6. Disorders of water and sodium homeostasis
Sodium
Sodium is an abundant electrolyte in the body, and sodium ion (Na+) is the dominant ion in the extracellular space. 65% of sodium is in the extracellular space. The main clinical function of sodium is to maintain osmolality.
Abnormally low or high sodium (hyponatraemia and hypernatraemia, respectively), are common but potentially lethal disorders in the worst case.
Reference ranges
| Parameter | Sample | Reference range |
|---|---|---|
| Sodium | Serum | 136 – 146 mM |
| Osmolality | Serum | 275 – 305 mOsmol/kg |
| Osmolality | Urine | 50 – 1400 mOsmol/kg |
Sodium in the body
70% of sodium in the body is free, not bound to any molecules.
The remaining 30% is not free but rather bound to large organic molecules in bone, cartilage, and connective tissue.
Sodium regulation
The level of sodium in the body is regulated by the renin-angiotensin-aldosterone system (RAAS) and by anti-diuretic hormone (ADH).
Sodium in laboratory medicine
When measuring sodium levels in a blood test, flame photometry or ion-selective electrodes (potentiometry) is used.
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. Determining the volume status and serum osmolality of the patient is important in determining the cause. Treatment involves water restriction or sodium repletion. The opposite of hyponatraemia is hypernatraemia.
| Hyponatraemia | |
|---|---|
| Other names | Hyponatremia |
| Definition | Serum sodium level < 136 mmol/L |
| Symptoms | Anything from headache and mild altered mental status to coma |
| Complications | Cerebral oedema, osmotic demyelination syndrome |
| Causes | Heart failure, liver failure, dehydration, and SIADH |
| Treatment | Water restriction, sodium repletion |
| Frequency | Relatively common |
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
- Hypertonic hyponatraemia
- Hyperglycaemia
- Intake of mannitol, sorbitol, glycerol, maltose
- Contrast material
For hypotonic hyponatraemia, possible causes depends on the fluid status:
| 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. Hyponatraemia is acute if it has developed over 48 hours or less.
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, and requires a systematic approach and determining tonicity, volume status, and renal sodium loss.
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.
Hypernatraemia
| Hypernatraemia | |
|---|---|
| Definition | Serum sodium level > 147 mmol/L |
| Symptoms | Thirst, irritability, weakness, eventually coma |
| Causes | Diabetes insipidus, vomiting, hypothalamic disease |
| Risk factors | Elderly, comatose, infants |
| Treatment | Administration of sodium-free fluids |
Hypernatraemia is a disorder of sodium homeostasis characterised by high levels of sodium (< 146 mmol/L). It's a rare condition, and much less common than hyponatraemia, due to the body's defence against hypernatraemia being very robust. Hypernatraemia due to loss of water is called dehydration.
Grading of severity
| Sodium level | Severity |
|---|---|
| 146 - 154 | Mild |
| 155 - 165 | Moderate |
| > 165 | 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 hypernatraemia. In case of hypotonic hyponatraemia, the fluid status is essential in the evaluation.
Etiology
Hypernatraemia most frequently occurs following loss of water or a body fluid which contains less sodium and potassium than plasma, and that water or body fluid is not replaced. In most cases, thirst increases appropriately, which replaces the lost water, preventing hypernatraemia from developing. However, people who cannot feel thirst or freely drink water in response to thirst, such as elderly, infants, and comatose people, cannot properly compensate and are therefore at higher risk for developing hypernatraemia.
- Loss of certain body fluids
- Vomiting
- Osmotic diarrhoea
- Infectious diarrhoea
- Diabetes insipidus
- Osmotic diuresis
- Significant glucosuria
- Mannitol
- Lesions of the hypothalamus (impairs thirst)
- Massive salt ingestion
- Excessive administration of saline
- Excessive muscle work (seizure or extreme exercise) (transient)
Hypothalamus lesions causes hypernatraemia by impairing thirst.
Excessive muscle work rapidly breaks down glucagon into smaller and more osmotically active molecules, causing rapid water movement from the extracellular to the intracellular space, causing transient (a few minutes) hypernatraemia.
Depending on whether the cause is acute or chronic, hypernatraemia can be acute or chronic as well. Hypernatraemia is acute if it has developed over 48 hours or less. Acute hypernatraemia is rare; most cases are chronic.
Pathophysiology
The body prevents elevated sodium levels by regulating thirst and anti-diuretic hormone (ADH) levels. When sodium levels increase, thirst increases, stimulating water intake, which decreases the plasma concentration of sodium. ADH decreases the loss of water in the urine, further decreasing the concentration of sodium. Thirst and ADH increases when the plasma osmolality increases beyond 280 mosmol/kg. These compensatory mechanisms are very effective, and so only a severe insult without appropriately increased water intake will cause hypernatraemia.
For loss of body fluid to cause hypernatraemia, the fluid lost must have a lower concentration of sodium plus potassium than the concentration of sodium in the plasma.
Hypernatraemia causes hypertonicity, which causes water to flow out of cells. This is most important in the brain, where the brain volume shrinks, potentially causing rupture of cerebral veins.
Clinical features
The major clinical feature of hypernatraemia is increased thirst. Other features include lethargy, muscle weakness, irritability, and seizures. Severe causes can cause coma and death.
Diagnosis and evaluation
Unlike hyponatraemia, the evaluation of hypernatraemia is relatively straightforward. The cause is usually evident from history alone. If not, the osmolality of the urine is of assistance.
In physiological cases, hypernatraemia causes an increase in ADH, which causes the urine osmolality to be increased to more than 600 mosmol/kg. If the urine osmolality is > 600, it's indicative of the hypothalamus and thirst response as well as kidney function being normal. The cause must therefore be extrarenal fluid loss or increased sodium intake.
A urine osmolality of < 600 mosmol/kg is indicative of disease of the kidney, causing the kidney to lose more water than normal, usually due to diabetes insipidus or osmotic diuresis.
A lack of thirst indicates a disorder of the hypothalamus.