Hyponatremia
Background
Pathophysiology
- Na+ is usually maintained at 135-144 mmol/L through an appropriate fluid balance. This is ensured by osmotic mechanisms (hypothalamic osmoreceptors) and non-osmotic mechanisms (hypovolaemia) which regulate ADH and thirst.
- ↓Na+ results most commonly from impaired water excretion, and less commonly from hypertonic urine loss or excess water ingestion.
- ↓Na+ is common (15% of hospital patients) and predicts poorer prognosis in many diseases, including those of the heart, liver, kidney, and brain.
- Severe ↓Na+ is defined as <120 mmol/L.
Classification
- Hypotonic (aka hypoosmotic). Commonest. Sub-classified into hypo-, eu-, and hyper-volaemic.
- Hypertonic: ↑glucose or mannitol pull H2O into ECF.
- Isotonic 'pseudo-hyponatraemia': artefact of measurement due to ↑proteins/lipids e.g. in multiple myeloma.
Causes of hypotonic hyponatraemia
- Renal causes: ↑Na+ in urine → ↓Na+ in serum.
- Non-renal causes: ↓Na+ in serum → ↓Na+ in urine.
Hypovolaemic (dry): ↓H2O, ↓↓Na+
Extra-renal sodium loss/deficiency, with urine Na+ <20:
- GI: ↓oral fluid intake, diarrhoea and vomiting.
- 3rd space: burns, pancreatitis, peritonitis.
Renal sodium loss, with urine Na+ >20:
- Excess diuretics, especially thiazides (may also be euvolaemic).
- Mineralocorticoid deficiency (Addison's).
- Renal salt losing disease e.g. interstitial nephritis, polycystic kidney disease.
- Cerebral salt wasting, post trauma or surgery.
Euvolaemic: ↑H2O, ↔Na+
Excess H2O intake, or at least greater than the kidney can excrete in the context of an illness or stressor that reduces renal blood flow. Urine Na+ <20. Due to:
- Excess IV fluid. A common cause in hospital, especially post-surgery.
- Excess oral fluid (polydipsia). Rare in normal contexts, but can occur among endurance athletes who follow fixed intake regimens and don't just rely on thirst. May also happen in the context of psychiatric illness (primary polydipsia) or drug use e.g. MDMA (ecstasy).
Failure of renal H2O excretion, with urine Na+ >20:
- Syndrome of inappropriate ADH secretion (SIADH).
- Endocrine: hypothyroidism (sometimes via SIADH), secondary adrenal insufficiency.
- NSAIDs: reduces prostaglandin-mediated suppression of ADH's renal effects.
Hypervolaemic (oedematous): ↑↑H2O,↑Na+
Organ failure, with urine Na+ <20:
- Heart failure
- Cirrhosis
- Nephrotic syndrome (rare as a cause of ↓Na+).
With urine Na+ >20:
- Advanced renal failure (AKI or CKD).
Signs and symptoms
- Headache
- Nausea, vomiting, and anorexia.
- Muscle cramps
- Tired, dizzy, disorientated.
- If severe: seizures, coma, cerebral oedema.
Signs of altered volume:
- ↓BP
- Peripheral oedema.
Symptoms with gradual onset:
- Symptoms may be mild if onset is gradual, with Na+ falling over days to weeks. This is due to cerebral adaptation, with neurons releasing inorganic (Na+, Cl-, K+) and organic osmolytes to preserve osmolality.
- However, it is possible that a lot of apparently 'asymptomatic' hyponatraemia in fact leads to an increased risk of falls due to subtle neurological effects.
Investigations
Na+ and osmolality
- Urine Na+ is a marker of aldosterone (and hence renin-angiotensin) activity. Low (<20 mmol/L) in hypovolaemia (↑aldosterone retains Na+) and excess H2O intake, but high in euvolaemia and renal Na+ loss.
- Urine osmolality is a marker of ADH activity. High (>100 mOsmol/kg) when ADH is active, concentrating urine, either appropriately in hypovolaemia or inappropriately in SIADH. Low (less common) in excess H2O intake.
Summary of urine findings by cause:
- Hypovolaemia: ↓Na+ and ↑osmo, as body retains salt and water. Also seen in hypervolaemia, as there may be intra-vascular hypovolaemia.
- SIADH and Addison's: ↑osmo and ↑Na+.
- Excess H2O intake: ↓Na+ and ↓osmo.
Note that most lab assays measure osmolality, but the difference between osmolality (mOsmol/kg) and osmolarity (mOsmol/L) is not clinically important.
Other investigations
- Lying-standing BP may be useful to detect hypovolaemia if there is uncertainty.
- Investigation of underlying cause is guided by the clinical picture, but basic tests would include FBC, U&E, LFT, cortisol, and TFT.
Management
- Investigate cause. Proceed to initiate treatment before investigations complete if patients are symptomatic.
- Slowly give normal saline if hypovolaemic, otherwise fluid restrict. If cause unclear (hypo vs. euvolaemic), give 2 L normal saline challenge over 24 hours → Na+ rise = hypovolaemia.
- Re-check Na+ regularly.
- Consider demeclocycline (ADH antagonist) or a vaptan (ADH-R antagonist aka vasopressin receptor antagonist) if fluid restriction ineffective.
Severe symptoms (coma/seizures), SALTY:
- HDU/ICU transfer and 3% SAline 1-2 ml/kg/hr.
- Loop diuretic (furosemide) if not hypovolaemic.
- Re-check Na+ every 2 hours. Aim to increase Na+ by 0.5 mmol/L/hr, up to Ten mmol/L/24hr, until 125 mmol/L or clinically well.
- Y is it happening? Investigate cause once stabilised.
Beware rapid Na+ replacement as there is a risk of osmotic demyelination syndrome (aka central pontine myelinolysis), which can present at 2-5 days with:
- Altered mental status: confusion, fatigue, coma.
- Motor impairment: pseudobulbar palsy, quadriplegia.
Syndrome of inappropriate ADH secretion (SIADH)
Diagnosis
- Diagnose if all other causes of euvolemic hyponatraemia have been ruled out.
- Serum hypotonic hyponatraemia – Na+ <130 mmol/L, osmolality <275 mOsmol/kg – and concentrated urine – Na+ >20 mmol/L, urine osmolality > serum osmolality.
Causes
- Cancer: small cell lung cancer, pancreatic, prostate, thymus, lymphatic.
- Chest: TB, pneumonia, abscess, aspergillosis.
- CNS: meningitis, abscess, stroke, SAH/SDH, trauma/surgery, GBS, vasculitis, SLE.
- Carbamazepine and other CNS drugs: opiates, anti-psychotics, SSRIs, MDMA. The other common drug cause is omeprazole.
- Very rarely, hypothyroidism.
Management
- Treat cause.
- Restrict fluids.
- If severe, consider hypertonic saline and loop diuretics.
- If chronic (>48 hours), consider a vaptan e.g. tolvaptan.
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