13th January 2024

Physiology of Breathing and Sleep

Regulating breathing while asleep differs from regulating wakeful breathing. While awake, ventilation is both a conscious and unconscious process, with a wakefulness drive to breathe augmenting our underlying rhythm of breathing. As we slumber, we lose our conscious stimulation of breathing, leaving our unconscious pathways in control. Therefore, we naturally hypoventilate (in comparison to wakefulness) when asleep. For those with respiratory abnormalities (e.g. smaller airways, underlying lung disease, etc.), the loss of conscious compensatory mechanisms can lead to sleep-disordered breathing.

There are two key components in breathing that are of interest to us: central (or neural) control and muscle tonicity (in the upper airways, the chest wall, and the diaphragm).

Central Control of Respiration

Central control of respiration is via the brain-stem respiratory network in the medulla and pons. There are three components to this complex series of neurons and nuclei:

1. Respiratory Neurons: that generate the underlying respiratory rhythm and act as the primary driver of respiratory activity. There are two groups of respiratory neurons: the Dorsal Respiratory Group (DRG) and the Ventral Respiratory Group (VRG).
2. Chemosensors: detect changes in blood gases and pH and trigger a physiological response to maintain each parameter within the normal range.
3. Respiratory Motor Groups: innervate the respiratory muscles.

The DRG is composed of inspiratory neurons and is closely associated with nucleus of the solitary tract. This area receives important vagal sensory input critical for reflex control of breathing: peripheral chemoreceptors (for pO2 and pCO2 from aorta and carotids), central chemoreceptors (pH in the ventral medulla) and lung vagal afferents (stretch, irritant and pain receptors). The VRG is composed of both inspiratory and expiratory neurons. The Pre-Botzinger Complex (a grouping of inspiratory neurons) within the VRG has some intrinsic pacemaker activity that generates an underlying respiratory rhythm. This complex contains mu-opioid receptors, which slow respiratory pacemaker activity when activated. Thus, we can see how opiates will trigger the mu receptors and slow the pacemaker activity, causing respiratory depression when given at sufficient doses.

The various chemosensors will respond to changes in the pCO2 and pO2 to trigger respiration. One of the primary aims of ventilation is to maintain the pCO2 within a range of 4.5- 6.0 kPa, and respiration is thus very sensitive to even slight changes in pCO2. Hypercarbia will trigger an increase in respiratory drive. In sleep, this can lead to an arousal, pulling patients from deeper sleep and thus disrupting sleep. Hypocapnia, in turn, can lead to a decrease in respiratory drive when, indeed, can lead to periodic central apnoeas (if it crosses the apnoeic threshold). The hypoxic drive alone is relatively insensitive, but when coupled with the hypercarbic drive, it has synergistic effects on increasing arousal and wakefulness and the initiation of some of the conscious waking respiratory drive.

Muscle Tone

As one progresses through the sleep cycle, one’s muscle activity and tone decreases. One loses the wakefulness drive to breathe, and our breathing lightens: the respiratory rate drops, the minute ventilation drops, and muscles become flaccid. This loss of ventilatory motor output is noted in the upper airway muscles, chest wall, and accessory muscles.

Upper Airway

The loss of tonicity in the upper airway manifests itself as a narrowing of the upper airway lumen and increased flaccidity of the upper airway walls. This, in turn, causes increased upper airway resistances and more turbulent airflow. In healthy individuals, this tends not to cause an issue. However, some people are at increased risk of having more substantial upper airway narrowing or even collapse leading. If the upper airway resistance increases enough (i.e. there is sufficient narrowing of the lumen), one can have noisier breathing or snoring (especially if the soft palate vibrates or flaps with inhalation). This can lead to reduced (but not absent) airflow. For some individuals, the increased resistance and the floppiness of their upper airway structures lead to collapse and obstruction, completely stopping airflow and leading to an obstructive apnoeic episode. This, in turn, leads to a rise in pCO2 and increased airway pressure until it triggers an arousal and a surge in catecholamines, leading to increased wakefulness and, therefore, increased drive to the respiratory muscles.

Chest Wall and Diaphragm

The reduction of tonicity in the chest wall muscles increases as our sleep deepens. The diaphragm remains the main respiratory pump during sleep but loses the assistance of the intercostal and accessory respiratory muscles. This leads to a reduction in the minute ventilation. In healthy individuals, the body can manage. However, for certain patient groups, the loss of the supporting respiratory muscles can lead to worsening of their breathing and gas exchange. They develop hypercarbia/hypoxia, which in turn triggers arousals.

References

• Punjabi N, Caffo B, Goodwin J, Gottlieb D, Newman A, O’Connor G et al. Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study. PLoS Medicine. 2009;6(8):e1000132.
• Mandal S, Kent B. Obstructive sleep apnoea and coronary artery disease. Journal of Thoracic Disease. 2018;10(S34):S4212-S4220.
• Beebe D, Groesz L, Wells C, Nichols A, McGee K. The Neuropsychological Effects of Obstructive Sleep Apnea: A Meta-Analysis of Norm-Referenced and Case-Controlled Data. Sleep. 2003;26(3):298-307.
• Sowho M, Amatoury J, Kirkness J, Patil S. Sleep and Respiratory Physiology in Adults. Clinics in Chest Medicine. 2014;35(3):469-481.
• Newton K, Malik V, Lee-Chiong T. Sleep and Breathing. Clinics in Chest Medicine. 2014;35(3):451-456.
• Malhotra A, Horner R. Control of breathing and upper airways during sleep. In: Broaddus V, Mason R, Gotway M, Ernst J, King Jr T, Lazarus S et al., ed. by. Murray & Nadel’s Textbook of Respiratory Medicine. 6th ed. Elsevier; 2015. p. 1511-1526.