Pathogenesis and Treatment of Hypoosmolar and Hyperosmolar States

  • J. Carlos Ayus
  • Allen I. Arieff


Under usual conditions, the osmolality of the extracellular fluid (ECF) is maintained within an extremely narrow range. When this range is exceeded, the cells of the body are subject to an injurious influx or efflux of water, which preserves uniform tonicity of all body fluids. Thus, in situations where the osmolality of body fluids is disturbed, the principal pathophysiology is related to the inability of cells to maintain normal volume (and hence structure and function). Of course, each of the somatic cells of the body has some ability to regulate its own volume; when this regulatory ability is exceeded, symptoms referable to hypoosmolality or hyperosmolality appear. Before discussing specific clinical syndromes of deranged plasma tonicity, it is appropriate to review some important aspects of cell volume regulation.


Serum Sodium Plasma Osmolality Cell Volume Regulation Central Pontine Myelinolysis Water Intoxication 
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  1. 1.
    Lewis SA, Donaldson P: Ion channels and cell volume regulation: chaos in an organized system. NIPS 5: 112–119, 1990.Google Scholar
  2. 2.
    Wong SME, Chase HS: Role of intracellular calcium in cellular volume regulation. Am J Physiol 250: C841 - C852, 1986.PubMedGoogle Scholar
  3. 3.
    Strange K: Regulation of solute and water balance and cell volume in the central nervous system. J Am Soc Nephrol 3: 12–27, 1992.PubMedGoogle Scholar
  4. 4.
    Hoffmann EK, Simonsen LO: Membrane mechanisms in volume and pH regulation in vertebrate cells. Physiol Rev 69 (2): 315–377, 1989.PubMedGoogle Scholar
  5. 5.
    Skou JC: The Na-K pump. NIPS 7:95–100, 1992.Google Scholar
  6. 6.
    Berl T, Anderson RJ, McDonald KM, Schrier RW: Clinical disorders of water metabolism. Kidney Int 10: 117–132, 1976.PubMedCrossRefGoogle Scholar
  7. 7.
    Covey CM, Arieff AI: Disorders of sodium and water metabolism and their effects on the central nervous system. In: BM Brenner, JH Stein, eds, Sodium and Water Homeostasis. Churchill Livingstone, New York, pp 212 241, 1978.Google Scholar
  8. 8.
    Barlow ED, DeWardener HE: Compulsive water drinking. Q J Med 28: 235–247, 1959.PubMedGoogle Scholar
  9. 9.
    Cheng JC, Zikos D, Skopicki HA, Peterson DR, Fisher KA: Long term neurologic outcome in psychogenic water drinkers with severe symptomatic hyponatremia: the effect of rapid correction. Am J Med 88: 561–566, 1990.PubMedCrossRefGoogle Scholar
  10. 10.
    Cronin RE: Psychogenic polydipsia with hyponatremia: report of eleven cases. Am J Kidney Dis 9: 410–416, 1987.PubMedGoogle Scholar
  11. 11.
    Vieweg WVR, David JJ, Rowe WT, Wampler GJ, Burns WJ, Spradlin WW: Death from self-induced water intoxication among patients with schizophrenic disorders. J Nervous Mental Dis 173 (3): 161–165, 1985.CrossRefGoogle Scholar
  12. 12.
    Epstein FH, Levitin H, Glaser G, Lavietes P: Cerebral hyponatremia. N Engl J Med 265: 513–518, 1961.PubMedCrossRefGoogle Scholar
  13. 13.
    Al-Mufti H, Arieff AI: Hyponatremia due to cerebral salt wasting syndrome: combined cerebral and distal tubular lesion. Am J Med 77 (4): 740–746, 1984.PubMedCrossRefGoogle Scholar
  14. 14.
    Ishikawa S-E, Saito T, Kaneko K, Okada K, Kuzuya T: Hyponatremia responsive to fludrocortisone acetate in elderly patients after head injury. Ann Intern Med 106: 187–191, 1987.PubMedCrossRefGoogle Scholar
  15. 15.
    Humes HD: Disorders of Water Metabolism. Saunders, Philadelphia, pp 118–149, 1986.Google Scholar
  16. 16.
    Schrier RA, Berl T: Osmotic and nonosmotic control of vasopressin release. Am J Physiol 236: F321 - F332, 1979.PubMedGoogle Scholar
  17. 17.
    Ayus JC, Arieff AI: Pathogenesis and prevention of hyponatremic encephalopathy. Endocrinol Metab Clin N Am 22 (2): 425–446, 1993.Google Scholar
  18. 18.
    Vexler ZS, Ayus JC, Roberts TPL, Kucharczyk J, Fraser CL, Arieff AI: Ischemic or hypoxic hypoxia exacerbates brain injury associated with metabolic encephalopathy in laboratory animals. J Clin Invest 93: 256–264, 1994.PubMedCrossRefGoogle Scholar
  19. 19.
    Thurston JH, Hauhart RE: Brain amino acids decrease in chronic hyponatremia and rapid correction causes brain dehydration: possible clinical significance. Life Sci 40(26):25392542, 1987.Google Scholar
  20. 20.
    Anderson RJ, Chung HM, Kluge R, Schrier RW: Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med 102: 164–168, 1985.PubMedCrossRefGoogle Scholar
  21. 21.
    Gross PA, Pehrisch H, Rascher W, Schömig A, Hackenthal E, Ritz E: Pathogenesis of clinical hyponatremia: observa- tions of vasopressin and fluid intake in 100 hyponatremic medical patients. Eur J Clin Invest 17: 123–129, 1987.PubMedCrossRefGoogle Scholar
  22. 22.
