Interactive physiology
Sodium & Water
Serum sodium reports water balance, not sodium balance. Its concentration sets plasma tonicity, tonicity moves water across cell membranes, and ADH and thirst defend it within a few mOsm/kg. Pick a scenario to watch a brain cell swell, shrink and adapt.
Normal volume
Plasma and cell are in osmotic equilibrium.
Na⁺ 140 mmol/L and glucose 5 mmol/L give an effective osmolality of 285 mOsm/kg. Water crosses the membrane both ways at equal rates, so the cell holds its volume.
Total body water 42.0 L. Water moves freely between all three spaces, so serum Na⁺ reflects exchangeable Na⁺ and K⁺ divided by total body water (Edelman). One litre of free water spread over 42 L lowers Na⁺ by about 3 mmol/L.
Control
ADH and thirst
Osmoreceptors in the hypothalamus release ADH (vasopressin) once plasma osmolality passes about 280–285 mOsm/kg. ADH inserts aquaporin-2 into the collecting duct, so urine concentrates within minutes. Thirst switches on a few mOsm/kg higher. Drag the marker.
Solid line: the active response. Dashed lines: the others for comparison. ADH and urine osmolality are model values that follow the classic human infusion studies.
Maximum free-water excretion
Even with ADH fully suppressed the kidney needs solute to carry water out. Daily urine volume cannot exceed the solute load divided by the lowest urine osmolality the kidney can reach.
600 mOsm/day ÷ 50 mOsm/kg = 12.0 L/day
Bedside
Hyponatraemia work-up
Enter the results and the path through the European 2014 algorithm (Spasovski et al.) lights up. Take serum and urine samples at the same time, ideally before treatment. Measured osmolality and urine studies do the sorting; clinical volume status comes last because it is the least reliable step.
Examples are illustrative values, not real patients.
Profound hyponatraemia · Na⁺ 122
Hypotonic hyponatraemia with a SIADH pattern
Decision path
Serum osmolality
Urine osmolality
Urine Na⁺
Diuretics or kidney disease?
ECF volume
Interpretation
SIADH: essential criteria
Supplemental features: serum uric acid below 0.24 mmol/L (4 mg/dL), urea below 3.6 mmol/L, failure to correct with 0.9% saline, and correction with fluid restriction.
Formulas used
Glucose-corrected Na⁺ = Na⁺ + 2.4 × (glucose mg/dL − 100) / 100 (Hillier). In mmol/L that is about + 0.43 per mmol/L of glucose above 5.5. The older Katz factor is 1.6 per 100 mg/dL.
Calculated osmolality = 2 × Na⁺ + glucose + urea, all in mmol/L. With mg/dL: 2 × Na⁺ + glucose/18 + BUN/2.8.
Osmolar gap = measured − calculated. Above 10 suggests unmeasured osmoles: ethanol, methanol, ethylene glycol, mannitol, glycine.
Effective osmolality = measured − urea. Urea crosses cell membranes freely, so it raises measured osmolality without moving water.
Treatment
Correction planner
The Adrogué–Madias formula predicts the change in serum Na⁺ from one litre of a chosen fluid, treating the body as a closed box of water. Use it to choose a starting rate, then let repeated Na⁺ measurements steer.
Expected rise 6 mmol/L · 115 → 121
0.65 L of 3% NaCl over 24 h, about 27 mL/h
Rate limits
Chronic hyponatraemia (≥ 48 h or unknown): aim for +4–8 mmol/L in 24 h. European 2014: do not exceed 10 mmol/L in the first 24 h and 8 mmol/L in each 24 h after that.
US expert panel 2013: minimum 4–8, limit 10–12 mmol/L per 24 h; limit 8 mmol/L per 24 h when osmotic-demyelination risk is high (Na⁺ ≤ 105, hypokalaemia, alcohol use disorder, malnutrition, advanced liver disease).
Chronic hypernatraemia: lower by ≤ 10 mmol/L per 24 h (about 0.5 mmol/L/h). Hypernatraemia known to be under 48 h old may be corrected faster.
Severe symptoms
Vomiting, seizures, reduced consciousness or cardiorespiratory distress: treat first, investigate after, whatever the timing.
European 2014: 150 mL 3% NaCl IV over 20 min, recheck Na⁺, repeat up to twice until Na⁺ has risen by 5 mmol/L.
US alternative: 100 mL 3% NaCl IV over 10 min, up to three times. Check local protocol.
Why the formula overshoots
It ignores ongoing losses and assumes urine output stays fixed. Once ADH switches off (volume repleted, thiazide stopped, cortisol replaced, nausea or pain relieved) a water diuresis can raise Na⁺ far faster than predicted. A sudden rise in dilute urine output is the warning sign.
Recheck Na⁺ every 2–4 h during active correction. Some units use a desmopressin clamp: desmopressin stops free-water excretion and the rise is then set by hypertonic saline alone. The same drugs can relower Na⁺ after an overshoot, under specialist guidance.
Reference
Classification and causes
Classifying hyponatraemia (European 2014)
| Axis | Category | Definition |
|---|---|---|
| Biochemical severity | Mild | Na⁺ 130–135 mmol/L |
| Moderate | Na⁺ 125–129 mmol/L | |
| Profound | Na⁺ < 125 mmol/L | |
| Time course | Acute | Documented < 48 h |
| Chronic | Documented ≥ 48 h, or duration unknown | |
| Symptoms | Moderately severe | Nausea without vomiting, confusion, headache |
| Severe | Vomiting, cardiorespiratory distress, abnormal and deep somnolence, seizures, coma (GCS ≤ 8) |
Causes of SIADH
| Group | Examples |
|---|---|
| Malignancy | Small-cell lung cancer above all; head and neck, gastrointestinal and genitourinary cancers, lymphoma |
| Pulmonary disease | Pneumonia, tuberculosis, lung abscess, positive-pressure ventilation |
| CNS disease | Meningitis, encephalitis, subarachnoid haemorrhage, stroke, head injury, brain tumour |
| Drugs | SSRIs, carbamazepine and oxcarbazepine, cyclophosphamide, vincristine, opioids, MDMA; desmopressin and oxytocin act on the V2 receptor directly |
| Non-osmotic stimuli | Pain, nausea, the postoperative state |
Causes of hypernatraemia
| Mechanism | Examples | Urine |
|---|---|---|
| Water loss without access to water | Older adults with impaired thirst or mobility, intubated or sedated patients, infants | Concentrated, low volume |
| Diabetes insipidus, central (AVP deficiency) | Pituitary surgery, head injury, tumours, infiltrative disease | Dilute, high volume |
| Diabetes insipidus, nephrogenic (AVP resistance) | Lithium, hypercalcaemia, hypokalaemia, inherited V2 receptor or aquaporin-2 defects | Dilute, high volume |
| Osmotic diuresis | Hyperglycaemia, mannitol, urea from high-protein feeds or recovering kidney injury | Isotonic-ish, high volume |
| Gastrointestinal and skin losses | Osmotic diarrhoea (including lactulose), vomiting, nasogastric drainage, burns, fever and sweating | Concentrated |
| Sodium gain | Hypertonic saline, sodium bicarbonate, salt ingestion | High Na⁺ |