hyponatremia
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Hyponatremia
Definition
Serum sodium < 135 mEq/L. It is the second most common electrolyte abnormality in clinical practice and is frequently a marker of underlying disease rather than a primary disorder. - Rosen's Emergency Medicine, p. 2514
Pathophysiology
Water moves freely across cell membranes to achieve osmotic equilibrium, so a fall in plasma sodium causes brain cell swelling. Neurons adapt by exporting K+ (with an anion) and organic osmolytes (taurine, myoinositol) to reduce intracellular volume.
If hyponatremia persists > 48 hours, this adaptation returns brain cells close to normal volume. A too-rapid correction then causes fluid to shift out of neurons, shrinks cerebral vascular endothelial cells, opens the blood-brain barrier, and allows lymphocytes, complement, and cytokines to enter - damaging oligodendrocytes and causing osmotic demyelination syndrome (ODS). - Brenner & Rector's The Kidney, p. 408
The underlying mechanism is almost always one of two problems:
- Low distal delivery of filtrate to the nephron (reduced GFR or increased proximal tubule NaCl reabsorption)
- Vasopressin (ADH) activity causing water reabsorption in the collecting duct - Brenner & Rector, p. 415-416
Classification by Volume Status
| Category | Total Body Na | Total Body Water | Common Causes |
|---|---|---|---|
| Hypovolemic | Decreased | Decreased (Na loss > water loss) | Vomiting, diarrhea, sweating, diuretics, mineralocorticoid deficiency, salt-wasting nephropathy, burns, pancreatitis |
| Euvolemic | Near normal | Increased | SIADH, hypothyroidism, adrenal insufficiency, psychogenic polydipsia, exercise-associated |
| Hypervolemic | Increased | Increased (water gain > Na gain) | Heart failure, cirrhosis, chronic renal failure |
Pseudohyponatremia (artifactual): caused by hyperlipidemia or hyperproteinemia (e.g., myeloma). Corrected/dilutional hyponatremia from hyperglycemia: for every 100 mg/dL glucose above 100, serum Na falls ~1.6-2.4 mEq/L. - Rosen's Emergency Medicine, p. 2516
SIADH (Syndrome of Inappropriate ADH Secretion)
The most common euvolemic cause. Criteria:
- Hyponatremia with plasma hypo-osmolality
- Urine osmolality > plasma osmolality (inappropriately concentrated urine)
- Urine Na > 20 mEq/L
- Euvolemia (no edema, normal skin turgor)
- Normal renal, adrenal, and thyroid function
Common causes of SIADH:
- CNS disorders (head trauma, meningitis, stroke, subarachnoid hemorrhage)
- Pulmonary (pneumonia, TB, positive-pressure ventilation)
- Malignancy - most notably small cell lung cancer (10-15% of patients), also head/neck tumors
- Medications - SSRIs, carbamazepine, cyclophosphamide, cisplatin, vincristine, oxytocin, NSAIDs, PPIs
- Postoperative state
Clinical Features
Symptoms correlate with both the degree and the rate of onset of hyponatremia:
| Sodium Level | Symptoms |
|---|---|
| 125-135 mEq/L | Often asymptomatic; nausea, anorexia, mild fatigue |
| 120-125 mEq/L | Headache, lethargy, cognitive impairment |
| < 120 mEq/L (acute) | Confusion, seizures, coma, brainstem herniation |
Acutely hyponatremic patients (Na drop within 24-48 h) are at highest risk of cerebral edema. Chronically hyponatremic patients (> 48 h) may be asymptomatic at levels that would be fatal if the drop were acute, because of cerebral adaptation.
