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.
Eunatremia: a normal concentration of sodium in the blood (i.e., 136–145 mEq/L).
Hyponatremia: reduced serum sodium concentration (< 135 mEq/L)
Classification [1]
Severity [2]
Mild hyponatremia: 130–135 mEq/L
Moderate hyponatremia: 125–129 mEq/L
Severe hyponatremia (profound): < 125 mEq/L
Disease onset [2]
Acute hyponatremia: < 48 hours [3]
Chronic hyponatremia: ≥ 48 hours or duration unknown [2]
Plasma osmolality (see "Etiology")
Hyponatremia is classified according to serum osmolality and extracellular volume status. [1][2]
Hypotonic hyponatremia [1][4]
Definition: : low measured serum Na+ concentration 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
Low extracellular fluid volume
Normal or minimal changes in extracellular fluid volume
High extracellular fluid volume
Renal causes
Acute or chronic renal failure with high urine output (polyuria)
Mineralocorticoid deficiency (Addison disease)
Recovery phase of acute tubular necrosis
Cerebral salt wasting syndrome
SIADH
Medication use
Exercise-associated hyponatremia (EAH)
Acute or chronic renal failure
Glucocorticoid deficiency (adrenal insufficiency) [5]
Severe hypothyroidism [1][5]
Acute or chronic renal failure with low urine output (i.e., failure to excrete free water)
Extrarenal causes
Dermal fluid loss (e.g., burns, sweating)
Third space fluid loss (e.g., peritonitis, ascites)
Bleeding/hemorrhage
Decreased salt intake (e.g., "tea and toast" diet)
Water intoxication (dilutional hyponatremia)
Excessive infusion of hypotonic (e.g., 0.45% NaCl) or sodium-free isotonic IV fluids
Primary polydipsia
Beer potomania
Reset osmostat syndrome
Severe hypoproteinemia (e.g., nephrotic syndrome)
Thiazide diuretic use and SIADH are the most common causes of hyponatremia in the emergency department. [6]
Exercise-associated hyponatremia (EAH) [7]
Definition: serum sodium level < 135 mmol/L that occurs during or up to 24 hours after prolonged, intense physical exercise
Ingestion of water or hypotonic beverages in excess of fluid losses
↑ ADH secretion → ↑ solute-free water retention
Sodium loss via diaphoresis
Nonspecific symptoms (e.g., dizziness, headache, nausea, vomiting, bloating)
Exercise-associated hyponatremic encephalopathy (EAHE): symptoms of cerebral edema (e.g., agitation, confusion, seizures)
Treatment: fluid restriction PLUS
Mild symptoms: oral hypertonic saline
Moderate to severe symptoms or EAHE: intravenous hypertonic saline
Limit fluid intake according to thirst
Education of individuals at risk (e.g., athletes)
Exercise-associated hyponatremia is most commonly associated with marathon running but has also been reported following other exertional activities such as football, cycling, fraternity hazing, and military training. [7]
Hypertonic hyponatremia [1][4]
Definition: : low measured serum Na+ concentration and high serum osmolality
Serum osmolality: > 295 mOsm/kg H2O
IV mannitol
IV radiocontrast use
Isotonic hyponatremia [1][4]
Definition: : low measured serum Na+ concentration and normal serum osmolality
Serum osmolality: 280–295 mOsm/kg H2O
TURP syndrome [8]
Pseudohyponatremia
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:
Diabetic ketoacidosis
Obstructive jaundice [9]
CRAB criteria in multiple myeloma
Isotonic hyponatremia should always be excluded as a cause of hyponatremia to avoid unnecessarily aggressive treatment.
Fluid compartment changes in hyponatremia
Defined by
Tonicity
Volume status
Serum osmolality
Total body water
Total body sodium
Hypotonic hyponatremia
↓ Or normal
↓ ↑↑ ↑
Isotonic hyponatremia (pseudohyponatremia)
↑ Normal
Hypertonic hyponatremia
↑ ↓ Normal
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. [4][10]
Severely symptomatic hyponatremia [4]
Symptoms usually develop acutely (onset < 48 hours). The severity tends to correlate with the extent of cerebral edema.
