Chapter 23 Normal Physiology of the Upper and Lower Airways

Abstract

The respiratory system can be divided into compartments made up of the upper and lower airways. The mechanics of both compartments are strongly influenced by sleep. Lung volume, rib cage muscle activity and minute ventilation tend to decrease during sleep, as does the activity of upper airway stabilizing muscles. The upper airway also plays a critical role in determining ventilation and breathing pattern during sleep. Its patency is influenced not only by pharyngeal and orofacial muscle activity but also by thoracopulmonary mechanics. Sleep thus has a strong impact on upper airway aperture and mechanical properties. Even though obesity and pharyngeal anatomy play an important role in the development of sleep-induced disordered breathing, sleep plays a key role in determining upper airway instability and therefore in determining the pathophysiology of this disorder.

Chapters 21 and 22 described the basis of the physiology of respiratory function during wake and sleep. In this chapter we focus on the physiologic determinants of respiration used to estimate the breathing function in normal persons. The ultimate goal is to allow readers who are not familiar with the field of respiratory medicine to benefit from the more subtle concepts that will help them to better understand sleep-disordered breathing.

The aim of breathing is to provide oxygen to the different body parts and to eliminate carbon dioxide resulting from cell metabolism. This is achieved through continuous gas exchange between inspired and exhaled air and the blood in the pulmonary circulation. Once blood coming from the right heart has been loaded with oxygen, it reaches the left heart, which sends it to every part of the body through the arterial system. The different organs then take up oxygen from the arterial blood and remove carbon dioxide. Blood loaded with carbon dioxide travels through the venous system to reach the pulmonary circulation, where carbon dioxide passively diffuses through the alveolocapillary membrane into the airway, where it is exhaled. Survival depends upon the integrity of this physiologic process, and death can occur if this system stops for more than a few minutes. Therefore, maintenance of normal arterial blood gases involves several physiologic systems (control of breathing, thoracopulmonary mechanics, circulatory characteristics, blood-transport characteristics) that are intimately linked to one another. This chapter focus only on the mechanical properties of the chest and upper and lower airway, which are the main determinants of ventilation during sleep (Box 23-1).

Anatomy and Physiology

The upper airway, which includes nasal cavities, pharynx, and larynx, serves to moisten and warm the air and conduct it to the trachea and lungs. Upper airway muscles are also involved in phonation and swallowing. A very subtle regulation of the cord vocal tension also allows humans to speak and sing during exhalation. It is hypothesized that the evolution of speech in humans, which requires substantial mobility of the pharynx, led to a loss of the rigid support of the upper airway, which makes it more collapsible than in most mammals.

Breathing is possible through either the nose or the mouth, but nasal breathing is the physiologic breathing route. The lower airway includes the trachea and the lungs (bronchi and alveoli). Thin blood vessels, the capillaries lining the alveoli, allow gas exchange between inspired air and blood. The rib cage provides protection for the lungs and also allows them to change volume from a minimum of about 1.5 L to a maximum of 6 to 8 L, depending on the height and sex of the person.¹

The ribs articulate with the transverse processes of the thoracic vertebrae and have flexible anterior cartilaginous connections with the sternum. The lungs are covered by thin visceral pleura. The inner aspects of each hemithorax are lined with parietal pleura. The virtual space between the visceral and parietal pleura contains a few milliliters of lubricating fluid, which allows them to slide against each other easily during ventilation. Due to its proximity to the pleural tissue, the esophageal pressure varies in parallel with the changes in pleural pressure and is often used to quantify respiratory efforts.

Respiratory Muscles

The diaphragm is the main muscle of respiration. It is a dome-shaped muscle that separates the thoracic and abdominal cavities. The diaphragm is innervated by the phrenic nerves. During inspiration, the neural outflow coming from the central respiratory centers leads to diaphragm contraction; the shortening of the diaphragm muscles fibers flattens the diaphragm, making it lose its dome shape and thus increasing intrathoracic volume. Intercostal muscles can also increase the intrathoracic volume by elevating ribs and increasing the anteroposterior diameter of the thorax (Fig. 23-1). Accessory breathing muscles such as the scalene or sternocleidomastoid are not active during normal breathing, but they can be recruited during an effort or in the presence of thoracopulmonary disorders.

