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Manifestations of hyponatremia and hypernatremia in adults

Author
Richard H Sterns, MD
Section Editor
Michael Emmett, MD
Deputy Editor
John P Forman, MD, MSc

INTRODUCTION

Symptoms of hyponatremia or hypernatremia are primarily neurologic. They are related to the severity and, in particular, the rapidity of the change in the serum sodium concentration [1-3]. Patients with hyponatremia and hypernatremia may also have complaints related to concurrent volume depletion and possible underlying neurologic diseases that predispose to the electrolyte abnormality. These include a wide variety of neurologic disorders that can lead sequentially to either the inappropriate secretion of antidiuretic hormone, water retention, and hyponatremia, or to the lack of expression of thirst, which is normally the major protective mechanism against the development of hypernatremia.

The cerebral adaptation and clinical manifestations of hyponatremia and hypernatremia will be reviewed here. The etiology and treatment of hyponatremia and hypernatremia are presented elsewhere. (See "Causes of hyponatremia in adults" and "Overview of the treatment of hyponatremia in adults" and "Etiology and evaluation of hypernatremia in adults" and "Treatment of hypernatremia".)

HYPONATREMIA

The symptoms directly attributable to hyponatremia primarily occur with acute and marked reductions in the serum sodium concentration and reflect neurologic dysfunction induced by cerebral edema [1,2,4,5], and possibly adaptive responses of brain cells to osmotic swelling [1]. In this setting, the associated fall in serum osmolality creates an osmolal gradient that favors water movement into the cells, leading to brain edema.

The development of cerebral edema in hyponatremic patients is dependent upon the transfer of water from plasma and cerebrospinal fluid into the brain. Insight into this process is provided by studies in mice without the genes for aquaporin-4, a water channel expressed at the interface between the brain and blood and between the brain and cerebrospinal fluid [6]. Compared with wild-type mice, knockout mice exhibit considerably less brain edema, morbidity, and mortality after the induction of acute hyponatremia, suggesting that aquaporin-4 mediates a substantial portion of osmotic water transport into the brain.

Hyponatremia-induced cerebral edema occurs primarily with rapid reductions in the serum sodium concentration, usually less than 24 hours [5], as most often occurs in postoperative patients given large quantities of hypotonic fluid and in patients with self-induced water intoxication due to primary polydipsia or exercise-associated hyponatremia. Hypoxic brain injury also may contribute to the neurologic deficit if respiratory arrest has occurred [7]. (See "Exercise-associated hyponatremia".)

              

