Hyponatraemia is the most common electrolyte disorder encountered in clinical practice and is seen in approximately 30% of hospitalised patients. It is also one of the most poorly understood and difficult to manage scenarios in medicine. It is rarely dangerous, but on occasion, it can be a life-threatening emergency, with potentially hazardous treatment in the acute setting.

 

What is hyponatraemia?

Hyponatraemia is defined as a serum sodium concentration of less than 135 mmol/L. It can be further classified according to the level of severity and rate of onset.

Classification according to severity is as follows:

  • Mild – serum sodium concentration 130-135 mmol/L
  • Moderate – serum sodium concentration 125-129 mmol/L
  • Severe – serum sodium concentration less than 125 mmol/L

 

Classification according to the rate of onset is as follows:

  • Acute – duration of less than 48 hours
  • Chronic – duration of 48 hours or more

 

The control of sodium balance 

To understand hyponatraemia, we must first understand the control of sodium balance. Sodium is the predominant cation in the extracellular fluid (ECF), and the volume of the ECF is directly proportional to the sodium content of the body. Disorders of sodium balance can, therefore, be viewed as disorders of ECF volume.

Under normal circumstances, serum sodium levels are tightly controlled within a range of 135-145 mmol/L. To maintain the volume of the ECF, the amount of sodium excreted needs to closely match the amount of sodium that is ingested via the diet.  Approximately 99% of the sodium filtered by the kidney is reabsorbed in the proximal convoluted tubule and the loop of Henle within the kidney. This reabsorption occurs at a relatively fixed rate, regardless of the amount of total body sodium.

It is, however, the smaller amount (approx. 1%) that is reabsorbed in the distal convoluted tubule and collecting ducts that exerts the most influence on total sodium balance. The principal regulator of sodium reabsorption here is the hormone aldosterone, which is produced by the zona glomerulosa of the adrenal cortex. Aldosterone acts on mineralocorticoid receptors in the distal convoluted tubule and collecting ducts to increase sodium reabsorption by promoting the expression of special channels and the NA+/K+-ATPase pumps that are situated here.

The other key player in the control of sodium balance is antidiuretic hormone (ADH), which is also known as vasopressin. ADH regulates the extracellular water and therefore serum osmolality and serum sodium concentration. The secretion of ADH is influenced by a number of factors including plasma osmolality and circulating volume. The primary function of ADH is to regulate the volume of ECF by regulating renal handling of water. ADH does this by acting on the renal collecting ducts via V2 receptors to increase water permeability, thereby reducing urine formation and increasing blood volume and arterial pressure. The majority of hyponatraemic states are caused by inappropriately elevated levels of ADH, which causes disproportionate water retention compared to sodium retention.

 

The causes of hyponatraemia

Hyponatraemia has a large number of potential causes that can be categorised according to the extracellular fluid volume status:

Decreased extracellular volumeGastrointestinal sodium loss, e.g. diarrhoea and vomiting
Transdermal sodium loss, e.g. burns, excessive sweating
Renal sodium loss, e.g. diuretic usage
Primary adrenal insufficiency
Renal disease, e.g. salt-wasting nephropathies
3rd space losses, e.g. bowel obstruction, pancreatitis, sepsis
Cerebral salt-wasting (underlying intracranial disease)
Normal extracellular volumeSyndrome of inappropriate antidiuresis (SIAD)
Secondary adrenal insufficiency
High water solute intake, e.g. primary polydipsia
Hypothyroidism (rare)
Increased extracellular volumeHeart failure
Liver failure
Kidney disease, e.g. chronic kidney disease, nephrotic syndrome

 

In addition to these causes, hyponatraemia can also occur as an artefact secondary to high serum protein levels, high lipid levels, or severe hyperglycaemia. In these circumstances, it is referred to as pseudo-hyponatraemia.

