Hyponatremia is a plasma sodium concentration below the normal range. It is the most common electrolyte disorder in clinical practice, and it has been reported in roughly 15–20% of patients in some emergency department populations. A patient with it can be entirely asymptomatic, or can arrive with a seizure or in a coma.
Why does the same sodium value make one patient ill and another well?
Symptoms come from the brain, because swelling inside the skull is what makes it malfunction. The gap between the two extremes is explained less by the sodium value alone than by how quickly that value developed. A slow fall gives the brain time to adapt, and a fast fall does not, so the speed of the fall shapes the symptoms more than the number alone does.
Four factors determine how a given plasma sodium is tolerated:
- the degree of hyponatremia
- the rate of progression
- the neurophysiological adaptive capacity of the individual
- comorbidities
The rate of progression is often the most decisive of the four. The brain can adapt when it has time, and a fall reached in hours leaves none.
What happens in the brain when sodium falls?
Effective solutes stay on one side of a membrane and pull water toward themselves, and sodium in the extracellular fluid holds its water there. So when the extracellular fluid becomes hypotonic, water moves along the osmotic gradient into the cells.
This matters most in the brain, because the brain sits inside a rigid skull and has nowhere to expand. The cerebral cells swell, and the swelling raises the intracranial pressure. That pressure is what produces the neurological symptoms.
How does the brain protect itself from swelling?
The brain defends against swelling by shedding intracellular electrolytes first, then organic osmolytes, over roughly 24–48 hours. Organic osmolytes are small organic molecules that act as osmotic solutes. A cell that has lost solute holds less water, so the brain lowers its own osmolality, water no longer enters, and the cell volume returns toward normal.
Why does a slow fall cause fewer symptoms?
This protection needs time. If the sodium has fallen slowly over days, the brain may have adapted, and the patient may feel well even at a low value. If the same value is reached in hours, the brain has no time to adapt, so its cells swell with no protection and the symptoms are severe.
Which symptoms come first as sodium falls?
Symptoms are uncommon while the sodium is only mildly reduced, because mild swelling raises the pressure only a little. They become more likely as the sodium falls further, because a larger fall means more water moves in, so the swelling and the pressure grow.
Headache, nausea, malaise and poor concentration appear first. Confusion, disorientation and unsteadiness follow. Vomiting, seizures, coma and cardiorespiratory distress mark the severe end of the spectrum.
How low must sodium fall before symptoms become common?
Symptoms become common below about 125 mmol/L, and severe symptoms are most likely below about 120 mmol/L. The value is only part of the story, though. A rapid fall can cause severe symptoms at higher values, because the brain has had no time to adapt at any level. A fully adapted patient may have no symptoms at lower values, because adaptation is what protects the brain.
What complications can the disorder itself cause?
Complications come from the disorder itself and from its treatment. The cardinal complication of the disorder is cerebral oedema. It is swelling inside a rigid skull, so its pressure is the central problem. Cerebral oedema is the mechanism behind seizures, coma and, in the worst cases, herniation, because swelling that the brain cannot relieve pushes the brain against the skull. It is most dangerous when the sodium falls acutely, and the same adaptation gap explains why.
What goes wrong when sodium rises too fast?
The cardinal complication of treatment is osmotic demyelination syndrome. It is a delayed non-inflammatory demyelination of the pons and other regions, and it follows correction of hyponatremia that is too rapid. A too-rapid rise makes the outside of the cells more concentrated than the inside, so water leaves the brain cells. The resulting cell shrinkage is thought to destroy the myelin and oligodendrocytes of the pons and some regions beyond it.
The damage does not appear at the time of correction but days later. It produces dysarthria, dysphagia, and weakness progressing to quadriparesis. In severe cases it causes a locked-in state, in which the patient is conscious but can move only the eyes.
The same adaptation that protected the brain makes a fast correction dangerous. A brain that has spent days losing solutes has less left to defend itself with when the sodium suddenly rises.
Who is most at risk of that damage?
The risk is greatest when hyponatremia has been long-standing, because the brain has adapted and has already lost solute, so a fast rise in sodium can pull water out of its cells. It is also greatest in patients with a very low starting sodium. Alcohol use disorder, malnutrition, hypokalemia or advanced liver disease raise the risk as well; these are associations, not proven causes.
Why do both complications come down to speed?
Both complications turn on the same question: whether the fall in sodium was slow and adapted or fast and unadapted. That same question decides how the sodium should be corrected. So how is the sodium corrected safely, and how is the speed of correction chosen?