Confusion, stupor, coma
Other: malaise; , lethargy, headache, nausea, vomiting
Mild and moderately symptomatic hyponatremia [4]
Symptoms usually develop slowly (onset > 48 hours) and are typically nonspecific (patients can also be asymptomatic).
Gait disturbances
Nausea, vomiting
Depending on the underlying etiology, patients may present with signs of fluid overload, euvolemia, or volume depletion.
Diagnostic approach to hyponatremia [1][2][4][8]
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) [1]
Low serum osmolality; (< 280 mOsmol/kg H2O): hypotonic hyponatremia (true hyponatremia; most common)
High serum osmolality; (> 295 mOsmol/kg H2O): hypertonic hyponatremia
Normal serum osmolality; (280–295 mOsmol/kg H2O): isotonic hyponatremia or pseudohyponatremia
Consider additional focused diagnostic evaluation to identify the underlying cause.
Initiate treatment immediately for acute or severely symptomatic hyponatremia.
Serum osmolality measurement is the first step in the evaluation of verified hyponatremia.
Diagnostic evaluation of hyponatremia based on serum osmolality
Hypotonic hyponatremia [2][4][8]
Initial laboratory studies
Serum studies: CBC, BMP; consider uric acid
Urine studies
Osmolality (UOsm)
Creatinine (UCreatinine)
Sodium (UNa)
Potassium (UK)
Consider also: urea (UUrea) , uric acid (UUA)
Interpretation of urine osmolality (UOsm): to determine antidiuretic hormone (ADH) activity ; [8]
UOsm ≤ 100 mOsm/kg H2O: Dilute urine (ADH is suppressed) indicates excess water intake.
UOsm > 100 mOsm/kg H2O: concentrated urine (ADH is appropriately or inappropriately elevated)
Determination of volume status: to determine if ADH activity is appropriate (i.e., in response to low effective arterial blood volume) or inappropriate (e.g., in SIADH)
History: e.g., significant nausea/vomiting or recent hemorrhage might suggest low effective arterial volume due to hypovolemia
Clinical assessment of volume status: somewhat limited utility for the distinction between hypovolemia and euvolemia [1][2][8]
Laboratory studies: See "Laboratory findings that suggest hypovolemia;" should include interpretation of urine sodium (next step)
Imaging assessment of volume status: e.g., IVC ultrasound
Useful additional tests in patients who are taking diuretics
↓ Fractional excretion of urea (FEUrea) [4][8]
FEUrea < 35%: suggests low effective arterial volume (e.g., in hypovolemia)
FEUrea > 55%: suggests euvolemia (e.g., SIADH)
↓ Fractional excretion of uric acid (FEUA) [8]
FEUA < 12%: suggests low effective arterial volume (e.g., in hypovolemia)
FEUA ≥ 12%: highly suggests euvolemia (e.g., SIADH) [2]
Interpretation of UNa and/or FENa ; : to determine if the cause is renal or extrarenal ; [8]
Findings [1][4][8]
UNa < 20–30 mEq/L and/or FENa < 1%: may suggest extrarenal loss of sodium
UNa ≥ 20–30 mEq/L and/or FENa > 1%: may suggest renal loss of sodium
Urinary sodium excretion is affected by the following: [2][11]
Effective arterial blood volume (see RAAS and ADH)
Dietary sodium intake
Use of diuretics
Interpretation of diagnostic evaluation in hypotonic hyponatremia [1][4][8]
Hypovolemic
Euvolemic
Hypervolemic
Urine osmolality
> 100 mOsm/kg H2O
≤ 100 mOsm/kg H2O
Urine sodium
< 20–30 mEq/L
≥ 20–30 mEq/L
< 1%
≥ 1%
Causes (See "Etiology" for more information.)