    Judd BA, Haycock GB, Dalton N, Chantler C: Antidiuretic hormone following surgery in children. Acta Paediatr Scand 79: 461–466, 1990.PubMedCrossRefGoogle Scholar
  23. 23.
    Arieff AI, Kozniewska E, Roberts TPL, Vexler ZS, Kanda F, Kucharczyk J: Role of vasopressin in brain damage from hyponatremic encephalopathy. In: P Gross, D Richter, GL Robertson, eds, Vasopressin. John Libbey Eurotext, Montrouge, France, pp 243–257, 1993.Google Scholar
  24. 24.
    Phillips PA, Abrams JM, Kelly J, et al.: Localization of vasopressin binding sites in rat brain by in vitro autoradiography using a radioiodinated V1 receptor antagonist. Neuroscience 27 (3): 749–761, 1988.PubMedCrossRefGoogle Scholar
  25. 25.
    Faraci FM, Mayhan WG, Heistad DD: Effect of vasopressin on production of cerebrospinal fluid: possible role of vasopressin (V1)-receptors. Am J Physiol 258 (Regul Integrat Comp Physiol 27 ): R94 - R98, 1990.Google Scholar
  26. 26.
    Rosenberg GA, Estrada E, Kyner WT: Vasopressin-induced brain edema is mediated by the Vl receptor. Adv Neurol 52: 149–154, 1990.PubMedGoogle Scholar
  27. 27.
    Fraser CL, Sarnacki P: Inositol 1,4,5 tris-phosphate may regulate cystolic Ca“ in rat brain synaptosomes. J Clin Invest 86 (6): 2169–2173, 1990.PubMedCrossRefGoogle Scholar
  28. 28.
    Williamson JR, Hansen CA, Verhoeven A: Mechanism of action of vasopressin as a calcium mobilizing hormone. In: AW Crowley, LF Laird, DA Ausiello, eds, Vasopressin: Cellular and Integrative Functions. Raven Press, New York, pp 33–45, 1988.Google Scholar
  29. 29.
    Snyder SH, Bredt DS: Nitric oxide as a neuronal messenger. Trends Pharmacol Sci 12 (4): 125–128, 1991.PubMedCrossRefGoogle Scholar
  30. 30.
    Kanda F, Sarnacki P, Arieff AI: Atrial natriuretic peptide inhibits the amelioride-sensitive sodium-hydrogen exchanger in rat brain. Am J Physiol 263 (Regul Integrat Comp Physiol 32 ): R279 - R283, 1992.Google Scholar
  31. 31.
    Kanda F, Arieff AI: Vasopressin inhibits calcium-coupled sodium efflux system in rat brain synaptosomes. Am J Physiol 266 (Regul Integrat Comp Physiol 35 ): R1169 - R1173, 1994.Google Scholar
  32. 32.
    Kozniewska E, Roberts TPL, Oseka M, Vexler ZS, Kucharczyk J, Arieff AI: Hormonal dependence of the effect of chronic hyponatremia on cerebral perfusion and oxygen utilization in the rat. Circ Res,in press.Google Scholar
  33. 33.
    Stone JD, Crofton JT, Share L: Sex differences in central adrenoreceptor-mediated vasopressin response to hemorrhage. Am J Physiol 260 (Endocrinol Metab 23 ): E780 - E786, 1991.Google Scholar
  34. 34.
    Uchida K, Takahashi N, Sumikura T, et al.: Evaluation of the changes in intracranial water, sodium, phosphorus metabolites and intracellular cerebral pH in rats with acute dilutional hyponatremia. Nippon Jinzo Gakkai Shi 32 (11): 1169–1177, 1990.PubMedGoogle Scholar
  35. 35.
    Arieff AI, Kozniewska E, Roberts T, Vexler ZS, Ayus JC, Kucharczyk J: Effects of age, gender and vasopressin on brain adaptation and mortality in rats with hyponatremic encephalopathy. Am J Physiol (Regul Integrat Comp Physiol),in press.Google Scholar
  36. 36.
    Fraser CL, Swanson RA: Female sex hormones inhibit volume regulation in rat brain astrocyte culture. Am J Physiol 267 (Cell Physiol 36 ): C909 - C914, 1994.Google Scholar
  37. 37.
    Fraser CL, Sarnacki P: Na’-K’ ATPase pump function in male rat brain synaptosomes is different from that of females. Am J Physiol 257 (Endocrinol Metab 20 ): E284 - E289, 1989.Google Scholar
  38. 38.
    Vexier ZS, Roberts T, Derugin N, Kucharczyk J, Arieff AI: Adaptation of the brain to hyponatremia in two different species: effects of gender. Abstr Soc Neurosci 24, in press.Google Scholar
  39. 39.
    Widdowson EM, Dickerson JWT: The effect of growth and function on the chemical composition of soft tissues. Biochem J 77: 30–43, 1960.PubMedGoogle Scholar
  40. 40.
    Gur RC, Mozley PD, Resnick SM, et al.: Gender differences in age effect on brain atrophy measured by magnetic resonance imaging. Proc Natl Acad Sci USA 88: 2845–2849, 1991.PubMedCrossRefGoogle Scholar
  41. 41.
    Dekaban AS, Sadowsky D: Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann Neurol 4: 345–356, 1978.PubMedCrossRefGoogle Scholar
  42. 42.