 

The syndrome of inappropriate antidiuresis (SIAD) 

The term ‘syndrome of inappropriate antidiuresis (SIAD)’ is now being used in European and UK practice, and has largely replaced the older and less accurate term ‘syndrome of inappropriate ADH secretion (SIADH)’. SIAD is one of the most common causes of hyponatraemia and is caused by excessive ADH secretion from the posterior pituitary or an ectopic source. It is characterised by urinary dilution impairment and hypotonic hyponatraemia, in the absence of renal disease or any identifiable non-osmotic stimulus able to induce ADH release.

SIAD is a diagnosis of exclusion that is confirmed in the secondary care setting. The causes of SIAD include the following:

  • Malignancy – small cell lung cancer, gastrointestinal malignancy, genitourinary tract malignancy, lymphoma, sarcoma
  • Respiratory disorders – pneumonia, tuberculosis, aspergillosis, asthma, cystic fibrosis
  • CNS disorders – meningitis, encephalitis, subarachnoid haemorrhage, CNS tumours, head trauma, cerebral malaria
  • Drugs – SSRIs, antipsychotics, NSAIDs, carbamazepine

 

The clinical features of hyponatraemia

Hyponatraemia is usually asymptomatic when the serum sodium level is between 130-135 mmol/L, and the majority of cases occur as an incidental finding on routine blood tests.

When symptoms do occur, they are often non-specific and can are related to both the severity of the hyponatraemia and its rate of onset. A rapid fall in the sodium level or severe hyponatraemia can cause symptoms such as vomiting, drowsiness, headache, seizures, reduced conscious level. In very severe cases cerebral oedema can occur, which can ultimately result in raised intracranial pressure and cardiac arrest. In contrast, chronic mild hyponatraemia may cause gait instability, falls and cognitive deficits.

In the presence of decreased or increased extracellular volume, signs of hypovolaemia or hypervolaemia may be present:

  • Hypovolaemia – dry mucous membranes, reduced tissue turgor, tachycardia, hypotension
  • Hypervolaemia – raised JVP, 3rd heart sound, bilateral basal crackles, peripheral oedema, ascites

 

When should a patient with hyponatraemia be admitted to referred to hospital?

The following criteria have been outlined by NICE for admission/referral:

  • Acute onset hyponatraemia (duration less than 48 hours)
  • Severe hyponatraemia (serum sodium < 125 mmol/L)
  • Symptomatic hyponatraemia
  • Signs of hypovolaemia present

 

It is recommended that the need for referral/admission is discussed with an endocrinologist if the person:

  • Has asymptomatic, moderate hyponatraemia (serum sodium 125-129 mmol/L)
  • If Addison’s disease is suspected (e.g. raised potassium also present)

 

An urgent 2-week wait referral should be arranged if malignant disease is suspected as the underlying cause.

A referral to an endocrinologist (urgency depending on clinical judgement) should be arranged if:

  • The cause of hyponatraemia is unclear
  • If SIAD or another endocrine cause is suspected
  • If cerebral salt-wasting is suspected

 

If the person has hyponatraemia that is thought to be caused by heart failure, kidney failure, or liver disease they should be referred to a specialist with appropriate expertise.

 

The investigation of hyponatraemia

Before embarking on further investigations, the serum sodium level should be repeated in case the result occurred as a result of lab error or as a result of dilution from blood being drawn close to the site of an intravenous infusion.

Once the serum sodium level has been repeated, and hyponatraemia confirmed serum osmolality should be assessed:

  • If the serum osmolality is low (<275 mOsmol/kg), the patient should be assessed for causes of true hyponatraemia
  • If the serum osmolality is normal (275-295 mOsmol/kg), pseudo-hyponatraemia should be considered as a spurious cause
  • If the serum osmolality is high (>295 mOsmol/kg), hyperglycaemia should be considered as a spurious cause

 

The next step should be the assessment of urine osmolality and urine sodium concentration.