Extrarenal causes (e.g., diarrhea, vomiting, third spacing)
Renal causes (e.g., diuretic use, salt-wasting nephropathy, mineralocorticoid deficiency)
Extrarenal causes (e.g., primary polydipsia, beer potomania)
Renal causes (e.g., SIADH, hypocortisolism, hypothyroidism, reset osmostat)
Extrarenal causes (e.g., CHF, cirrhosis, hypoalbuminemia)
Renal causes (e.g., renal failure)
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. [8]
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. [1][2][8]
Additional tests [1][2][8]
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) [1]
Serum cortisol and ACTH to evaluate for hypocortisolism and hypoaldosteronism (see "Adrenal insufficiency")
Urine drug screen to evaluate for suspected MDMA use (see "Amphetamine use disorder")
BNP to evaluate for CHF (see "Diagnostics" in "CHF")
Urine chloride (UCl) may be helpful in rare cases.
Imaging [12]
CXR or CT chest: to look for possible pulmonary causes of SIADH
CT or MRI head: to identify cerebral edema or suspected CNS etiology
Hypertonic hyponatremia [4]
Check serum glucose and calculate corrected sodium for hyperglycemia.
Calculate in all patients with hyponatremia to assess for sodium imbalance due to high glucose levels.
Low corrected Na+: hypotonic hyponatremia likely
High corrected Na+: hypernatremia likely
Normal corrected Na+: no hyponatremia
Identify and treat the underlying cause (see "Etiology").
Isotonic hyponatremia or pseudohyponatremia [13][14]
Confirm or exclude hyponatremia by measuring whole blood sodium (direct potentiometry): Normal Na+ concentration confirms the diagnosis of pseudohyponatremia. [15]
Further diagnostic workup of pseudohyponatremia should be guided by clinical suspicion and may include the following: [9][15]
Lipid panel
Serum protein electrophoresis and urine protein electrophoresis
If pseudohyponatremia is suspected, confirm or exclude hyponatremia using whole blood sodium.
Formulas for hyponatremia
Hyponatremia formulas [4]
(2 x Na+) + (glucose/18) + (BUN/2.8) + (ethanol/4.6)
Corrected serum sodium concentration for hyperglycemia [16][17]
Katz formula: measured Na+ concentration + [0.016 × (serum glucose concentration - 100)]
Hillier formula: measured Na+ concentration + [0.024 × (serum glucose concentration - 100)]
Fractional excretion of sodium (FENa) [8][11]
(SCreatinine × UNa)/(UCreatinine x SNa) × 100%
Fractional excretion of urea (FEUrea) [18]
(UUrea x SCreatinine)/(UCreatinine x SUrea) x 100%
Fractional excretion of uric acid (FEUA) ) [2][8][19]
(UUA × SCreatinine)/(UCreatinine × SUA) × 100%
Urine-to-serum electrolyte ratio [20]
(UNa + UK)/SNa
Total body water (TBW) [21]
Weight (kg) x k
k depends on the age and sex:
0.6 in males
0.5 in females and elderly males
0.45 in elderly females
Watson formula
Males: 2.447 - 0.09156 x age (years) + 0.1074 x height (in cm) + 0.3362 x weight (in kg)
Females: -2.097 + 0.1069 x height (in cm) + 0.2466 x weight (in kg)
Change in sodium concentration [22]
Δ [Na+] = [(Sodium infusate + potassium infusate) - Serum Na+)]/(TBW + 1)
Sodium infusate is the amount of sodium present in 1 L of the given solution.
See "Crystalloid solutions" for the sodium (and potassium) mEq contained in each fluid.
IV fluid rate for correction of hyponatremia (mL/hour) [22]
1000 x (Na+ correction rate in mEq/L/hr)/(change in sodium concentration)
Approach [1][23]
The rate of sodium correction depends on acuity and severity of symptoms. 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. [23]
Acute hyponatremia and/or severely symptomatic hyponatremia
Initial aggressive treatment with IV hypertonic saline to prevent cerebral edema
Aim to initially increase serum sodium by 4–6 mEq/L. [1][3]
Once stabilized, identify and treat the underlying cause.
Chronic hyponatremia
Careful correction by treating the underlying cause
Avoid sodium overcorrection to minimize the risk of osmotic demyelination syndrome (ODS).
Recommended sodium correction rates for chronic hyponatremia depend on the presence of high-risk factors for ODS.