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References
Top
  1. Sterns RH. Disorders of plasma sodium--causes, consequences, and correction. N Engl J Med 2015; 372:55.
  2. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.716, 761.
  3. Yeates KE, Singer M, Morton AR. Salt and water: a simple approach to hyponatremia. CMAJ 2004; 170:365.
  4. McManus ML, Churchwell KB, Strange K. Regulation of cell volume in health and disease. N Engl J Med 1995; 333:1260.
  5. Strange K. Regulation of solute and water balance and cell volume in the central nervous system. J Am Soc Nephrol 1992; 3:12.
  6. Manley GT, Fujimura M, Ma T, et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 2000; 6:159.
  7. Ayus JC, Wheeler JM, Arieff AI. Postoperative hyponatremic encephalopathy in menstruant women. Ann Intern Med 1992; 117:891.
  8. Ashraf N, Locksley R, Arieff AI. Thiazide-induced hyponatremia associated with death or neurologic damage in outpatients. Am J Med 1981; 70:1163.
  9. Ellis SJ. Severe hyponatraemia: complications and treatment. QJM 1995; 88:905.
  10. Moritz ML, Ayus JC. The pathophysiology and treatment of hyponatraemic encephalopathy: an update. Nephrol Dial Transplant 2003; 18:2486.
  11. Ayus JC, Varon J, Arieff AI. Hyponatremia, cerebral edema, and noncardiogenic pulmonary edema in marathon runners. Ann Intern Med 2000; 132:711.
  12. Laureno R, Karp BI. Myelinolysis after correction of hyponatremia. Ann Intern Med 1997; 126:57.
  13. Sterns RH, Thomas DJ, Herndon RM. Brain dehydration and neurologic deterioration after rapid correction of hyponatremia. Kidney Int 1989; 35:69.
  14. 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.
  15. Strange K, Jackson PS. Swelling-activated organic osmolyte efflux: a new role for anion channels. Kidney Int 1995; 48:994.
  16. Lien YH, Shapiro JI, Chan L. Study of brain electrolytes and organic osmolytes during correction of chronic hyponatremia. Implications for the pathogenesis of central pontine myelinolysis. J Clin Invest 1991; 88:303.
  17. Verbalis JG, Gullans SR. Hyponatremia causes large sustained reductions in brain content of multiple organic osmolytes in rats. Brain Res 1991; 567:274.
  18. Videen JS, Michaelis T, Pinto P, Ross BD. Human cerebral osmolytes during chronic hyponatremia. A proton magnetic resonance spectroscopy study. J Clin Invest 1995; 95:788.
  19. Sterns RH, Cappuccio JD, Silver SM, Cohen EP. Neurologic sequelae after treatment of severe hyponatremia: a multicenter perspective. J Am Soc Nephrol 1994; 4:1522.
  20. Chow KM, Kwan BC, Szeto CC. Clinical studies of thiazide-induced hyponatremia. J Natl Med Assoc 2004; 96:1305.
  21. Schrier RW, Gross P, Gheorghiade M, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 2006; 355:2099.
  22. Renneboog B, Musch W, Vandemergel X, et al. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 2006; 119:71.e1.
  23. Gankam Kengne F, Andres C, Sattar L, et al. Mild hyponatremia and risk of fracture in the ambulatory elderly. QJM 2008; 101:583.
  24. Verbalis JG, Barsony J, Sugimura Y, et al. Hyponatremia-induced osteoporosis. J Bone Miner Res 2010; 25:554.
  25. Waikar SS, Mount DB, Curhan GC. Mortality after hospitalization with mild, moderate, and severe hyponatremia. Am J Med 2009; 122:857.
  26. Wald R, Jaber BL, Price LL, et al. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med 2010; 170:294.
  27. Doshi SM, Shah P, Lei X, et al. Hyponatremia in hospitalized cancer patients and its impact on clinical outcomes. Am J Kidney Dis 2012; 59:222.
  28. Leung AA, McAlister FA, Rogers SO Jr, et al. Preoperative hyponatremia and perioperative complications. Arch Intern Med 2012; 172:1474.
  29. Gankam-Kengne F, Ayers C, Khera A, et al. Mild hyponatremia is associated with an increased risk of death in an ambulatory setting. Kidney Int 2013; 83:700.
  30. Holland-Bill L, Christiansen CF, Heide-Jørgensen U, et al. Hyponatremia and mortality risk: a Danish cohort study of 279 508 acutely hospitalized patients. Eur J Endocrinol 2015; 173:71.
  31. Corona G, Giuliani C, Verbalis JG, et al. Hyponatremia improvement is associated with a reduced risk of mortality: evidence from a meta-analysis. PLoS One 2015; 10:e0124105.
