Obesity Hypoventilation Syndrome - Mechanism

Mechanism

It is not fully understood why some obese people develop obesity hypoventilation syndrome while others do not. It is likely that it is the result of an interplay of various processes. Firstly, work of breathing is increased as adipose tissue restricts the normal movement of the chest muscles and makes the chest wall less compliant, the diaphragm moves less effectively, respiratory muscles are fatigued more easily, and airflow in and out of the lung is impaired by excessive tissue in the head and neck area. Hence, people with obesity need to expend more energy to breathe effectively. These factors together lead to sleep-disordered breathing and inadequate removal of carbon dioxide from the circulation and hence hypercapnia; given that carbon dioxide in aqueous solution combines with water to form an acid (CO₂ + H₂O + excess H₂O --> H₂CO₃), this causes acidosis (increased acidity of the blood). Under normal circumstances, central chemoreceptors in the brain stem detect the acidity, and respond by increasing the respiratory rate; in OHS, this "ventilatory response" is blunted.

The blunted ventilatory response is attributed to several factors. Obese people tend to have raised levels of the hormone leptin, which is secreted by adipose tissue and under normal circumstances increases ventilation. In OHS, this effect is reduced. Furthermore, episodes of nighttime acidosis (e.g. due to sleep apnea) lead to compensation by the kidneys with retention of the alkali bicarbonate. This normalizes the acidity of the blood. However, bicarbonate stays around in the bloodstream for longer, and further episodes of hypercapnia lead to relatively mild acidosis and reduced ventilatory response in a vicious circle.

Low oxygen levels lead to hypoxic pulmonary vasoconstriction, the tightening of small blood vessels in the lung to create an optimal distribution of blood through the lung. Persistently low oxygen levels causing chronic vasoconstriction leads to increased pressure on the pulmonary artery (pulmonary hypertension), which in turn puts strain on the right ventricle, the part of the heart that pumps blood to the lungs. The right ventricle undergoes remodeling, becomes distended and is less able to remove blood from the veins. When this is the case, raised hydrostatic pressure leads to accumulation of fluid in the skin (edema), and in more severe cases the liver and the abdominal cavity.

The chronically low oxygen levels in the blood also lead to increased release of erythropoietin and the activation of erythropoeisis, the production of red blood cells. This results in polycythemia, abnormally increased numbers of circulating red blood cells and an elevated hematocrit.