Total body albumin content

  • A random 70kg guy has about 360g of albumin. The average plasma concentration is about 40g per L.
  • The total intravascular albumin content is about 118g, and another 177g is sloshing around in the interstitial fluid. However, because the interstitial fluid compartment is larger, interstitial albumin is still more dilute, and the oncotic pressure gradient still favours the movement of fluid into the intravascular compartment. (At least until the serum albumin concentration falls to a level resembling that of interstitial fluid). Additionally, there is some 65g of albumin trapped in a non-exchangeable state in various body compartments. These numbers are derived not from my calculations of volumes and concentration, but from measured iodo-labelled albumin experiments (see Chapter 5 of Theodore Jr Peters' book)
  • Albumin is weakly acidic, and contributes to the Gibbs-Donnan effect by sitting in the intravascular compartment and repelling all the other anions.

Its surprising mobility between body fluid compartments

albumin distribution

The wandering of albumin molecules

Theodore Jr. Peters describes (and plots on a graph) the destiny of infused molecules of albumin, which are traditionally labelled with radioactive iodine. The graph below is an approximation of what occurs.

graph of radiolabelled albumin redistribution after infusion

Initial redistribution: the Transcapillary Escape

As albumin is infused, its serum concentration falls rapidly. 50% of it is already gone by the end of the first day. This albumin is migrating into the extracellular compartment, where (it would appear) much of the albumin in your body resides.

This might sound weird (given how much weight is attributed to the plasma oncotic pressure as a mechanism of keeping fluid in the intravascular compartment).

One might be fooled into thinking that interstitial fluid is some sort of crystal-clear mountain stream, devoid of oncotic pressure-generating solids. This is far from the truth. Remember how much protein ends up in transudative fluids. Remember also how an entire system of lymphatic vessels is required to de-proteinate this supposedly protein-free extracellular fluid.

No, indeed the interstitial fluid is a hideous swamp of protein, of which albumin is only one member.

The transcapillary movement rate is an average of two rates, on fast (12%, into the viscera) and one slow (2%, into the skin and muscle).

Some of this movement is by filtration, and some is (surprisingly) by active transcytosis. The responsible protein ("albondin") has been identified. It is present on selective endothelia; for instance, not in the brain (in keeping with the low albumin content of the CSF)

The compartment distribution of albumin

The diagram below is a crude approximation of the multi-compartment comings and goings of human albumin, with numbers calculated for your standard 70kg Homo vulgaris.Theodore Jr Peters offers a table where the distribution of albumin among the tissues is broken down; the data therein is offered below, because it is excellent even though much of it is derived from rat and rabbit models.

There is at any given time about twice as much albumin outside the circulation as there is inside. (118g in circulation, 177g outside, and 65g locked up somewhere in a non-exchangeable state).

The multi-compartment disposition of albumin

For reasons not entirely clear, most ( ~ 80%) of the extravascular albumin resides in the skin and muscle. Not the whole compartment is available- for instance, in human skin only 35% of the fluid volume ends up having albumin distributed into it. The rest of the fluid is albumin-free.

The gradual fractional degradation

At a degradation rate of 3.7% per day, an average albumin molecule lives for 27 days, circulating around the fluid compartments. Theodore Jr Peters mentions that albumin molecules collect various small molecules by covalent binding along their life in the circulation, like "barnacles" collected by "any tramp steamer doing its rounds".

catabolism of albumin

The degradation occurs at a rate of 13.3-13.6g/day in a typical 70kg person. The sites of degradation are ubiquitous. The liver contributes only about 15%. The kidneys degrade 10%, and a further 10% is lost via leakage into the GI lumen. Persisting radiolabels which remain in lysosomes have demonstrated that muscle and skin are the major sites of albumin degradation, accounting for 40-60%. The major cell types involved seem to be the fibroblasts and macrophages.

The degradation rate is increased by catabolism-inducing hormones, such as corticosteroids. Sensibly, a rising plasma albumin level increases the rate of degradation (and conversely a falling plasma albumin increases the rate of synthesis). The change in the rate of degradation with albumin excess seems to reflect the change in total albumin store (intravascular + extravascular) rather than plasma concentration alone. When Andersen and Rossing overloaded their healthy volunteer with albumin (and doubled his albumin stores), the rate of degradation increased to 200%, but the plasma concentration only rose from 40g/L to 55g/L.

The "barnacle-encrusted" albumin with lots of covalently bound small molecules deforming its structure is more easily degraded. Healthy normal albumin seems to survive and recirculate.

Albumin is ultmately degraded into amino acids, which enter the free amino acid pool (of the total amino acids available for portein synthesis or enegry production). Its destruction contributes to about 5% of the total daily protein turnover in the body.

On a final note- albumin is not an essential component of human life. Some rare examples of its total congenital absence demonstrate that "the virtual absence of albumin is tolerable despite its multiple functions."

References, as always

Theodore Jr. Peters, “All About Albumin: Biochemistry, Genetics, and Medical Applications” Academic Press,1995. Chapter 5

Schultze, Heremans "Nature and metabolism of extracellular proteins" Elsevier, 1966

Schnitzer JE, Oh P. Albondin-mediated capillary permeability to albumin. Differential role of receptors in endothelial transcytosis and endocytosis of native and modified albumins.J Biol Chem. 1994 Feb 25;269(8):6072-82.

Reeve, E. B., and Roberts, J. E. (1959). The kinetics of the distribution and breakdown of I131-albumin in the rabbit. J. Gen. Physiol. 43, 415-444.

Bert, J. L., Pearce, R. H., and Mathieson, J. M. (1986). Concentration of plasma albumin in its accessible space in postmortem human dermis. Microvasc. Res. 32, 211-223.

Katz, J., Bonorris, G., Golden, S., and Sellers, A. L. (1970a). Extravascular albumin mass and exchange in rat tissues. Clin. Sci. 39, 705-3999.

Andersen, S. B., and Rossing, N. (1967). Metabolism of albumin and y-G globulin during plasmapheresis. Stand. J. Clin. Lab. Invest. 20, 183-184.

Watkins S, Madison J, Galliano M, Minchiotti L, Putnam FW (1994). "Analbuminemia: three cases resulting from different point mutations in the albumin gene". Proc. Natl. Acad. Sci. U.S.A. 91 (20): 9417–21