    Melton JE, Nattie EE: Brain and CSF water and ions during dilutional and isomotic hyponatremia in the rat. Am J Physiol 244: R724 - R732, 1983.PubMedGoogle Scholar
  43. 43.
    Rosomoff HL, Zugibe FT: Distribution of intracranial contents in experimental edema. Arch Neurol 9: 36–44, 1963.CrossRefGoogle Scholar
  44. 44.
    Nattie EE, Edwards WH: Brain and CSF water in newborn puppies during acute hypo-and hypernatremia. J Appl Physiol 51: 1086–1091, 1981.PubMedGoogle Scholar
  45. 45.
    Arieff AI, Ayus JC, Fraser CL: Hyponatraemia and death or permanent brain damage in healthy children. Br Med J 304: 1218–1222, 1992.CrossRefGoogle Scholar
  46. 46.
    Keating JP, Schears GJ, Dodge PR: Oral water intoxication in infants. Am J Dis Child 145: 985–990, 1991.PubMedGoogle Scholar
  47. 47.
    Arieff AI: Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women. N Engl J Med 314 (24): 1529–1535, 1986.PubMedCrossRefGoogle Scholar
  48. 48.
    Ayus JC, Arieff AI: Pulmonary complications of hyponatremic encephalopathy: noncardiogenic pulmonary edema and hypercapnic respiratory failure. Chest,in press.Google Scholar
  49. 49.
    Drinker HR, Shields T, Grayhack JT, Laughlin L: Simulated transurethral resection in the dog: early signs and optimal treatment. J Urol 89: 595–602, 1963.Google Scholar
  50. 50.
    Hornbein TF, Townes BD, Schoene RB, Sutton JR, Houston CS: The cost to the central nervous system of climbing to extremely high altitude. N Engl J Med 321 (25): 1714–1719, 1989.PubMedCrossRefGoogle Scholar
  51. 51.
    Oelz O, Regard M, Wichmann W, et al.: Cognitive impairment, neurologic performance and MRI after repeat exposure to extreme altitude. In: JR Sutton, J Coates, J Remmers, eds, Hypoxia, The Adaptations. B.C. Becker, Philadelphia, pp 206–209, 1990.Google Scholar
  52. 52.
    Shimojyo S, Scheinberg P, Kogure K, Reinmuth OM: The effects of graded hypoxia upon transient cerebral blood flow and oxygen consumption. Neurology 18: 127–133, 1968.PubMedCrossRefGoogle Scholar
  53. 53.
    Tien R, Arieff AI, Kucharczyk W, Wasik A, Kucharczyk J: Hyponatremic encephalopathy: is central pontine myelinolysis a component? Am J Med 92 (5): 513–522, 1992.PubMedCrossRefGoogle Scholar
  54. 54.
    Caronna JJ, Finklestein S: Neurological syndromes after cardiac arrest. Stroke 9: 517–520, 1978.PubMedCrossRefGoogle Scholar
  55. 55.
    Thompson PD, Glendhill RF, Quinn NP, Rossor MN, Stanley P, Coomes EN: Neurological complications associated with parenteral treatment: central pontine myelinolysis and Wernicke’s encephalopathy. Br Med J 292: 684–685, 1986.CrossRefGoogle Scholar
  56. 56.
    Tomlinson BE, Pierides AM, Bradley WG: Central pontine myelinolysis: two cases with associated electrolyte disturbance. Q J Med 65: 373–386, 1976.Google Scholar
  57. 57.
    Brunner JE, Redmond JM, Hagger AM, Kruger DF, Elias DF: Central pontine myelinolysis and pontine lesions after rapid correction of hyponatremia: a prospective magnetic resonance imaging study. Ann Neurol 27: 61–66, 1990.PubMedCrossRefGoogle Scholar
  58. 58.
    Worthley LIG, Thomas PD: Treatment of hyponatraemic seizures with intravenous 29.2% saline. Br Med J 292: 168170, 1986.Google Scholar
  59. 59.
    Zimmermann B, Wangensteen OH: Observations on water intoxication in surgical patients. Surgery 31: 654–669, 1952.PubMedGoogle Scholar
  60. 60.
    Chung HM, Kluge R, Schrier RW, Anderson RJ: Postoperative hyponatremia: a prospective study. Arch Intern Med 146: 333–336, 1986.PubMedCrossRefGoogle Scholar
  61. 61.
    Deutsch S, Goldberg M, Dripps RD: Postoperative hyponatremia with the inappropriate release of antidiuretic hormone. Anesthesiology 27: 250–256, 1966.PubMedGoogle Scholar
  62. 62.
    Ayus JC, Wheeler JM, Arieff AI: Postoperative hyponatremic encephalopathy in menstruant women. Ann Intern Med 117: 891–897, 1992.PubMedCrossRefGoogle Scholar
  63. 63.
    Fraser CL, Arieff AI: Fatal central diabetes mellitus and insipidus resulting from untreated hyponatremia: a new syndrome. Ann Intern Med 112 (2): 113–119, 1990.PubMedCrossRefGoogle Scholar
  64. 64.
    Arieff AI, Ayus JC: Endometrial ablation complicated by fatal hyponatremic encephalopathy. JAMA 270: 1230–1232, 1993.PubMedCrossRefGoogle Scholar
  65. 65.
    Still JA Jr., Modell JH: Acute water intoxication during transurethral resection of the prostate, using glycine solution for irrigation. Anesthesiology 38: 98–99, 1973.PubMedCrossRefGoogle Scholar
  66. 66.
