Hyponatremia is a state of low sodium levels (< 135 mEq/L). Sodium is the most important osmotically active particle in the extracellular space and is closely linked to the body's fluid balance. Causes of hyponatremia include dehydration, excessive free water intake (e.g., primary polydipsia), and increased release of ADH causing reabsorption of free water in the kidneys (e.g., SIADH, CHF). The onset can be acute or chronic and symptoms are predominantly neurological and often nonspecific (e.g., nausea, headache, confusion). Investigating the cause of hyponatremia requires consideration of the patient's volume status and renal ability to retain sodium. Some conditions with very high protein (e.g., multiple myeloma) or glucose levels (e.g., DKA) in the blood may result in a laboratory artifact of falsely low serum sodium concentrations (pseudohyponatremia). Treatment involves careful correction of the sodium deficit and/or fluid imbalance. A rapid increase of the serum sodium concentration can have damaging osmotic effects, as seen in osmotic demyelination syndrome.
See the section “Core IM podcast 5 pearls on hyponatremia (episode 1: diagnosis)” for their show notes on this topic.
- Hyponatremia: reduced serum sodium concentration (< 135 mEq/L)
- Severity 
- Mild hyponatremia: 130–135 mEq/L
- Moderate hyponatremia: 125–129 mEq/L
- Severe hyponatremia (profound): < 125 mEq/L
- Disease onset 
- Acute hyponatremia: < 48 hours 
- Chronic hyponatremia: ≥ 48 hours or duration unknown 
- Plasma osmolality (see “Etiology”)
- Severity 
Hypotonic hyponatremia 
- Definition: : low measured serum Na+ levels and low serum osmolality (true hyponatremia)
- Serum osmolality: < 280 mOsm/kg H2O
- Forms: hypovolemic, euvolemic, hypervolemic
- Causes: extrarenal and renal (see “Causes of hypotonic hyponatremia”)
Pathophysiology: relative excess of water compared to sodium in the extracellular compartments
- Dilution: excess body water → dilution of the blood → lower serum sodium concentration
- Depletion: ↓ body sodium → relative excess body water → lower serum sodium concentration
|Causes of hypotonic hyponatremia|
|Hypovolemic hypotonic hyponatremia||Euvolemic hypotonic hyponatremia||Hypervolemic hypotonic hyponatremia|
|Description|| || || |
Exercise-associated hyponatremia (EAH) 
- Definition: serum sodium level < 135 mmol/L that occurs during or up to 24 hours after prolonged, intense physical exercise
- Clinical features
- Treatment: fluid restriction PLUS
- Limit fluid intake according to thirst
- Education of individuals at risk (e.g., athletes)
Hypertonic hyponatremia 
- Definition: : low measured serum Na+ levels and high serum osmolality
- Serum osmolality: > 295 mOsm/kg H2O
Isotonic hyponatremia 
- Definition: : low measured serum Na+ levels and normal serum osmolality
- Serum osmolality: 280–295 mOsm/kg H2O
- TURP syndrome
- Asymptomatic laboratory artifact falsely indicating hyponatremia when sodium has not been reduced or diluted
- Due to very high amounts of protein or lipids in the plasma (e.g., hyperlipidemia, multiple myeloma), which then alter the plasma water concentration
- Clinical features may include:
Isotonic hyponatremia should always be excluded as a cause of hyponatremia to avoid unnecessarily aggressive treatment.
Fluid compartment changes in hyponatremia
|Serum osmolality||Total body water||Total body sodium|
|Hypotonic hyponatremia||Hypovolemic hypotonic hyponatremia|| |
|Euvolemic hypotonic hyponatremia||↓|| |
|↓ Or normal|
|Hypervolemic hypotonic hyponatremia||↓||↑↑||↑|
|Isotonic hyponatremia (pseudohyponatremia)|| |
Clinical features depend on the onset, duration, and severity of hyponatremia. Most patients with chronic hyponatremia are asymptomatic and symptoms typically only occur with serum sodium concentration < 120 mEq/L. 
Severely symptomatic hyponatremia 
Symptoms usually develop acutely (onset < 48 hours). The severity tends to correlate with the extent of cerebral edema.
- Confusion, stupor, coma
- Respiratory failure
- Other: malaise; , lethargy, headache, nausea, vomiting
Mild and moderately symptomatic hyponatremia 
Symptoms usually develop slowly (onset > 48 hours) and are typically nonspecific (patients can also be asymptomatic).
