Hypertonicity: Pathophysiologic Concept and Experimental Studies

Abstract

Disturbances in tonicity (effective osmolarity) are the major clinical disorders affecting cell volume. Cell shrinking secondary to hypertonicity causes severe clinical manifestations and even death. Quantitative management of hypertonic disorders is based on formulas computing the volume of hypotonic fluids required to correct a given level of hypertonicity. These formulas have limitations. The major limitation of the predictive formulas is that they represent closed system calculations and have been tested in anuric animals. Consequently, the formulas do not account for ongoing fluid losses during development or treatment of the hypertonic disorders. In addition, early comparisons of serum osmolality changes predicted by these formulas and observed in animals infused with hypertonic solutions clearly demonstrated that hypertonicity creates new intracellular solutes causing rises in serum osmolality higher than those predicted by the formulas. The mechanisms and types of intracellular solutes generated by hypertonicity and the effects of the solutes have been studied extensively in recent times. The solutes accumulated intracellularly in hypertonic states have potentially major adverse effects on the outcomes of treatment of these states. When hypertonicity was produced by the infusion of hypertonic sodium chloride solutions, the predicted and observed changes in serum sodium concentration were equal. This finding justifies the use of the predictive formulas in the management of hypernatremic states.

Keywords: hypertonicity; osmolality; osmolarity; osmolytes; serum sodium concentration.

Figure 1. Stages of hypertonicity caused by extracellular gain of a hypertonic solution.

Stage I: Addition of a hypertonic solution to the EC prior to any mixing between the EC and the hypertonic solution. Stage II: Hypothetical stage of complete mixing of EC fluid and infused hypertonic solution prior to any interaction with the IC. Stage IIII: Final steady state after osmotic transfer of water from the IC into the EC that led to equal osmolalities in the two compartments. Ordinates: volumes. Abscissae: osmolalities. The figure was constructed assuming that V_i1 = 2xV_e1, V₃ = 0.5xV_e1, and Os₃ = 2xOs₁. The numbers within the boxes show osmolalities.

Figure 2. Estimates of body water and the osmotic and sodium volume of distribution in acute hypernatremia.

Shown here are the average estimates of body water (VH₂O) measured by tritiated water dilution, the osmotic volume of distribution (VOsm) calculated by formula 11, and sodium volume of distribution (VNa) calculated by formula 12 in a study of anuric dogs infused with hypertonic saline [26]. The figure makes two points: (a) Even in acute hypertonicity, VOsm is substantially lower than VH₂O and (b) VNa is equal to VH₂O. The equality of VNa and VH₂O provides the basis for applying equations 9 or 10 in the management of dysnatremias.

Figure 3. Time course of brain organic osmolytes in hypertonicity.

From experimental studies in rats subjected to acute and chronic hypernatremia [35] and from the stage of correction of experimental chronic hyponatremia [36].