    Roesch RP, Stoelting RK, Lingeman JE, Kahnoski RJ, Backes DJ, Gephardt SA: Ammonia toxicity resulting from glycine absorption during a transurethral resection of the prostate. Anesthesiology 58: 577–579, 1983.PubMedCrossRefGoogle Scholar
  67. 67.
    Ryder KW, Olson JF, Kahnoski RJ, Karn RC, Oei TO: Hyperammonia after transurethral resection of the prostate: a report of 2 cases. J Urol 132: 995–997, 1984.PubMedGoogle Scholar
  68. 68.
    Weissman JD, Weissman BM: Pontine myelinolysis and delayed encephalopathy following the rapid correctioon of acute hyponatremia. Arch Neurol 48: 926–927, 1989.CrossRefGoogle Scholar
  69. 69.
    Perino A, Cittadini E, Colacurci N, DePlacido G, Hamou J: Endometrial ablation: principles and technique. Acta Eur Fertility 21: 313–317, 1990.Google Scholar
  70. 70.
    Baggish MS, Brill AI, Rosenweig B, Barbot JE, Indman PD: Fatal acute glycine and sorbitol toxicity during operative hysteroscopy. J Gynecol Surg 9: 137–143, 1993.CrossRefGoogle Scholar
  71. 71.
    Perry CP: Syndrome of inappropriate antidiuretic hormone after laparoscopic-assisted vaginal hysterectomy. J Am Assoc Gynecol Laparoscopists 1: 273–275, 1994.CrossRefGoogle Scholar
  72. 72.
    Gupta DR, Cohen NH: Oxytocin, “salting out,” and water intoxication. JAMA 220: 681–683, 1972.Google Scholar
  73. 73.
    Morgan DB, Kirwan NA, Hancock KW, Robinson D, Howe JG, Ahmad S: Water intoxication and oxytocin infusion. Br J Obstet Gynecol 84: 6–12, 1977.CrossRefGoogle Scholar
  74. 74.
    Raskind M, Barnes RF: Water metabolism in psychiatric disorders. Semin Nephrol 4: 316–324, 1984.Google Scholar
  75. 75.
    Peck V, Shenkman L: Haloperidol-induced syndrome of inappropriate secretion of antidiuretic hormone. Clin Pharmacol Ther 20: 442–444, 1979.Google Scholar
  76. 76.
    Ajlouni K, Kern MW, Tures JF: Thiothixene-induced syndrome of inappropriate secretion of antidiuretic hormone. Arch Intern Med 134: 1103–1105, 1974.PubMedCrossRefGoogle Scholar
  77. 77.
    Shah DK, Wig NN, Chaudhury RR: Antidiuretic hormone levels in patients with weight gain after chlorpromazine therapy. Indian J Med Res 61: 771–776, 1973.PubMedGoogle Scholar
  78. 78.
    Fischman C, Oster J: Toxic effects of toluene: a new cause of high anion gap metabolic acidosis. JAMA 241: 1713–1715. 1979.Google Scholar
  79. 79.
    Fowler RC, Kronfol ZA, Perry PJ: Water intoxication, 100. Vin-Christian K, Arieff AI: Diabetes insipidus, massiveGoogle Scholar
  80. pyschosis, and inappropriate secretion of antidiuretic hor polyuria and hypernatremia leading to permanent brain mone. Arch Gen Psychiatr 34:1097–1099, 1977. damage. Am J Med 94:341–342, 1993. Google Scholar
  81. 80.
    Kosten TR, Camp W: Inappropriate secretion of antidiuretic 101. Forrest JN, Cox M, Hong C, Morrison G, Bia M, Singer I:Google Scholar
  82. hormone in a patient receiving piperazine phenothiazines. Superiority of demeclocycline over lithium in the treatment Psychosomatics 21:351–355, 1980. of chronic syndrome of inappropriate secretion of antidi-Google Scholar
  83. 81.
    Miller M, Mo-es AM, Rao KJ: Water intoxication and uretic hormone. N Engl J Med 298: 173–177, 1978.CrossRefGoogle Scholar
  84. 82.
    Kendler KS, Weitzman RE, Rubin RT: Lack of arginine proximal and distal tubular reabsorption in rat. Fed Proc vasopressin response to central dopamine blockade in 32:381A, 1973. normal adults. J Clin Endocrinol Metab 47:204–207, 103.Google Scholar
  85. Hullin RP, Coley VP, Birch NS, Thomas TH, Morgan DB: 1978. Renal function after long-term treatment with lithium. BrGoogle Scholar
  86. 83.
    Rowe JW, Shelton RL, Helderman H: Influence of the Med J 1:1457–1459, 1979. emetic reflex on vasopressin release in man. Kidney Int 104. Hallgren R, Alm PO, Hellsing K: Renal function in patients 16:729–735, 1979. on lithium treatment. Br J Psychiatr 135: 22–27, 1979.CrossRefGoogle Scholar
  87. 84.
    Raskind MA, Courtney ND, Backus FL: Antipsychotic 105. Hansen HE, Hestbech J, Sorenson JL, Norgaard K, Heliskov Drugs and Plasma Vasopressin. Toronto, pp 222–223, J, Amdisen A: Chronic interstitial nephropathy in patients on 1982. long-term lithium treatment. Q J Med 68: 577–591, 1979.Google Scholar
  88. 85.
