Osmotic pressure and oncotic pressure

This chapter is relevant to Section I1(ii) of the 2023 CICM Primary Syllabus, which expects the exam candidates to "define osmosis, colloid osmotic pressure and reflection coefficients and explain the factors that determine them". As osmotic pressure has already been dealt with elsewhere, this chapter can focus on the relatively straightforward task of defining and explaining colloid osmotic pressure, otherwise known as oncotic pressure. 

In summary:

  • Reflective coefficients for small molecules and barrier membranes are very small, in the order of 0.1-0.5; i.e. small molecules equilibrate easily on either side of biological membranes
  • Thus, small molecules like glucose urea and sodium are not "effective" osmoles for the purposes of generating osmotic pressure gradients.
  • Larger molecules, such as proteins, are not able to cross these membranes, and are therefore responsible for most of the transmembrane osmotic pressure gradient between the body fluid compartments (eg. between the intravascular fluid and the interstitial fluid, or between the intracellular and extracellular fluid)
  • The pressure generated by these proteins is called "oncotic pressure" or "colloid osmotic pressure"
  • Because of the high molecular weight of proteins, their osmolality in the bloodstream is very small (for albumin, 0.6 mOsm/kg)
  • Thus, under normal circumstances, the plasma oncotic pressure is less than 30 mmHg, of which 75-80% is contributed by albumin. 
  • Of this, 10mmHg is contributed by the Gibbs Donnan effect, as extra cations (mainly sodium) are attracted into the intravascular compartment by the negatively charged albumin

Weil et al (1979), if you can get a hold of it, is an excellent resource for oncotic pressure. A free alternative is Darwish & Lui (2020).

Osmotic pressure, again

Osmotic pressure has already been introduced as the hydraulic pressure required to prevent the migration of solvent from the area of low solute concentration to an area of high solute concentration, or 

P = (nRT) / V

where

  • P is the osmotic pressure,
  • is the number of particles into which the substance dissociates, i.e. your sodium acetate dissociates into sodium and acetate, and therefore the n = 2
  • is the universal gas constant, which is 0.082 L atm mol-1 K-1
  • T is the absolute temperature (Kº)
  • V is the volume

Best not to look directly at it. Suffice to say, using standard values, the total osmotic pressure of the human plasma is 5535mmHg. The reason for this massive pressure is the presence of small-molecular-weight ionised solutes such as sodium, potassium, chloride, lactate, glucose and urea. All of these substances contribute a massive number of particles which dissociate in the fluid compartments and increase the osmotic pressure of each fluid. 

Fortunately, they do this in all the compartments. The total concentration of these major osmotically active solutes in the intracellular, intersitial and intravascular compartments is all basically the same, to the point where all of these compartments are essentially isotonic with one another.

The reason for this is the permeability of cellular and other tissue membrane barriers to these small molecules. Particularly permeable are the capillary endothelium and basement membrane; they really do not stand in the way of the smaller solutes. Wolf & Watson (1989), measuring the reflective coefficient values for small molecules such as sodium glucose and urea, found σ values no higher than 0.6, and mostly around 0.1. In short, when considering the osmotic pressure gradient across the capillary wall which separates the intravascular and interstitial fluid compartments, all of these small molecules are ineffective osmoles. The only molecules which cannot cross this barrier are large molecules, such as proteins. Thus, these big colloid molecules are the only molecules which can contribute to the osmotic pressure gradient between these two compartments.

Oncotic pressure, or colloid osmotic pressure

Colloid osmotic pressure is the part of osmotic pressure which is contributed by the large molecules, the "colloid" molecules of protein, of which albumin is the dominant contributor. The term "oncotic", often used to refer to this concept, originated in a publication by Schade & Claussen (1924), which means it would have originally been onkotische Druck.  

Just as osmotic pressure, this is a pressure which is generated by the number of solute particles dissolved in the body water. As you might imagine, for proteins this is not a very large number. Given that human albumin has a molecular weight of around 66 kDa, one mole of albumin weighs 66kg, and therefore the whole body of a 70kg person only has about 3 mmol of albumin in their entire blood volume. Thus, when you measure the entire plasma oncotic pressure, it is only about 25-30 mmHg, or about 0.5% of the total osmotic pressure. 

oncotic pressure

Protein contribution to the Gibbs Donnan effect

So. At normal protein levels, the protein molar (molal?) concentration in the bloodstream is something like 0.9-1.0 mmol/kg, of which 0.6 mmol/kg is albumin. Under normal conditions, plugging the variables into the standard equation, this 1mmol/L would be expected to generate an oncotic pressure of 17.4-9.3 mmHg. However, when plasma proteins are added to water, the oncotic pressure is measured as 25-30 mmHg. This is because of the Gibbs-Donnan Effect (Nguyen et al, 2004).  Because the anionic proteins in the blood attract sodium cations, the plasma sodium is about 0.4 mOsm/kg higher than the interstitial sodium. This contributes to the difference in osmotic pressure (0.4 × 19.3 = 7.72mmHg).  

Because it is the most negatively charged plasma protein (thus contributing the most to the plasma Gibbs Donnan effect), and because it is  the protein present in the highest concentration in the bloodstream, albumin contributes 75% to the oncotic pressure of the plasma. There are four albumin molecules for every globulin molecule. All of this works only while there is not much protein in the interstitial fluid. If there was lots of protein there (or conversely if protein were lost from the intravascular space) the oncotic pressure would drop, and fluid would migrate easily between the intravascular space and interstitial space, causing tissue oedema.  It is said that oedema does not develop until plasma oncotic pressure has decreased below 11mmHg, which equates to an albumin level around 20g/L; however this is probably not entirely accurate, as the microvascular fluid exchange is also governed by hydrostatic pressure. All of this is discussed in greater detail in the cardiovascular system entries involving Starling's Principle.

References

WEIL, MAX HARRY, ROBERT J. HENNING, and VINOD K. PURI. "Colloid oncotic pressure: clinical significance." Critical Care Medicine 7.3 (1979): 113-116.

Wolf, MATTHEW B., and PHILIP D. Watson. "Measurement of osmotic reflection coefficient for small molecules in cat hindlimbs." American Journal of Physiology-Heart and Circulatory Physiology 256.1 (1989): H282-H290.

Schade, H., and F. Claussen. "Der onkotische Druck des Blutplasmas und die Entstehung der renal bedingten Ödeme." Ztschr. f. klin. Med 100 (1924): 363.

Nguyen, Minhtri K., and Ira Kurtz. "Determinants of plasma water sodium concentration as reflected in the Edelman equation: role of osmotic and Gibbs-Donnan equilibrium." American Journal of Physiology-Renal Physiology 286.5 (2004): F828-F837.

Darwish, Alex, and Forshing Lui. "Physiology, Colloid Osmotic Pressure." StatPearls [Internet] (2020).

Odunayo, Adesola. "Albumin and colloid osmotic pressure." Monitoring and Intervention for the Critically Ill Small Animal: The Rule of 20 (2016): 43-53.

Shah, Maulik M., and Pujyitha Mandiga. "Physiology, Plasma Osmolality and Oncotic Pressure." (2019).