Osmolarity vs Tonicity

Tonicity is the measure of osmotic pressure gradient between two solutions

Tonicity is aka effective osmolality because tonicity is only influenced by solutes that cannot cross the semipermeable cell membrane, such as sodium, potassium, etc. However, they contribute to total osmolarity and are thus referred to “effective osmoles,” to distinguish them from freely-crossing “ineffective osmoles” such as urea.

“Effective” osmoles are defined as those osmolytes that influence the osmotic pressure gradient, i.e. tonicity.

Consider urea and glucose, which are commonly described as ineffective osmoles:

1. Urea freely equilibrates across most cell membranes.
2. On the other hand, glucose is too large and polar to freely diffuse across cell membranes. However, it does not accumulate extracellularly due to highly efficient transporters. Thus, metabolic removal of glucose abrogates its effect on tonicity. By extension, accumulation of glucose in plasma creates an aberrant osmotic pressure that favours ICF contraction.

Besides the intrinsic ability of a molecule to diffuse across cell membranes, processes that remove an osmolyte from the ECF minimizes its contribution to osmotic gradients.

Consequently, the rate of removal is crucial – sufficient disruption of the metabolism of an impermeant yet “ineffective” osmolyte such as glucose can produce major osmotic shifts, which can wreak havoc in areas of vulnerability such as the CNS, where there is limited room for extracellular volume expansion.

Isotonicity does not imply iso-osmolarity.

On the one hand, if the ICF and ECF have equal osmolality, there is no osmotic pressure gradient, so they would be isotonic.

Conversely, an iso-osmotic solution can be isotonic if it contains solutes that are rapidly cleared and thus cannot contribute to tonicity. This underlies the “ineffective”-ness of both glucose and dextrose.

5% dextrose thus acts as both a source of glucose and a hypotonic solution.

Infused 5% dextrose is iso-osmolar with body fluids, but is hypotonic.

Dextrose is metabolized similarly to glucose. As such, it is rapidly cleared (~15min) by metabolism in the absence of pathology.

The remainder of infused fluid is thus free water, which will distribute accordingly, on the order of 1-2 hours: ⅔ into the ICF and ⅓ into the ECF, of which ¼ will remain in the circulation.

The ultimate fate of dextrose should parallel that of glucose. It will be metabolized into CO2 and H2O, and the latter will contribute a small increase to TBW.