I enjoyed the interesting article by Jungner et al.  1on the effects of crystalloid versus  albumin fluid resuscitation in rats with traumatic brain injury, and the excellent editorial by Dr. Drummond.2Thanks to these authors for highlighting the principles of osmosis that underlie the behavior of semipermeable membranes, a key difference between peripheral and brain vasculature.

This letter is to note two typographical errors in a key part of the editorial that render the otherwise elegant explanations incorrect. The second paragraph explains the consequences of dilutional changes in colloid osmotic pressure (COP) in the periphery and in the brain. A key sentence states, “For example, a 50% reduction in COP produces a [small] transmembrane pressure gradient... but because small solvents move easily... fluid moves extravascularly and edema forms.” This is incorrect as written; it should read, “because small solutes  move easily.” Shortly thereafter, the sentence describing the situation in the brain states, “With COP reduction, some transendothelial movement of water probably does occur, but dissolved solvent cannot follow and opposing osmolar and hydrostatic gradients develop immediately and measurable edema differences are prevented.” Again, this should read, “dissolved solute  cannot follow.”

For readers less familiar with the physical chemistry, the explanation is this: A solvent (water) passes easily through a membrane, but an impermeant solute (colloid) does not. Because of an entropic effect, the solvent will diffuse into the compartment that has the higher concentration of the impermeant solute, as if  it is acted upon by a physical driving pressure (the “osmotic pressure”).* This is the phenomenon called osmosis. In our example, initially, the system is in equilibrium: the hydrostatic pressure inside the vessels exactly opposes the “osmotic pressure” due to intravascular colloid. In the next step, the colloid is diluted; now, the hydrostatic pressure overwhelms the opposing “osmotic pressure,” and fluid extravasates.

Dr. Drummond's teaching point is that in the periphery, any reduction in colloid has a significant osmotic effect, because only the colloid is impermeant. The other solutes , small molecules such as electrolytes, pass freely through the membranes and therefore do not have an osmotic effect. In the brain, however, many solutes are impermeant (or diffuse only “with difficulty”[i.e. , to a small degree]). A reduction only in colloid will cause only a small reduction in the total osmotic effect. Therefore, as soon as a small amount of water has extravasated across the membrane (if any passes out at all), the balance of “osmotic pressure” and hydrostatic pressure is already restored.

There is an additional teaching point to make here: We may ask, how is it that only the colloid concentration, but not the small-solute concentration, changed with dilution in this example? The answer is two-fold: (1) The dilution was with crystalloid solution that contained small solutes of its own; and (2) the small solutes pass freely through the membranes elsewhere in the body, promptly equalizing the small-solute concentration (but not the colloid concentration) across the peripheral vasculature. The resulting solution, wherein only colloid concentration has changed, is what then enters the brain.

Again thanks to all for the beautiful demonstration of the relevance of physical chemistry to physiology!

New York University School of Medicine, New York, New York. elana.lubit@nyumc.org

Jungner M, Grände PO, Mattiasson G, Bentzer P: Effects on brain edema of crystalloid and albumin fluid resuscitation after brain trauma and hemorrhage in the rat. Anesthesiology 2010; 112:1194–203
Drummond JC: Colloid osmotic pressure and the formation of posttraumatic cerebral edema. Anesthesiology 2010; 112:1079–81