Medicine – Causes of Hyponatraemia

Hyponatraemia is a reduction in the serum sodium concentration, usually defined as:

Serum Na⁺ <135 mmol/L.

An important principle is that hyponatraemia is usually a disorder of water balance relative to sodium, rather than simply a lack of sodium in the body. In many cases, there is too much water relative to the amount of exchangeable sodium and potassium.

A useful clinical approach is to first determine whether the hyponatraemia is truly hypotonic, and then assess the patient’s extracellular fluid volume status.

1. Modern Classification of Hyponatraemia

Hyponatraemia is best approached as:

Hypovolaemic hyponatraemia – patient is volume depleted/dehydrated.

Euvolaemic hyponatraemia – no obvious volume depletion or oedema.

Hypervolaemic hyponatraemia – excess total body water with oedema/volume expansion.

There are also:

Non-hypotonic forms of hyponatraemia, including hyperglycaemia-related hyponatraemia and true laboratory pseudohyponatraemia.

This is more precise than simply dividing patients into:

“dehydrated” versus “well hydrated.”

2. Why Serum Sodium Falls

Serum sodium concentration reflects the relationship between:

Body sodium/potassium

and

Body water.

Therefore serum sodium can fall because:

Sodium is lost and replaced with relatively more water.

or

Excess water is retained.

or

Water shifts from cells into extracellular fluid.

or, occasionally,

A laboratory measurement artefact produces pseudohyponatraemia.

3. Hypovolaemic Hyponatraemia

In hypovolaemic hyponatraemia, the patient has lost both:

Sodium

and

Water.

However, sodium loss is proportionally greater, or the losses are subsequently replaced with relatively hypotonic fluid.

The resulting reduction in effective circulating volume stimulates:

ADH secretion.

ADH then promotes water retention, which further lowers serum sodium.

4. Clinical Features of Hypovolaemia

Depending on severity, the patient may have:

Thirst.

Dry mucous membranes.

Reduced skin turgor.

Postural hypotension.

Tachycardia.

Reduced jugular venous pressure.

Oliguria.

Severe volume depletion may progress to:

Hypotension and circulatory shock.

5. Diuretic Excess

The original notes correctly identify:

Diuretic excess

as an important cause of hypovolaemic hyponatraemia.

The most important drug association is:

Thiazide diuretics.

Thiazides impair urinary dilution while causing renal sodium loss.

Therefore:

THIAZIDE → Na⁺ LOSS + IMPAIRED FREE-WATER EXCRETION → HYPONATRAEMIA.

6. Thiazides Versus Loop Diuretics

Although both can cause volume and electrolyte depletion, clinically significant hyponatraemia is particularly associated with:

Thiazides.

Loop diuretics can also contribute, but they interfere with the renal medullary concentration gradient and are generally less characteristically associated with severe hyponatraemia than thiazides.

7. Gastrointestinal Loss

The original notes correctly include:

Vomiting

and

Diarrhoea.

Both can produce:

Extrarenal sodium and water loss.

The resulting hypovolaemia stimulates:

ADH.

If the patient drinks water or receives relatively hypotonic replacement fluid:

Serum sodium can fall further.

8. Vomiting

Persistent vomiting causes loss of:

Hydrogen ions.

Chloride.

Sodium and water.

Volume depletion activates:

RAAS + ADH.

Therefore vomiting can produce:

Hypovolaemic hyponatraemia.

It is also characteristically associated with:

Hypokalaemic metabolic alkalosis.

9. Diarrhoea

Severe diarrhoea causes substantial loss of:

Water.

Sodium.

Potassium.

Bicarbonate.

Therefore a patient may develop:

Hypovolaemia + hyponatraemia + hypokalaemia + normal-anion-gap metabolic acidosis.

10. Addison Disease

The original notes correctly identify:

Addison disease – primary adrenal insufficiency.

This is an important endocrine cause of hyponatraemia.

Primary adrenal insufficiency produces deficiencies of:

Cortisol

and

Aldosterone.

11. Why Addison Disease Causes Hyponatraemia

Aldosterone deficiency causes:

Renal sodium loss.

↓

Volume depletion.

↓

Cortisol deficiency also increases:

ADH secretion.

↓

Water retention.

↓

Hyponatraemia.

Because aldosterone normally promotes potassium excretion, primary adrenal insufficiency may also cause:

Hyperkalaemia.

