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The pathogenesis of carbon dioxide retention associated with obesity, the obesity hypoventilation syndrome (OHS), remains obscure. In an attempt to Identify factors which might Initiate or contribute to this syndrome, we reviewed respiratory and circulatory function in two groups of obese subjects: those who were not hypercapnic (simple obesity) and those who were (OHS). Obese subjects in both groups display reduction of lung and chest wall compliance, normal airway resistance, closure of peripheral lung units and increased energy cost of breathing. These abnormalities are more severe in those who hypoventilate, especially the reduction In compliance. Respiratory muscle efficiency is reduced in both groups. Inspiratory muscle strength of patients with OHS is 60 to 70 per cent of normal. In OHS arterial carbon dioxide tension (PaCO 2 ), vital capacity and maximum voluntary ventilation improve significantly with weight toss, whereas in simple obesity there Is little change in these factors with weight loss. In both groups the major circulatory findings are increased total and pulmonary blood volume, with preservation of a normal ratio between the two; and good perfusion but marked underventilation of dependent regions of the lung. These changes are more pronounced In OHS. Left ventricular end diastolic pressure is elevated in some patients, but the rise is not confined to those with OHS. In OHS alveolar hypoxia and acidemia produce pulmonary arterial vasoconstriction and pulmonary arterial hypertension. As a consequence pulmonary artery pressure exceeds left ventricular pressure at the end of diastole. We suggest that excessive reduction of chest wall compliance and inspiratory muscle weakness interact with the circulatory abnormalities already present in simple obesity to generate carbon dioxide retention. The contribution of altered central nervous system function to this process remains controversial.

Summary In a patient showing a typical pickwickian syndrome a study was made of respiratory functions and arterial gasometry, with polygraphic registrations carried out during the day and at night in an attempt to evaluate sleep, respiration, blood oxyhaemoglobin and CO2 concentration of the expiratory air. It was demonstrated that, at the onset of an authentic pickwickian syndrome, the symptomatology may be confined to obesity and diurnal drowsing episodes of the type described by Dickens in his novel. This means that the permanent alveolar hypoventilation regarded by some authors as an indispensable feature of the syndrome, In the patient under discussion, the numerous episodes of diurnal slumber which characterized his condition and occurred while the blood oxyhaemoglobin saturation and alveolar CO2 concentration were entirely normal, cannot be explained on the basis of hypoxia and hypercapnia as suggested by a majority of authors. One must resort to other hypotheses, bearing in mind that the one does not necessarily exclude the other. A first hypothesis suggests that the subject drowses during the day as a result of a primary disturbance of centres in the brain stem which regulate wakefulness and sleep by a mechanism not yet understood. According to this hypothesis, we are confronted with some sort of narcolepsy. A second hypothesis holds that the subject drowses during the day because he does not sleep sufficiently at night as a result of an exaggeration of the physiological phenomenon of hypnic hypoventilation. Nocturnal polygraphic registrations disclosed respiratory pauses which occurred in the initial phase of sleep, quite apart from hypotonia of the muscles of the floor of the mouth, so rapid and pronounced that the tongue moves back and causes the obstructive apnoea responsible for a hypoxia which arouses the subject, who returns to sleep after a short while. The cyclic repetition of arousal and slumber reduces nocturnal sleep to 2–3 h a night. This loss of nocturnal sleep is held responsible for the diurnal somnolence. Unfortunately the subject's diurnal sleep is disturbed even more than his nocturnal sleep because the slightest slumber immediately produces episodes of central or obstructive apnoea. Regardless of the respective values of these two hypotheses, the authors are convinced that the majority of individuals suffering from the pickwickian syndrome drowse during the day and sleep badly at night because of a primary disturbance in the wakefulness-sleep regulation which as such is based on their obesity. This affords an obvious explanation of the established fact that the only way to suppress hypnic disturbances in pickwickian patients is to have them lose weight.