If the urine osmolality is <100 mOsm/kg:

  • Consider primary polydipsia or low solute intake (e.g. ‘tea and toast diets’)

 

If the urine osmolality is >100 mOsm/kg and the urine sodium concentration > 30 mmol/L:

  • In a person who is hypovolaemic consider vomiting, primary adrenal insufficiency, renal-salt wasting, cerebral salt wasting or non-prescribed diuretics
  • In a person who is euvolaemic consider syndrome of inappropriate antidiuresis (SIAD), secondary adrenal insufficiency, hypothyroidism, or non-prescribed diuretics

 

If the urine osmolality is >100 mOsm/kg and the urine sodium concentration is <30 mmol/L:

  • In a person with fluid overload consider heart failure, liver cirrhosis, or nephrotic syndrome
  • In a person with hypovolaemia consider diarrhoea and vomiting, third spacing, or diuretics

 

Other investigations that should be considered include:

  • Serum potassium – if elevated consider Addison’s disease
  • Thyroid function tests – check to exclude hypothyroidism
  • Serum cortisol and/or ACTH stimulation test – in patients with suspected adrenal suppression
  • Imaging – when clinically indicated, e.g. chest X-ray for suspected respiratory causes or CT head for suspected CNS causes

 

The management of hyponatraemia in the primary care setting

Patients with asymptomatic, mild hyponatraemia (Serum sodium 130-135 mmol/L) can be safely managed in the primary care setting. NICE guidelines recommend the following approach to management in primary care:

  • In all people, ensure a repeat serum sodium measurement has been taken to exclude a rapidly decreasing serum sodium concentration that will require admission to hospital.
  • If the person has an acute illness that may be contributing to the hyponatraemia, treat the underlying problem and recheck the serum sodium concentration after 2 weeks or sooner based on clinical judgement.
  • If the person is taking a drug that may be contributing to the hyponatraemia, stop this if appropriate, and recheck the serum sodium concentration after 2 weeks.
    • If the person is taking a drug that cannot be stopped (for example an antipsychotic drug), contact their appropriate specialist to discuss whether to stop the drug, monitor the serum sodium concentration, or refer to an endocrinologist or nephrologist.
    • If the serum sodium concentration remains low after stopping the drug, look for another underlying cause, or refer the person to an endocrinologist.

 

The management of hyponatraemia in the secondary care setting

Secondary care management is aimed at determining and treating the underlying cause of hyponatraemia. The treatment algorithm is complex and largely based on the Clinical practice guideline on diagnosis and treatment of hyponatraemia guideline developed by a collaboration between the European Society of Intensive Care Medicine, the European Society of Endocrinology and the European Renal Association-European Dialysis and Transplant Association represented by European Renal Association.

Management strategies depend on the rate of onset of hyponatraemia, the person’s symptoms, and volume status:

  • Acute hyponatraemia with moderate or severe symptoms – hypertonic saline restores serum sodium concentration to a safe level to correct any cerebral oedema and reduce the risk of complications.
  • Acute hyponatraemia with mild or no symptoms – non-essential parenteral fluids and medications that can provoke hyponatraemia are stopped and treatment is directed at the underlying cause.
  • Chronic hyponatraemia without moderate or severe symptoms – non-essential supplementary fluids and medications that can provoke hyponatraemia are stopped and treatment is directed at the underlying cause.
  • People with hypervolaemia – fluid restriction is recommended to prevent further fluid overload.
  • People with syndrome of inappropriate antidiureis (SIAD) – fluid restriction is recommended. If there is no clear cause for SIAD following initial investigations, CT chest/abdomen/pelvis and MRI head may be arranged to exclude underlying malignancy.
  • People with hypovolaemia – extracellular volume is restored with an infusion of 0.9% saline.

 

The full algorithm is summarised below:

 

Further reading:

NICE Clinical Knowledge Summary

European Journal of Endocrinology: Clinical practice guideline on diagnosis and treatment of hyponatraemia

 

Header image used on licence from Shutterstock


Thank you to the joint editorial team of www.plabprep.co.uk for this article.

 

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