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Pathogenesis of obesity hypoventilation syndrome

Amanda Piper, PhD
Brendon Yee, MBChB, PhD
Section Editor
M Safwan Badr, MD
Deputy Editor
Geraldine Finlay, MD


Obesity hypoventilation syndrome (OHS) is defined as obesity (body mass index [BMI] ≥30 kg/m2) and chronic alveolar hypoventilation (arterial carbon dioxide tension [PaCO2] >45 mmHg) during wakefulness occurring in the absence of other conditions that would better explain hypoventilation [1]. When first described, this was referred to as Pickwickian syndrome after a character in Charles Dickens' book, The Posthumous Papers of the Pickwick Club [2].

The pathogenesis of OHS and factors that contribute to it are reviewed here. Clinical manifestations, diagnosis, and treatment are discussed separately. (See "Clinical manifestations and diagnosis of obesity hypoventilation syndrome" and "Treatment of the obesity hypoventilation syndrome" and "Noninvasive positive pressure therapy of the obesity hypoventilation syndrome".)


Alveolar hypoventilation in patients with obesity occurs when the normal compensatory ventilatory mechanisms that maintain adequate ventilation fail [3]. The main physiologic abnormalities of obesity hypoventilation syndrome (OHS) are obesity, sleep disordered breathing (obstructive sleep apnea [OSA] and/or sleep hypoventilation), altered pulmonary mechanics, and impaired ventilatory control, with a complex interaction between each of these factors (figure 1 and table 1 and algorithm 1) [3].

Obesity — In patients with OSA, increasing body mass index (BMI) increases the likelihood of OHS being present [4,5]. This is due, in part, to excess carbon dioxide (CO2) production associated with increased body surface area [6]. The distribution of excess weight is important, with OHS individuals being more centrally obese than individuals with eucapnic obesity, even at the same BMI [7]. The important role obesity plays in the pathogenesis of this disorder is supported by the observation that weight loss alone decreases the partial pressure of carbon dioxide (PaCO2) during wakefulness in patients with OHS [8]. Nevertheless, obesity cannot be the only mechanism accounting for hypoventilation, as the majority of morbidly obese individuals are able to compensate for the increased load on the respiratory system and maintain daytime eucapnia. Hence, OHS develops when the usual compensatory mechanisms necessary to maintain ventilation in the presence of obesity fail.

Sleep disordered breathing — Patients with OHS may present OSA syndrome with hypercapnia, sleep hypoventilation, or a combination of the two [1,9]. OSA is a syndrome characterized by episodic hypopnea or apnea due to recurrent partial or complete upper airway obstruction during sleep. (See "Overview of obstructive sleep apnea in adults".)


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Literature review current through: Apr 2017. | This topic last updated: Nov 23, 2015.
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