    Berl T, Cadnapaphornchai P, Harbottle JA, Schrier RW: 106. Tangedahl TN, Gau GT: Myocardial irritability associated Mechanism of suppression of vasopressin during alpha with lithium carbonate therapy. N Engl J Med 287:867–869, adrenergic stimulation with norepinephrine. J Clin Invest 1972. 53:219–227, 1974. 107. Hurtig HI, Dyson WL: Lithium toxicity enhanced by diuresis.Google Scholar
  89. 86.
    Rosenbaum JF: Pyschosis and water intoxication. J Clin N Engl J Med 290:748–749,1974. Psychiatr 40:287, 1979. 108. Lazar P, Kerman L, Kanter A: DemethylchlorotetracyclineGoogle Scholar
  90. 87.
    Dubovsky SL, Grabson S, Berl T, Schrier RW: Syndrome of hydrochloride and nephtogenic diabetes insipidus. Cutis 881- inappropriate secretion of antidiuretic hormone with exacer 883, 1970. bated psychosis. Ann Intern Med 79:551–554, 1973. 109. White MG, Fetner CD: Treatment of the syndrome of inap-Google Scholar
  91. 88.
    Brown RP, Kocsis JH, Cohen SK: Delusional depression and propriate secretion of antidiuretic hormone. N Engl J Med inappropriate antidiuretic hormone secretion. Biol Psychiatr 292:390–392, 1975. 18:1059–1063, 1983. 110. Cherrill DA, Stote RM, Birge JR, Singer I: DemeclocyclineGoogle Scholar
  92. 89.
    Robertson GL: The pathophysiology of ADH secretion. In: treatment in the syndrome of inappropriate antidiuretic hor- G Tolis, ed Clinical Neuroendocrinology: A Pathophysi mone secretion. Ann Intern Med 83:654–656, 1975. ological Approach. Raven Press, New York, pp 247–260, 111. DeTroyer A: Demeclocycline treatment of syndrome ofGoogle Scholar
  93. 90.
    Inappropriate antidiuretic hormone secretion. JAMA 90. Lipschutz JH, Arieff AI: Reset osmostat in a healthy patient. 237:2723–2726,1977. Ann Intern Med 120:574–576, 1994. 112. Miller PD, Linas SL, Schrier RW: Plasma demeclocyclineGoogle Scholar
  94. 91.
    Hariprasad MK, Eisinger RP, Nadler IM, Padmanabhan CS: levels and nephrotoxicity. Correlation in hyponatremic cir-Google Scholar
  95. Hyponatremia in psychogenic polydipsia. Arch Intern Med rhotic patients. JAMA 243:2513–2515, 1980. 140:1639–1642, 1980. 113. Oster JR, Epstein M, Ulano HB: Deterioration of renal func-Google Scholar
  96. 92.
    Ayus JC: Diuretic induced hyponatremia. Arch Intern Med tion with demeclocycline administration. Curr Ther Res 146:1295–1296, 1986. 20:794–800, 1976.Google Scholar
  97. 93.
    Ashouri OS: Severe diuretic-induced hyponatremia in the 114. Carrilho F, Bosch J, Arroyo V, Mas B, Viver J, Rodes J: elderly: a series of eight patients. Arch Intern Med 146:1355 Renal failure associated with demeclocycline in cirrhosis. 1357, 1986. Ann Intern Med 87:195–197, 1977. Google Scholar
  98. 94.
    Friedman E, Shade[M, Halkin H, Farfel Z: Thiazide-induced 115. Cox M, Shook A, Singer I: Demeclocycline-induced hyponatremia. Reproducibility by single dose rechallenge azotemia, natriuresis, and antikaliuresis in congestive heart and an analysis of pathogenesis. Ann Intern Med 110:24–30, failure. Clin Res 27:495A, 1979. 1989. 116. Decaux G, Brimioulle S, Genette F, Mockel J: Treatment ofGoogle Scholar
  99. 95.
    Ashraf N, Locksley R, Arieff AI: Thiazide-induced the syndrome of inappropriate secretion of antidiuretic hor- hyponatremia associated with death or neurologic damage in mone by urea. Am J Med 69:99–106, 1980. outpatients. Am J Med 70(6):1163–1168, 1981. 117. Decaux G, Genette F: Urea for long term treatment of syn-Google Scholar
  100. 96.
    Abramow M, Cogan E: Clinical aspects and pathophysiology drome of inappropriate secretion of antidiuretic hormone. Br of diuretic-induced hyponatremia. Adv Nephrol 13:1–28 Med J 283:1081–1083, 1981. 1984. 118. Sawyer WH, Pang PKT, Seto J, McEnroe M, Lammek BGoogle Scholar
  101. 97.
    Arieff AI: Management of hyponatraemia. Br Med J 307: Manning M: Vasopressin analogs that antagonize antidi- 305–308, 1993. uretic responses by rats to the antidiuretic hormone. ScienceGoogle Scholar
  102. 98.
    Arieff AI, Fraser CL, Rowley H, Truwit C, Kucharczyk J: 212:49–58, 1981. Metabolic encephalopathy. In: J Kucharczyk, M Moseley, AJ 119. Greig PD, Blendis M, Lanyer B, Taylor BR, Colapinto RF: Barkovich, eds, Magnetic Resonance Neuroimaging, CRC Renal and hemodynamic effects of perioneovenous shunt. II. Press, Boca Raton, FL, pp 319–349, 1994. Long term effects. Gastroenterology 80:119–125, 1981.Google Scholar
  103. 99.