- Gait disturbances
- Muscle weakness
- Nausea, vomiting
- Euvolemia: no signs of hypovolemia or hypervolemia
- Effusions (e.g., )
- Weight gain
- Shortness of breath 
Hypovolemic hyponatremia resulting from extrarenal causes typically manifests with oliguria due to hypovolemia while hypovolemic hyponatremia resulting from renal causes manifests with hypovolemia due to polyuria.
Diagnostic approach to hyponatremia 
- Confirm hyponatremia: Repeat BMP.
- Exclude hyperglycemia: Check serum glucose.
Check the serum osmolality (SOsm): first step in the evaluation of confirmed hyponatremia
- Measured in serum or calculated (see “Hyponatremia formulas” below) 
- Perform focused diagnostic evaluation based on serum osmolality.
If the patient has acute hyponatremia or severe symptoms, proceed directly to treatment.
After confirming hyponatremia, serum osmolality is the most appropriate initial laboratory test to assess the etiology.
Diagnostic evaluation based on serum osmolality
Hypotonic hyponatremia 
- Initial workup to order
- Interpretation of urine osmolality (UOsm): to determine antidiuretic hormone (ADH) activity 
Determination of volume status: to determine if ADH activity is appropriate (i.e., in response to low effective arterial blood volume) or inappropriate
- History: e.g., significant nausea/vomiting or recent hemorrhage might suggest hypovolemia → low effective arterial blood volume → appropriate ADH secretion
- Physical examination: somewhat limited utility for the distinction between hypovolemia and euvolemia (see “Clinical assessment of volume status”) 
- Laboratory studies: See “Laboratory findings that suggest hypovolemia”; should include interpretation of urine sodium (next step)
- Useful additional tests in patients who are taking diuretics
- ↓ Fractional excretion of urea (FEUrea) 
- ↓ Fractional excretion of uric acid (FEUA) 
The distinction between hypovolemia and euvolemia is usually difficult to make on examination alone; examination findings have low sensitivity and specificity. Many authors recommend focusing on urinary sodium rather than clinical features to distinguish between the two. 
Interpretation of UNa and/or FENa : to determine if the cause is renal or extrarenal 
- Findings 
- Urinary sodium excretion is affected by the following: 
|Interpretation of diagnostic evaluation in hypotonic hyponatremia |
|Urine sodium|| || || || || || |
|FENa|| || || || || || |
|Urine osmolality|| || || || |
|Causes (See “Etiology” for more information.)|| |
In patients taking diuretics, urinary sodium concentrations should be interpreted with caution. A FEUa < 12 % can provide more diagnostic accuracy than UNa to differentiate hypovolemia from euvolemia. 
Additional tests 
Consider the following based on clinical suspicion:
- TSH to evaluate for hypothyroidism (hyponatremia usually only occurs with signs of myxedema or TSH > 50 mIU/mL) 
- Serum cortisol and ACTH to evaluate for hypocortisolism and hypoaldosteronism (see “Adrenal insufficiency”)
- Urine drug screen to evaluate for suspected use (see “Amphetamine use disorder”)
- BNP to evaluate for CHF (see “Diagnostics” in “CHF”)
- Urine chloride (UCl) may be helpful in rare cases
- Check serum glucose and calculate corrected sodium for hyperglycemia.
- Identify and treat the underlying cause (see “Etiology”).
Isotonic hyponatremia (pseudohyponatremia) 
- Confirm or exclude hyponatremia with direct measurement of sodium (direct potentiometry): Normal Na+ levels confirm the diagnosis of pseudohyponatremia. 
- Further diagnostic workup should be guided by clinical suspicion and may include the following: 
|Hyponatremia formulas |
|Serum osmolality|| |
|Corrected serum sodium concentration for hyperglycemia || |
|Fractional excretion of sodium (FENa) || |
|Fractional excretion of urea (FEUrea) || |
|Fractional excretion of uric acid (FEUA) ) || |
|Urine to serum electrolyte ratio || |
|Total body water (TBW) || |
|Change in sodium concentration || |
|IV fluid rate for correction of hyponatremia (mL/hour) || |
General principles 
Recommended rate of sodium correction depends on acuity and severity of symptoms: 
- Acute hyponatremia and/or severely symptomatic hyponatremia
- Chronic hyponatremia
- Some experts suggest that the maximum correction rate for all patients should be 6–8 mEq/L within the first 24 hours, regardless of the duration of symptoms and clinical presentation. 
