Oncotic pressure, osmolality, and tonicity (Proceedings)

Osmotic "control" of transmembrane fluid flux

There are three major body fluid compartments in the body: intravascular, interstitial, and intracellular. These three compartments are separated by semipermeable membranes which are freely permeable to water. The distribution of water across these membranes is determined by the osmotic gradients of solutes that are not permeable to the respective membrane. In order for a solute to be osmotically effective, it must be maintained in higher concentrations on one side of the membrane.

Intravascular, interstitial, and intracellular fluid compartments

Oncotic Pressure

Colloids are large molecules that are not freely permeable across the vascular membrane, are present in the vascular fluid compartment in larger concentrations than in the interstitium, and therefore are osmotically responsible for retaining crystalloids within the vascular fluid compartment according to the Starling equilibrium of transvascular fluid flux, assuming normal vascular permeability.

Albumin is the prominent intravascular colloid. Hypoproteinemia may be associated with simultaneous hypovolemia, and subcutaneous edema and ascites. This is not a straight-line relationship since decreases in plasma albumin concentration are initially offset by a dilutional decrease in perivascular albumin concentration. An increased capillary permeability to the extent that albumin and other colloids are freely permeable would also result in hypovolemia and interstitial edema. Crystalloids are freely permeable across the vascular membrane. Changes in sodium concentration have no effect on transvascular fluid flux. Intravenously administered crystalloid fluids are rapidly redistributed to the interstitial fluid compartment in an amount proportional to the relative size of the interstitial fluid compartment.

Colloid osmotic pressure (or oncotic pressure) is measured with a colloid osmometer which employs a semipermeable membrane and measures the change in pressure in the reference chamber when an unknown solution is placed in the test chamber. The membrane pore size in these instruments is 20 or 30 kilodaltons and therefore are freely permeable to the small electrolytes. This analyzer is "blind" to the sodium concentration and the osmolality of the solution.

Measuring oncotic pressure

Normal colloid osmotic pressure is 20 to 25 mm Hg. Values in the high "teens" are common in critically ill patients but are not considered to warrant treatment, per se. Values in the low "teens" are considered to be too low, and warrant treatment with an artificial colloid or plasma. Values in the single digits (commonly seen in patients with portocaval shunts) also need to be treated but there is a need to do it slowly. Rapid administration of colloids to these patients has caused edema, presumably by increasing capillary hydrostatic pressure ahead of increases in colloid osmotic pressure and upsetting the precariously balanced starling forces.

Osmolality

Sodium is pumped out of the cell by the sodium-potassium-ATPase pump in the cellular membrane. As sodium and its related anion (predominantly chloride and bicarbonate) are maintained in the extravascular fluid compartment, they are primarily responsible for the osmotic attraction and retention of water in the extracellular fluid compartment.

Acute changes in extracellular sodium concentration result in transcellular fluid fluxes (hyponatremia causes cellular edema; hypernatremia causes cellular dehydration). Diseases associated with inadequate cellular energy production and ATP depletion are associated with the influx of sodium (and water) into the cell, cellular edema, and, eventually, cellular disruption. The endothelial membrane is freely permeable to these crystalloids and sodium concentration has no impact upon the transvascular fluid flux.

It is actually extracellular osmolality, rather than sodium concentration, that is important to transcellular fluid flux. Sodium (and its related anion) are by far the largest component of measured osmolality. Osmolality is normally calculated as 2 x [Na+] + 10 (which accounts for the normal contributions of glucose and blood urea nitrogen [BUN]). If the glucose and BUN are known, their contributions can be calculated as glucose (mg/dl)/18 + BUN (mg/dl)/2.8. While hyponatremia is the only cause of hypo-osmolality, there are many causes of hyperosmolality. The measured osmolality is normally about 10 to 15 mOsm/Kg higher than the calculated value. A higher osmolar gap is indicative of unmeasured osmols.

Osmolality is measured by freezing point depression. Some the osmoles that effect freezing point depression are small and noncharged, and are permeable across the cellular membrane and therefore do not influence transcellular fluid flux; they are ineffective osmoles. The "effective" or in vivo osmolality can be calculated by subtracting the "ineffective" osmoles (those that are measured in vitro but are known to be ineffective osmols in vivo - urea nitrogen) from the measured osmolality. This is a relevant exercise when considering whether to administer a drug like mannitol for diuresis or cerebral edema reduction in a patient that is hyperosmolar due to uremia. For instance, a patient that has an in vitro osmolality of 400 because the blood urea nitrogen is 266 (Na = 150 and glucose = 90) has an effective in vivo osmolality of only 305. Mannitol therapy is not contra-indicated.

Tonicity is the term used to describe the in-vivo osmolality of a fluid; the manner in which the infused fluid will effect transcellular fluid flux. We don't normally administer urea solutions but we do commonly administer dextrose in water solutions. Once administered, the glucose is rapidly metabolized, leaving just the water. In the net, it is like administering distilled water (without the hemolysis that would be associated with the administration of distilled water). Five and ten percent dextrose in water solutions would have an in vitro measured osmolality of 250 and 500 mOsm/kg, respectively, but both would have an in vivo osmolality of zero. They are both hypotonic fluids. Five% dextrose in water is almost iso-osmotic in the bottle while 10% dextrose in water is hyperosmotic in the bottle (both are hypo-osmotic in vitro). Ten % mannitol, on the other hand, would be hypersomotic in the bottle and hypertonic in the body (mannitol is not metabolized).

Causes of hyperosmolality

Osmolality and colloid osmotic pressure both use the phrase "osmo" and both are important by virtue of osmotic differentials across a semi-permeable membrane. Functionally they are entirely different and should not even be used together in the same sentence. They are measured differently, utilize different units, are due to different solutes, and act at different levels in the body.

Comparison of osmolality and colloid oncotic pressure