  32. Arieff AI. Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women. N Engl J Med 1986; 314:1529.
  33. Fraser CL, Kucharczyk J, Arieff AI, et al. Sex differences result in increased morbidity from hyponatremia in female rats. Am J Physiol 1989; 256:R880.
  34. Arieff AI, Ayus JC, Fraser CL. Hyponatraemia and death or permanent brain damage in healthy children. BMJ 1992; 304:1218.
  35. Adrogué HJ, Madias NE. Hypernatremia. N Engl J Med 2000; 342:1493.
  36. Furukawa S, Takaya A, Nakagawa T, et al. Fatal hypernatremia due to drinking a large quantity of shoyu (Japanese soy sauce). J Forensic Leg Med 2011; 18:91.
  37. Soupart A, Penninckx R, Namias B, et al. Brain myelinolysis following hypernatremia in rats. J Neuropathol Exp Neurol 1996; 55:106.
  38. Brown WD, Caruso JM. Extrapontine myelinolysis with involvement of the hippocampus in three children with severe hypernatremia. J Child Neurol 1999; 14:428.
  39. Chang L, Harrington DW, Milkotic A, et al. Unusual occurrence of extrapontine myelinolysis associated with acute severe hypernatraemia caused by central diabetes insipidus. Clin Endocrinol (Oxf) 2005; 63:233.
  40. Odier C, Nguyen DK, Panisset M. Central pontine and extrapontine myelinolysis: from epileptic and other manifestations to cognitive prognosis. J Neurol 2010; 257:1176.
  41. van der Helm-van Mil AH, van Vugt JP, Lammers GJ, Harinck HI. Hypernatremia from a hunger strike as a cause of osmotic myelinolysis. Neurology 2005; 64:574.
  42. Ismail FY, Szóllics A, Szólics M, et al. Clinical semiology and neuroradiologic correlates of acute hypernatremic osmotic challenge in adults: a literature review. AJNR Am J Neuroradiol 2013; 34:2225.
  43. Moder KG, Hurley DL. Fatal hypernatremia from exogenous salt intake: report of a case and review of the literature. Mayo Clin Proc 1990; 65:1587.
  44. Pullen RG, DePasquale M, Cserr HF. Bulk flow of cerebrospinal fluid into brain in response to acute hyperosmolality. Am J Physiol 1987; 253:F538.
  45. Heilig CW, Stromski ME, Blumenfeld JD, et al. Characterization of the major brain osmolytes that accumulate in salt-loaded rats. Am J Physiol 1989; 257:F1108.
  46. Lien YH, Shapiro JI, Chan L. Effects of hypernatremia on organic brain osmoles. J Clin Invest 1990; 85:1427.
  47. Paredes A, McManus M, Kwon HM, Strange K. Osmoregulation of Na(+)-inositol cotransporter activity and mRNA levels in brain glial cells. Am J Physiol 1992; 263:C1282.
  48. De Petris L, Luchetti A, Emma F. Cell volume regulation and transport mechanisms across the blood-brain barrier: implications for the management of hypernatraemic states. Eur J Pediatr 2001; 160:71.
  49. Lee JH, Arcinue E, Ross BD. Brief report: organic osmolytes in the brain of an infant with hypernatremia. N Engl J Med 1994; 331:439.
  50. Leung AA, McAlister FA, Finlayson SR, Bates DW. Preoperative hypernatremia predicts increased perioperative morbidity and mortality. Am J Med 2013; 126:877.
  51. Hogan GR, Dodge PR, Gill SR, et al. Pathogenesis of seizures occurring during restoration of plasma tonicity to normal in animals previously chronically hypernatremic. Pediatrics 1969; 43:54.
  52. Strange K, Morrison R, Shrode L, Putnam R. Mechanism and regulation of swelling-activated inositol efflux in brain glial cells. Am J Physiol 1993; 265:C244.
  53. Fang C, Mao J, Dai Y, et al. Fluid management of hypernatraemic dehydration to prevent cerebral oedema: a retrospective case control study of 97 children in China. J Paediatr Child Health 2010; 46:301.
  54. Bolat F, Oflaz MB, Güven AS, et al. What is the safe approach for neonatal hypernatremic dehydration? A retrospective study from a neonatal intensive care unit. Pediatr Emerg Care 2013; 29:808.
  55. Bataille S, Baralla C, Torro D, et al. Undercorrection of hypernatremia is frequent and associated with mortality. BMC Nephrol 2014; 15:37.
  56. Alshayeb HM, Showkat A, Babar F, et al. Severe hypernatremia correction rate and mortality in hospitalized patients. Am J Med Sci 2011; 341:356.
  57. Galcheva-Gargova Z, Dérijard B, Wu IH, Davis RJ. An osmosensing signal transduction pathway in mammalian cells. Science 1994; 265:806.