More on plasma protein osmotic equations for humans

The following is the abstract of the article discussed in the subsequent letter:

	ABSTRACT

Yamada, S., M. K. Grady, V. Licko, and N. C. Staub. Plasma protein osmotic pressure equations and nomogram for sheep. J Appl Physiol 71: 481-487, 1991.The equations developed by Landis and Pappenheimer (Handbook of Physiology. Circulation, 1963, p. 961-1034) for calculating the protein osmotic pressure of human plasma proteins have been frequently used for other animal species without regard to the fractional albumin concentration or correction for protein-protein interaction. Using an electronic osmometer, we remeasured the protein osmotic pressure of purified sheep albumin and sheep plasma partially depleted of albumin. We measured protein osmotic pressures of serial dilutions over the concentration range 0-180 g/l for albumin and 0-100 g/l for the albumin-depleted proteins at room temperature (26°C). Using a nonlinear least squares parameter-fitting computer program, we obtained the equation of best fit for purified albumin, and then we used that equation together with the measured albumin fraction to obtain the best-fit equation for the nonalbumin proteins. The equation for albumin is II_cmH2O,39°C = 0.382C + 0.0028C² + 0.000013C³, where C is albumin concentration in g/l. The equation for the nonalbumin fraction is II_cmH2O,39°C = 0.119C + 0.0016C². Up to 200- and 100-g/l protein concentration, respectively, these equations give the least standard error of the estimate for each of the virial coefficients. The computed number-average molecular weight for the nonalbumin proteins is 222,000. Using the new equations, we constructed a nomogram, based on the one of Nitta and co-workers (Tohoku J. Exp. Med. 135: 43-49, 1981). We tested the nomogram using 144 random samples of sheep plasma and lymph from 31 sheep. We obtained a correlation coefficient of 0.99 between the measured and nomogram estimates of protein osmotic pressure.

	LETTER

To the Editor: I am grateful to Dr. Staub for his firm "No" (1) to a cubic term in the nonalbumin part of equations for approximation of colloid osmotic pressure (_appr) from total protein (TP) and albumin. His reasons became clear when I compiled the figure (see Fig. 1), which opened my eyes.

View larger version (42K): [in this window] [in a new window]   Fig. 1.   Colloid osmotic pressure () of plasma or serum approximated (appr) from albumin and nonalbumin fractions calculated from total protein (TP) and albumin (difference = fibrinogen + globulins) according to Yamada et al. (see Ref. 1). If serum TP is 75 g/l and albumin is 45 g/l, appr is 37.1 cmH2O. Increase of IgG by 5 g/l raises appr to 39.7 cmH2O. If, furthermore, 1- and 2-globulins increase by 5 g/l, appr is 42.3 cmH2O. If the latter 5 g/l is transferred to the albumin fraction (see text), appr is 44.6 cmH2O. This is exceeded by only one measured  of serum in a series of 55 sera (3).

Unbalanced increase of fibrinogen and globulins much larger than IgG increases TP and _appr more than protein molality and true , whereas small globulins have an opposite effect. Orosomucoid (₁-), ₁-antitrypsin, and ₁-antichymotrypsin are smaller than or close to the size of albumin, and (₂-) haptoglobin is smaller than IgG. All are acute-phase reaction (APR) globulins. Guyton's figures on protein fractions and  (2) could be traced (3rd ed.) to Ott (3).

Ott measured  of serum (_serum) and approximated it from TP and electrophoretic serum fractions (3). At normal to high TP, the influence on  of ₁-globulins was over twice that of albumin and that of ₂-globulins was almost twice that of -globulin. The normal concentration of the above APR ₁-globulins is ~2.5 g/l and that of haptoglobin is ~1.5 g/l (C-reactive proteins and so forth are less important quantitatively). These small globulins balance the influence of large proteins on _appr, but in APRs they may undergo up to fourfold increase.

In APRs, _appr underestimates _serum, possibly even when the increase of -globulins is transferred to the albumin fraction (Fig. 1). If APR-associated lowering of albumin parallels or is preceded by -globulin elevation, _serum may undergo a sudden increase. On activation of joint disease in rheumatoid arthritis, _appr decreased by only 2.5 cmH₂O due to 10 g/l increase of (APR?) globulins (1). If that 10 g/l is transferred to the albumin fraction, _appr is increased.

An equation for _serum based on electrophoretic fractions and TP might be useful in clinical work. How precisely is _serum regulated in individuals? An increase of IgG of varying specificity, and of _appr, precedes many inflammatory diseases. The clinical onset of such diseases is often associated with APRs that may suddenly increase an already high _serum.

Thank you Dr. Staub, but so it went, I think.

	ACKNOWLEDGEMENTS

I am grateful to Veikko Näntö and Martti Lalla for checking the calculations and to Mikael Lampinen for Fig. 1.

	FOOTNOTES

10.1152/japplphysiol.01177.2002

	REFERENCES

1.   Ahlqvist, J, and Staub NC. Plasma protein osmotic pressure equations for humans (Letter). J Appl Physiol 94: 1288-1289, 2003[Free Full Text].

2.   Guyton, AC. Textbook of Medical Physiology (6th ed.). Philadelphia, PA: Saunders, 1981.

3.   Ott, H. Die Errechnung des kolloidosmotischen Serumdruckes as dem Eiweiss-spektrum und das mittlere Molekulargewicht der Serumeiweissfraktionen. Klin Wschr 34: 1079-1063, 1956.

Johan Ahlqvist 25830 Västanfjärd, Finland E-mail: johan.ahlqvist{at}kolumbus.fi