eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders

Hypernatremia: Differential Diagnoses & Workup

Author: Ivo Lukitsch, MD, Faculty, Department of Internal Medicine, Section of Nephrology, Tulane University School of Medicine
Coauthor(s): Trung Q Pham, MD, Consulting Staff, Department of Internal Medicine, Kayenta Health Center
Contributor Information and Disclosures

Updated: Apr 27, 2009

Differential Diagnoses

Cirrhosis
Diabetes Mellitus, Type 1
Hypocalcemia
Hyponatremia

Other Problems to Be Considered

Other problems to consider include all other etiologies for metabolic or drug-induced encephalopathy (eg, cirrhosis, hyponatremia).

Metabolic encephalopathy accompanied by a history of poor oral intake, nursing home residency, the use of certain medications, the presence of appropriate comorbid conditions, increased volume, or insensible loss and obtundation should raise the suspicion of an elevated serum sodium concentration as a possible etiology for mental status changes.

Workup

Laboratory Studies

Diagnosis of hypernatremia is based on an elevated serum sodium concentration (Na+ >145 mEq/L). It is necessary to obtain the following lab studies:

  • Serum electrolytes (Na+, K+, Ca2 +)
  • Glucose level
  • Urea
  • Creatinine
  • Urine electrolytes (Na+, K+)
  • Urine and plasma osmolality
  • 24-hour urine volume
  • Plasma AVP level (if indicated)

The first step in the diagnostic approach is to estimate the volume status (intravascular volume) of the hypernatremic patient. The associated volume contraction may be mirrored in a low urine Na+ (usually <10 mEq/L).

In the hypovolemic patient, a hypertonic urine with a UNa+ <10 mEq/L will point towards extrarenal fluid losses (GI, dermal), whereas an isotonic or hypotonic urine with a UNa+ >20 mEq/L indicates renal fluid loss (diuretics, osmotic diuresis, intrinsic renal disease).

In the euvolemic patient with preserved intravascular volume, hypernatremia is most likely due to pure-water losses. In the presence of hypernatremia, urine osmolality normally should be maximally concentrated (>800 mOsm/kg H2 O). Measurement of the urine osmolality will allow differentiation of the following:

  • Nonrenal causes with appropriately high urine osmolality - Isolated hypodipsia, increased insensible losses
  • Renal water loss indicated by inappropriately low urine osmolality - Diabetes insipidus (often Uosm <300 mOsm/kg H2 O [central, nephrogenic, partial, gestational diabetes insipidus])

Caveat: Unfortunately, concentrating ability tends to fall with age; the maximum Uosm in an elderly patient may be only 500-700 mOsm/kg.

To distinguish between central and nephrogenic diabetes insipidus, first obtain a plasma AVP level and then determine the response of the urine osmolality to a dose of AVP (or preferably, the V2-receptor agonist DDAVP). Generally, an increase in urine osmolality of greater than 50% reliably indicates central diabetes insipidus, while an increase of less than 10% indicates nephrogenic diabetes insipidus; responses between 10% and 50% are indeterminate. Hyperosmolar patients with an elevated AVP level have nephrogenic diabetes insipidus; those with central diabetes insipidus will have inadequately low AVP level.

If the patient has polyuria without hypernatremia and will be evaluated for diabetes insipidus, the plasma sodium has to be above 145 mOsm/kg H 2 O prior to testing (via water deprivation test, hypertonic saline).

It is also clinically very useful to calculate the free-water clearance (cH 2 O), and it is even more important to calculate the electrolyte – free-water clearance (cH 2 Oe), to estimate the ongoing renal losses of hypotonic fluid (cH 2 O = Vurine [1-(UOsm/SOsm) ]; cH 2 Oe = Vurine [1-(UNa +UK)/SNa])

An example of the use of above calculations is a follows: An 80-year-old, partially demented man with poor nutritional status is admitted to the hospital because of pneumonia. Hyperalimentation with high protein supplementation is started (containing 30 mEq/L each of Na+ and K+). Following 5 days:

  • Urine output: 4 L/day
  • BUN: 20-88 mg/dL
  • Cr: Stable at 1.4 mg/dL
  • [Na+]: From 140 mEq/L up to 156 mEq/L (despite a relatively high fluid intake)
  • Posm: 342 mOsm/kg
  • Uosm: 510 mOsm/kg
  • UNa+: 10 mEq/L
  • UK+: 42 mEq/L 

The free-water clearance is calculated as follows:

cH2O = 4 x ( 1 - [510 ÷ 342] ) =  -2 L/day

By this calculation, taking all osmoles into account, the patient retains 2 liters of water, improving hypernatremia; however, he is actually getting worse.

