Obesity hypoventilation syndrome

Obesity hypoventilation syndrome (also known as Pickwickian syndrome) is a condition in which severely overweight people fail to breathe rapidly enough or deeply enough, resulting in low blood oxygen levels and high blood carbon dioxide (CO2) levels. Many people with this condition also frequently stop breathing altogether for short periods of time during sleep (obstructive sleep apnea), resulting in many partial awakenings during the night, which leads to continual sleepiness during the day. The disease puts strain on the heart, which eventually may lead to the symptoms such as heart failure, leg swelling and various other related symptoms. The most effective treatment is weight loss, but it is often possible to relieve the symptoms by nocturnal ventilation with positive airway pressure (CPAP) or related methods. Obesity hypoventilation syndrome (also known as Pickwickian syndrome) is a condition in which severely overweight people fail to breathe rapidly enough or deeply enough, resulting in low blood oxygen levels and high blood carbon dioxide (CO2) levels. Many people with this condition also frequently stop breathing altogether for short periods of time during sleep (obstructive sleep apnea), resulting in many partial awakenings during the night, which leads to continual sleepiness during the day. The disease puts strain on the heart, which eventually may lead to the symptoms such as heart failure, leg swelling and various other related symptoms. The most effective treatment is weight loss, but it is often possible to relieve the symptoms by nocturnal ventilation with positive airway pressure (CPAP) or related methods. Obesity hypoventilation syndrome is defined as the combination of obesity (body mass index above 30 kg/m2), hypoxemia (falling oxygen levels in blood) during sleep, and hypercapnia (increased blood carbon dioxide levels) during the day, resulting from hypoventilation (excessively slow or shallow breathing). The disease has been known since the 1950s, initially as 'Pickwickian syndrome' in reference to a Dickensian character but currently under a more descriptive name. Most people with obesity hypoventilation syndrome have concurrent obstructive sleep apnea, a condition characterized by snoring, brief episodes of apnea (cessation of breathing) during the night, interrupted sleep and excessive daytime sleepiness. In OHS, sleepiness may be worsened by elevated blood levels of carbon dioxide, which causes drowsiness ('CO2 narcosis'). Other symptoms present in both conditions are depression, and hypertension (high blood pressure) that is difficult to control with medication. The high carbon dioxide can also cause headaches, which tend to be worsening in the morning. The low oxygen level leads to physiologic constriction of the pulmonary arteries to correct ventilation-perfusion mismatching, which puts excessive strain on the right side of the heart. When this leads to right sided heart failure, it is known as cor pulmonale. Symptoms of this disorder occur because the heart has difficulty pumping blood from the body through the lungs. Fluid may, therefore, accumulate in the skin of the legs in the form of edema (swelling), and in the abdominal cavity in the form of ascites; decreased exercise tolerance and exertional chest pain may occur. On physical examination, characteristic findings are the presence of a raised jugular venous pressure, a palpable parasternal heave, a heart murmur due to blood leaking through the tricuspid valve, hepatomegaly (an enlarged liver), ascites and leg edema. Cor pulmonale occurs in about a third of all people with OHS. 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. Formal criteria for diagnosis of OHS are: