Pediatric disorders of water balance

Abstract

Fluid homeostasis requires adequate water intake, regulated by an intact thirst mechanism and appropriate free water excretion by the kidneys, mediated by appropriate secretion of arginine vasopressin (AVP, also known as antidiuretic hormone). AVP exerts its antidiuretic action by binding to the X chromosome-encoded V2 vasopressin receptor (V2R), a G protein-coupled receptor on the basolateral membrane of renal collecting duct epithelial cells. After V2R activation, increased intracellular cyclic adenosine monophosphate mediates shuttling of the water channel aquaporin 2 to the apical membrane of collecting duct cells, resulting in increased water permeability and antidiuresis. Clinical disorders of water balance are common, and abnormalities in many steps involving AVP secretion and responsiveness have been described. This article focuses on the principal disorders of water balance, diabetes insipidus, and the syndrome of inappropriate antidiuretic hormone secretion.

Figure 1

Antidiurectic action of AVP on the renal collecting duct epithelial cell. AVP binding to the V2R, located on the basolateral membrane, results in an increase in cAMP and activation of protein kinase A (PKA). Ser-256 on the C-terminal of AQP-2 is phosphorylated by PKA, resulting in the shuttling of AQP-2 to the apical membrane, allowing the normally impermeable apical membrane to become permeable to water. In addition, acting through a cAMP-response element in the AQP-2 promoter, chronic exposure of these cells to AVP results in increased synthesis of AQP-2. AQP-3 and AQP-4, constitutively located on the basolateral border of the collecting duct membrane, provide channels for the transport of water out of the collecting duct cells and into the interstitium and circulation. Modified from Prog Biophys Mol Biol, Schrier RW et al. Renal aquaporin water channels: from molecules to human disease 2003; 81:117-131, with permission from Elsevier.