Therefore:

HYPONATRAEMIA + HYPERKALAEMIA + HYPOTENSION → THINK PRIMARY ADRENAL INSUFFICIENCY.

12. Renal Sodium Loss

The original notes include:

Renal failure – diuretic phase.

A better modern description is that renal sodium loss can occur during certain phases of:

Recovering acute kidney injury, particularly when urine output increases before tubular reabsorptive function has fully recovered.

This can produce:

Polyuria + sodium loss + potassium loss + volume depletion.

However, kidney disease can cause hyponatraemia through several different mechanisms, so it should not automatically be classified as hypovolaemic.

13. Other Renal Causes of Hypovolaemic Hyponatraemia

Other causes of renal sodium wasting include:

Salt-wasting nephropathies.

Mineralocorticoid deficiency.

Cerebral salt wasting in selected neurological patients.

The key clue is:

Volume depletion despite inappropriate urinary sodium loss.

14. Hyperglycaemia – Important Correction

The original notes describe DKA as:

“Pseudo-hyponatraemia because glucose is very high.”

This requires an important correction.

Hyperglycaemia usually causes:

Hypertonic/translocational hyponatraemia, not true laboratory pseudohyponatraemia.

15. Why Hyperglycaemia Lowers Sodium

When extracellular glucose becomes markedly elevated:

Extracellular osmolality rises.

↓

Water moves:

From intracellular → extracellular fluid.

↓

Extracellular water dilutes sodium.

↓

Measured serum sodium falls.

Therefore:

HYPERGLYCAEMIA → WATER SHIFTS OUT OF CELLS → DILUTION OF SERUM Na⁺.

This is particularly relevant in:

DKA

and

Hyperosmolar hyperglycaemic state – HHS.

16. Corrected Sodium in Hyperglycaemia

Because hyperglycaemia lowers the measured sodium through water redistribution, clinicians may estimate a:

Corrected serum sodium.

The exact correction varies with glucose concentration and formula used, but the central concept is:

The measured Na⁺ underestimates what the sodium would be after glucose is normalised.

Therefore DKA-associated low sodium should not simply be labelled:

Pseudohyponatraemia.

17. Euvolaemic Hyponatraemia

In euvolaemic hyponatraemia, there is:

No obvious clinical dehydration

and

No major peripheral oedema.

The most important cause is:

SIADH.

Other causes include:

Adrenal insufficiency.

Severe hypothyroidism in appropriate settings.

Primary polydipsia/water excess.

Low-solute intake.

18. SIADH

The original notes correctly identify:

Syndrome of inappropriate antidiuretic hormone secretion – SIADH

as a major cause of euvolaemic hyponatraemia.

In SIADH:

Inappropriate ADH effect

↓

↑ Renal water reabsorption

↓

Water retained disproportionately to sodium

↓

Dilutional hyponatraemia.

19. Typical SIADH Pattern

The characteristic pattern is:

↓ Serum Na⁺.

↓ Serum osmolality.

Inappropriately concentrated urine.

Urine osmolality usually >100 mOsm/kg.

Urinary sodium often >30 mmol/L when intake and renal function are appropriate.

Clinical euvolaemia.

Before diagnosing SIADH, important mimics such as:

Adrenal insufficiency

should be excluded.

20. Hypothyroidism

The original notes include:

Hypothyroidism.

Severe hypothyroidism can impair free-water excretion and contribute to:

Hyponatraemia.

However, mild or uncomplicated hypothyroidism is a much less common explanation for significant hyponatraemia than older teaching sometimes implies.

The association is strongest with:

Severe hypothyroidism/myxoedema.

21. Water Overload

Excessive water intake can overwhelm the kidneys’ ability to excrete free water.

This may occur with:

Primary polydipsia.

Psychogenic polydipsia.

Excessive hypotonic fluid administration.

If water intake exceeds maximal renal excretory capacity:

Plasma becomes diluted

↓

Hyponatraemia develops.

22. Primary Polydipsia

Primary polydipsia is particularly associated with:

Very high water intake.

Unlike SIADH, ADH is appropriately suppressed.

Therefore the urine is generally:

Very dilute.

This distinction is useful:

SIADH → urine inappropriately concentrated.

Primary polydipsia → urine appropriately very dilute.

23. Alcohol Excess – Important Clarification

The original notes include:

Alcohol excess.

