Article Author:
Helbert Rondon
Article Editor:
William Gossman
10/27/2018 12:31:39 PM
PubMed Link:


Hyponatremia is defined as a serum sodium concentration of less than 135 mEq/L. Hyponatremia is not a sodium disorder; hyponatremia is a water disorder. Edelman discovered that serum sodium concentration does not depend on total body sodium but on the ratio of total body solutes (e.g., total body sodium and total body potassium) to total body water. Hyponatremia represents an imbalance in this ratio where total body water is more than total body solutes.


Most hyponatremia is either hypertonic, normotonic, or hypotonic in origin.

Physiologic stimuli that cause vasopressin release combined with fluid intake can result in hyponatremia. Additionally, reduced thyroid function or adrenal insufficiency may contribute to an increased release of vasopressin. Physiologic stimuli for vasopressin release include loss of intravascular volume (hypovolemic hyponatremia) and the loss of effective intravascular volume (hypervolemic hyponatremia).

Causes of Hypovolemic Hyponatremia

  • Gastrointestinal fluid loss (diarrhea or vomiting)
  • Third spacing of fluids (pancreatitis, hypoalbuminemia)
  • Salt-wasting nephropathy
  • Cerebral salt-wasting syndrome (urinary salt wasting, possibly caused by increased brain natriuretic peptide)
  • Mineralocorticoid deficiency

Causes of Hypervolemic Hyponatremia

  • Acute/chronic kidney injury/disease (low sodium levels in advanced kidney disease or dialysis patients may be due to relatively higher water versus salt intake with poor excretion due to the underlying kidney disease)
  • Congestive heart failure
  • Cirrhosis
  • Nephrotic syndrome
  • Iatrogenic

Causes of Euvolemic Hyponatremia

Nonosmotic, pathologic vasopressin release may occur in the setting of normal volume status, as with euvolemic hyponatremia.

Causes of euvolemic hyponatremia include:

  • Vasopressin, diuretics, antidepressants, opioids
  • Syndrome of inappropriate antidiuretic hormone can result from malignancy, central nervous system (CNS) disorders, pulmonary disease, or drugs
  • High fluid intake can result from prolonged physical activity; surgery; primary polydipsia; or potomania (caused by a low intake of solutes with relatively high fluid intake)
  • Medical testing related to excessive fluids such as a colonoscopy or cardiac catheterization
  • Iatrogenic

Many drugs cause hyponatremia and the most common include:

  • Vasopressin analogs such as desmopressin and oxytocin
  • Medications that stimulate vasopressin release or potentiate the effects of vasopressin such as selective serotonin-reuptake inhibitors and other antidepressants morphine and other opioids
  • Medications that impair urinary dilution such as thiazide diuretics
  • Medications that cause hyponatremia such as carbamazepine or its analogs, vincristine, nicotine, antipsychotics, chlorpropamide, cyclophosphamide, nonsteroidal anti-inflammatory drugs
  • Illicit drugs such as methylenedioxymethamphetamine (MDMA or ecstasy).


Hyponatremia is the most common electrolyte disorder with a prevalence of 20% to 35% in hospitalized patients. Hyponatremia, even mild (125 mEq/L to 135 mEq/L) has been associated with increased mortality and morbidity in the form of attention deficits, gait disturbances, falls, fractures, and osteoporosis.


Hypertonic hyponatremia (plasma tonicity of greater than 285 mOsm/kg)

  • Hyperglycemia
  • Mannitol

Isotonic hyponatremia (plasma tonicity between 270 and 285 mOsm/kg)

  • Pseudohyponatremia: a laboratory artifact. Usually caused by hypertriglyceridemia, cholestasis (lipoprotein X), and hyperproteinemia (monoclonal gammopathy, IVIG). Two-thirds of clinical labs in use still use indirect ion-selective electrode technology and therefore this problem is still present.
  • Nonconductive irrigant solutions: these solutions contain mannitol, glycine or sorbitol, and are used in urological and gynecological procedures such as TURP.

Hypotonic hyponatremia (plasma tonicity of less than 270 mOsm/kg)

Hypotonic hyponatremia represents an excess of free water. This excess free water can be caused by two mechanisms:

  • Increased free water intake: Patient drinks a large volume of free water (greater than 18L/day or greater than 750 mL/h) that overwhelms kidney capacity to excrete free water. Examples of this are psychogenic polydipsia, marathon runners, water drinking competitions, and ecstasy.
  • Decreased free water excretion: Patients drink a normal volume of free water, but the kidneys cannot excrete the water for some reason.

