physiol (1985) 1987; 62:2201.
- Badr MS, Toiber F, Skatrud JB, Dempsey J. Pharyngeal narrowing/occlusion during central sleep apnea. J Appl Physiol (1985) 1995; 78:1806.
- Isono S, Remmers JE, Tanaka A, et al. Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects. J Appl Physiol (1985) 1997; 82:1319.
- Sanders MH, Moore SE. Inspiratory and expiratory partitioning of airway resistance during sleep in patients with sleep apnea. Am Rev Respir Dis 1983; 127:554.
- Morrell MJ, Arabi Y, Zahn B, Badr MS. Progressive retropalatal narrowing preceding obstructive apnea. Am J Respir Crit Care Med 1998; 158:1974.
- Morrell MJ, Badr MS. Effects of NREM sleep on dynamic within-breath changes in upper airway patency in humans. J Appl Physiol (1985) 1998; 84:190.
- Sankri-Tarbichi AG, Rowley JA, Badr MS. Expiratory pharyngeal narrowing during central hypocapnic hypopnea. Am J Respir Crit Care Med 2009; 179:313.
- EFFECT OF SLEEP ON RESPIRATORY MECHANICS
- Upper airway mechanics
- - Decreased muscle activity
- - Changes in caliber and compliance
- - Loss of load compensation
- Thoracic cage dynamics
- Increased arterial carbon dioxide
- DETERMINANTS OF UPPER AIRWAY PATENCY
- Structural factors
- - Craniofacial structure
- - Soft tissue structures
- Vascular factors
- - Rostral fluid displacement
- Neuromuscular factors
- - Upper airway muscle activity
- Decreased activity
- Decreased responsiveness
- Mechanical corollary
- Changes during rapid eye movement sleep
- - Effect of lung volume
- PHARYNGEAL OBSTRUCTION DURING SLEEP
- Upper airway mechanics
- Ventilatory motor output
- Surrounding tissue
- Role of expiratory narrowing