Figure 23-1 Representation of inspiratory and expiratory muscles from abdomen to neck. The main inspiratory muscles include the diaphragm and external intercostal muscles. Accessory inspiratory muscles include the scalene and sternocleidomastoid muscles. Expiration is usually a passive process. However internal intercostals and abdominal muscles are recruited during forced expiration.

(Reproduced from Netter FH. Atlas of human anatomy. Philadelphia: Elsevier Saunders; 2006.)

Elastic Forces and Lung Volumes

An isolated lung (not surrounded by the thoracic cage) will tend to contract until it eventually collapses owing to the large amount of elastic fibers inside the lung tissue. The lung is thus submitted to a constant recoil force. In contrast, the isolated thoracic cage tends to expand to a volume about 1 L more than its natural in vivo resting position. In a relaxed subject with an open airway and no airflow, the inward elastic recoil of the lungs will be balanced by the outward resting force coming from the thoracic cage. Lung compliance or distensibility is defined as the change in lung volume per unit change in transmural pressure gradient:

where V is volume and P is pressure.

The lung volume, in the natural resting end-expiratory position, is its functional residual capacity (FRC). Total lung capacity (TLC) is reached when the thoracic cage and lungs are fully expanded (maximal inspiratory effort). Residual volume (RV) represents the volume remaining in the lungs at the end of a forced expiration. Vital capacity (VC) is the maximum amount of air that can be expelled after the lungs have been fully inflated. Tidal volume (VT) is the volume of air inspired or expired during each quiet breathing cycle (Fig. 23-2). The typical VT value is 500 mL, but it can dramatically increase during exercise. Only about two thirds of inspired air participates in oxygen and carbon dioxide exchange because the volume corresponding to upper airway, trachea, and bronchi do not contribute to gas exchanges; this area is the dead space (VDS) of the respiratory tract.¹

Figure 23-2 Schematic illustration of the static lung volumes determined by a spirometer in which airflow velocity does not play a role. Lung capacity is estimated by the sum of two or more lung-volume subdivisions. ERV, expiratory reserve volume; FRC, functional residual capacity; IC, inspiratory capacity; IRV, inspiratory reserve volume; RV, residual volume; TLC, total lung capacity; VC, vital capacity; VT;, tidal volume.

Reproduced with permission from AARC Clinical Practice Guideline Static Lung Volumes: 2001 Revision and Update. Respir Care 2001;46:531539.

Breathing Cycle and Minute Ventilation

Air always flows from an area of higher pressure to one of lower pressure. The pressure inside the pleural space is generated by the forces developed during inspiration and expiration and is proportional to the amount of respiratory effort. The pleural pressure represents the driving pressure. During inspiration, the diaphragm and intercostal muscles contract and the pressure inside the thorax decreases below the atmospheric pressure (negative transpulmonary pressure gradient). This gradient is responsible for air movement from the nose (atmosphere) to the tracheobronchial tree down to the alveoli. During expiration, the inspiratory muscles relax, making resting expiration a passive phenomenon. However, during active expiration (volitional or during exercise), the contraction of abdominal and external intercostal muscles enhances the changes in intrathoracic pressure. This causes an abrupt increase in pleural pressure to a less-negative value. This rise in pleural pressure causes the alveolar pressure to rise by the same amount, thus resulting in a positive pressure gradient from the alveoli to the mouth, which is responsible for exhalation. Lung and chest volume decrease as air flows out, causing lung recoil pressure to fall until a new equilibrium is reached at FRC.

Respiratory rate, or breathing frequency, represents the number of breaths per minute. Average respiratory rate in a healthy adult at rest is about 12 (range, 10 to 18) per minute. Minute ventilation () can be calculated with the following equation:

where RR is the respiratory rate. During quiet breathing, a typical value is 6 L/min but the volume can rise to 180 L/min during exercise.

