What is the pathophysiology of Obesity Hypoventilation Syndrome (OHS)?

Pathophysiology of Obesity Hypoventilation Syndrome

Obesity Hypoventilation Syndrome results from a complex interplay of mechanical respiratory impairment, blunted central respiratory drive, and metabolic derangements that create a self-perpetuating cycle of worsening hypoventilation. 1

Mechanical Respiratory Dysfunction

The excessive adipose tissue, particularly in the abdomen and chest wall, creates significant mechanical barriers to normal ventilation:

• Increased work of breathing and oxygen cost result from the physical weight on the chest wall and thoracic cage, which mechanically interferes with lung expansion 1
• Low lung volumes and decreased respiratory system compliance develop as abdominal fat mass restricts diaphragmatic excursion, particularly when lying supine 1
• Increased small airway resistance occurs due to poor expansion of lung bases and altered chest wall mechanics 1
• Reduced respiratory capacity when supine worsens as abdominal pressure pushes up the diaphragm, increasing intrathoracic pressure 1

Impaired Central Respiratory Drive

A critical distinguishing feature of OHS is the failure of the respiratory control center to compensate adequately:

• Decreased ventilatory responsiveness to CO2 represents impaired central respiratory drive, preventing appropriate compensatory hyperventilation despite rising PaCO2 1
• Blunted chemoreceptor response to hypercapnia and hypoxemia fails to trigger adequate ventilatory effort 2
• Leptin resistance likely contributes to inadequate respiratory drive, as leptin normally stimulates ventilation, but obesity-related leptin resistance blunts this effect 2
• Shallow and inefficient breathing patterns develop as the respiratory center adapts maladaptively to chronic hypercapnia 1

Metabolic and Compensatory Changes

The body's attempts to compensate ultimately prove counterproductive:

• Elevated metabolism and CO2 production in obesity may be instrumental in OHS-related hypercapnia, as increased metabolic demands exceed the impaired ventilatory capacity 2
• Adaptive changes in respiratory physiology become maladaptive over time, with the respiratory system "resetting" to tolerate higher baseline PaCO2 levels 2
• Compensatory metabolic changes attempt to buffer chronic respiratory acidosis but ultimately fail to prevent progressive deterioration 2

Sleep-Related Breathing Disorders

Nocturnal respiratory disturbances amplify daytime pathophysiology:

• Obstructive sleep apnea coexists in approximately 90% of OHS patients, with nearly 70% having severe OSA (AHI >30 events/h) 1
• Nocturnal alveolar hypoventilation occurs even during periods without discrete apneas or hypopneas 1
• Inadequate respiratory muscle strength fails to meet the increased ventilatory demand during sleep, when respiratory drive is naturally reduced 1

Progressive Pathophysiologic Cycle

OHS represents a vicious cycle where each component worsens the others:

• Diurnal hypercapnia and hypoxia induce pathologic cardiovascular effects including pulmonary hypertension, right ventricular hypertrophy, and cor pulmonale 1
• Sleep-related breathing disorders worsen daytime respiratory physiology, creating a slowly progressive deterioration 2
• Resting daytime hypoxemia and hypercarbia (PaCO2 >45 mm Hg) develop as the final common pathway of these multiple mechanisms 1

Clinical Consequences of Pathophysiology

The underlying mechanisms lead to severe morbidity:

• Pulmonary hypertension and cor pulmonale develop from chronic hypoxemia and hypercapnia 1
• Increased risk of acute-on-chronic hypercapnic respiratory failure requiring hospitalization 1
• Higher mortality rates compared to eucapnic obese patients with sleep-disordered breathing 1
• Impaired exercise tolerance, disability, and reduced quality of life result from the combined cardiopulmonary dysfunction 1

Key Pathophysiologic Distinction

OHS differs fundamentally from simple obesity or obstructive sleep apnea alone by the presence of daytime hypercapnia (PaCO2 >45 mm Hg), which reflects the failure of compensatory mechanisms rather than just mechanical or upper airway obstruction. 1 This distinguishes patients who maintain normal daytime PaCO2 despite obesity and OSA from those who have progressed to true OHS.