- Patients with serum sodium values < 120 mEq/L typically require intensive care; specialists should be involved early on.
Alleviate Acute hyponatremia Aggressively and Correct Chronic hyponatremia Carefully!
The goal of treating acute and/or severely symptomatic hyponatremia is the rapid correction of serum sodium with hypertonic saline to reverse neurological symptoms and prevent brain herniation. Early specialist consultation (intensive care, nephrology) is advised.
- Indications 
- Initial sodium goal: ↑ serum sodium 1–2 mEq/L/hour until an increase of 4–6 mEq/L has been reached within six hours 
- Regimens for rapid correction
- Further management and sodium goals: Once the acute sodium goal has been reached, start cause-specific treatment.
Six in Six hours for Severe Symptoms and Stop 
Chronic hyponatremia without severe symptoms 
The goal of treating chronic hyponatremia is a slow correction of serum sodium levels to prevent overcorrection and subsequent osmotic cell damage. Treatment depends on the underlying cause (see “Cause-specific treatment” below).
- Goal: The goal correction rate depends on the risk of ODS (see table).
Monitoring: Monitor patients closely for signs of overcorrection (see “Management of sodium overcorrection” below).
- Monitor urine output closely (e.g., every hour): > 100 mL/hour is concerning for overcorrection. 
- Check serum sodium frequently (at least every 4–6 hours until serum sodium is ≥ 125 mEq/L). 
|Recommended sodium correction rates for chronic hyponatremia |
|Patients at normal risk for ODS||Patients with high-risk factors for ODS|
|Minimum correction rate (goal)|| || |
|Maximum correction rate (limit)|| || |
Cause-specific treatment 
- Recommended in the following situations:
- Stop all medications that may be causing hyponatremia.
- If the cause is unknown, consider a trial of volume expansion to differentiate between hypovolemic hypotonic hyponatremia and euvolemic hypotonic hyponatremia.
- Isotonic saline (e.g., 0.9% NaCl)
- To determine the initial rate, determine the goal sodium level, and calculate the corresponding desired sodium correction rate for hyponatremia (see “IV fluid rate for correction of hyponatremia”). 
- Adjust the infusion rate to achieve target goals (see “Sodium correction rate for chronic hyponatremia”).
- Fluid restriction (all fluids, not just free water)
- Consider pharmacological interventions. 
- Identify and treat the underlying cause (see “ ,” “ ,” and “ ”).
Serum sodium should be monitored every 6–8 hours in patients receiving vaptan therapy in order to identify overcorrection. 
- Fluid restriction with or without loop diuretics (e.g., furosemide )
- Consider vaptans (e.g., conivaptan , tolvaptan ) in hospitalized patients with hyponatremia refractory to fluid restriction. 
If hyponatremia persists after diuretic use has been stopped, consider other causes. 
Management of sodium overcorrection 
- Initial serum Na+ ≥ 120 mEq/L: Management of overcorrection is probably not necessary. 
- Initial serum Na+ < 120 mEq/L: If the increase in sodium exceeds sodium correction limits (e.g., > 8 mEq/L/24 hours in a patient at high risk for ODS), start treatment to lower serum sodium.
- Monitor urine output and fluid balance closely (typically every hour).
- Check serum sodium frequently (e.g., hourly) until sodium goals and limits are achieved. 
- Edema: sudden decrease in intravascular Na+ level → reduced intravascular osmotic pressure → water moving into the interstitium and intracellular space → edema
- Bone fractures
- Permanent neurological damage
- Treatment-associated complications
We list the most important complications. The selection is not exhaustive.
- Definition: damage to the myelin sheath of the white matter in the CNS caused by a sudden rise in serum osmolality
Clinical features 
- Symptoms first develop several days after the correction of hyponatremia.
- There can be a wide range of symptoms, depending on the degree and location of demyelination.
- Central pontine myelinolysis
- Extrapontine myelinolysis: parkinsonism (tremor, rigidity), dystonia, chorea or choreoathetosis, myoclonus, opsoclonus, ataxia, gait disorders
- Other general symptoms: seizures, encephalopathy, catatonia, mutism, frontal release signs, depression
- Diagnostics: Imaging may only show signs of ODS days to weeks after the onset of symptoms.
- Treatment: supportive care (with close monitoring of electrolytes); prevention is key to improving patient outcomes.