There are three mechanisms involved in the inability of kidneys to excrete water:

1. High ADH activity: High ADH can be caused by three different mechanisms:

  • Decreased effective arterial blood volume (EABV): antidiuretic hormone (ADH) is released when there is a reduction of 15% or more of the EABV. This occurs with hypovolemia (e.g., vomiting, diarrhea), decreased cardiac output (e.g. heart failure), or vasodilation (e.g., cirrhosis).
  •  SIADH: ADH is secreted autonomously. Four general causes of this are brain disorders, lung disorders, drugs (e.g., SSRI), and miscellanea (e.g., nausea and pain).
  • Cortisol deficiency: Cortisol exerts an inhibitory effect on ADH release. When cortisol is decreased, ADH is inhibited and released in large amounts. Adrenal insufficiency is the cause of this mechanism.

2. Low glomerular filtration rate (GFR): a low glomerular filtration rate would impair kidney's ability to get rid of water. Typical examples are Acute kidney injury (AKI), chronic kidney disease (CKD), and end-stage renal disease (ESRD).

3. Low solute intake: Patients on a regular diet consume 600 to 900 mOsm of solute per day. Solutes are defined as substances that are freely filtered by the glomeruli but have relative or absolute difficulty in being reabsorbed by the tubules in relationship to water. The main solutes are urea (which comes from the metabolism of proteins) and electrolytes (e.g., salt). Carbohydrates do not contribute to solute load. In steady state conditions, solute intake is equal to urine solute load. Therefore, it is expected that these patients also excrete 600 to 900 mOsm of solute in the urine. Urine volume, and hence water excretion, is dependent on the urine solute load. The more solute one needs to excrete, the larger the urine volume one needs to produce. The less solute one needs to excrete, the smaller the urine volume one needs to produce. Patients who eat a low amount of solute per day (e.g., 200 mOsm/day), on steady state conditions, will also excrete a low amount of solute in the urine and therefore they will do it in a smaller volume of urine. This decreased urine volume will limit the capacity of the kidneys to excrete water. Typical examples of this are beer potomania and tea-and-toast diet.

History and Physical

Important elements of the history and physical include:

  • The presence of neurological symptoms. They determine the degree of brain edema and urgency and type of therapy.
  • Duration of hyponatremia. Acute (less than 48 hours) versus chronic (more than 48 hours). Duration determines the grade of adaptation to hyponatremia. The more chronic, the more the brain is adapted. Chronic hyponatremia, when corrected rapidly, puts patients at risk for osmotic demyelination syndrome.
  • Extracellular fluid (ECF) volume status gives clues as to the etiology. Edematous states such as heart failure and cirrhosis are classically associated with hyponatremia.


Step 1: Plasma osmolality.

  • Can help differentiate among hypertonic, isotonic, and hypotonic hyponatremia.

Step 2: Urine osmolality

  • Urine osmolality less than 100 mOsm/kg indicates either excess water intake or low solute intake hyponatremia.
  • Urine osmolality less than 100 mOsm/kg usually indicates a high ADH state.

Step 3: Urine Sodium

  • Urine sodium less than 30 mEq/L indicates decrease effective arterial blood volume or cortisol deficiency. Cortisol deficiency can be easily ruled out with a random cortisol level or ACTH stimulation test.
  • Urine sodium greater than 30 mEq/L suggests SIADH.

Treatment / Management

Treatment of hyponatremia is based on the severity of symptoms:

  • Severely-symptomatic hyponatremia: Sodium chloride 3% 100 mL intravenous (IV) bolus (repeat up to twice if symptoms persist).
  • Moderately-symptomatic hyponatremia: Sodium chloride 3% slow infusion (use sodium deficit formula to calculate the rate of infusion but recalculate rate with frequent sodium monitoring).
  • Mildly-symptomatic or "asymptomatic" hyponatremia: Target underlying pathophysiology (e.g., volume expansion for hypovolemia).

The goal of correction:

  • Increase by 4 mEq/L to 6 mEq/L in any 24 hour period

Risk factors for osmotic demyelination syndrome (ODS):

  • Hypokalemia, liver disease, malnutrition, alcoholism.

Limits of correction:

  • High-risk for ODS: less than 8 mEq/L in any 24 hour period
  • Average-risk for ODS: less than 10 mEq/L in any 24 hour period

Pearls and Other Issues

Overcorrection of hyponatremia:

  • It is defined as correction of serum sodium concentration over the limits of correction.
  • This is a medical emergency.
  • Re-lowering serum sodium with D5W +/- DDAVP has been shown to prevent ODS.
  • Prevention of overcorrection can be done by matching urine output with D5W cc per cc after goal of correction is achieved.