Alcohol itself does not provide one single mechanism for hyponatraemia.

An important alcohol-associated condition is:

Low-solute intake, classically called beer potomania.

24. Beer Potomania

Patients consuming large quantities of beer while eating very little may have extremely low dietary:

Protein

and

Salt/solute.

The kidneys require solute to excrete water efficiently.

Therefore:

Very low solute intake + substantial fluid intake

↓

Limited renal free-water excretion

↓

Hyponatraemia.

A similar mechanism can occur with other forms of severe low-solute nutrition.

25. Hypervolaemic Hyponatraemia

Several conditions listed under the original heading:

“Patient well hydrated”

are actually better classified as:

Hypervolaemic hyponatraemia.

These include:

Congestive heart failure.

Liver cirrhosis.

Nephrotic syndrome.

Advanced kidney failure.

These patients have increased total-body water and often increased total-body sodium, but:

Water retention exceeds sodium retention.

26. Congestive Heart Failure

The original notes correctly identify:

Congestive cardiac failure – heart failure.

In significant heart failure, cardiac output and effective arterial blood volume fall.

The kidneys interpret this as inadequate perfusion despite the patient having excess total body fluid.

This activates:

RAAS.

Sympathetic nervous system.

ADH.

27. Why Heart Failure Causes Hyponatraemia

↓ Effective arterial blood volume

↓

↑ ADH

↓

↑ Free-water retention

↓

Water retention exceeds sodium retention

↓

Dilutional hyponatraemia.

Therefore patients may simultaneously have:

Peripheral oedema + pulmonary congestion + hyponatraemia.

28. Liver Cirrhosis

The original notes correctly include:

Liver cirrhosis.

Advanced cirrhosis causes:

Splanchnic vasodilatation

and reduced effective arterial blood volume.

This activates:

RAAS + sympathetic activity + ADH.

The result is:

Sodium retention + even greater water retention.

Therefore:

CIRRHOSIS → ASCITES/OEDEMA + DILUTIONAL HYPONATRAEMIA.

29. Nephrotic Syndrome

The original notes correctly include:

Nephrotic syndrome.

Severe nephrotic syndrome causes:

Heavy proteinuria

↓

Hypoalbuminaemia

↓

Altered effective circulating volume in some patients

↓

Neurohormonal sodium/water retention

↓

Oedema.

If water retention is excessive relative to sodium, hyponatraemia can develop.

30. Kidney Failure

Kidney failure can produce hyponatraemia because the kidneys may lose the ability to:

Excrete free water effectively.

If water intake exceeds renal excretory capacity:

Water accumulates

↓

Dilutional hyponatraemia.

Therefore advanced kidney failure commonly belongs conceptually to the:

Hypervolaemic or impaired-water-excretion group, rather than simply the “dehydrated” group.

31. Hypoalbuminaemia – Important Clarification

The original notes list:

Hypoalbuminaemia

as a cause.

Hypoalbuminaemia itself does not automatically produce hyponatraemia.

Rather, disorders associated with severe hypoalbuminaemia—such as:

Cirrhosis

or

Nephrotic syndrome

may produce reduced effective circulating volume and neurohormonal water retention.

Therefore it is better to identify the:

Underlying disease and volume status

rather than treating hypoalbuminaemia itself as a stand-alone major mechanism.

32. Pseudohyponatraemia

True:

Pseudohyponatraemia

is a laboratory measurement artefact.

It can occur when the non-aqueous fraction of plasma becomes markedly increased, particularly with extreme:

Hyperlipidaemia

or

Hyperproteinaemia.

33. Hyperlipidaemia

The original notes correctly associate severe:

Hyperlipidaemia

with pseudohyponatraemia.

Marked lipid elevation reduces the proportion of the plasma sample composed of water.

Certain laboratory methods using:

Indirect ion-selective electrodes

can then report a falsely low sodium concentration.

34. Pseudohyponatraemia and Plasma Osmolality

Because the actual sodium concentration in the plasma water is normal:

Plasma tonicity is not reduced by the pseudohyponatraemia itself.

Therefore:

PSEUDOHYPONATRAEMIA = LOW REPORTED Na⁺ WITHOUT TRUE HYPOTONICITY.

Modern direct ion-selective electrode measurements, such as those commonly used in blood-gas analysers, are not affected in the same way.

35. Hyperproteinaemia

Another classic cause of true pseudohyponatraemia is severe:

Hyperproteinaemia.

