Background: Disorders of body fluids are among the most commonly encountered problems in the practice of clinical medicine. This is in large part because many different disease states can potentially disrupt the finely balanced mechanisms that control the intake and output of water and solute. It therefore behooves all clinicians treating such patients to have a good understanding of the pathophysiology, the differential diagnosis and the management of these disorders. Since body water is the primary determinant of the osmolality of extracellular fluid, disorders of body water homeostasis can be divided into hypoosmolar disorders, in which there is an excess of body water relative to body solute, and hyperosmolar disorders, in which there is a deficiency of body water relative to body solute. The classic hyperosmolar disorder is diabetes insipidus, and the classic hypoosmolar disorder is the syndrome of inappropriate antidiuretic hormone secretion. Conclusions: Despite the complexity of this regulatory system, most disorders of water homeostasis can be understood by applying knowledge of the physiology and pathophysiology of arginine vasopressin (AVP) secretion and effects, as summarized in the ten essential points of this review. Understanding therapy for disorders of water homeostasis, including appropriate use of the new AVP receptor antagonists, can similarly be best understood by appreciating these same essential points.

Keywords:
Arginine vasopressin, Diabetes insipidus, Hypernatremia, Hyponatremia, Syndrome of inappropriate antidiuretic hormone secretion
1.
Robertson GL: Diabetes insipidus. Endocrinol Metab Clin North Am 1995;24:549–572.
2.
Verbalis JG: The syndrome of inappropriate antidiuretic hormone secretion and other hypoosmolar disorders; in Schrier RW (ed): Diseases of the Kidney and Urinary Tract. Philadelphia, Lippincott, Williams & Wilkins, 2001, pp 2511–2548.
3.
Robinson AG, Verbalis JG: The posterior pituitary; in Larsen PR, Kronenberg HM, Melmed S, Polonsky KS (eds): Williams Textbook of Endocrinology, ed 10. Philadelphia, Saunders, 2003, pp 281–329.
4.
Adrogue HJ, Madias NE: Hyponatremia. N Engl J Med 2000;342:1581–1589.
5.
Adrogue HJ, Madias NE: Hypernatremia. N Engl J Med 2000;342:1493–1499.
6.
Knepper MA: Molecular physiology of urinary concentrating mechanism: regulation of aquaporin water channels by vasopressin. Am J Physiol 1997;272:F3–F12.
7.
Fujiwara TM, Bichet DG: Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol 2005;16:2836–2846.
8.
Robertson GL: The regulation of vasopressin function in health and disease. Recent Prog Horm Res 1976;33:333–385.
9.
Robertson GL: Posterior pituitary; in Felig P, Baxter J, Frohman L (eds): Endocrinology and Metabolism. New York, McGraw-Hill, 1995, pp 385–432.
10.
Cowley AW Jr: Vasopressin and cardiovascular regulation. Int Rev Physiol 1982;26:189–242.
11.
Zerbe R, Stropes L, Robertson G: Vasopressin function in the syndrome of inappropriate antidiuresis. Annu Rev Med 1980;31:315–327.
12.
Saito T, Ishikawa SE, Ando F, Okada N, Nakamura T, Kusaka I, Higashiyama M, Nagasaka S, Saito T: Exaggerated urinary excretion of aquaporin-2 in the pathological state of impaired water excretion dependent upon arginine vasopressin. J Clin Endocrinol Metab 1998;83:4034–4040.
13.
Goldman MB, Luchins DJ, Robertson GL: Mechanisms of altered water metabolism in psychotic patients with polydipsia and hyponatremia. N Engl J Med 1988;318:397–403.
14.
DeVita MV, Gardenswartz MH, Konecky A, Zabetakis PM: Incidence and etiology of hyponatremia in an intensive care unit. Clin Nephrol 1990;34:163–166.
15.
Hawkins RC: Age and gender as risk factors for hyponatremia and hypernatremia. Clin Chim Acta 2003;337:169–172.
16.
Flear CT, Gill GV, Burn J: Hyponatraemia: mechanisms and management. Lancet 1981;2:26–31.
17.
Anderson RJ, Chung HM, Kluge R, Schrier RW: Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med 1985;102:164–168.
18.
Sorensen IJ, Matzen LE: Serum electrolytes and drug therapy of patients admitted to a geriatric department [in Danish]. Ugeskr Laeger 1993;155:3921–3924.
19.
Miller M, Morley JE, Rubenstein LZ: Hyponatremia in a nursing home population. J Am Geriatr Soc 1988;43:1410–1413.
20.
Upadhyay A, Jaber BL, Madias NE: Incidence and prevalence of hyponatremia. Am J Med 2006;119:S30–S35.
21.
Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G: Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 2006;119:71.e1–8.
22.
Holliday MA, Kalayci MN, Harrah J: Factors that limit brain volume changes in response to acute and sustained hyper- and hyponatremia. J Clin Invest 1968;47:1916–1928.
23.
Melton JE, Patlak CS, Pettigrew KD, Cserr HF: Volume regulatory loss of Na, Cl, and K from rat brain during acute hyponatremia. Am J Physiol 1987;252:F661–F669.
24.
Verbalis JG, Drutarosky MD: Adaptation to chronic hypoosmolality in rats. Kidney Int 1988;34:351–360.