- Prognosis: variable; ranging from fatal to residual deficits or a complete recovery
Core IM podcast 5 pearls on hyponatremia (episode 1: diagnosis)
AMBOSS has partnered with the popular Core IM podcast to bring you digestible internal medicine content on complex medical topics. In this section, you will find Core IM's 5 clinical pearls on the diagnosis of hyponatremia. Check out their website for the full show notes and listen to our coproduced episode on your favorite podcast platform.
Pearl 1: general approach
- Hyponatremia is a significant clinical problem.
- The most common electrolyte disorder, occurring in up to 30% of hospitalized patients 
- May result from:
- Underlying medical conditions
- Mild chronic hyponatremia is associated with more frequent falls. 
- Understand what each diagnostic test adds vs. rote dependence on algorithms.
Patient history and physical examination: may be helpful, but do not ignore other objective data that contradicts them!
- Physical examination
- Our approach focuses on understanding what each diagnostic test adds rather than rote dependence on algorithms.
- What if we encounter a patient after intervention and with incomplete labs or urine studies?
- Hyponatremia is a significant clinical problem.
Pearl 2: serum osmolality
- Patients with true hyponatremia are expected to have ↓ osmolality.
- This makes sense because sodium is the most significant contributor to osmolality (see “ ”). 
Serum osmolality can be thought of as a quality check to verify the hypothesis that low sodium is accompanied by low osmolality, as it should be.
- Normal osmolality: Assess if the patient has ↑ triglycerides or paraproteinemia.
- Such cases are referred to as “ .” 
- Serum osmolality is not subject to this error.
- Pseudohyponatremia is not of clinical significance.
- ↑ Osmolality : Look for extra osmoles, either measured or unmeasured!
Serum osmolality assessment prompts a consideration of effective and ineffective osmoles at play.
- Effective osmoles do not cross the plasma membrane freely → shifts in water movement (impact tonicity)
- Most of the clinical complications that arise as a result of hyponatremia (and its correction) are driven by the fact that sodium is an effective osmole that impacts tonicity and, therefore, cell size.
- Ineffective osmoles cross the plasma membrane more readily and, therefore, do not cause shifts in water movement (do not change tonicity).
- Serum osmolarity is not a serially measured lab! Measure it once, unless you are following clearance of an unmeasured osmole (such as a toxic alcohol) or if there is a significant sodium change that is difficult to contextualize.
- Patients with true hyponatremia are expected to have ↓ osmolality.
Pearl 3: Urine osmolality (UOsm) acts as a window into ADH activity.
- UOsm is the nearest to a direct measure of ADH activity in clinical practice. 
- If ADH is not active, the result is dilute urine (↓ UOsm).
- Low UOsm on presentation indicates:
- Low UOsm can also occur in the setting of acute illness, in which many patients will push large volumes of hypotonic fluids (i.e., sports drinks) in the setting of GI losses.
- The story of hyponatremia is often the story of ADH activity. 
- Remember that renal insufficiency impacts our ability to maximally dilute urine. 
- Changes in UOsm (and urine output) can be assessed serially to evaluate treatment response.
- If urine osmolality gently declines with an intervention (e.g., volume resuscitation): Your intervention has resulted in suppression of ADH (proving the hypothesis).
- Heads up! If urine output and UOsm change dramatically in response to an intervention, this may be an early indicator that a patient is correcting too quickly!
Pearl 4: Urine sodium (UNa), fractional excretion of sodium (FeNa), and (FeUrea) reveal RAAS activity.
- UOsm acts as a window into ADH activity at a given time; it does not tell us why ADH is activated.
- UNa provides a window into the activity of renin-angiotensin-aldosterone, which is more sensitive than ADH to ↓ EABV states. 
- In patients with intermediate UNa , FeNa is more sensitive than UNa for reflecting ↓ EABV. 
- Caveats to UNa and FeNa use 
Pearl 5: A low serum uric acid can be helpful when considering SIADH (in order words, it points away from hypovolemic states)
- Theoretically, the lower the serum uric acid level, the less likely it is that the patient's hyponatremia is driven by low-EABV-mediated ADH release.
- Expected characteristics of uric acid in SIADH 
- FeUA may be a more helpful diagnostic test when trying to distinguish between causes of hyponatremia with ↓ EABV and normal or ↑ EABV. 
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Related One-Minute Telegram
- One-Minute Telegram 13-2020-3/3: Push it fast or push it slow: for hyponatremia, which is the best way to go?
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