Hyponatraemia

1. Introduction
2. Definitions and Severity
3. Why Hyponatraemia Matters
4. Approach: Tonicity and Clinical Assessment
5. Non-Hypotonic Hyponatraemia
   • Hypertonic Hyponatraemia
   • Isotonic (Pseudohyponatraemia)
6. Hypotonic Hyponatraemia
   • Hypovolaemic
   • Euvolaemic
   • Hypervolaemic
7. SIADH
8. Investigations
9. Clinical Features
10. Principles of Management
11. Summary
12. Quiz

• Hyponatraemia is defined as a serum sodium concentration below 135 mmol/L (millimoles per litre). It is the most common electrolyte abnormality in hospital practice. It results from a relative excess of body water compared with total body sodium.
• The first triage step is to confirm that the hyponatraemia is hypotonic. This means that the plasma osmolality (the concentration of dissolved particles in the blood) is low. Hyperglycaemia (high blood glucose) or mannitol (an osmotic drug sometimes given to reduce pressure inside the skull) can produce hyponatraemia with normal or raised osmolality. Severe hyperlipidaemia (high blood fats) or paraproteinaemia (excess abnormal antibody protein in the blood) can produce a laboratory artefact (pseudohyponatraemia) with normal osmolality.
• Hypotonic hyponatraemia is then classified by volume status. Hypovolaemic means low circulating volume, from renal (kidney) or extra-renal losses. Euvolaemic means normal volume. The causes of euvolaemic hyponatraemia are the syndrome of inappropriate antidiuresis (SIAD, also called SIADH, in which the kidneys hold on to water and pass concentrated urine), hypothyroidism (underactive thyroid, a very rare cause), glucocorticoid deficiency (too little cortisol, the main glucocorticoid hormone) and primary polydipsia (excessive drinking). Hypervolaemic means fluid overload. The causes of hypervolaemic hyponatraemia are heart failure, cirrhosis, nephrotic syndrome (kidney disease with heavy protein loss in the urine) and advanced renal failure.
• The major risk of treatment is osmotic demyelination syndrome (damage to myelin, the insulating sheath around nerve fibres, formerly called central pontine myelinolysis), caused by overly rapid correction. The sodium should rise by no more than 10 mmol/L in 24 hours and 18 mmol/L in 48 hours. Severe symptomatic hyponatraemia is an emergency. It needs prompt treatment with hypertonic saline (a concentrated sodium chloride solution), supervised by a senior clinician in a monitored setting.

Introduction

The plasma sodium concentration is one of the most tightly regulated variables in physiology, normally kept between 135 and 145 mmol/L by the coordinated action of antidiuretic hormone (ADH) and thirst. The serum sodium is in fact a measure of body water rather than total body sodium; if water intake or retention rises faster than sodium intake, the sodium concentration falls.

This article follows a structured approach to hyponatraemia. First define it. Then work out whether the low sodium is genuinely hypotonic, meaning that the plasma tonicity (its effective concentration) is low. Next classify by volume status to find the cause. Finally, think carefully about how to correct it. The underlying physiology is in Control of Plasma Osmolarity and Control of Plasma Volume.

Definitions and Severity

Hyponatraemia is defined biochemically as serum sodium below 135 mmol/L. It is conventionally graded:

• Mild: 130-134 mmol/L.
• Moderate: 125-129 mmol/L.
• Severe: below 125 mmol/L.

An equally important axis is the rate of fall, which determines the symptom burden:

• Acute: documented to have developed within 48 hours.
• Chronic: present for longer than 48 hours, or duration unknown (always assume chronic if the timeline is not certain).

An acute fall to 125 mmol/L can cause cerebral oedema and seizures, whereas a chronic value of 120 mmol/L may produce only mild lethargy (unusual tiredness and low energy) or be entirely asymptomatic. The brain compensates for chronic hypotonicity by pushing out intracellular osmolytes (small dissolved particles that hold water inside cells, such as potassium, taurine and myo-inositol). This adaptation takes hours to days, which is why fast correction of chronic hyponatraemia is dangerous. If sodium is corrected quickly, plasma osmolality rises before the osmolytes can be put back, so brain volume falls below normal.

