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Over the past two decades our understanding of the mechanisms that control water balance in health and disease has increased substantially. Following the establishment of reliable assay techniques to measure circulating vasopressin, the application of molecular biological methods to define hormonal and receptor abnormalities, and a greater knowledge of intracellular events within the renal tubular cells, it is now possible to characterise disorders of water balance more accurately.
The physiology of water homeostasis is briefly discussed before the pathophysiology, diagnosis, and treatment of diabetes insipidus are described in detail.
Physiology of water homeostasis
It is essential that body water, both intracellular and extracellular, remains stable to allow normal cellular functions to take place. In humans, the maintenance of normal water balance is achieved principally by three interrelated determinants: vasopressin, thirst, and the kidneys. The secretion of vasopressin from the posterior pituitary is under very precise control. Small changes in blood solute concentration (plasma osmolality) regulate vasopressin release.1 An increase in plasma osmolality, usually indicating a loss of extracellular water, stimulates vasopressin secretion and, conversely, a decrease in plasma osmolality inhibits its release into the systemic circulation (fig 1). Vasopressin then acts on its major target organ, the kidneys. The hormone binds to its V2 receptor (the antidiuretic receptor) on the basal aspect of the renal collecting tubular cell to activate an adenyl cyclase system that stimulates intracellular protein kinases. These, in turn, control the arrangement and insertion of “water channel” proteins (aquaporin 2) into the cell membrane to allow water to pass from the lumen of the nephron into the cells of the collecting duct along an osmotic gradient, thus concentrating the urine. Aquaporin 4, and possibly aquaporin 3, mediate the subsequent passage of water from within the cell into the renal interstitium and, finally, the circulation. A total of six aquaporins …