title: Sodium balance is not just a renal affair.
abstract: OBJECTIVE
  The equilibration theory of extracellular body fluids is tightly linked to sodium (Na) metabolism. It is accepted that with changes in salt intake, renal sodium elimination will prevent any change in interstitial Na content and concentration. This review summarizes recent anomalous findings regarding salt and water homeostasis that are inconsistent with current assumptions.
  
  
  RESULTS
  Recent findings from chemical analysis studies of laboratory animals, as well as noninvasive quantitative Na MRI (Na-MRI) studies in patients, have shown that remarkable amounts of Na are stored in muscle and in skin without commensurate water retention. Furthermore, an ultra-long Na balance study in humans suggests the presence of endogenous clocks that generate weekly and monthly infradian rhythmicity of Na storage independent of salt intake. Animal experiments suggest that fluids in the skin interstitium are hypertonic compared with plasma, and that interstitial osmotic stress induces local extrarenal immune cell and lymph-capillary driven mechanisms for electrolyte clearance and maintenance of the internal environment.
  
  
  CONCLUSIONS
  Recent quantitative evidence challenges current ideas on salt and water homeostasis, and suggests that Na homeostasis cannot be maintained without additional previously unappreciated extrarenal regulatory mechanisms.
authors.affiliation: aInterdisciplinary Center for Clinical Research and Department of Nephrology and Hypertension, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany bDivision of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Titze
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D018482:Muscle, Skeletal / Q000378:metabolism; D009997:Osmotic Pressure; D012867:Skin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D012982:Sodium, Dietary / Q000378:metabolism; D013997:Time Factors; D014882:Water-Electrolyte Balance
chemical_list: D012982:Sodium, Dietary; D012964:Sodium