Disposition [24][25]
Severe symptomatic hyponatremia and/or treatment with hypertonic saline: ICU admission
Acute, symptomatic, or severe hyponatremia and/or risk factors for ODS: inpatient care
Asymptomatic mild hyponatremia with underlying cause identified and treated: Consider outpatient management with close follow-up.
Patients with serum sodium values < 120mEq/L typically require intensive care; specialists should be involved early on.
Once specific treatment is given (e.g., discontinuation of diuretics, corticosteroids for hypocortisolism), there is a high risk of rapid autocorrection causing a dangerous increase in sodium.
Acute hyponatremia and/or severely symptomatic hyponatremia [1]
The goal of treating acute and/or severely symptomatic hyponatremia is the rapid increase of serum sodium with hypertonic saline to reverse neurological symptoms and prevent brain herniation. Early specialist consultation (intensive care, nephrology) is advised.
Indications (any of the following): [1]
Severely symptomatic hyponatremia (regardless of onset)
Symptomatic acute hyponatremia (< 48 hours)
Asymptomatic acute hyponatremia (< 48 hours) with decrease in Na+ concentration of > 10 mEq/L [8]
Suspected or known increased ICP or intracranial pathology
Initial sodium goal: ↑ serum sodium 1–2 mEq/L/hour until an increase of 4–6 mEq/L has been reached within 6 hours [1]
Regimens for rapid correction
Severely symptomatic hyponatremia: hypertonic saline bolus (e.g., 3% NaCl ) [1]
Acute hyponatremia without severe symptoms: hypertonic saline infusion (e.g., 3% NaCl infusion ) [1][8]
Consider adding desmopressin to prevent overcorrection in patients with sodium < 120 mEq/L. [26]
Further management and sodium goals: Once the acute sodium goal has been reached, start cause-specific treatment.
For acute hyponatremia: Recommendations vary; consider rapid autocorrection vs. slower correction goals. [1][8]
For chronic hyponatremia: See "Sodium correction rates for chronic hyponatremia."
Serial serum sodium measurement
While receiving hypertonic saline bolus: every 20 minutes until symptoms resolve [8]
After the initial goal is reached: every 2–4 hours, then every 6–12 hours after stabilization [8][20]
Monitor urine output closely (e.g., every hour). [27][28]
If there is any uncertainty about the chronicity of the hyponatremia, maximum sodium correction rates for chronic hyponatremia should not be exceeded in order to avoid the risk of ODS. [1]
Rapid sodium correction of 4–6 mEq/L should be achieved in the first 6 hours of therapy for patients with acute hyponatremia and/or severely symptomatic hyponatremia. [1]
Six in Six hours for Severe Symptoms and Stop [1]
Chronic hyponatremia without severe symptoms [1]
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): > 1 mL/kg/hour is concerning for overcorrection. [1]
Check serum sodium frequently (at least every 4–6 hours until serum sodium is ≥ 125 mEq/L). [1]
Recommended sodium correction rates for chronic hyponatremia [1][2]
Patients at normal risk for ODS
Patients with high-risk factors for ODS
Minimum correction rate (goal)
4–8 mEq/L within 24 hours
Maximum correction rate (limit)
10–12 mEq/L within 24 hours
8 mEq/L within 24 hours
Rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome! Do not exceed hourly or daily maximum correction limits.
In patients with chronic hyponatremia, urine output > 1 mL/kg/hour suggests sodium overcorrection and risk of impending osmotic damage.
Cause-specific treatment for hyponatremia [1]
Recommended in the following situations:
Chronic hyponatremia without severe symptoms
Acute and/or severely symptomatic hyponatremia after stabilization and resolution of symptoms
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.
Administer isotonic saline infusion (0.9% NaCl ) and monitor serum sodium [20]
↑ Serum sodium: Hypovolemic hypotonic hyponatremia is likely.
↓ Serum sodium: SIADH is likely. [2]
Hypovolemic hyponatremia [1]
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"). [20][22]
Adjust the infusion rate to achieve target goals (see "Sodium correction rate for chronic hyponatremia").