This can occur in conditions such as:

Paraproteinaemia, for example selected plasma-cell disorders.

Therefore:

Extreme lipids/proteins + low Na⁺ + normal measured tonicity → consider pseudohyponatraemia.

36. Hyperglycaemia Versus Pseudohyponatraemia

This distinction is particularly important:

HYPERGLYCAEMIA

causes:

Hypertonic/translocational hyponatraemia.

The sodium is genuinely diluted by movement of water into extracellular fluid.

SEVERE HYPERLIPIDAEMIA/HYPERPROTEINAEMIA

can cause:

Laboratory pseudohyponatraemia

with certain measurement techniques.

Therefore:

DKA ≠ classic pseudohyponatraemia.

37. Symptoms of Hyponatraemia

Symptoms depend strongly on:

Severity

and especially:

Speed of development.

Mild or slowly developing hyponatraemia may cause:

Nausea.

Headache.

Fatigue.

Difficulty concentrating.

Gait disturbance.

Confusion.

38. Severe Acute Hyponatraemia

A rapid fall in sodium causes water to enter brain cells.

This can produce:

Cerebral oedema.

Severe manifestations include:

Vomiting.

Marked confusion.

Seizures.

Reduced consciousness.

Coma.

Therefore:

ACUTE SEVERE SYMPTOMATIC HYPONATRAEMIA IS A MEDICAL EMERGENCY.

39. Initial Investigation

When hyponatraemia is discovered, the first important questions are:

Is it truly hypotonic?

What is the patient’s volume status?

Is ADH appropriately suppressed or active?

Useful investigations include:

Serum osmolality.

Urine osmolality.

Urinary sodium.

Glucose.

Renal function.

Potassium.

Further endocrine testing may include adrenal and thyroid assessment when indicated.

40. Step 1 – Check Serum Osmolality

Low serum osmolality

suggests:

True hypotonic hyponatraemia.

High serum osmolality

with hyponatraemia suggests an effective extracellular osmole, classically:

Severe hyperglycaemia.

A low reported sodium without corresponding hypotonicity may suggest:

Pseudohyponatraemia, depending on the clinical and laboratory context.

41. Step 2 – Check Urine Osmolality

If urine is:

Very dilute, around ≤100 mOsm/kg,

ADH is largely suppressed.

Think particularly about:

Primary polydipsia

or

Very low solute intake.

If urine is:

>100 mOsm/kg,

ADH is active.

The next step is to determine:

Why ADH is active.

42. Step 3 – Assess Volume Status and Urinary Sodium

In hypovolaemia, ADH secretion is physiologically appropriate because the body is attempting to preserve circulating volume.

Urinary sodium can then help distinguish:

Extrarenal sodium loss

from

Renal sodium loss.

For example:

Diarrhoea → kidneys generally conserve sodium.

Whereas:

Diuretics/mineralocorticoid deficiency → urinary sodium loss may persist.

Interpretation can be complicated by recent diuretic use and kidney disease.

43. Hypovolaemic Hyponatraemia – Note Form

GI LOSS:

Vomiting.

Diarrhoea.

RENAL LOSS:

Thiazide diuretics – particularly important.

Other diuretics.

Salt-wasting renal disease.

Recovering AKI with excessive urinary losses.

ENDOCRINE:

Primary adrenal insufficiency – Addison disease.

Think:

Low Na⁺ + high K⁺ + hypotension.

44. Euvolaemic Hyponatraemia – Note Form

SIADH – major cause.

Adrenal insufficiency.

Severe hypothyroidism.

Primary polydipsia/water excess.

Low-solute intake, including beer potomania.

45. Hypervolaemic Hyponatraemia – Note Form

HEART FAILURE:

Reduced effective arterial volume

↓

ADH activation

↓

Water retention

↓

Hyponatraemia + oedema/congestion.

LIVER CIRRHOSIS:

Splanchnic vasodilatation

↓

Reduced effective arterial volume

↓

ADH + RAAS activation

↓

Ascites/oedema + hyponatraemia.

NEPHROTIC SYNDROME:

Heavy proteinuria + oedema physiology

↓

Sodium/water retention

↓

Possible dilutional hyponatraemia.

ADVANCED KIDNEY FAILURE:

Impaired free-water excretion

↓

Water accumulation

↓

Dilutional hyponatraemia.

