Hypernatremia Clinical Presentation

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^{[10, 13]}

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

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.

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)

In a prospective, case-control, multicenter study, Chassagne and colleagues looked at the symptoms associated with hypernatremia in 150 geriatric patients.^[14] 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).

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.^{[15, 16]}

Hypernatremia often is the result of several concurrent factors. The most prominent is poor fluid intake. 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:

• 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

  • Diuretic drugs (loop and thiazide diuretics)
  • Osmotic diuresis (hyperglycemia, mannitol, urea [tube feeding])
  • Renal salt wasting
  • Postobstructive diuresis
  • Diuretic phase of acute tubular necrosis
• Nonrenal hypotonic fluid loss

  • Gastrointestinal - 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

  • Lack of access to water (through incarceration, restraints, intubation, immobilization)
  • Altered mental status (through medications, disease)
  • Neurologic disease (dementia, impaired motor function)
  • Abnormal thirst
    • Geriatric hypodipsia
    • “Essential” hypernatremia with 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.
  • Loss of pure water through the respiratory tract

Vasopressin (AVP) deficiency (diabetes insipidus)

Central diabetes insipidus^[17] 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
• 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-AVP gene defect

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

• Genetic - V2-receptor defects, aquaporin defects (AQP2 and AQP1)
• Structural - Urinary tract obstruction, papillary necrosis, sickle-cell nephropathy
• Tubulointerstitial disease - Medullary cystic disease, polycystic kidney disease, nephrocalcinosis, Sj ö gren’s syndrome, lupus, analgesic-abuse nephropathy, sarcoidosis, M-protein disease
• 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
• Medications that induce nephrogenic diabetes insipidus

  • Lithium
  • Amphotericin B
  • Demeclocycline
  • Dopamine
  • Ofloxacin
  • Orlistat
  • Ifosfamide
• Medications that possibly cause nephrogenic diabetes insipidus

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

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.

• Administration of hypertonic electrolyte solutions - Eg, sodium bicarbonate solutions, hypertonic alimentation solutions
• Sodium ingestion - NaCl tablets, seawater ingestion
• Sodium modeling in hemodialysis