Conseguenze metaboliche dell'ipossia.

Survival under hypoxic conditions depends on the activation of complex cellular processes, with development of some adaptive responses (such as increased oxygen transport obtained by increasing erythropoiesis, activation of angiogenesis and increased glycolysis) and inhibition of the metabolic processes that require high availability of oxygen. Such adaptations allow maintenance of energy homeostasis despite decreased oxygen availability. In the physiological model of sojourn at high altitude, decreased body weight is associated with a lower exercise capacity and loss of skeletal muscle mass, but these changes are reversible on return to sea level. Hypoxia-induced alterations vary according to the features of hypoxic exposure, depending in part on its duration and intensity. Some populations well adapted to altitude show increased metabolic efficiency under hypoxic conditions compared to subjects living at sea level. Adaptation to hypoxia is altered or insufficient under pathological conditions. In patients with chronic obstructive pulmonary disease (COPD), loss of muscle mass occurs but is largely irreversible, possibly because of the effects of the inflammatory activation typical of the disease. In obstructive sleep apnea (OSA), intermittent hypoxia occurs during the night. OSA is characterized by altered energy metabolism, in part due to the associated obesity, and by a predominant inflammatory activation over the classic adaptive response to hypoxia. Some data suggest that the metabolic response of skeletal muscle may be altered in OSA patients during exercise, but the frequent occurrence of obesity associated with insulin resistance in skeletal muscle complicates the interpretation of these results. Further understanding of the adaptations to hypoxia will be useful to better understand the pathophysiology of respiratory diseases, and may suggest new treatment approaches, as it is already occurring for cancer.