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Hypernatremia Clinical Presentation

  • Author: Ivo Lukitsch, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Jul 14, 2016
 

History

Patients developing hypernatremia outside of the hospital setting are generally elderly and debilitated, and often present with an intercurrent acute (febrile) illness. Hospital-acquired hypernatremia affects patients of all ages.

The history should be used to discover why the patient was unable to prevent hypernatremia with adequate oral fluid intake; eg, it should be determined whether the patient is suffering from an altered mental status or whether there are any factors causing increased fluid excretion (eg, the use of diuretic therapy, the existence of diabetes mellitus, or the occurrence of fever, diarrhea, and vomiting). The history should also cover the symptoms and causes of possible diabetes insipidus (eg, the presence of preexisting polydipsia or polyuria, a history of cerebral pathology, or medication use [lithium]).

It is important to find out if the hypernatremia developed acutely or over time, because this will guide treatment decisions.

Risk factors for hypernatremia include the following:

  • Advanced age
  • Mental or physical impairment
  • Uncontrolled diabetes (solute diuresis)
  • Underlying polyuria disorders
  • Diuretic therapy
  • Residency in nursing home, inadequate nursing care
  • Hospitalization [11, 21]

Hospitalized patients may develop hypernatremia because of any of the following:

  • Decreased baseline levels of consciousness
  • Tube feeding
  • Hypertonic infusions
  • Osmotic diuresis
  • Lactulose
  • Mechanical ventilation
  • Medication (eg, diuretics, sedatives)
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Physical

The examination should include an accurate assessment of volume status and cognitive function. Symptoms can be related to volume deficit and/or hypertonicity and shrinkage of brain cells, which can tear cerebral blood vessels in severe cases, leading to cerebral hemorrhage.

The worsening symptoms associated with hypernatremia may go unnoticed in elderly patients who have a preexisting impairment of their mental status and decreased access to water.

Table 1. Characteristics and symptoms of hypernatremia (Open Table in a new window)

Characteristics of hypernatremia Symptoms related to the characteristics of hypernatremia
Cognitive dysfunction and symptoms associated with neuronal cell shrinkage Lethargy, obtundation, confusion, abnormal speech, irritability, seizures, nystagmus, myoclonic jerks
Dehydration or clinical signs of volume depletion Orthostatic blood pressure changes, tachycardia, oliguria, dry oral mucosa, abnormal skin turgor, dry axillae,
Other clinical findings Weight loss, generalized weakness

In a prospective, case-control, multicenter study, Chassagne and colleagues looked at the symptoms associated with hypernatremia in 150 geriatric patients.[22] The likelihood that patients with hypernatremia would have low blood pressure, tachycardia, dry oral mucosa, abnormal skin turgor, and a recent change in consciousness was significantly greater than that of the controls. The only clinical findings to occur in at least 60% of patients with hypernatremia were orthostatic blood pressure and abnormal subclavicular and forearm skin turgor (poor specificity and sensitivity for all physical findings).

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Causes

Several risk factors exist for hypernatremia. The greatest risk factor is age older than 65 years. In addition, mental or physical disability may result in impaired thirst sensation, an impaired ability to express thirst, and/or decreased access to water.[23, 24]

Hypernatremia often is the result of several concurrent factors. The most prominent is poor fluid intake. Again, developing hypernatremia is virtually impossible if the thirst response is intact and water is available. Normally, an increase in osmolality of just 1-2% stimulates thirst, as do hypovolemia and hypotension. For clinical purposes, hypernatremia can, in a simplified view, be classified on the basis of the concurrent water loss or electrolyte gain and on corresponding changes in extracellular fluid volume, as follows:

  • Hypotonic fluid deficits (loss of water and electrolytes)
  • Nearly pure-water deficits
  • Hypertonic sodium gain (gain of electrolytes in excess of water).

Loss of hypotonic fluid (loss of water in excess of electrolytes)

Patients who lose hypotonic fluid have a deficit in free water and electrolytes (low total body sodium and potassium) and have decreased extracellular volume. In these patients, hypovolemia may be more life threatening than hypertonicity. When physical evidence of hypovolemia is present, fluid resuscitation with normal saline is the first step in therapy.

