What Causes Hyponatremia?

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Patient Presentation
A 13-month-old female came to clinic with vomiting of stomach contents, diarrhea that was watery without blood or mucous that saturated her diaper, and fever to 100.5°F for 48 hours. She had been drinking reasonably well but over the past 12 hours had refused. Her last wet diaper was 8 hours ago. The past medical history was non-contributory and she had all of her vaccinations including seasonal influenza. The social history showed that she was an only child who attended daycare. The pertinent physical exam showed an ill-appearing female with an 800 gram weight loss, respiratory rate of 22, heart rate of 128 and temperature of 99.8°F. Her mucous membranes were tacky and her capillary refill was 3 seconds. Her abdominal examination showed increased bowel sounds.

The diagnosis of of gastroenteritis was made. The patient refused to drink anything in the office and had 1 emesis and 2 stools that were sent for culture and eventually showed norovirus. She was sent to the emergency room where she failed to improve and was admitted for 24 hours. Initially her laboratory evaluation showed a sodium of 131 mEq/L, chloride of 101 mEq/L and otherwise normal electrolytes and an unremarkable complete blood count that returned to normal after fluids.

The patient’s clinical course after she returned home found her to be improving with no vomiting, emesis or fever but 36 hours after discharge she began having copious rhinorrhea, increased eye tearing, coughing, lethargy and fever to 103F°. She had continued to drink and was having wet diapers every 4-6 hours and her weight was only 10 grams down from her normal weight. She however was very lethargic and would easily arouse but would instantly go to sleep again. Respiratory testing found her to have influenza A and she was admitted for observation and treatment. Laboratory testing at that time showed no bacterial pneumonia on chest radiograph but a plasma sodium of 130 mEq/L again. The patient was evaluated for recurrent hyponatremia including having normal aldosterone and thyroid testing. She was eventually diagnosed with SIADH presumably due to influenza after showing a urine sodium of 137 mEq/L, and urine osmolality of 966 mOsm/kg. She was started on fluid restriction initially and after another 48 hours of oseltamivir and fluid support, her electrolytes returned to normal and she was discharged to home. Three days later she followed up in outpatient clinic and was well. Her repeat electrolytes at that time were normal.

Discussion
Normal kidneys regulate water balance to maintain a plasma osmolality of 275-290 mOsm/kg normally. Thirst and arginine vasopressin or antidiuretic hormone (ADH) are the primary regulators of plasma osmolality. ADH is made in the hypothalamus and released by the posterior pituitary gland. ADH acts on the kidney’s distal collecting duct to increase water reabsorption. ADH is appropriately released in hypovolemic states, such as dehydration caused by gastroenteritis. ADH has an ~10 minute half-life and therefore can respond to rapid changes in volume status. Sodium balance is regulated by aldosterone (as part of the renin-angiotensin system) causing sodium to be reabsorbed from the distal kidney tubules and secreting potassium and hydrogen. Atrial naturitic peptide is released from the atrium in hypervolemic states causing the kidney to excrete sodium and excessive water. In normal states, urine sodium is < 20 mmol/L.

Hyponatremia occurs when the body has a relative excess of free water relative to sodium. Rapid shifts in water can cause cellular damage particularly in the central nervous system (CNS). Normally, water and solutes pass through the cellular membrane to maintain homeostasis, but solutes generally pass slower than free water. Therefore with hyponatremia there is a relatively low amount of sodium and higher amount of water in the plasma with the opposite true for the cell. Therefore water will try to move into the cell to balance the intracellular and extracellular osmolality. The increased intracellular water volume can cause cellular damage or death especially in the CNS where it can cause cerebral edema and seizures. Rapid shifting of solutes and water usually causes more problems than shifts that occur over longer periods of time, when the body is able to compensate.

Hyponatremia signs and symptoms may be non-specific and insidious including headache, malaise, nausea, myalgia and decreased deep tendon reflexes when concentration is < 125-130 mEq/L. Mental status changes then usually develop with agitation, confusion, disorientation, depression, lethargy, psychosis, seizures, coma or death.