25.
Verbalis JG: Control of brain volume during hypoosmolality and hyperosmolality. Adv Exp Med Biol 2006;576:113–129.
26.
Arieff AI, Llach F, Massry SG: Neurological manifestations and morbidity of hyponatremia: correlation with brain water and electrolytes. Medicine 1976;55:121–129.
27.
Daggett P, Deanfield J, Moss F: Neurological aspects of hyponatraemia. Postgrad Med J 1982;58:737–740.
28.
Sterns RH: Severe symptomatic hyponatremia: treatment and outcome. A study of 64 cases. Ann Intern Med 1987;107:656–664.
29.
Kleeman CR: The kidney in health and disease. X. CNS manifestations of disordered salt and water balance. Hosp Pract 1979;14:59–68, 73.
30.
Arieff AI: Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women. N Engl J Med 1986;314:1529–1535.
31.
Noakes TD, Sharwood K, Collins M, Perkins DR: The dipsomania of great distance: water intoxication in an Ironman triathlete. Br J Sports Med 2004;38:E16.
32.
Wright DG, Laureno R, Victor M: Pontine and extrapontine myelinolysis. Brain 1979;102:361–385.
33.
Sterns RH, Silver SM: Brain volume regulation in response to hypo-osmolality and its correction. Am J Med 2006;119:S12–S16.
34.
Adler S, Verbalis JG, Williams D: Effect of rapid correction of hyponatremia on the blood brain barrier of rats. Brain Res 1995;679:135–143.
35.
Adler S, Martinez J, Williams DS, Verbalis JG: Positive association between blood brain barrier disruption and osmotically-induced demyelination. Mult Scler 2000;6:24–31.
36.
Baker EA, Tian Y, Adler S, Verbalis JG: Blood-brain barrier disruption and complement activation in the brain following rapid correction of chronic hyponatremia. Exp Neurol 2000;165:221–230.
37.
Ohnishi A, Orita Y, Okahara R, Fujihara H, Inoue T, Yamamura Y, Yabuuchi Y, Tanaka T: Potent aquaretic agent. A novel nonpeptide selective vasopressin 2 antagonist (OPC-31260) in men. J Clin Invest 1993;92:2653–2659.
38.
Macion-Dazard R, Callahan N, Xu Z, Wu N, Thibonnier M, Shoham M: Mapping the binding site of six nonpeptide antagonists to the human V2-renal vasopressin receptor. J Pharmacol Exp Ther 2006;316:564–571.
39.
Verbalis JG, Robinson AG, Moses AM: Postoperative and post-traumatic diabetes insipidus; in Czernichow P, Robinson AG (eds): Diabetes Insipidus in Man. Basel, Karger, 2006, vol 13, pp 247–265.
40.
Cusick JF, Hagen TC, Findling JW: Inappropriate secretion of antidiuretic hormone after transsphenoidal surgery for pituitary tumors. N Engl J Med 1984;311:36–38.
41.
Olson BR, Rubino D, Gumowski J, Oldfield EH: Isolated hyponatremia after transsphenoidal pituitary surgery. J Clin Endocrinol Metab 1995;80:85–91.
42.
Ultmann MC, Hoffman GE, Nelson PB, Robinson AG: Transient hyponatremia after damage to the neurohypophyseal tracts. Neuroendocrinology 1992;56:803–811.
43.
Hew-Butler T, Almond C, Ayus JC, Dugas J, Meeuwisse W, Noakes T, Reid S, Siegel A, Speedy D, Stuempfle K, Verbalis J, Weschler L: Consensus statement of the 1st international exercise-associated hyponatremia consensus development conference, Cape Town, South Africa. Clin J Sport Med 2005;15:208–213.
44.
Irving RA, Noakes TD, Buck R, van Zyl Smit R, Raine E, Godlonton J, Norman RJ: Evaluation of renal function and fluid homeostasis during recovery from exercise-induced hyponatremia. J Appl Physiol 1991;70:342–348.
45.
Speedy DB, Noakes TD, Rogers IR, Thompson JM, Campbell RG, Kuttner JA, Boswell DR, Wright S, Hamlin M: Hyponatremia in ultradistance triathletes. Med Sci Sports Exerc 1999;31:809–815.
46.
Almond CS, Shin AY, Fortescue EB, Mannix RC, Wypij D, Binstadt BA, Duncan CN, Olson DP, Salerno AE, Newburger JW, Greenes DS: Hyponatremia among runners in the Boston marathon. N Engl J Med 2005;352:1550–1556.
47.
Noakes T: Fluid replacement during marathon running. Clin J Sport Med 2003;13:309–318.
48.
Siegel AJ: Exercise-associated hyponatremia: role of cytokines. Am J Med 2006;119:S74–S78.
49.
Johnson AK, Buggy J: Periventricular preoptic-hypothalamus is vital for thirst and normal water economy. Am J Physiol 1978;234:R122–R129.
50.
Baylis PH, Thompson CJ: Diabetes insipidus and hyperosmolar syndromes; in Becker KL (ed): Principles and Practice of Endocrinology and Metabolism. Philadelphia, Lippincott Williams & Wilkins, 2001, pp 285–293.
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