Resistance

Different profiles of airflow may be observed inside the airways depending on airway anatomy (division of tracheobronchial tree) and mechanical properties (caliber, shape, collapsibility) of the airway structures and on the amount of driving pressure. With a constant laminar flow regimen, the resistance is directly proportional to the pressure gradient along the tube:

where ΔP is the pressure difference and R is the resistance. Airflow is described as turbulent when the pressure drop along the airway is proportional to flow and its square values:

where ΔP is the pressure difference and V is the air flow. Airflow along airways is complex and usually consists of a mixture of laminar and turbulent flow. In normal lungs, respiratory resistance depends mainly on airways diameter. The velocity of airflow and airways diameter decreases in successive airways generation from a maximum in the trachea to almost zero in the smallest bronchioles.

A third flow regimen is represented by flow limitation, where flow plateaus once the driving pressure has reached a given level. In this regimen, the flow value depends on the difference between intraluminal and extraluminal pressure as well as on the compliance of the concerned airway. Flow limitation can occur during expiration when the pressure generated by expiratory forces increases intraluminal pressure and induces an external compression of the airway walls at the same time. This pattern of flow is, however, more prone to occur during inspiration at the level of the upper airway. Upper airway resistance depends on nasal and pharyngeal anatomy, position of the vocal cords, and lung volume (see later).

Effects of Obesity and Body Posture on Lung Volumes

In an awake normal and healthy subject, there is a reduction in FRC and TLC in the supine position in comparison to upright body position.² This reduction is thought to be due to an increase in intrathoracic blood volume or to the gravitational effect of abdominal contents pushing the relaxed diaphragm into a more rostral position.³ This change in diaphragm position reduces the diaphragm’s ability to contract, as suggested by a decreased maximal inspiratory pressure in the supine posture with respect to the upright and sitting positions.⁴ Moreover, this restrictive defect in lung volume increases the work of breathing and deteriorates gas exchange by decreasing the ventilation-perfusion ratio in the dependent parts of the lungs. Decreased lung volume can also increase upper airway resistance by reducing the caudal traction of the mediastinum and trachea on the pharyngeal walls, making them more collapsible during inspiration (discussed further later).⁵^–⁸

In obese subjects, a restrictive defect in lung volume is also observed when they are sitting. There is a further small decrease of about 70 to 80 mL from about 2.4 L (for an average-sized man) in FRC and TLC when obese subjects lay supine.² Considering the effects of abdominal volume on lung function in sitting obese subjects, one would expect a greater reduction in lung volume when they adopt the supine position compared to lean persons. However, a lesser decline in FRC and TLC in obese subjects in the supine position is reported.^2,^3,⁹ One possible explanation is that in sitting obese subjects, the diaphragm is already shifted in a more rostral position and it cannot move much farther in the supine position. Two experimental studies also suggest that there may be a protective or adaptive mechanism against large changes in end-expiratory lung volume during wakefulness¹⁰ and sleep.¹¹

Maximal minute ventilation, expiratory reserve volume, forced vital capacity (FVC), and, to a lesser extent, forced expiratory volume in 1 second (FEV₁) are also affected by obesity.¹² The estimated reduction of FVC is 17.4 mL/kg weight gain for men and 10.6 mL/kg weight gain for women.¹³ Men show more impairment of FVC with weight gain than women, possibly because of differential patterns of fat deposition: waist circumference is negatively associated with FVC and FEV₁. On average, a 1-cm increase in waist circumference was associated with a 13-mL reduction in FVC.¹⁴ All these changes observed from upright to supine positions and in obese persons may contribute to the exacerbation of respiratory disturbances in the presence of sleep-disordered breathing as described in Section 13 of this volume.

