Nephrology
A 45 year old woman is brought to the Emergency Department after collapsing at work. She is now alert. Her blood results shows a significant hyponatraemia. Which of the following is the main complication in hyponatraemia?
Answer:
Hyponatraemia is potentially life-threatening, particularly when it is severe (less than 125 mmol/L) and/or of acute onset (over a period of less than 48 hours). This is due to swelling of brain cells when water moves from the extracellular to the intracellular compartment because of differences in the osmolality between brain and plasma. Cerebral oedema and raised intracranial pressure can lead to seizures, coma, or cardiorespiratory arrest.Hyponatraemia
Nephrology
Last Updated: 30th April 2023
Hyponatraemia is defined as a serum sodium concentration < 135 mmol/L.
Biochemical severity:
- Mild hyponatraemia — serum sodium 130–135 mmol/L.
- Moderate hyponatraemia — serum sodium 125–129 mmol/L.
- Severe hyponatraemia — serum sodium less than 125 mmol/L.
Pathophysiology
Hyponatraemia results from a relative excess of body water to sodium. Serum sodium concentration is determined by serum water content. Serum water increases with water intake (driven by thirst or habit), and decreases through insensible losses (for example sweating) and urinary dilution, regulated by antidiuretic hormone (ADH). ADH is produced by the hypothalamus and then stored in and released from the posterior pituitary gland. It increases the reabsorption of water by the kidney and prevents excessive loss of water from the body. Hyponatraemia is usually associated with a disturbance in ADH secretion. This can be through physiological (for example hypovolaemia), pathological (for example heart failure), or iatrogenic (for example thiazide diuretics) mechanisms.
Hyponatraemia is potentially life-threatening, particularly when it is severe (less than 125 mmol/L) and/or of acute onset (over a period of less than 48 hours). This is due to swelling of brain cells when water moves from the extracellular to the intracellular compartment because of differences in the osmolality between brain and plasma. Cerebral oedema and raised intracranial pressure can lead to seizures, coma, or cardiorespiratory arrest.
Clinical features
- Hyponatraemia is usually an incidental finding on routine blood tests.
- Most people with hyponatraemia are asymptomatic, particularly if hyponatraemia is mild (serum sodium concentration of 130–135 mmol/L) and has developed slowly.
- When symptoms of hyponatraemia are present, they are often non-specific and are related to both the severity of the hyponatraemia and its rate of onset.
- Rapid changes in sodium levels or severe hyponatraemia can cause symptoms such as vomiting, drowsiness, headache, seizures, coma and cardio-respiratory arrest due to cerebral oedema and raised intracranial pressure.
- Chronic mild hyponatraemia can lead to gait instability, falls, concentration and cognitive deficits.
Diagnostic approach
- Patient history
- Any drugs that can cause hyponatraemia. Commonly implicated drugs include:
- Diuretics, particularly thiazide diuretics
- Selective serotonin reuptake inhibitors (SSRIs)
- Antipsychotics such as haloperidol and phenothiazines
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Carbamazepine
- Drugs that less commonly cause hyponatraemia include sulphonylureas, tricyclic antidepressants, dopamine agonists, opiates, theophylline, chlorpropamide, clofibrate, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists (AIIRAs), melphalan, proton pump inhibitors, amiodarone, domperidone and MDMA ('ecstasy').
- Intercurrent illness (such as gastroenteritis or pneumonia) or chronic illness (such as anorexia nervosa).
- Renal disease — renal function test and urinalysis for urine protein and blood.
- Hypothyroidism — thyroid function tests.
- Addison's disease — serum cortisol (morning sample, at 8–9 am).
- Heart failure and liver disease—B-type natriuretic peptide and liver function tests.
- Myeloma — serum and urine protein electrophoresis, including Bence–Jones proteins.
- Cancers (especially lung and upper gastrointestinal cancers).
- Ask about fluid intake and nocturnal polyuria (suggesting a possible diagnosis of primary polydipsia).
- Any drugs that can cause hyponatraemia. Commonly implicated drugs include:
- Assess volume status (pulse rate, postural changes in blood pressure, jugular venous pressure, and presence or absence of oedema or clinical signs of dehydration). Determining volume status can help identify the cause of hyponatraemia, however changes may be subtle and difficult to interpret.
- Initial tests to identify underlying cause
- Plasma osmolality
- Urine osmolality
- Urine sodium
Plasma osmolality
- True hyponatraemia of any cause is associated with a low plasma osmolality.
- If the plasma osmolality is normal (275–295 mOsmol/kg), consider pseudo-hyponatraemia (due to high levels of serum lipids or proteins) as a spurious cause of hyponatraemia.
- If the plasma osmolality is high (greater than 295 mOsmol/kg), consider hyperglycaemia as a spurious cause of hyponatraemia. A high blood glucose will require investigation for underlying diabetes and appropriate management.
- If the plasma osmolality is low (less than 275 mOsmol/kg) and the serum sodium is low, assess for causes of true hyponatraemia.
Urine osmolality
Low urine osmolality (≤ 100 mosmol/kg):
- Primary polydipsia
- Inappropriate administration of IV fluids
- Low salt diet
Raised urine osmolality (> 100 mosmol/kg):
- Urinary Na+ ≤ 30 mmol/L
- Patient hypovolaemic
- Gastrointestinal salt loss - diarrhoea and vomiting
- Transdermal salt loss - sweating, extensive skin burns
- Third space loss - pancreatitis, bowel obstruction, sepsis, muscle trauma
- Renal salt loss e.g. thiazide diuretics
- Patient hypervolaemic
- Congestive cardiac failure
- Liver cirrhosis
- Chronic kidney disease or nephrotic syndrome
- Patient hypovolaemic
- Urinary Na+ > 30 mmol/L
- Patient euvolaemic (normal circulating volume)
- Syndrome of antidiuretic hormone secretion (SIADH)
- Hypopituitarism and secondary adrenal insufficiency
- Hypothyroidism
- Patient hypovolaemic (low circulating volume)
- Primary adrenal insufficiency
- Cerebral salt-wasting e.g. subarachnoid haemorrhage, traumatic brain injury, intracranial injury
- Renal salt-wasting e.g. tubulopathy after chemotherapy.
- Vomiting (causes loss of hydrogen ions and a metabolic alkalosis which is corrected by the renal excretion of sodium bicarbonate)
- Patient euvolaemic (normal circulating volume)
Management
Management is aimed at determining and treating the underlying cause of hyponatraemia. 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 SIADH — fluid restriction is recommended. If there is no clear cause for SIADH 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 infusion of 0.9% saline.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