Euvolemic hyponatremia [1]
Fluid restriction (all fluids, not just free water)
Usually 500–1000 mL/day
Consider < 500 mL/day if the urine-to-serum electrolyte ratio is > 1 (see "Hyponatremia formulas"). [20]
Consider pharmacological interventions. [1][8][20]
High urine osmolality (especially if Uosm is > 500 mOsm/kg) [1]
Euvolemic hyponatremia refractory to fluid restriction
Urea [1]
Demeclocycline [1]
Vaptans (e.g., conivaptan , tolvaptan ) [1][20]
Identify and treat the underlying cause (see "Hypothyroidism," "Adrenal insufficiency," and "SIADH").
Serum sodium should be monitored every 6–8 hours in patients receiving vaptan therapy in order to identify overcorrection. [1]
Hypervolemic hyponatremia [1]
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. [1]
Vaptans are unlikely to be effective if creatinine levels are > 3 mg/dL.
The use of vaptans is controversial in patients with cirrhosis. [1][8]
If hyponatremia persists after diuretic use has been stopped, consider other causes. [8]
Management of sodium overcorrection [1]
Initial serum Na+ ≥ 120 mEq/L: Management of overcorrection is probably not necessary. [1]
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.
Discontinue hyponatremia treatment and consider early specialist consult (e.g., nephrology, intensive care).
Replace free water losses (e.g., 5% dextrose in water ). [1]
Consider adding desmopressin . [1]
Consider glucocorticoids (e.g., dexamethasone ) to prevent ODS. [1]
Monitor urine output and fluid balance closely (typically every hour).
Check serum sodium frequently (e.g., hourly) until sodium goals and limits are achieved. [1]
Acute management checklist
Repeat BMP to verify hyponatremia.
Check serum glucose to exclude hyperglycemia.
Calculate corrected sodium for hyperglycemia.
Consider emergent treatment with 3% IV NaCl for:
Severely symptomatic hyponatremia
Symptomatic acute hyponatremia or acute sodium decrease of > 10mEq/L
Known or suspected intracranial pathology or ↑ ICP
Check serum osmolality.
Check urine osmolality and electrolytes.
Estimate volume status.
Consider further diagnostics for hyponatremia based on serum osmolality.
Stop administration of free water (IV or PO).
Consider hypertonic saline and/or cause-specific treatment of hyponatremia.
Check serum sodium frequently during correction with 3% NaCl.
Monitor urine output for excessive diuresis.
Begin management of sodium overcorrection if necessary.
Edema: sudden decrease in intravascular Na+ level → reduced intravascular osmotic pressure → water moving into the interstitium and intracellular space → edema
Cerebral edema → elevated intracranial pressure → risk of brain herniation [29]
Noncardiogenic pulmonary edema
Permanent neurological damage
Treatment-associated complications
Osmotic demyelination syndrome (ODS)
Correcting hyponatremia too rapidly may cause two complications: From low to high, your pons will die (osmotic demyelination syndrome); from high to low, your brain will blow (cerebral edema).
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
Central pontine myelinolysis
Most common type
Affects the central region of the pons
Extrapontine myelinolysis: can affect the cerebellum, lateral geniculate body, thalamus, putamen, cortical, and/or subcortical white matter
Iatrogenic: rapid correction of chronic hyponatremia
High-risk factors for ODS: alcohol use disorder, malnutrition, liver disease, hypokalemia, initial sodium concentration ≤ 105 mEq/L [1]
Rapid changes in other osmotically active solutes (e.g., glucose)
Acute severe hypernatremia
Clinical features [30][31]
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.
Altered level of consciousness, including coma
Locked-in syndrome
Impaired cranial nerve function: dysarthria, dysphagia , and diplopia
Worsening quadriparesis (initially flaccid, later spastic)
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.
MRI: imaging technique of choice
T2: hyperintense lesion
T1: hypointense lesion
No contrast enhancement of the lesion
CT: easier to conduct in ventilated patients
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
Avoid overcorrection of chronic hyponatremia (see "Sodium correction rates for chronic hyponatremia").
Frequent reevaluation of the serum sodium concentration
See "Management of sodium overcorrection." [32]
Correcting hyponatremia too rapidly can cause osmotic damage to the axonal myelin sheath in the CNS.