Physical examination clues:
- Hypovolemia: poor skin turgor, dry mucous membranes, orthostasis, tachycardia
- Hypervolemia: JVD, peripheral edema, pulmonary crackles
- SIADH/euvolemia: no edema, normal skin turgor, no orthostasis
In geriatric patients, the risk of hyponatremia doubles with large-bone fractures. - Rosen's Emergency Medicine, p. 2519
Diagnostic Workup
First-line labs:
- Serum sodium, osmolality, glucose, BUN, creatinine
- Urine sodium (spot), urine osmolality
- TSH, cortisol (to exclude hypothyroidism/adrenal insufficiency)
Spot urine sodium interpretation:
| Setting | Urine Na |
|---|---|
| Hypovolemic - extrarenal (vomiting, diarrhea) | < 20 mEq/L |
| Hypovolemic - renal (diuretics, salt-wasting) | > 20 mEq/L |
| Euvolemic (SIADH, endocrinopathies) | > 20 mEq/L |
| Psychogenic polydipsia | < 20 mEq/L (dilute urine) |
| Hypervolemic - CHF, cirrhosis | < 20 mEq/L |
| Hypervolemic - renal failure | > 20 mEq/L |
- Rosen's Emergency Medicine, Table 114.3, p. 2521
Treatment
1. General Principles
Three factors guide therapy:
- Presence of symptoms
- Duration (acute < 48 h vs. chronic > 48 h)
- Volume status
Treat the underlying cause whenever possible. - Brenner & Rector, p. 1921
2. Correction Rate - THE Critical Safety Concern
- Acute symptomatic hyponatremia: Aim to raise Na by 1-2 mEq/L/hour for the first few hours to control symptoms (seizures, herniation)
- Chronic hyponatremia: Correct no faster than 8-10 mEq/L per 24 hours (some guidelines say max 10-12 mEq/L/24 h), or 18 mEq/L per 48 hours
- Exceeding these rates risks osmotic demyelination syndrome (central pontine myelinolysis), which is irreversible
A 2025 JAMA Internal Medicine systematic review and meta-analysis (PMID: 39556338) examined correction rates and clinical outcomes in hospitalized adults with severe hyponatremia - the most current evidence on this topic.
3. Treatment by Etiology
| Cause | Treatment |
|---|---|
| Hypovolemic | Isotonic saline (0.9% NaCl) to restore volume |
| SIADH / Euvolemic | Free water restriction (primary), demeclocycline, vaptans (tolvaptan/conivaptan) |
| Hypervolemic (CHF, cirrhosis) | Free water restriction + diuresis + treat underlying disease |
| Acute symptomatic (seizures/coma) | Hypertonic saline (3% NaCl) - bolus approach increasingly favored |
| Adrenal insufficiency | Hydrocortisone |
| Hypothyroidism | Thyroid hormone replacement |
4. Hypertonic Saline (3% NaCl)
Indicated for:
- Severe but asymptomatic hyponatremia with Na ≤ 110 mEq/L
- Acute symptomatic hyponatremia with Na < 120 mEq/L
Monitor sodium every 2-4 hours during correction. If overcorrection occurs, give dextrose 5% water (D5W) with desmopressin (DDAVP) to re-lower sodium. - Rosen's Emergency Medicine, p. 2522
5. Vaptans (Vasopressin V2 Receptor Antagonists)
- Tolvaptan (oral) and conivaptan (IV): cause aquaresis (free water excretion) without sodium loss
- Used for SIADH, heart failure-associated hyponatremia
- Avoid tolvaptan in liver disease (hepatotoxicity risk)
- Require monitoring for overcorrection
Hyponatremia in Special Populations
Cancer patients: Prevalence 4-47%; associated with doubled hospital length of stay and 3-5-fold increased 90-day mortality. SIADH most common mechanism (small cell lung cancer, head/neck tumors; chemo agents: cyclophosphamide, cisplatin, vincristine). Treatment mirrors general principles but directed at underlying malignancy. - Brenner & Rector, p. 1903-1921
Subarachnoid hemorrhage: Hyponatremia is common and management approaches are reviewed in a 2026 meta-analysis (PMID: 41730335).
Beer potomania: Low solute intake (beer + poor nutrition) limits the kidney's ability to excrete free water, causing hyponatremia even without excess ADH - reviewed in a 2025 systematic review (PMID: 40573123).
Key Mnemonics
SIADH criteria (CHIPES): CNS disorders, Hypothyroidism excluded, Infections/pulmonary, Pain/psychiatric meds, Ectopic ADH (malignancy), Surgical/postoperative
Hyponatremia risks: Too fast = demyelination (ODS); Too slow in acute setting = brain herniation. The art is finding the right rate.
Recent evidence note: A 2025 meta-analysis in JAMA Internal Medicine (PMID 39556338) reassessed correction rate thresholds and outcomes in severe hyponatremia - it is worth reviewing if current guideline updates are relevant to your clinical question.
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