Correction of hyponatremia can cause additional problems such as cerebral edema if it occurs too quickly. Therefore depending on the causes, hyponatremia severity, and signs and symptoms, slow correction over several days may be needed. Hyponatremia is often associated with hypovolemia and may require 0.9% normal saline for initial repletion. This should stop ADH from being released. Intravenous fluids are usually then changed to hypotonic fluids such as 0.45 normal saline so as not to correct the sodium too quickly. Patients who are euvolemic or hypervolemic are usually treated by fluid restriction.

SIADH or syndrome of inappropriate antidiuretic hormone is ADH being triggered in inappropriate states of euvolemia or hypervolemia. In adults, malignancy and drugs are common causes. In pediatrics, infectious diseases of the CNS and respiratory systems are common along with head injuries. The differential diagnosis of SIADH includes:

  • Central nervous system problems
    • Infectious
      • Abscess
      • Meningitis
      • Encephalitis
      • Sepsis
    • Surgery/Trauma
      • Cerebrovascular accident
      • Head trauma
      • Surgical procedures
  • Pulmonary problems
    • Bronchiolitis
    • Pneumonia
    • Empyema
    • Aspergillosis
    • Tuberculosis
    • Chronic obstructive pulmonary disease
  • Malignancy
    • Leukemia
    • Lymphoma
    • Central nervous system
    • Lung – especially small cell in adults
    • Other organs
  • Drugs
    • Antineoplastic agents
    • Antiepileptics
    • Abuse drugs – MDMA, ectasy
    • Nonsteroidal anti-inflammatory drugs
    • Oral hypoglycemic agents
    • Phenothiazine
    • Tricyclic antidepressants
    • Selective serotonin uptake inhibitors

Learning Point
The differential diagnosis of hypoosmolar hyponatremia (note all will be hypoosmolar with plasma < 275 mOsm/kg) includes:

  • Hypo- or euvolemic and urine Osm < 100 mOsm/kg
    • Psychogenic polydipsia
    • Reset osmostat
    • Beer potomania
    • Water intoxication – enema, IV therapy
  • Hypo- or euvolemic and urine Osm > 100 mOsm/kg
    • Urine sodium < 20 mmol/L
      • Gastrointestinal losses
      • Skin loss
      • Cystic fibrosis
      • Third spacing such as ascites, burns
    • Urine sodium > 20 mmol/L
      • SIADH
      • Adrenal insufficiency
      • Congenital adrenal hyperplasia
      • Hypothyroidism
      • Salt-wasting syndromes
      • Renal losses
      • Urinary tract obstruction
  • Hypervolemic
    • Cirrhosis
    • Diuretic
    • Enteropathy
    • Heart failure
    • Nephrotic syndrome
    • Renal failure

Questions for Further Discussion
1. What causes hypernatremia? The differential diagnosis can be reviewed here.
2. What are indications for admission to the hospital for hyponatremia?
3. How is plasma osmolality calculated?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Sodium, Norovirus Infections, and Flu.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Lin M, Liu SJ, Lim IT. Lim Disorders of Water Imbalance. Emerg Med Clin North Am. 2005 Aug;23(3):749-770.

Arvanitis ML, Pasqual JL. External causes of metabolic disorders. Emerg Med Clin North Am. 2005 Aug;23(3):827-41, x.

Rivkees SA. Differentiating appropriate antidiuretic hormone secretion, inappropriate antidiuretic hormone secretion and cerebral salt wasting: the common, uncommon, and misnamed. Curr Opin Pediatr. 2008 Aug;20(4):448-52.

Lavagno C, Milani GP, Uestuener P, Simonetti GD, Casaulta C, Bianchetti MG, Fare PB, Lava SAG. Hyponatremia in children with acute respiratory infections: A reappraisal. Pediatr Pulmonol. 2017 Jul;52(7):962-967.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Published