The pharyngeal airway is a complex structure that serves several purposes including speech, swallowing, and respiration. The human pharynx is composed of more than 20 muscles and divided into four sections that include the nasopharynx (from the nasal turbinates to the start of the soft palate), velopharynx (from the start of the soft palate to the tip of the uvula), oropharynx (from the tip of the uvula to the tip of the epiglottis), and hypopharynx (from the tip of the epiglottis to the level of the vocal cords) (Fig. 24.1). The human pharynx can be considered as a collapsible tube that is uniquely susceptible to collapse due to the presence of a floating hyoid bone, a longer airway, and a less direct route for inspired air to travel when compared to other mammals. The presence of soft tissues and bony structures, which increase extraluminal tissue pressures surrounding the upper airway, can predispose the pharynx to collapse. In contrast, the actions of pharyngeal dilator muscles maintain pharyngeal patency due to reflex pathways from the central nervous system and within the pharynx. The presence of these opposing forces suggests that increased pharyngeal collapsibility is due to alterations in anatomically imposed mechanical loads and/or in dynamic neuromuscular responses to upper airway obstruction during sleep.

Mechanical determinants of airway caliber of the human pharynx in sleep are similar to those regulating caliber of any collapsible tube (Schwab et al. 2005). Other well-known biological examples in respiratory physiology include intrathoracic airway collapse upon forced exhalation, collapse of pulmonary capillaries in the lung apex, and collapse of alae nase at high inspiratory flow rates. A Starling resistor model developed by Schwartz and colleagues consists of a collapsible tube with a sealed box interposed between two rigid segments (Gold and Schwartz 1996). The critical closing pressure (P _crit) of the passive airway is defined as the pressure inside the airway (P _in) at which the airway collapses. The pressure gradient during airflow through the system is defined by Pupstream and P _crit and remains independent of Pdownstream. Therefore, with increasing P _crit, as the differential between Pupstream and P _crit decreases, inspiratory airflow limitation will eventually develop, and when the P _us falls below P _crit, complete airway occlusion occurs (Fig. 24.2). Effective therapy for sleep apnea requires that the P _us to P _crit pressure differential be widened, and this can be accomplished by either:

Clearly the effects of airway anatomy on airway collapsing pressure in a hypotonic airway are a critical determinant of obstructive apnea. However, several lines of evidence also support neuromuscular factors as significant determinants of airway collapsibility in sleep. First, tonic and phasic EMG activities of pharyngeal airway dilator muscles (genioglossus and tensor palatine) are progressively reduced from wakefulness to NREM to REM sleep and further inhibited coincident with the “phasic” eye movement events in REM. This powerful effect of state has been adequately documented in tracheostomized animal models and recently has been demonstrated in OSA patients in whom the potentially confounding, compensatory responses to sleep-induced changes in upper airway resistance, negative pressure, PaCO₂, and respiratory motor output were controlled through the use of either CPAP or positive pressure controlled mechanical ventilation (Lu et al. 2006). These state effects on the neuromuscular control of the upper airway likely explain, along with reductions in lung volume, why P _crit is never positive in the waking state, even in OSA patients.

Second, neuromuscular factors also play a significant role in the dynamic breath-to-breath and intrabreath regulation of upper airway caliber, through changes in proprioceptive and chemoreceptor feedback. During inspiration, the passive pharynx narrows as intraluminal pressure is progressively reduced because of energy lost in overcoming frictional airway resistance and increases in flow velocity secondary to the Bernoulli effect operating in a reduced lumen size (Schwab et al. 2005). This collapsing effect of a reduced luminal pressure is opposed during inspiration by a reduction in dynamic compliance, i.e., collapsibility, of the airway achieved via reflex activation of pharyngeal dilator muscles. In turn, the reflex activation occurs in response to negative pressure airway mechanoreceptors located principally in the larynx and to a lesser extent in the superficial layers of the pharyngeal wall, with their afferent projections located in the superior laryngeal nerve, and also in glossopharyngeal and trigeminal nerves (Schneider et al. 2002). Large changes in negative pressure in the isolated upper airway trigger a dual protective reflex, which restores airway patency by both activating airway dilators (to reduce airway compliance) while inhibiting diaphragm EMG activity (which minimizes intraluminal negative pressure) (Fig. 24.3). Vagally mediated feedback influences on laryngeal, tongue, and hyoid muscle via pulmonary stretch receptors also protect against airway collapse as the rate of lung inflation is slowed in the face of increased airway resistance, thereby reflexly activating upper airway motor neurons.

Finally, chemoreceptor influences also have substantial effects on upper airway muscle recruitment, and in the case of CO₂, upper airway motor neurons relative to phrenic motor neurons have been shown to have a substantially higher threshold for inhibition (via hypocapnia) and activation (via hypercapnia) (Weiner et al. 2002).

In summary, the evidence to date supports important roles for both anatomical and neural control of dilator muscles to the regulation of upper airway caliber in the sleeping human. The relative contributions of these factors will vary widely among and within individuals with, for example, patterns of fat deposition on the one hand and neurochemical sensitivity for dilator muscle recruitment on the other.