46. Non-Hypotonic Hyponatraemia – Note Form

HYPERGLYCAEMIA:

High extracellular glucose

↓

Water shifts out of cells

↓

Serum sodium diluted

↓

Hypertonic/translocational hyponatraemia.

This is not classic pseudohyponatraemia.

SEVERE HYPERLIPIDAEMIA:

Laboratory measurement artefact with susceptible methods

↓

Pseudohyponatraemia.

SEVERE HYPERPROTEINAEMIA:

Laboratory measurement artefact

↓

Pseudohyponatraemia.

47. Treatment Principles

Treatment depends completely on:

The cause.

Volume status.

Severity of symptoms.

Duration of hyponatraemia.

A patient with hypovolaemic hyponatraemia requires a different strategy from someone with SIADH or heart failure.

48. Hypovolaemic Hyponatraemia Treatment

The underlying sodium and volume deficit generally needs correction, often using:

Isotonic saline

when clinically appropriate.

Restoration of effective circulating volume suppresses the non-osmotic ADH stimulus, allowing the kidneys to excrete excess water.

The underlying cause must also be treated.

49. SIADH Treatment

Depending on severity and context, treatment may include:

Fluid restriction

and treatment of the underlying cause.

Selected persistent cases may require other specialist therapies.

50. Severe Symptomatic Hyponatraemia

Patients with severe neurological manifestations such as:

Seizures or markedly impaired consciousness

may require carefully controlled:

Hypertonic saline.

Serum sodium must be monitored closely.

51. Danger of Rapid Correction

Overly rapid correction of chronic hyponatraemia can cause:

Osmotic demyelination syndrome – ODS.

Therefore:

CHRONIC HYPONATRAEMIA MUST NOT BE CORRECTED TOO RAPIDLY.

The risk is particularly important in patients with severe chronic hyponatraemia, malnutrition, alcohol-related disease, liver disease or hypokalaemia.

52. Important Corrections to the Original Notes

The original division into:

“Patient dehydrated”

and

“Patient well hydrated”

is useful as a starting point, but the more accurate classification is:

HYPOVOLAEMIC + EUVOLAEMIC + HYPERVOLAEMIC HYPONATRAEMIA.

Heart failure, cirrhosis and nephrotic syndrome should not simply be described as “well hydrated.”

These patients are typically:

Hypervolaemic, often with oedema or ascites, while their effective arterial circulating volume is reduced.

The original statement:

“DKA = pseudohyponatraemia because glucose is very high”

should be corrected to:

DKA/HYPERGLYCAEMIA → HYPERTONIC TRANSLOCATIONAL HYPONATRAEMIA.

True laboratory:

Pseudohyponatraemia

is classically associated with extreme:

Hyperlipidaemia

or

Hyperproteinaemia

when susceptible laboratory measurement methods are used.

Hypoalbuminaemia alone should not be memorised as a major independent cause. Think instead of the underlying disease, such as:

Cirrhosis or nephrotic syndrome.

Key Clinical Pattern

For rapid recall, approach hyponatraemia according to tonicity first, then volume status.

LOW Na⁺ + LOW SERUM OSMOLALITY = TRUE HYPOTONIC HYPONATRAEMIA.

HYPOVOLAEMIC:

Think:

DIURETICS + VOMITING + DIARRHOEA + ADDISON DISEASE.

EUVOLAEMIC:

Think:

SIADH + ADRENAL INSUFFICIENCY + SEVERE HYPOTHYROIDISM + PRIMARY POLYDIPSIA + LOW-SOLUTE INTAKE.

HYPERVOLAEMIC:

Think:

HEART FAILURE + CIRRHOSIS + NEPHROTIC SYNDROME + ADVANCED KIDNEY FAILURE.

HIGH GLUCOSE + LOW Na⁺:

Think:

HYPERTONIC/TRANSLOCATIONAL HYPONATRAEMIA.

EXTREME LIPIDS OR PROTEINS + LOW REPORTED Na⁺ WITHOUT TRUE HYPOTONICITY:

Think:

PSEUDOHYPONATRAEMIA.

And the most important safety principle is:

SEVERE NEUROLOGICAL SYMPTOMS → URGENT TREATMENT, BUT CHRONIC HYPONATRAEMIA MUST BE CORRECTED CAREFULLY TO AVOID OSMOTIC DEMYELINATION.