    Simard M, Gumbiner B, Lee A, Lewis H, Norman D: 120. Sterns RH: Severe symptomatic hyponatremia: treatment Lithium carbonate intoxication. Arch Intern Med 149:36–46, and outcome. A study of 64 cases. Ann Intern Med 107:656- 1989. 664, 1987.Google Scholar
  104. 121.
    Arieff AI, Llach F, Massry SG, Kerian A: Neurological manifestations and morbidity of hyponatremia: correlation with brain water and electrolytes. Medicine (Baltimore) 55 (2): 121–129, 1976.CrossRefGoogle Scholar
  105. 122.
    Ayus JC, Krothapalli RK, Arieff AI: Changing concepts in the treatment of severe symptomatic hyponatremia: Rapid correction and the possible relation to central pontine myelinolysis. Am J Med 78 (6): 897–902, 1985.PubMedCrossRefGoogle Scholar
  106. 123.
    Ayus JC, Krothapalli R, Armstrong DL, Norton HJ: Symptomatic hyponatremia in rats: effect of treatment on mortality and brain lesions. Am J Physiol 257 (Renal Fluid Electrolyte Physiol 26 ): F18 - F22, 1989.Google Scholar
  107. 124.
    Hantman D, Rossier B, Zohlman R, Schrier R: Rapid correction of hypontremia in the syndrome of inappropiate secretion of antidiuretic hormone: an alternative treatment to hypertonic saline. Ann Intern Med 78: 870–875, 1973.PubMedCrossRefGoogle Scholar
  108. 125.
    Ayus JC, Krothapalli RK, Arieff AI: Treatment of symptomatic hyponatremia and its relation to brain damage. A prospective study. N Engl J Med 317: 1190–1195, 1987.PubMedCrossRefGoogle Scholar
  109. 126.
    Arieff AI: Hyponatremia associated with permanent brain damage. In: GH Stollerman, WJ Harrington, JT LaMont, JL Leonard, MD Siperstein, eds, Advances in Internal Medicine. Year Book Publishers, Chicago, pp 325–344, 1987.Google Scholar
  110. 127.
    Ayus JC, Krothapalli RK, Armstrong DL: Rapid correction of severe hyponatremia in the rat: histopathological changes in the brain. Am J Physiol (Renal Fluid Electrolyte Physiol) 248: F711 - F719, 1985.Google Scholar
  111. 128.
    Sarnaik AP, Meert K, Hackbarth R, Fleischmann L: Management of hyponatremic seizures in children with hyper-tonic saline: a safe and effective strategy. Crit Care Med 19: 758–762, 1991.PubMedCrossRefGoogle Scholar
  112. 129.
    Soupart A, Penninckx R, Stenuit A, Perier O, Decaux G: Treatment of chronic hyponatremia in rats by intravenous saline: comparison of rate verus magnitude of correction. Kidney Int 42: 1662–1667, 1992.CrossRefGoogle Scholar
  113. 130.
    Verbalis JG, Martinez AJ, Drutarosky MD: Neurological and neuropathological sequelae of correction of chronic hyponatremia. Kidney Int 39: 1274–1282, 1991.PubMedCrossRefGoogle Scholar
  114. 131.
    Ayus JC, Armstrong DL, Arieff AI: Central nervous system effects of hypernatremia and its therapy in rats and rabbits. J Physiol, (London) 492: 243–255, 1996.Google Scholar
  115. 132.
    Clark WR: Diffuse demyelinating lesions of the brain after the development of hypernatremia. West J Med 157: 571–573, 1992.PubMedGoogle Scholar
  116. 133.
    Brennan S, Ayus JC: Systemic disorders and cerebral demyelinating lesions. In: AI Arieff, RC Griggs, eds, Metabolic Brain Dysfunction in Systemic Disorders. Little, Brown, Boston, pp 247–263, 1992.Google Scholar
  117. 134.
    Cheng JC, Zikos D, Skopicki HA: Correction of symptomatic hyponatremia. Kidney Int 33: 186, 1988.Google Scholar
  118. 135.
    Decaux G, Unger J, Brimioulle S, Mockel J: Hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone. JAMA 247: 471–474, 1982.Google Scholar
  119. 136.
    Worthley L: Hyperosmolar coma treated with intravenous sterile water. Arch Intern Med 146: 945–947, 1986.PubMedCrossRefGoogle Scholar
  120. 137.
    Ghanem A: Hyponatremia and hypo-osmolality (letter). Lancet 2: 572, 1988.PubMedCrossRefGoogle Scholar
  121. 138.
    Ayus JC, Olivero JJ, Frommer JP: Rapid correction of severe hyponatremia with intravenous hypertonic saline solution. Am J Med 72: 43–48, 1982.PubMedCrossRefGoogle Scholar
  122. 139.
    Arieff AI, Guisado R, Lazarowitz VC: Pathophysiology of hyperosmolar states. In: TE Andreoli, JJ Grantham, FC Rector Jr., eds, Disturbances in Body Fluid Osmolality. American Physiological Society, Bethesda, MD, pp 227–250, 1977.Google Scholar
  123. 140.
    Arieff AI, Carroll HJ: Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of therapy in 37 cases. Medicine (Baltimore) 51 (2): 73–94, 1972.CrossRefGoogle Scholar
  124. 141.
    Cserr HF, DePasquale M, Patlak CS: Regulation of brain water and electrolytes during acute hyperosmolality in rats. Am J Physiol 253: F522 - F529, 1987.PubMedGoogle Scholar
  125. 142.