Why Hyponatraemia Matters

Hyponatraemia is common: it is estimated to occur in about 15 to 20% of emergency hospital admissions. It is associated with higher mortality, although it is uncertain whether this is due to the low sodium itself or to the underlying illness and medicines. It is clinically important for three reasons:

• It causes neurological symptoms (lethargy, confusion, falls, seizures and coma) through osmotic swelling of brain cells.
• It usually points to an important underlying cause: heart failure, cirrhosis, malignancy (cancer), adrenal insufficiency (too little adrenal hormone), hypothyroidism (underactive thyroid, a very rare cause) or a disturbance caused by diuretics.
• Its treatment is itself dangerous: too rapid correction can cause osmotic demyelination (damage to the myelin around nerve fibres) that may be irreversible, while too slow correction can leave a symptomatic patient with cerebral oedema.

Approach: Tonicity and Clinical Assessment

Assess symptoms and volume status immediately, alongside repeat sodium, glucose and plasma osmolality. Osmolality classifies tonicity; once hypotonic hyponatraemia is established, clinical findings and urine tests help identify the cause. This diagnostic sequence must not delay examination or urgent treatment for severe symptoms. See the Gloucestershire Hospitals NHS Foundation Trust hyponatraemia guideline (2024 update), a local guideline that draws on Society for Endocrinology guidance. For a national summary, see the NICE Clinical Knowledge Summaries (CKS) topic on hyponatraemia.

1. Measure plasma osmolality to confirm that the hyponatraemia is genuinely hypotonic. Most hyponatraemia is hypotonic, but a small but important group is not, and the wrong treatment in those patients can be harmful.
2. Assess volume status clinically and biochemically (urine sodium and urine osmolality) to sort the cause into hypovolaemic (low volume), euvolaemic (normal volume) or hypervolaemic (fluid overload) categories.

Diagram: laboratory classification of hyponatraemia by tonicity and clinical findings (P_osm = plasma osmolality, U_Na = urine sodium, IVIg = intravenous immunoglobulin, AKI = acute kidney injury). Assess symptoms and volume status immediately while investigations proceed; do not wait for osmolality before examining the patient. Correction must respect the rate limit regardless of category.

Non-Hypotonic Hyponatraemia

Hypertonic Hyponatraemia

An additional osmotically active solute in the extracellular fluid (something that does not enter cells) draws water out of cells, diluting plasma sodium. The classical examples are:

• Hyperglycaemia. Each 5 mmol/L rise in plasma glucose above the upper limit of normal lowers measured sodium by approximately 2 mmol/L. The hyponatraemia is real (not artefactual) but the management is to correct the glucose; sodium will rise as water re-enters cells. Always correct measured sodium for glucose before interpreting.
• Mannitol and similar non-permeating solutes (solutes that cannot cross cell membranes, so they stay outside cells and draw water out of them). Mannitol is used in raised intracranial pressure or as an osmotic diuretic.
• Maltose (a sugar used as a stabiliser) in concentrated immunoglobulin preparations (intravenous immunoglobulin, IVIg): an under-recognised cause in hospital practice.

Isotonic (Pseudohyponatraemia)

Pseudohyponatraemia is a laboratory artefact, not a real biochemical change. Flame photometry (older, measuring sodium by the light it gives off in a flame) and indirect ion-selective electrode (ISE) methods (which dilute the sample before measuring, and are the most widely used laboratory method) report sodium as a concentration in total plasma volume, including the lipid and protein fraction. Sodium is carried only in the plasma water. When the lipid or protein fraction is enlarged, there is less water in each litre of plasma. This happens in severe hypertriglyceridaemia (very high triglycerides, a type of fat), other severe hyperlipidaemia (very high blood fats) and paraproteinaemia (excess abnormal antibody protein). The reported sodium then falls, although the sodium concentration in the plasma water and the osmolality are normal.

Clues:

• Normal measured plasma osmolality.
• The patient is asymptomatic and has none of the usual causes.
• The discrepancy resolves when sodium is measured by direct ISE on undiluted plasma or whole blood (e.g. on a blood gas analyser).

Pseudohyponatraemia requires no treatment. The underlying lipid or protein abnormality is treated separately.

Hypotonic Hyponatraemia

Hypotonic hyponatraemia (the ‘real’ hyponatraemia) is then divided by volume status. Volume status is judged clinically from skin turgor (how quickly pinched skin springs back), mucous membranes (the moist lining of the mouth), jugular venous pressure (the height of the pulsation in the neck veins), postural blood pressure (the fall in blood pressure on standing), oedema and ascites (fluid in the abdominal cavity). These signs are not very reliable and can misclassify the cause, so volume status is interpreted together with urine sodium and urine osmolality.