The electrolyte free-water clearance is calculated as follows:

eCH 2 O =  4 (1 - [(10 + 41) ÷ 156] ) = 2.7 L/day

The etiology of the hypernatremia is now apparent; the patient is losing approximately 2.7 L of free water per day in his urine, likely secondary to osmotic diuresis from hyperalimentation.

Imaging Studies

  • A magnetic resonance imaging (MRI) or computed tomography (CT) scan of the brain may be helpful in cases of central diabetes insipidus eventuating from head trauma or infiltrative lesions.

Histologic Findings

Histologic findings usually are noncontributory (although they may be helpful in central diabetes insipidus).

More on Hypernatremia

Overview: Hypernatremia
Differential Diagnoses & Workup: Hypernatremia
Treatment & Medication: Hypernatremia
Follow-up: Hypernatremia
Multimedia: Hypernatremia
References
Further Reading

References

  1. Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med. May 18 2000;342(20):1493-9. [Medline].

  2. Verbalis JG, Berl T. Disorders of water balance. In: Brenner BM, ed. Brenner and Rector's The Kidney. 8th ed. Philadelphia, Pa: Saunders Elsevier; 2008:Chapter 13.

  3. Chumlea WC, Guo SS, Zeller CM, et al. Total body water data for white adults 18 to 64 years of age: the Fels Longitudinal Study. Kidney Int. Jul 1999;56(1):244-52. [Medline].

  4. Sterns HR. Renal function and disorders of water and sodium balance. In: ACP Medicine: A Publication of the American College of Physicians. New York, NY: WebMD; 2005:10.1-10.19.

  5. Boone M, Deen PM. Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption. Pflugers Arch. Sep 2008;456(6):1005-24. [Medline][Full Text].

  6. Loh JA, Verbalis JG. Disorders of water and salt metabolism associated with pituitary disease. Endocrinol Metab Clin North Am. Mar 2008;37(1):213-34, x. [Medline].

  7. Kumar S, Berl T. Sodium. Lancet. Jul 18 1998;352(9123):220-8. [Medline].

  8. Lindner G, Funk GC, Schwarz C, et al. Hypernatremia in the critically ill is an independent risk factor for mortality. Am J Kidney Dis. Dec 2007;50(6):952-7. [Medline].

  9. Stelfox HT, Ahmed SB, Khandwala F, et al. The epidemiology of intensive care unit acquired hyponatremia and hypernatremia in medical-surgical intensive care units. Crit Care. Dec 18 2008;12(6):R162. [Medline][Full Text].

  10. Hawkins RC. Age and gender as risk factors for hyponatremia and hypernatremia. Clin Chim Acta. Nov 2003;337(1-2):169-72. [Medline].

  11. Chassagne P, Druesne L, Capet C, et al. Clinical presentation of hypernatremia in elderly patients: a case control study. J Am Geriatr Soc. Aug 2006;54(8):1225-30. [Medline].

  12. Palevsky PM. Hypernatremia. Semin Nephrol. Jan 1998;18(1):20-30. [Medline].

  13. Lin JJ, Lin KL, Hsia SH, et al. Combined central diabetes insipidus and cerebral salt wasting syndrome in children. Pediatr Neurol. Feb 2009;40(2):84-7. [Medline].

  14. Fried LF, Palevsky PM. Hyponatremia and hypernatremia. Med Clin North Am. May 1997;81(3):585-609. [Medline].

  15. Lindner G, Schwarz C, Kneidinger N, et al. Can we really predict the change in serum sodium levels? An analysis of currently proposed formulae in hypernatraemic patients. Nephrol Dial Transplant. Nov 2008;23(11):3501-8. [Medline].

Keywords

hypernatremia, sodium, potassium, dehydration, electrolyte, electrolytes, sodium potassium, diabetes, diabetes insipidus, diabetes mellitus, vasopressin, high sodium, electrolyte imbalance, antidiuretic, antidiuretic hormone, sodium level, blood sodium, hyperosmolar, serum sodium, sodium concentration, sodium in blood, symptoms sodium, blood salt, high blood sodium, hypertonic, hypotonic, hyperosmolality, inadequate fluid intake, water loss, poor water intake

Contributor Information and Disclosures

Author

Ivo Lukitsch, MD, Faculty, Department of Internal Medicine, Section of Nephrology, Tulane University School of Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Trung Q Pham, MD, Consulting Staff, Department of Internal Medicine, Kayenta Health Center
Disclosure: Nothing to disclose.

Medical Editor

Anil Kumar Mandal, MD, Clinical Professor, Department of Internal Medicine, Division of Nephrology, University of Florida School of Medicine
Anil Kumar Mandal, MD is a member of the following medical societies: American College of Clinical Pharmacology, American College of Physicians, American Society of Nephrology, and Central Society for Clinical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

 
 
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