The symptoms and imaging findings of osmotic demyelination syndrome (ODS) first appear several days after the correction of hyponatremia!
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 [33]
May result from:
Underlying medical conditions
Mild chronic hyponatremia is associated with more frequent falls. [34]
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!
Quickly assess for red flags (i.e., confusion, seizures) that require immediate intervention and ICU admission.
Ask about dietary history, fluid and alcohol intake, new medications, endocrine ROS, relevant comorbidities.
Volume status is theoretically helpful, as diagnostic algorithms depend on it, but error-prone. [35]
Our approach focuses on understanding what each diagnostic test adds rather than rote dependence on algorithms.
More helpful given that most cases of hyponatremia in the hospital are multifactorial [36]
Ask yourself where your patient with hyponatremia is located on a "Cartesian space" with:
Anti-diuretic hormone (ADH) secretion relative to effective arterial blood volume (EABV).
What if we encounter a patient after intervention and with incomplete labs or urine studies?
Still obtain appropriate serum and urine studies to assess:
Response to interventions
Patient's current ADH/EABV state
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 "Hyponatremia formulas"). [37]
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 "pseudohyponatremia." [38]
Serum osmolality is not subject to this error.
Pseudohyponatremia is not of clinical significance.
↑ Osmolality : Look for extra osmoles, either measured or unmeasured!
Measured: severe hyperglycemia, BUN, and, depending on the equation used, ethanol [16]
Unmeasured: toxic alcohols, iodinated contrast, sucrose [39]
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.
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. [2][40]
The range of possible urine osmolality in healthy kidneys is broad (50–1200 mOsm/kg).
ADH secretion → resorption of free water in the collecting duct → ↑ UOsm
ADH suppression → ↓ UOsm
If ADH is not active, the result is dilute urine (↓ UOsm).
Low UOsm on presentation indicates:
Too little solute to keep up with normal fluid intake ("tea-toast syndrome") [41]
Too much fluid despite normal solute intake (primary polydipsia) [42][43]
Some combination of low solute and high intake of hypoosmolar fluid (beer potomania) [44]
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. [45]
ADH activity is reflected by ↑ UOsm in patients with hyponatremia.
If ADH is present: Figure out if this is because of ↓ EABV, ↑ osmolality, or is independent of physiological stimulus (see "Pearl 4").
Remember that renal insufficiency impacts our ability to maximally dilute urine. [46]
Hyponatremia may develop as a result of acute or chronic renal failure for this reason.
Renal insufficiency limits our ability to interpret UOsm as a direct window into ADH activity. [47]
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 fractional excretion of urea (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.
Physiological (appropriate) ADH activity can occur in the following circumstances:
↑ Osmolality
↓ Sensed EABV [48]
ADH activity that is not stimulated by one of the above mechanisms is by definition inappropriate. [49]
UNa provides a window into the activity of renin-angiotensin-aldosterone, which is more sensitive than ADH to ↓ EABV states. [50]
↓ EABV → RAAS activation → ↓ UNa
SIADH → no RAAS activation → ↑ UNa
In patients with intermediate UNa , FeNa is more sensitive than UNa for reflecting ↓ EABV. [51]
↓ FeNa: RAAS is active, ↓ EABV
Validated in oliguric patients; less reliable in patients producing large quantities of dilute urine
Caveats to UNa and FeNa use [2]
Use of diuretics (thiazide or loop) increases UNa, in which case, ↓ FeUrea is a reasonable surrogate (↓ FeNa PLUS ↓ FeUrea is better than either alone). [51]
CKD impairs Na reabsorption, making UNa less helpful in this patient group.
UNa will be low in patients with ↓ Na diets (rare in the US).
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.
EABV contraction → urinary sodium and uric acid retention
EABV expansion → urinary sodium and uric acid wasting
Expected characteristics of uric acid in SIADH [52]
↓ Serum uric acid [53][54]
↑ Urine uric acid
↑ Fractional excretion of uric acid (FeUA)
FeUA may be a more helpful diagnostic test when trying to distinguish between causes of hyponatremia with ↓ EABV and normal or ↑ EABV. [19][51]
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