Pathophysiology
Clinical meaning
Obesity hypoventilation syndrome (OHS, Pickwickian syndrome) is defined by the triad of obesity (BMI greater than or equal to 30 kg/m2), daytime hypercapnia (PaCO2 greater than 45 mmHg), and sleep-disordered breathing in the absence of other causes of hypoventilation. The pathophysiology involves multiple mechanisms: excessive adipose tissue around the chest wall and abdomen reduces respiratory system compliance and increases the work of breathing; the diaphragm is displaced cephalad, reducing functional residual capacity and causing basal atelectasis; leptin resistance impairs the normal ventilatory drive response to hypercapnia; and coexisting obstructive sleep apnea (present in 90%) causes intermittent nocturnal hypoxemia and hypercapnia. Chronic hypercapnia leads to renal bicarbonate retention (metabolic compensation), blunting the central chemoreceptor response and further reducing ventilatory drive. Untreated OHS causes pulmonary hypertension (from chronic hypoxic pulmonary vasoconstriction), cor pulmonale, erythrocytosis, and significantly increased mortality.