    Cserr HF, DePasquale M, Patlak CS: Volume regulatory influx of electrolytes from plasma to brain during acute hyperosmolarity. Am J Physiol 253: 530–537, 1987.Google Scholar
  126. 143.
    Cserr HF, DePasquale M, Nicholson C, Patlak CS, Pettigrew KD, Rice ME: Extracellular volume decreases while cell volume is maintained by ion uptake in rat brain during acute hypernatremia. J Physiol (Lond) 442: 277–295, 1991.Google Scholar
  127. 144.
    Pullen RGL, DePasquale M, Cserr HF: Bulk flow of cerbrospinal fluid into brain in response to acute hypersmolarity. Am J Physiol 253: 538–545, 1987.Google Scholar
  128. 145.
    Heilig CW, Stromski ME, Blumenfeld JD, Lee JP, Gullans SR: Characterization of the major brain osmolytes that accumulate in salt-loaded rats. Am J Physiol 257 (6, Pt. 2): F1108 - F1116, 1989.PubMedGoogle Scholar
  129. 146.
    Lien YH, Shapiro JI, Chan L: Effects of hypernatremia on organic brain osmoles. J Clin Invest 85 (5): 1427–1435, 1990.PubMedCrossRefGoogle Scholar
  130. 147.
    Finberg L, Luttrell C, Redd H: Pathogenesis of lesions in the nervous system in hypernatremic states: experimental studies of gross anatomic changes and alterations of chemical composition of the tissues. Pediatrics 23: 46–57, 1959.PubMedGoogle Scholar
  131. 148.
    Arieff AI: Acid-base, electrolyte, and metabolic abnormalities. In: JE Parrillo, RC Bone, eds, Critical Care Medicine: Principles of Diagnosis and Management. Mosby-Year Book, Philadelphia, in press.Google Scholar
  132. 149.
    Banister A, Siddiqi S, Hatcher GW: Treatment of hypernatremia dehydration in infancy. Arch Dis Child 50: 179, 1975.PubMedCrossRefGoogle Scholar
  133. 150.
    Bruck E, Abal G, Aceto T: Pathogenesis and pathophysiology of hypertonic dehydration with diarrhea. Am J Dis Child 115: 122–144, 1968.PubMedGoogle Scholar
  134. 151.
    Park R, Arieff AI: Lactic acidosis: current concepts. In: DS Schade, ed, Clinics in Endocrinology and Metabolism. W.B. Saunders, Philadelphia, pp 339–358, 1983.Google Scholar
  135. 152.
    Zierler KL: Hyperosmolarity in adults: a critical review. J Chronic Dis 7 (1): 1–23, 1958.PubMedCrossRefGoogle Scholar
  136. 153.
    Snyder NA, Feigal DW, Arieff AI: Hypernatremia in elderly patients. A heterogeneous, morbid, and iatrogenic entity. Ann Intern Med 107 (3): 309–319, 1987.PubMedCrossRefGoogle Scholar
  137. 154.
    Finberg L, Kiley J, Luttrell CN: Mass accidental salt poisoning in infancy: a study of a hospital disaster. JAMA 184: 187190, 1963.Google Scholar
  138. 155.
    Arneil GC, Chin KC: Lower-solute milks and reduction of hypernatraemia in young Glasgow infants. Lancet 2: 840–841, 1979.PubMedCrossRefGoogle Scholar
  139. 156.
    Arieff AI: Central nervous system manifestations of disordered sodium metabolism. In: DB Morgan, ed, Clinics in Endocrinology and Metabolism: Electrolyte Disorders. W.B. Saunders, Philadelphia, pp 269–294, 1984.Google Scholar
  140. 157.
    Park R, Guisado R, Arieff AI: Nutrient deficiencies in man and animals: water. In: M Rechcigl Jr., ed., CRC Handbook of Nutrition and Food. Section E, Nutritional Disorders. CRC Press, W. Palm Beach, FL, pp 363–400, 1978.Google Scholar
  141. 158.
    Mattar JA, Weil MH, Shubin H, Stein L: Cardiac arrest in the critically ill. II. Hyperosmolar states following cardiac arrest. Am J Med 56: 162–168, 1974.PubMedCrossRefGoogle Scholar
  142. 159.
    Cameron JM, Dayan AD: Association of brain damage with therapeutic abortion induced by amniotic-fluid replacement: report of two cases. Br Med J 1: 1010–1013, 1966.Google Scholar
  143. 160.
    Kreisberg RA: Pathogenesis and management of lactic acidosis. Annu Rev Med 35: 181–193, 1984.PubMedCrossRefGoogle Scholar
  144. 161.
    Arieff AI: Indications for use of bicarbonate in patients with 177. metabolic acidosis. Br J Anaesth 67: 165–177, 1991.PubMedCrossRefGoogle Scholar
  145. 162.
    Fraser CL, Arieff AI: Hepatic encephalopathy. N Engl J Med 313 (14): 865–873, 1985.PubMedCrossRefGoogle Scholar
  146. 163.
    Norenberg MD, Leslie KO, Robertson AS: Association be- 178. tween rise in serum sodium and central pontine myelinolysis. Ann Neurol 11: 128–135, 1982. 179.Google Scholar
  147. 164.
    Warren SE, Mitas JA, Swerdlin HR: Hypernatremia in hepatic failure. JAMA 243(12): 1257–1260, 1980. 180.Google Scholar
  148. 165.
    Arieff AI, Papadakis MA: Hyponatremia and hypernatremia in liver disease. In: M Epstein, ed, The Kidney in Liver Disease. Williams & Wilkins, Baltimore, MD, pp 73–88, 181. 1988.Google Scholar
  149. 166.