Renal hypotonic fluid loss results from anything that will interfere with the ability of the kidney to concentrate the urine or osmotic diuresis, such as the following:

  • Diuretic drugs (loop and thiazide diuretics)
  • Osmotic diuresis (hyperglycemia, mannitol, urea [high-protein tube feeding])
  • Postobstructive diuresis
  • Diuretic phase of acute tubular necrosis

Nonrenal hypotonic fluid loss can result from any of the following:

  • GI - Vomiting, diarrhea, lactulose, cathartics, nasogastric suction, gastrointestinal fluid drains, and fistulas
  • Cutaneous - Sweating (extreme sports, marathon runs), burn injuries

Pure-water deficits

Patients with pure-water deficits in the majority of cases have a normal extracellular volume with normal total body sodium and potassium. This condition most commonly develops when impaired intake is combined with increased insensible (eg, respiratory) or renal water losses.

Free-water loss will also result from an inability of the kidney to concentrate the urine. The cause of that can be either from failure of the hypothalamic-pituitary axis to synthesize or release adequate amounts of AVP (central diabetes insipidus) or a lack of responsiveness of the kidney to AVP (nephrogenic diabetes insipidus). Patients with diabetes insipidus and intact thirst mechanisms most often present with normal plasma osmolality and serum NA+, but with symptoms of polyuria and polydipsia.

Water intake less than insensible losses may result from any of the following:

  • Lack of access to water (through incarceration, restraints, intubation, immobilization)
  • Altered mental status (through medications, disease)
  • Neurologic disease (dementia, impaired motor function)
  • Abnormal thirst (eg, geriatric hypodipsia; osmoreceptor dysfunction (reset of the osmotic threshold); injury to the thirst centers by any lesions to the hypothalamus, including from metastasis, granulomatous diseases, vascular abnormalities, and trauma; autoantibodies to the sodium-level sensor (Na x) in the brain [25]
  • Loss of water through the respiratory tract

Vasopressin (AVP) deficiency (diabetes insipidus)

Central diabetes insipidus[26] can be caused by any pathologic process that destroys the anatomic structures of the hypothalamic-pituitary axis involved in AVP production and secretion. Such processes include the following:

  • Pituitary injury - Posttraumatic, neurosurgical, hemorrhage, ischemia (Sheehan’s), idiopathic-autoimmune, lymphocytic hypophysitis, IgG4-related disease
  • Tumors - Craniopharyngioma, pinealoma, meningioma, germinoma, lymphoma, metastatic disease, cysts
  • Aneurysms - Particularly anterior communicating
  • Inflammatory states and granulomatous disease - Acute meningitis/encephalitis, Langerhans cell histiocytosis, neurosarcoidosis, tuberculosis
  • Drugs - Ethanol (transient), phenytoin
  • Genetic - Neurophysin II (AVP carrier protein) gene defect

Nephrogenic diabetes insipidus (decreased responsiveness of the kidney to vasopressin)

Causes include the following:

  • Genetic - V2-receptor defects, aquaporin defects (AQP2 and AQP1); 90% by AVPR2 mutations (X-liked recessive), AQP2 gene mutation
  • Structural - Urinary tract obstruction, papillary necrosis, sickle-cell nephropathy
  • Tubulointerstitial disease - Medullary cystic disease, polycystic kidney disease, nephrocalcinosis, Sjögren’s syndrome, lupus, analgesic-abuse nephropathy, sarcoidosis, M-protein disease, cystinosis, nephronophthisis
  • Others - Distal renal tubular acidosis, Bartter syndrome, apparent mineralocorticoid excess [27]
  • Electrolyte disorders -Hypercalcemia, hypokalemia
  • Any prolonged state of severe polyuria - By washing out the renal medullary- intramedullary concentration gradient needed for urinary concentration, and by down-regulating kidney AQP2 water channels (partial diabetes insipidus)
  • Medications

Medications that induce nephrogenic diabetes insipidus include the following:

  • Lithium (40% of patients)
  • Amphotericin B
  • Demeclocycline
  • Dopamine
  • Ofloxacin
  • Orlistat
  • Ifosfamide

