Brain Volume Regulation in Response to Hypo-osmolality and Its Correction

https://doi.org/10.1016/j.amjmed.2006.05.003Get rights and content

Abstract

Hyponatremia exerts most of its clinical effects on the brain. An acute onset (usually in <24 hours) of hyponatremia causes severe, and sometimes fatal, cerebral edema. Given time, the brain adapts to hyponatremia, permitting survival despite extraordinarily low serum sodium concentrations. Adaptation to severe hyponatremia is critically dependent on the loss of organic osmolytes from brain cells. These intracellular, osmotically active solutes contribute substantially to the osmolality of cell water and do not adversely affect cell functions when their concentration changes. The adaptation that permits survival in patients with severe, chronic (>48 hours’ duration) hyponatremia also makes the brain vulnerable to injury (osmotic demyelination) if the electrolyte disturbance is corrected too rapidly. The reuptake of organic osmolytes after correction of hyponatremia is slower than the loss of organic osmolytes during the adaptation to hyponatremia. Areas of the brain that remain most depleted of organic osmolytes are the most severely injured by rapid correction. The brain’s reuptake of myoinositol, one of the most abundant osmolytes, occurs much more rapidly in a uremic environment, and patients with uremia are less susceptible to osmotic demyelination. In an experimental model of chronic hyponatremia, exogenous administration of myoinositol speeds the brain’s reuptake of the osmolyte and reduces osmotic demyelination and mortality caused by rapid correction.

Section snippets

Brain volume regulation and the consequences of hyponatremia

The osmolality of extracellular and intracellular fluid must be equal. If extracellular osmolality is reduced, cells must either swell with water or rid themselves of solute. Because water is able to cross the blood-brain barrier much more readily than sodium, a low serum sodium concentration osmotically drives water flow into the brain’s interstitial space and into brain cells. However, the severity of the induced brain swelling diminishes with time.

Initially, the increase in brain water

Brain composition in acute versus chronic hyponatremia

In animals that have hyponatremia for <24 hours, cerebral edema is severe and rapid correction of hyponatremia returns brain water content to normal with no adverse consequences.8 After 3 days of hyponatremia, brain swelling is minimal and brain histology remains normal, even when the serum sodium concentration is maintained at very low levels for several weeks.14 However, if more sustained hyponatremia is rapidly corrected, the animals deteriorate neurologically and myelinolysis develops.8, 15

Urea and myelinolysis

Intravenous and oral urea are commonly used in Belgium to treat hyponatremia.26 Van Reeth and Decaux27 noted that rapid correction of hyponatremia with urea in an animal model of severe hyponatremia did not appear to cause myelinolysis. Nephrologists know that a rapid increase of the serum sodium concentration is extremely common in patients receiving dialysis, yet myelinolysis in this population is also very rare. Exploring these observations, Soupart and coworkers20, 28 demonstrated that

Myoinositol and myelinolysis

If urea protects against injury and this protection is associated with a rapid uptake of brain myoinositol in the brain, can myoinositol be given exogenously to protect against brain injury due to rapid correction of chronic hyponatremia? Studies in our laboratory have shown that hyponatremic animals have brain myoinositol levels that are approximately 50% of those of normonatremic controls. If myoinositol is administered in conjunction with hypertonic saline to hyponatremic animals (increasing

Clinical guidelines

Our knowledge of the brain’s adaptation to hyponatremia can be applied to the bedside. All patients with a serum sodium concentration <120 mEq/L (i.e., >10% below normal) have adapted to some degree because the brain cannot increase its volume by >10% without herniating. The recovery of brain solutes during correction of hyponatremia is slower than is the loss of brain solutes during the evolution of hyponatremia. Therefore, correction rates should not exceed a 10% increase in sodium

References (30)

  • A.I. Arieff et al.

    Neurological manifestations and morbidity of hyponatremiacorrelation with brain water and electrolytes

    Medicine

    (1976)
  • B.E. Tomlinson et al.

    Central pontine myelinolysistwo cases with associated electrolyte disturbance

    Q J Med

    (1976)
  • R.D. Adams et al.

    Central pontine myelinolysisa hitherto undescribed disease occurring in alcoholic and malnourished patients

    AMA Arch Neurol Psychiatry

    (1959)
  • R.J. Martin

    Central pontine and extrapontine myelinolysisthe osmotic demyelination syndromes

    J Neurol Neurosurg Psychiatry

    (2004)
  • R.H. Sterns et al.

    Osmotic demyelination syndrome following correction of hyponatremia

    N Engl J Med

    (1986)
  • Cited by (0)

    View full text