What is the pathophysiology of hypernatremia?

Updated: Mar 17, 2020
  • Author: Zina Semenovskaya, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Answer

Water homeostasis is maintained by a balance between water intake and the combined water loss from renal excretion, respiratory, skin, and GI sources. Under normal conditions, water intake and losses are matched. To maintain salt homeostasis, the kidneys similarly adjust urine concentration to match salt intake and loss. See the image below.

Figure A: Normal cell. Figure B: Cell initially re Figure A: Normal cell. Figure B: Cell initially responds to extracellular hypertonicity through passive osmosis of water extracellularly, resulting in cell shrinkage. Figure C: Cell actively responds to extracellular hypertonicity and cell shrinkage in order to limit water loss through transport of organic osmolytes across the cell membrane, as well as through intracellular production of these osmolytes. Figure D: Rapid correction of extracellular hypertonicity results in passive movement of water molecules into the relatively hypertonic intracellular space, causing cellular swelling, damage, and ultimately death.

Hypernatremia results from disequilibrium of one or both of these balances. Most commonly, the disorder is caused by a relative free water loss, although it can be caused by salt loading. The various ways in which these equilibria can be disturbed are discussed in Causes.

When hypernatremia (of any etiology) occurs, cells become dehydrated. Either the osmotic load of the increased sodium acts to extract water from the cells or a portion of the burden of the body's free water deficit is borne by the cell. (Sodium, primarily an extracellular ion, is actively pumped out of most cells and is the primary determinant of serum osmolarity.) Dehydrated cells shrink from water extraction.

Cells immediately respond to combat this shrinkage and osmotic force by transporting electrolytes across the cell membrane, thus altering rest potentials of electrically active membranes. After an hour of hypernatremia, intracellular organic solutes are generated in an effort to restore cell volume and to avoid structural damage. This protective mechanism is important to remember when treating a patient with hypernatremia. Cerebral edema ensues if water replacement proceeds at a rate that does not allow for excretion or metabolism of accumulated solutes.

The effects of cellular dehydration are seen principally in the CNS, where stretching of shrunken neurons and alteration of membrane potentials from electrolyte flux lead to ineffective functioning. If shrinkage is severe enough, stretching and rupture of bridging veins may cause intracranial hemorrhage.


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