Hypovolaemic

Total body water is low; total body sodium is even lower. The patient looks dry. The cause is loss of sodium in excess of water. ADH (antidiuretic hormone, released in response to volume depletion) then makes the kidneys retain water. This partly restores the volume but dilutes the sodium.

Sub-classify by urine sodium:

• Urine Na⁺ < 30 mmol/L: extra-renal losses (losses from outside the kidneys), with the kidneys appropriately conserving sodium. Causes include vomiting, diarrhoea, severe burns, third-space sequestration (fluid trapped outside the circulation, for example in pancreatitis or ileus, a paralysed bowel) and excessive sweating.
• Urine Na⁺ > 30 mmol/L: renal losses (losses through the kidneys), with the kidney inappropriately wasting sodium. Causes include thiazide diuretics (water tablets such as bendroflumethiazide; the single most common drug-induced hyponatraemia), acute kidney injury, salt-losing nephropathy (kidney disease that leaks sodium), mineralocorticoid deficiency (loss of aldosterone, the adrenal hormone that makes the kidney retain sodium, as in Addison's disease, where the adrenal glands fail) and cerebral salt wasting (a rare cause after brain injury or brain surgery, in which the kidneys lose sodium).

The principle of correction is to restore volume with isotonic saline (0.9% sodium chloride). Once volume is restored, ADH switches off and the kidney excretes the surplus water. This loss of water can be abrupt, so the rate of rise in serum sodium must still be controlled.

Euvolaemic

Total body sodium is essentially normal but total body water is increased. The patient appears clinically euvolaemic: no oedema, no signs of dehydration. Causes:

• Syndrome of inappropriate antidiuresis (SIADH): covered in detail in the next section.
• Hypothyroidism (underactive thyroid): a very rare cause. Severe hypothyroidism may cause hyponatraemia, possibly by reducing cardiac output and the glomerular filtration rate (the rate at which the kidneys filter blood).
• Glucocorticoid deficiency (too little cortisol, the main glucocorticoid hormone): cortisol normally helps to keep ADH suppressed, so without it ADH stays active and the body retains water inappropriately. This is the pattern in secondary adrenal insufficiency (too little ACTH, adrenocorticotropic hormone, the pituitary hormone that drives cortisol release), for example after abrupt withdrawal of long-term steroid treatment. In primary adrenal insufficiency (Addison's disease) aldosterone is also lost, so it is usually listed with the hypovolaemic causes above. See The Adrenal Glands and Adrenal Disorders.
• Primary polydipsia (excessive drinking): intake of so much water that even maximally suppressed ADH and a normal kidney cannot keep up. Urine osmolality is appropriately low (< 100 mOsm/kg, milliosmoles per kilogram).
• Beer-drinker's potomania / "tea and toast" diet: potomania means drinking excessive amounts of fluid. Inadequate solute (dissolved particle) intake limits the kidney's ability to excrete free water (water without solute). The biochemical picture is the same as primary polydipsia, at lower volumes of fluid intake.
• Exercise-associated hyponatraemia: described in endurance athletes such as marathon runners, and in military personnel, who drink large volumes of hypotonic fluid (fluid more dilute than plasma) during prolonged exercise. ADH is also released by non-osmotic stimuli, which means stimuli other than a raised plasma osmolality, such as physical stress, pain and nausea.

Hypervolaemic

Total body water is increased; total body sodium is also increased, but water retention has outpaced sodium retention. The patient is oedematous. In heart failure and cirrhosis the underlying mechanism is a reduced effective circulating volume (the volume the body senses as filling the arteries, which is low even though total body water is high). Baroreceptors (pressure sensors in the arteries and chest) detect this and drive ADH release. In advanced renal failure the dominant mechanism is a primary failure to excrete free water.

The principal causes are:

• Heart failure: see Heart Failure.
• Liver cirrhosis with portal hypertension (raised pressure in the portal vein) and splanchnic vasodilatation (widening of the blood vessels supplying the gut): see Hepatic, Biliary and Pancreatic Pathology.
• Nephrotic syndrome (heavy protein loss in the urine): reduced plasma oncotic pressure (the pull of plasma proteins that holds water in the blood vessels) shifts fluid into the interstitium (the space between cells).
• Advanced renal failure: failure to excrete water, see Chronic Kidney Disease.

Urine sodium in hypervolaemic states is usually ≤ 30 mmol/L (the kidneys avidly retain sodium). It can be higher in advanced renal failure and in people taking diuretics.

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