The brain sits inside the skull, a rigid vault that cannot expand, so extra volume in the brain has nowhere to go. Water crosses cell membranes freely and moves toward the side that holds more of the solutes that cannot cross. When plasma sodium falls, the fluid around brain cells becomes more dilute and water moves into them, so they swell. When plasma sodium rises, water leaves them and they shrink. The brain can adapt to either change, so the speed of the change, as well as the number, sets how much harm it does.
The number still defines the disorder. Hyponatremia is a plasma sodium concentration below 135 mmol/L, and hypernatremia is a plasma sodium concentration above 145 mmol/L. But the number does not by itself say how ill the patient is, because the brain responds to how far the sodium has moved and how fast, and it can adapt over time. The danger lies in the brain cells, not in the figure on the laboratory report.
Why does the brain show the change first?
Other tissues tolerate the same shift of water far better. What singles out the brain is the fixed volume of the skull. Other tissues are not enclosed in such a vault and do not meet this fixed limit. That is why the brain is the tissue on which the change presses.
If the brain swells inside the vault, the brain is compressed, and this compression produces the neurological features.
What does low sodium do to brain cells?
With no spare room in the skull, the question is what the cells do with water when sodium falls. Plasma osmolality is the concentration of dissolved solute in plasma, and plasma sodium is its main determinant, as the urea-paradox note showed. Tonicity counts only the solutes that cannot cross the cell membrane, because only those exert osmotic pressure. Water crosses cell membranes freely and moves toward whichever side holds more of the solutes that cannot cross, as the sodium regulation note showed.
So a fall in plasma osmolality draws water into cells. The fluid outside is more dilute, the cells hold more solute that cannot cross, and the brain cells swell. The swelling is what the brain then has to adjust to.
What does high sodium do to brain cells?
Here the direction reverses. A rise in plasma osmolality draws water out of cells. The fluid outside is more concentrated, water leaves the brain cells, and they shrink. The same skull now holds shrinking tissue.
The neurological features of hypernatremia follow from this shrinkage. Shrinkage can also damage the cerebral vessels. Vessel damage is therefore one route by which the shrinkage does harm.
Does the brain stay swollen or shrunken?
The brain’s response depends on how long the change lasts, so the next question is what the cells do over time.
In hyponatremia, over one to two days brain cells adapt. They unload intracellular solutes, including potassium, the main cation of the intracellular fluid, as the body-water note showed. Other solutes leave too, and water leaves with them, which restores the cell volume.
In hypernatremia the adaptation runs the other way. Over days, brain cells generate osmotically active solutes, which raise the osmolality inside them. With more solute inside, less water leaves, and the generated solutes limit the shrinkage.
Why does speed matter more than the number?
Adaptation takes time, so a change faster than that outruns the brain.
In hyponatremia, the symptoms depend on how low the sodium falls, and more importantly on how quickly it falls. A larger fall moves more water into the cells. But the loss of solutes halts the swelling, so a slow fall can be tolerated with few symptoms even at a low value. A fast fall leaves no time for that adaptation. The same sodium value then leaves the cells more swollen and causes far more symptoms. A fall that develops within 24 to 48 hours is counted as acute.
Hypernatremia follows the same rule. A quick rise gives the brain no time to build the solutes that limit shrinkage, so severe features are more likely when the sodium has risen quickly. Hypernatremia of slow onset is tolerated better than a rapid rise of the same size, because over time the brain has built those solutes.
The same adaptation is why high sodium that has been present for some time must not be lowered quickly. If the sodium is lowered too fast, the cells stay more concentrated than the fluid around them, and water rushes in.
What does low sodium feel like?
The symptoms follow the swelling, and the speed decides how much. The features run from mild to life-threatening, as the swelling compresses the brain more and more.
- Mild: headache, fatigue, nausea, dizziness, forgetfulness and an unsteady gait.
- Confusion, lethargy and a reduced level of consciousness.
- Seizures and coma.
In the worst cases hyponatremia causes respiratory arrest and death from brain herniation. Seizures are unusual when sodium is above 115 mmol/L.
Chronic hyponatremia is not harmless even when it looks quiet. It is associated with attention deficit and with falls, particularly in older patients. Attention deficit and falls can improve when the sodium is corrected.
What does high sodium feel like?
Shrinking cells give the mirror-image picture, and the main symptom is thirst. Thirst is the main symptom of hypernatremia. Plasma osmolality rises when water is lost, and the osmoreceptor cells of the hypothalamus shrink, which starts the sensation of thirst. Working thirst and free access to water are what normally prevent hypernatremia, as the disorders note showed. So a conscious patient with hypernatremia who has no thirst points either to a defective thirst mechanism or to no access to water.
The remaining features are neurological and follow from brain-cell shrinkage: lethargy, weakness, irritability, confusion, neuromuscular excitability, hyperreflexia, seizures and coma.
In adults, severe features usually appear only above 160 mmol/L. Infants may instead show tachypnea, muscle weakness, restlessness, a high-pitched cry and lethargy.
What can the picture not show?
The clinical picture shows that the sodium is abnormal. It also shows how urgent the abnormal sodium may be. It does not show why the sodium is abnormal, so what is pushing the sodium off course?