Why does a count of solutes not settle where water goes?
Plasma holds many dissolved solutes, but water does not respond to all of them in the same way. Water crosses cell membranes freely and moves toward whichever side holds more of the solutes that cannot cross, as the sodium regulation note showed. So the word chosen for solute concentration matters, because only some solutes move water across cell membranes.
Four related terms separate these ideas. Tonicity counts only the solutes that cannot cross the membrane. Osmolality counts every solute, including the ones that do cross. Urea is a solute that crosses. Once it has spread evenly on both sides, it holds water on neither side, though it still adds to the osmolality the lab reports. The gap between the two counts is what matters here. It shows up while urea is not yet evenly spread, which is what happens during dialysis.
What, then, does each of the four words count?
What does each of the four words count?
Counting solutes is only the start, because the four words describe that count in different ways.
An osmole is the number of moles of dissolved solute. For a substance that does not dissociate, one osmole equals one mole. For a substance that dissociates, the osmole equals the mole multiplied by the number of particles it forms.
Osmolarity is the amount of solute per unit volume of solution. It is colligative, so it depends on the number of particles and not on their nature. But a volume changes with the temperature and pressure of the solution, so a number given per volume changes with those conditions too.
Osmolality is the osmoles of solute per kilogram of solvent. It is also colligative. It is defined per mass and not per volume, and a mass does not change with temperature or pressure. A count per kilogram of water therefore stays fixed. That is why osmolality is the term preferred for body fluids.
What number does the lab report as plasma osmolality?
Osmolality is a sum of solutes, so the reported number has parts that can be named.
Reported plasma osmolality can be calculated as 2 × [Na+] + [Glucose] + [Urea]. Sodium is the main cation of the ECF, and its partner anions, chloride and bicarbonate, are the other main particles there. Doubling the sodium counts those partners. Glucose and urea are then added as the other solutes. Plasma osmolality can also be measured in the laboratory, from the freezing-point depression of plasma.
In health, glucose and urea contribute little. Insulin moves glucose into cells, so glucose does not build up much. Their contribution grows in diabetes mellitus and in reduced kidney function. In diabetes, insulin is short, glucose enters cells less well, and plasma glucose stays high and adds to the count. When kidney function falls, urea’s share of the count grows.
But a sum of every solute does not say whether water will move. Which solutes actually do that?
Which solutes actually move water?
Tonicity is effective osmolality. It counts only the solutes that cannot cross the semipermeable membrane, because only those exert osmotic pressure. Water moves toward a solute that cannot cross, so only that solute holds water on its side. A solute that can cross ends up on both sides and holds none.
Two often-confused definitions follow from this.
- An iso-osmolar solution has a total osmolarity, effective and ineffective solutes together, equal to that of body fluids.
- An iso-tonic solution has an effective osmolarity equal to that of body fluids.
A solution can match body fluid in total osmolality and still not match it in tonicity, if the matching solutes can cross the membrane.
What does dextrose 5% do to water?
A solution can match plasma in total osmolality and still not hold water. Dextrose 5% shows this.
Dextrose 5% is iso-osmolar, because its glucose is counted in total osmolality. But it is hypotonic. Its solute crosses the cell membrane easily, entering the cells, so it no longer holds water outside them. Nothing outside holds the water, so the water acts as free water.
That raises a question about glucose itself, since plasma tonicity does count it.
Why is urea kept in osmolality but dropped from tonicity?
Glucose stays in the tonicity count and urea does not.
Plasma tonicity is 2 × [Na+] + [Glucose]. Glucose is counted in the formula, and its entry into cells depends on insulin. While plasma glucose is high, it keeps holding water outside the cells.
Urea is a term in the osmolality formula but is left out of the tonicity formula. Urea crosses cell membranes freely. It is uncharged but polar, so it passes membranes slowly on its own. In practice, urea transporter proteins move it passively down its concentration gradient. Because it crosses freely, it reaches the same level on both sides, so it holds no water across the membrane. Osmolality counts all solutes, urea included, while tonicity counts only solutes that hold water. So urea raises plasma osmolality but not plasma tonicity.
This holds once urea is evenly spread. What happens when urea leaves the blood faster than it leaves the brain?
What happens to urea in kidney failure, and then in dialysis?
Urea crosses membranes, so it adds to osmolality but not to tonicity.
In kidney failure, urea accumulates in the ECF. It crosses cell membranes freely, so it spreads into the cells as well.
The blood–brain barrier is different. Urea moves across the blood–brain barrier more slowly than across other membranes and takes longer to equilibrate.
This is where the problem arises, during hemodialysis. Urea is removed from blood and ECF faster than it can equilibrate with brain cells. For a time, blood osmolality is low while brain-cell osmolality is still high, because urea remains inside the brain cells. A commonly proposed mechanism for the water shift is this gap. Water therefore moves into brain cells, toward the side holding more solutes that cannot cross quickly enough. This movement of water into brain cells can cause neurological damage.
If the fluid lost or retained has a different osmolality from body fluid, which way do the body fluids move?