The morbid anatomy of high altitude DONALD HEATH

PROLONGED exposure to the chronic hypoxia of high altitude is associated with structural changes in many systems of the body. Such effects are developed to the greatest extent in native highlanders and they have been studied largely in the Quechua and Aymara peoples of the High Andes of Peru. This account is based on experience gained on four expeditions to the area around Cerro de Pasco in Central Peru at an altitude of 4000-4500 m. The mining activity in this region sustains a sizeable Indian population which thus lives permanently at an elevation exceeding the summit ofthe Matterhorn. The chemoreceptor system of the body has the specific function of monitoring the oxygen content of systemic arterial blood and one would assume that it would undergo changes in the face of a sustained stimulus of chronic hypoxaemia at high altitude. Such is indeed the case but the discovery that the carotid bodies enlarge in states of chronic hypoxia was made only a decade ago, pathologists before that time restricting their interest in the pathology of the carotid bodies to its tumour the chemodectoma. In 1969, Arias-Stella noticed that the carotid bodies of the Quechua Indians of the Peruvian Andes were larger than those of the mestizos living on the coast. Subsequently it was possible to show that the carotid bodies of guineapigs, rabbits and dogs from high altitude are larger than representatives of the same species at sea level (Edwards et al., 1971b). This investigation led the author and his colleagues to show that the carotid bodies of patients with chronic bronchitis and emphysema were also enlarged if there was associated hypoxaemia and right ventricular hypertrophy (Edwards, Heath and Harris, 1971a). When the carotid bodies of animals enlarge rapidly on acute exposure to the hypoxia of simulated high altitude, the increase in size appears to be due simply to vascular congestion (Laidler and Kay, 1975) and under these circumstances it is not surDrising that the enlargement of the carotid bodies is rapidly and largely reversible (Heath et al., 1973a). When the increase in size of the carotid bodies becomes chronic, however, owing to a persistent hypoxic stimulation, it has an organic basis of hyperplasia of chief (Type I) cells in the carotid bodies (Heath, Edwards and Harris, 1970). The sustentacular (Type II) cells do not appear to be involved in the enlargment. In cattle, the hyperplasia may become so extreme as to resemble the histological appearance of the tumour of the chemoreceptor tissues, the chemodectoma (Arias-Stella and Bustos, 1976). In man too it has now been established that the chemodectoma is much commoner at high altitude (Saldania, Salem and Travezan, 1973). The enlarged carotid bodies show characteristic ultrastructural changes. The author found that the neurosecretory vesicles in the chief cells of eupoxic guinea-pigs were composed of a dense, central osmiophilic core with a surrounding thin clear halo and an outer limiting membrane (Edwards, Heath and Harris, 1972). In high altitude guinea-pigs the vesicles enlarge and the central osmiophilic core becomes smaller, fainter and eccentric. The surrounding halo swells to something resembling a small vacuole (Edwards et al., 1972). The functional significance of these electron-microscopic changes is as yet not worked out precisely, although in a general way they are probably associated with the blunted response of chemoreceptors to hypoxia which is known to occur in native highlanders or in patients with cardio-pulmonary disease predisposing to chronic hypoxia (Heath and Williams, 1977). Within the bronchi, bronchioles and alveolar walls of the lung are cells which resemble those of carotid body in containing neurosecretory vesicles (Fig. 1). The cytoplasm of these cells has a limited affinity for silver salts which has to be reinforced by the introduction of reducing agents in the staining method, such as the Grimelius technique, used to demonstrate them. Sometimes these isolated pulmonary argyrophil or Feyrter cells as they are called (Fig. 2) are grouped together to form neuroepithelial bodies (Fig. 3). It has been shown recently that in rabbits born and spending their entire lives at an altitude of over 4300 m there is an increase in number of