Central Pontine Myelinolysis - Pathophysiology

Pathophysiology

The currently accepted theory states that the brain cells adjust their osmolarities by changing levels of certain osmolytes like inositol, betaine, and glutamine. In hyponatremia the levels of these osmolytes fall, causing the cells to absorb free-water. The reverse is true for hypernatremia, in which cells will shrink to dilute the hypernatremic fluid. So rapid correction of sodium in hyponatremia would cause the extracellular fluid to be relatively hypertonic. Free water would then move out of the cells to decrease this relative hypertonicity. This leads to a central pontine myelinolysis, manifesting as the paralysis. This would look like the brain is shrinking.

The demyelination of the axons (nerve fibers in the brain) damages them.

In the context of chronic low plasma sodium, the brain's cells (neurons and glia) adapt by taking in a small amount of water; the net effect is to move water out of the interstitium and equilibrate (or nearly so) the intracellular and extracellular tonicities. The chronic hyponatremia is thus compensated.

With correction of the hyponatremia with intravenous fluids, the intra- and extra-cellular tonicities are again changed, this time in the opposite direction. With the use of intravenous hypertonic saline, the correction can be too quick, not allowing enough time for the brain's cells to adjust to the new tonicity. With a rise in extracellular tonicity, the cells compensate by losing a small amount of water. This loss will continue until the intra- and extra-cellular tonicities are equal. If hypertonic therapy continues or is too rapid, the extracellular tonicity will continue to drive water out of the brain's cells, leading to cellular dysfunction and the condition of central pontine myelinolysis.

Rapid correction of hypernatremia causes water to move into cells, leading to multiple cerebral hemorrhages, equally catastrophic as osmotic demyelination.