The term “empty sella” is a gross descriptive term introduced by Busch in 1951 (3) and applied to the appearance of the sella turcica when the diaphragma sellae is incomplete or forms only a small peripheral rim and the pituitary gland is not visible grossly as one views the sella turcica from above at necropsy or at surgery. Actually, the pituitary gland is not absent, but is flattened in such a manner as to form a thin layer of tissue at the bottom of the sella turcica. In 1924, Schaeffer (35) described the gross appearance of the diaphragma sellae in 125 cases and noted that it varied from a very dense and complete roof, transmitting the infundibulum, to a mere peripheral rim with a huge infundibular foramen. Busch (3) grossly examined 788 sellae of patients with no known pituitary disease and described three main types of the diaphragma sellae. In Type 1-A the diaphragma sellae forms a complete covering transmitting the hypophyseal stalk. Type 1-B exhibits a slight funnel-shaped depression in the comp...

Obesity, hypoventilation, somnolence and cardiac failure are the cardinal clinical manifestations of the Pickwickian syndrome. A fifty-two year old woman presented with a typical Pickwickian syndrome of at least five years' duration; she died of congestive heart failure and secondary hepatic failure. Examination of the heart at autopsy revealed myocardial hypertrophy, endocardial fibroelastosis and ventricular dilatation. This case study suggests that prolonged hypoxic injury to the overworking heart may play a role in the pathogenesis of endocardial fibroelastosis. Of interest in this chronically hypoxemic adult was the enlargement of renal glomeruli, analogous to that seen in cyanotic children with congenital malformation of the heart.

The weights of the carotid bodies have been measured in an unselected group of 40 successive cases coming for routine necropsy. Although the mean weight of the carotid bodies was higher in those subjects with emphysema or Pickwickian syndrome, this difference did not reach a level of statistical significance. Nevertheless, in a group of two patients with cor pulmonale and one with the Pickwickian syndrome the mean weight of the carotid bodies was significantly higher than that of the rest. Such observations would be consistent with enlargement of the glomic tissue in response to chronic hypoxia. In addition to these observations there was a significant correlation between the size of the carotid bodies and the weights of the left and right ventricles separately, while there was a substantially higher correlation between the weights of the carotid bodies and the combined weights of the two ventricles. Should such a correlation be determined by a causative link between these two measurements, a new metabolic role of glomic tissue will have to be considered. The histology of the carotid bodies was studied and differential cell counts were carried out in 21 cases. Enlargement of the carotid bodies was not accompanied by any change in the differential cell count, except that in one case with `cor pulmonale' and large carotid bodies areas of hyperplasia showed a predominance of the dark variety of type 1 (chief) cell.

Spontaneous afternoon sleep was studied polygraphically and clinically in eleven patients with diverse types of diurnal hypersomnolence and in four controls (3 of whom were not recorded). All the tracings showed normal EEG sleep patterns. Sleep stages III and IV were rarely reached and rapid eye movement (REM) sleep only appeared in a cataplectic-narcoleptic and in a patient under light barbiturate sedation. All the tracings showed predominance of intermediate sleep, composed of light slow wave sleep and accompanied by slow or, especially, medium fast eye movements and the presence of twitches and jerks. The nature and importance of intermediate sleep and its relationship to slow wave sleep on the one hand and to REM sleep on the other is discussed. A hypothesis is proposed whereby there is a constant potential possibility for REM sleep to appear but this possibility, under normal conditions, is totally inhibited by wakefulness and slow wave sleep and only partly inhibited by light slow wave sleep.

Ten patients were observed during 11 episodes of progressive ventilatory failure secondary to gross obesity in a 5 year interval in one hospital. In-hospital mortality was high; seven patients died. Three deaths were related to hypoventilation. Despite effective therapy of ventilatory failure with improvement in clinical status and blood gases, four other patients died, three of pulmonary embolism and one of acute renal failure. In addition, in one surviving patient transitory renal failure developed. In treating patients with the Pickwickian syndrome, close surveillance, prompt recourse to supported ventilation and prophylactic anticoagulation are mandatory. Unexpected death may occur despite clinical and physiologic improvement.