Hyponatraemia

Hyponatraemia is a disorder of sodium homeostasis characterised by low levels of sodium (< 135 or 136 mmol/L). It's the most common electrolyte abnormality, affecting 3-10% of patients in the emergency department. It's usually mild and is self-limiting, but severe hyponatraemia is lethal.

Grading of severity

Sodium level	Severity
136 - 130	Mild
129 - 120	Moderate
> 120	Severe

Classification

Establishing the patient's fluid status and serum osmolality (tonicity) is important to determine the underlying cause. We usually distinguish between hypotonic, isotonic, and hypertonic hyponatraemia. In case of hypotonic hyponatraemia, the fluid status is essential in the evaluation.

Etiology

Hyponatraemia can occur secondary to many disorders.

• Isotonic hyponatraemia
  • Hyperproteinaemia
  • Hyperlipidaemia
• Hypertonic hyponatraemia
  • Hyperglycaemia
  • Intake of mannitol, sorbitol, glycerol, maltose
  • Contrast material

For hypotonic hyponatraemia, possible causes depends on the fluid status:

Causes of hypotonic hyponatraemia

Hypovolaemic hypotonic hyponatraemia	Normovolaemic hypotonic hyponatraemia	Hypervolaemic hypotonic hyponatraemia
Extrarenal fluid loss (dehydration, diarrhoea, vomiting, burn injury)	Syndrome of inappropriate anti-diuretic hormone (SIADH)	Acute kidney injury or chronic kidney disease
Renal fluid loss (diuretic (especially thiazides), nephropathy, mineralocorticoid deficiency, cerebral salt wasting syndrome)	Postoperative hyponatraemia	Heart failure
	Hypothyroidism	Liver failure
	Low sodium intake (usually in elderly or people with alcohol use disorder)	Nephrotic syndrome

Hyponatraemia is most commonly hypotonic. The most common causes overall are heart failure, liver failure, dehydration, and SIADH.

Depending on whether the cause is acute or chronic, hyponatraemia can be acute or chronic as well.

Pathophysiology

One of sodium's main functions is to maintain tonicity, i.e. the same osmolality in the intracellular and extracellular spaces. When hyponatraemia occurs, the plasma osmolality usually decreases while the intracellular osmolality remains. This causes fluid to flow from the extracellular space to the intracellular space, causing oedema. This is most dangerous in the brain. The symptoms and potential lethality of hyponatraemia is caused by swelling of brain cells, intracellular brain oedema.

Cells can compensate for the change in tonicity. When the osmolality of the extracellular space decreases, cells can release electrolytes (like potassium) and osmotically active organic molecules (like myoinositol and choline compounds) to decrease the intracellular osmolality to try to achieve isotonicity. However, this compensation takes several days, explaining why acute hyponatraemia is more dangerous than a chronic one.

Clinical features

Clinical features in hyponatraemia depends on the degree of intracellular brain oedema. As such, mild acute hyponatraemia or chronic hyponatraemia (even if moderate) usually does not lead to brain oedema and is therefore asymptomatic. However, if the sodium levels are severely decreased, or the drop in sodium level occurs suddenly, brain oedema occurs. The symptoms are non-specific. Typical symptoms include (in increasing order of severity):

• Dizziness
• Fatigue
• Headache
• Impaired mental status
• Seizures
• Coma

Diagnosis and evaluation

Determining the cause is the first priority.

Determining tonicity

To determine the cause, we must know the tonicity of the hyponatraemia. Evaluation of effective serum osmolality is important for this. The (non-effective) serum osmolality can be measured in a lab test, but this also counts so-called ineffective osmoles, which are osmotically active compounds which do not affect the movement of water between cells and extracellular fluid because these ineffective osmoles can freely cross cell membranes. Urea and ethanol are two such ineffective osmoles.

In any case, the effective serum osmolality can be calculated by either:

• Effective osmolality = serum glucose + 2 x serum sodium
• Effective osmolality = measured serum osmolality - (urea + ethanol)

We can then use this value to determine the tonicity of the hyponatraemia:

• Effective serum osmolality < 281 mosm/kg -> hypotonic hyponatraemia
• Effective serum osmolality 281-295 mosm/kg -> isotonic hyponatraemia
• Effective serum osmolality > 295 mosm/kg -> hypertonic hyponatraemia

... which can be used to narrow the list of possible causes.

Determining fluid status

Determining fluid or volume status also helps us determining the cause, especially if there is hypotonic hyponatraemia. Determining fluid status can be difficult, but there are some features which can help:

• Features of hypovolaemia
  • Lower weight compared to normal
  • Tachycardia or hypotension or orthostatic hypotension
  • Increased capillary refill
  • Weak peripheral pulse
  • Decreased skin turgor
  • Dry mucous membranes of the oral cavity and tongue
  • Sunken fontanelle (in infants)
• Features of hypervolaemia
  • Higher weight compared to normal
  • Oedema (peripheral or pulmonary)
  • Ascites
  • Distended jugular vein

Evaluation of the skin turgor for volume status is unreliable in elderly, as they have decreased turgor regardless of fluid status.

Determining renal sodium loss

Measuring