    Kaupke C, Sprague T, Gitnick GL: Hypernatremia after the administration of lactulose. Ann Intern Med 86: 745–746, 1977. 182.Google Scholar
  150. 167.
    Wilkinson SP, Blendis JM, Williams R: Frequency and type of renal and electrolyte disorders in fulminant hepatic failure. Br Med J 1: 186, 1974. 183.Google Scholar
  151. 168.
    Nelson DC, McGrew WRG, Hoyumpa AM: Hypernatremia and lactulose therapy. JAMA 249 (10): 1295–1298, 1983.Google Scholar
  152. 169.
    Lutrell CN, Finberg L: Hemorrhagic encephalopathy induced by hypernatremia I. Clinical, laboratory and patho- 184. logical observations. Arch Neurol Psychiatr 81: 424–432, 1959.CrossRefGoogle Scholar
  153. 170.
    Simmons MA, Adcock EW, Bard H, Battaglia FC: 185. Hypernatremia and intracranial hemorrhage in neonates. N Engl J Med 291: 6–10, 1974.PubMedCrossRefGoogle Scholar
  154. 171.
    Dodge PR, Sotos JF, Gomstrop I, et al.: Neurophysiologic 186. disturbances in hypertonic dehydration. Trans Am Neurol Assoc 87: 33–36, 1962.PubMedGoogle Scholar
  155. 172.
    Hill ID, Mann MD, Bowie MD: Hypernatremic dehydration: a prospective study in children with diarrhoeal disease. South 187. Afr Med J 59: 479–481, 1981.Google Scholar
  156. 173.
    Haddow JE, Cohen DE: Understanding and managing hypernatremic dehydration. Pediatr Clin N Am 21: 435–441, 188. 1974.Google Scholar
  157. 174.
    Hogan GR: Hypernatremia-problems in management. 189. Pediatr Clin N Am 23: 569–574, 1976.Google Scholar
  158. 175.
    Ross EJ, Christie SBM: Hypernatremia. Medicine (Baltimore) 48: 441–473, 1969.Google Scholar
  159. 176.
    Perkin RM, Levin DL: Common fluid and electrolyte probGoogle Scholar
  160. 177.
    lems in the pediatric intensive care unit. Pediatr Clin North Am 27: 567–586, 1980.Google Scholar
  161. Snyder NA, Arieff AI: Neurological manifestations of hypernatremia. In: RA Griggs, AI Arieff, eds, Metabolic Brain Dysfunction in Systemic Disorders. Little, Brown, Boston, pp 87–106, 1992.Google Scholar
  162. Macauley D, Watson M: Hypernatremia as a cause of brain damage. Arch Dis Child 42: 485–491, 1967.CrossRefGoogle Scholar
  163. Miller NL, Finberg L: Peritoneal dialysis for salt poisoning. N Engl J Med 263: 1347–1350, 1960.PubMedCrossRefGoogle Scholar
  164. Finberg L: Pathogenesis of lesions in the nervous system in hypernatremic states: I. Clinical observations of infants. Pediatrics 23: 40, 1959.PubMedGoogle Scholar
  165. Hogan G, Dodge PR, Gill SR, et al.: Pathogenesis of seizures occurring during restoration of plasma tonicity to normal in animal previously chronically hypernatremic. Pediatrics 43: 54, 1969.PubMedGoogle Scholar
  166. Welsh FA, Ginsberg MD, Rieder W, Budd WW: Deleterious effect of glucose pretreatment on recovery from diffuse cerebral ischemia in the cat. Stroke 11: 355–363, 1980.PubMedCrossRefGoogle Scholar
  167. Pulsinelli WA, Waldman S, Rawlinson D, Plum F: Moderate hyperglycemia augments ischemic brain damage: a neuropathologie study in the rat. Neurology 32: 1239–1246, 1982.PubMedCrossRefGoogle Scholar
  168. Longstreth WT, Inui TS: High blood glucose level on hospital admission and poor neurological recovery after cardiac arrest. Ann Neurol 15: 59–63, 1984.PubMedCrossRefGoogle Scholar
  169. Sheldon RA, Partridge JC, Ferriero DM: Postischemic hyperglycemia is not protective to the neonatal rat brain. Pediatr Res 32: 489–493, 1992.PubMedCrossRefGoogle Scholar
  170. Lundy EF, Kuhn JE, Kwoon JM, Zelenock GB, D’Alecy LG: Infusion of five percent dextrose increases mortality and morbidity following six minutes of cardiac arrest in resuscitated dogs. J Crit Care 2: 4–14, 1987.CrossRefGoogle Scholar
  171. Marsden PA, Halperin ML: Pathophysiologic approach to patients presenting with hypernatremia. Am J Nephrol 5: 229–235, 1985.PubMedCrossRefGoogle Scholar
  172. Nitzan M, Zelmanovsky S: Glucose intolerance in hypernatremic rats. Diabetes 17: 579–581, 1968.PubMedGoogle Scholar
  173. Freidenberg GR, Kosnik EJ, Sotos JF: Hyperglycemic coma after suprasellar surgery. N Engl J Med 303: 863–865, 1980.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • J. Carlos Ayus
    • 1
  • Allen I. Arieff
    • 2
  1. 1.Baylor College of MedicineHoustonUSA
  2. 2.Geriatrics Research & Education San Francisco V.A. Medical CenterUniversity of California School of MedicineSan FranciscoUSA

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