Aetiology

Some disease states have been associated with hypoventilation syndromes. These include obesity hypoventilation syndrome and restrictive thoracic disorders, such as in patients with chest-wall deformities (e.g., kyphoscoliosis, fibrothorax, or thoracoplasty) and neuromuscular disorders, particularly Duchenne muscular dystrophy and other types of muscular dystrophies and spinal muscular atrophies. Also included are patients with central sleep apnoea syndromes, such as idiopathic central sleep apnoea, and patients with Cheyne-Stokes respiration. Another central but rare disorder is primary alveolar hypoventilation. Finally, obstructive airway disease (in particular, COPD) can develop alveolar hypoventilation and be included in the hypoventilation syndromes.

Pathophysiology

The mechanisms responsible for the development of hypoventilation include:

  • A decrease in central respiratory drive

  • Chest wall and lung parenchymal deformities

  • Respiratory muscle weakness.

In many disorders that provoke hypoventilation, more than one mechanism is responsible. In addition, in many disorders hypoventilation may first occur during sleep, when hypoxic and hypercapnic ventilatory responses are normally decreased compared with during wakefulness, and REM-sleep-related inhibition of spinal motor neurons can have a major effect.[9][10]​ CO₂ retention during sleep will lead to a compensatory retention of bicarbonate by the kidney, which further blunts central drive and promotes more CO₂ retention, contributing to sleep fragmentation with arousals. In patients with obesity-related hypoventilation, a blunted central response, decreases in chest wall and lung parenchymal compliance, presence of obstructive sleep apnoea (OSA), and a leptin-resistance state (a satiety protein that increases ventilation) all contribute.[11][12][13][14][15] In patients with neuromuscular disease, hypoventilation, especially during REM sleep, is the result of the loss of accessory muscle contribution to breathing in the setting of a weakened diaphragm, as well as upper airway obstruction resulting in OSA.[16] Similar mechanisms are responsible for the hypoventilation in patients with thoracic cage abnormalities.[17] Hyperventilation-induced hypocapnia, in the presence of an increased central and peripheral responsiveness to CO₂, seems an important mechanism for the development of Cheyne-Stokes respiration during sleep in patients with congestive heart failure.[18][19][20][21][22]

Use of this content is subject to our disclaimer