A 36-year-old man comes to the office due to chronic, mild dyspnea and fatigue. The patient also says that his mind seems "foggy" all the time and he is not able to think clearly. He has no significant past medical history and does not take any medication. He lives a sedentary lifestyle and has smoked a half-pack of cigarettes a day for 5 years. Blood pressure is 140/85 mm Hg, pulse is 84/min, and respirations are 18/min. BMI is 32 kg/m2. Lung auscultation is unremarkable. Chest x-ray is normal. Arterial blood gas analysis shows partial pressure of oxygen (PaO2) is 66 mm Hg and partial pressure of carbon dioxide (PaCO2) is 58 mm Hg. His estimated alveolar to arterial oxygen gradient is 10 mm Hg. Which of the following best explains this patient's laboratory findings?
Causes of hypoxemia | ||
Examples | A-a gradient | |
Reduced PiO2 | High altitude | Normal |
Hypoventilation | CNS depression, morbid obesity | Normal |
Diffusion limitation | Emphysema, ILD | Increased |
V/Q mismatch* | Pulmonary embolism, pneumonia | Increased |
*Caused by regional dead-space ventilation and/or intrapulmonary shunting. A-a gradient = alveolar to arterial oxygen gradient; ILD = interstitial lung disease; PiO2 = partial pressure of inspired oxygen; V/Q = ventilation/perfusion ratio. | ||
This patient with chronic fatigue, dyspnea, difficulty concentrating, hypoxemia (PaO2 <75 mm Hg), and hypercapnia (PaCO2 >45 mm Hg) in the setting of obesity (BMI >30 kg/m2) likely has obesity hypoventilation syndrome (OHS). OHS results from physical restriction of lung expansion by excessive thoracic tissue mass. As such, the hypoventilation mostly results from reduced tidal volume and patients may have normal or increased respiratory rate. Most patients with OHS also have concomitant obstructive sleep apnea (OSA); unlike isolated OSA that involves hypoventilation only with sleep, OHS involves hypoventilation throughout the waking hours.
In healthy individuals, a normal alveolar to arterial (A-a) gradient ranges from 4-15 mm Hg, with older individuals having a gradient towards the higher end of normal. A normal A-a gradient indicates that the efficiency of gas exchange between the alveoli and the blood is intact; therefore, hypoxemia must result from low partial pressure of alveolar oxygen (PAO2). Low PAO2 can occur due to alveolar hypoventilation (eg, OHS, neuromuscular disease, central depression of respiratory drive) or inspiration of low partial pressure of oxygen at high altitude.
(Choices B and C) Destruction of lung parenchyma occurs with both emphysema and interstitial lung disease. This leads to disruption of the alveolar-capillary membrane and impaired diffusion capacity with an increased A-a gradient. In OHS, the lung parenchyma is undamaged and diffusion capacity is intact.
(Choice D) Although the lung parenchyma is unaffected in OHS, restricted expansion of the chest wall secondarily restricts lung expansion, effectively decreasing lung compliance.
(Choice E) Tissue oxygen consumption does increase with increased body mass, but it is a relatively minor factor and would not cause hypoxemia or hypercapnia in the absence of hypoventilation.
(Choice F) Right-to-left shunting (eg, Eisenmenger syndrome) results in hypoxemia with an elevated A-a gradient because a large percentage of cardiac output bypasses the alveolar capillaries and does not undergo gas exchange.
Educational objective:
Obesity hypoventilation syndrome commonly presents with chronic fatigue, dyspnea, and difficulty concentrating. Patients will have BMI >30 kg/m2 and arterial blood gas while awake showing evidence of hypoventilation, including hypercapnia (PaCO2 >45 mm Hg) and usually hypoxemia (PaO2 <75 mm Hg). The expected alveolar to arterial oxygen gradient is normal (4-15 mm Hg) with hypoventilation.