Effects of Sleep on Lung Volume

There is a modest but significant decrease in FRC occurring during sleep in most healthy subjects. FRC decreases by about 200 mL in stage 2 non–rapid eye movement (NREM) sleep and by 300 mL during slow-wave sleep and REM sleep when measured with a helium dilution technique in comparison to normal value awake (~2.4 L for an average-sized man).¹⁵ When plethysmongraphy is used to measure differences in lung volume, a 440 to 500 mL decrease in lung volume was reported in NREM sleep (stages 2 to 3 and 4), with a similar decrease in REM sleep.¹⁶ Possible mechanisms of the decrease in FRC during sleep are diaphragm hypotonia inducing rostral displacement of the diaphragm, alteration of the respiratory timing from central generator of breathing, decrease in lung compliance, decrease in thoracic compliance, and central pooling of blood (see Chapters 21 and 22).

A reduction in tidal volume by about 6% to 15% has been reported during NREM sleep (stages 2 to 4), with a further decrease during REM sleep (about 25% lower than during wake).¹⁷^,¹⁸ Minute ventilation is significantly lower during all NREM sleep stages compared to wake and further decreases during REM sleep, especially during phasic REM (about 84% of the level during wake) (Fig. 23-3).¹⁷^–²⁰ This is due to a faster and shallower breathing pattern in all sleep stages with a lower tidal volume, especially during REM sleep. This is, however, controversial because another study showed no significant change in VT between wakefulness and any sleep stage and suggested that the decrease in minute ventilation (8% in NREM and 4% in REM sleep) is due to a decrease in respiratory rate.²¹ Most studies agree, however, that during NREM sleep there is an increase in the rib cage’s contribution to VT associated with an approximately 34% increase in the activity of intercostal muscles.²⁰^–²² There is thus an apparent contradiction between the increase in electromyogram (EMG) activity of thoracic muscles and a decrease in minute ventilation. A possible explanation is that even though muscle activity increases, the actual negative thoracic pressure decreases because of a decrease in the efficiency of muscle contraction during NREM sleep.²³ During REM sleep the relative contribution of the rib cage and abdomen is not significantly different compared to wakefulness.²⁰ Age and sex do not seem to significantly alter sleep-related changes in lung volume.

Figure 23-3 Effects of sleep on ventilation and lung volumes. Minute ventilation (), tidal volume (VT) and breathing frequency (f) during wakefulness and different sleep stages are illustrated. is reduced during NREM sleep, with a further reduction in REM sleep. +, P < .05 vs. awake; X: P < .05 vs. REM sleep.

(Reproduced with permission from Douglas NJ, White DP, Pickett CK, et al. Respiration during sleep in normal man. Thorax 1982;37[11]:840-844.)

Effects of Sleep on Breathing Pattern and Blood Gases

During NREM sleep, the decrease in minute ventilation induces a drop in PaO₂ of 3 to 9 mm Hg and an increase in PaCO₂ and Paco₂ levels ranging from 2 to 4 mm Hg.²⁴^,²⁵ During stable NREM sleep, the breathing pattern is usually regular. However, periodic breathing with waxing and waning ventilation is commonly observed at sleep onset (unstable NREM sleep).²⁶^,²⁷ Complete cessation of breathing for more than 10 seconds with respiratory effort (obstructive sleep apnea) or without respiratory effort (central sleep apnea) can even occur at this time in healthy persons. In these circumstances, this transient periodic breathing seems to be due to an unstable ventilatory feedback loop (loop gain). A low arousal threshold during this stage can also induce instability in the sleep–wake cycle and contribute to unstable breathing. Because of the higher CO₂ set point during sleep, arousals are associated with a sudden increase in ventilation, which will then decrease CO₂ level. If the CO₂ level is below the apnea threshold (CO₂ level below which the central respiratory drive is abolished) when sleep resumes, an apnea can occur and breathing will resume only when the CO₂ level again reaches the sleep set point. The magnitude and the breathing fluctuation depend on several factors such as chemoreceptor sensitivity (controller gain), lung-to-chemoreceptor circulation delay, and the efficiency of the respiratory system in inducing changes in CO₂ level (plant gain) (see also Chapter 22).²⁸