Medications that possibly cause nephrogenic diabetes insipidus include the following:

  • Contrast agents
  • Cyclophosphamide
  • Cidofovir
  • Ethanol
  • Foscarnet
  • Indinavir
  • Libenzapril
  • Mesalazine
  • Methoxyflurane
  • Pimozide
  • Rifampin
  • Streptozocin
  • Tenofir
  • Triamterene hydrochloride
  • Cholchicine

Adipsic diabetes insipidus (central diabetes insipidus with deficient thirst)

This is caused by a combination of damage to the osmoreceptors regulating thirst sensation and central diabetes insipidus (see above).[28] Etiologies include the following:

  • Congenital conditions (septo-optic dysplasia, germinoma)
  • Vascular (anterior communicating artery aneurysm clipping/rupture)
  • Others - Craniopharyngioma, pinealoma, Langerhans cell histiocytosis, neurosarcoidosis, head trauma, cytomegalovirus encephalitis

Gestational diabetes insipidus

In this form of diabetes insipidus, AVP is rapidly degraded by a high circulating level of oxytocinase/vasopressinase. It is a rare condition, because increased AVP secretion will compensate for the increased rate of degradation. Gestational diabetes insipidus occurs only in combination with impaired AVP production.

Hypertonic sodium gain

Patients with hypertonic sodium gain have a high total-body sodium and an extracellular volume overload (rare, mostly iatrogenic). When thirst and renal function are intact, this condition is transient. Causes include the following:

  • Administration of hypertonic electrolyte solutions - Eg, sodium bicarbonate solutions, hypertonic alimentation solutions, normal saline with or without potassium supplements
  • Sodium ingestion - NaCl tablets, seawater ingestion
  • Sodium modeling in hemodialysis

Water shift (transient)

Water shifts into muscle cells during extreme exercise or seizures because of increased intracellular osmoles). In clinical practice, a combination of the two may be present. For example, an intubated patient in the ICU develops hypernatremia due to hypertonic sodium gain caused by normal saline volume resuscitation and, in addition, increased free water excretion due to recovering renal failure and/or osmotic urea-diuresis caused by high-protein tube feeding.

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Contributor Information and Disclosures
Author

Ivo Lukitsch, MD Consulting Staff/Faculty, Department of Nephrology, Ochsner Medical Center

Ivo Lukitsch, MD is a member of the following medical societies: American Society of Nephrology, American Society of Transplantation

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, International Society of Nephrology, American Society for Biochemistry and Molecular Biology, American Federation for Medical Research, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, Kentucky Medical Association, National Kidney Foundation, Phi Beta Kappa

Disclosure: Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, 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, International Society of Nephrology

Disclosure: Nothing to disclose.

Additional Contributors

Anil Kumar Mandal, MD Clinical Professor, Department of Internal Medicine, Division of Nephrology, University of Florida College 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, Central Society for Clinical and Translational Research

Disclosure: Nothing to disclose.

Acknowledgements

Trung Q Pham, MD Consulting Staff, Department of Internal Medicine, Kayenta Health Center

Disclosure: Nothing to disclose.

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Figure A: Normal cell. Figure B: Cell initially responds to extracellular hypertonicity through passive osmosis of water extracellularly, resulting in cell shrinkage. Figure C: Cell actively responds to extracellular hypertonicity and cell shrinkage in order to limit water loss through transport of organic osmolytes across the cell membrane, as well as through intracellular production of these osmolytes. Figure D: Rapid correction of extracellular hypertonicity results in passive movement of water molecules into the relatively hypertonic intracellular space, causing cellular swelling, damage, and ultimately death.
Table 1. Characteristics and symptoms of hypernatremia
Characteristics of hypernatremia Symptoms related to the characteristics of hypernatremia
Cognitive dysfunction and symptoms associated with neuronal cell shrinkage Lethargy, obtundation, confusion, abnormal speech, irritability, seizures, nystagmus, myoclonic jerks
Dehydration or clinical signs of volume depletion Orthostatic blood pressure changes, tachycardia, oliguria, dry oral mucosa, abnormal skin turgor, dry axillae,
Other clinical findings Weight loss, generalized weakness
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