Effects of Plasmapheresis on Albumin Pools in Rabbits

Abstract

The normal regulation of intravascular plasma protein mass has not been fully investigated. It has long been known that plasma proteins rapidly return to normal concentrations after plasmapheresis, but the means by which this takes place has not been clearly demonstrated. In pathological states, such as nephrosis and hypercatabolic hypoproteinemia, where there may be a steady loss of plasma protein, some compensatory mechanism (see next paragraph) must be involved in cases in which the intravascular plasma proteins are in a steady state. Frequently the protein concentration alone is determined, so that it is not known whether changes are due to variations in plasma volume or in total intravascular protein mass. A steady state can only be said to exist when the plasma protein synthesized is equal to that catabolized, so that the total mass of protein, but not necessarily the concentration, is constant.Disturbances of intravascular protein mass could be compensated for by a) change in synthesis rate, b) change in catabolic rate, c) net transfer of protein between extravascular and intravascular protein pools or d) a combination of several of these. There is also the possibility that the proportion of the different protein fractions is altered and that loss of one fraction is replaced by an increase of another fraction.The purpose of this investigation was to obtain further evidence on this problem by removing protein by plasmapheresis and observing the effect on the catabolic rate, intravascular pool mass, concentration and volume, and on the sum of synthesis rate plus net transfer rate from extravascular to intravascular pool. Rabbits on a normal diet were used, and a single protein fraction, albumin, was considered.I131-rabbit albumin was injected intravenously into rabbits, and plasma albumin specific activity (microcuries per gram), total body radioactivity * Present address: Radiotherapeutic Research Unit, Hammersmith Hospital, London, England. and urinary radioactivity were measured. It is assumed throughout that I131-albumin behaves as normal rabbit albumin (1, 2), that after catabolism the I131 is rapidly excreted, and that there is rapid mixing in each separate protein pool so that within any one pool the specific activity is uniform.A control period of ten days from the injection was allowed before starting plasmapheresis. The normal catabolic rate and pool masses were thus determined for each animal. Daily determinations of intravascular protein mass, concentration and volume were also made throughout each experiment in a control animal not subject to plasmapheresis.Intravascular protein mass and plasma volume were determined by isotope dilution. Since the proportion of albumin to total plasma protein was found to be constant throughout the experiment, albumin masses could be calculated from total protein masses. METHODS TheoreticalExtravascular pool. During the control period, the extravascular protein mass was determined by the equilibrium time method (3-5). In this method the ratio of extravascular t...

Complement metabolism in man: hypercatabolism of the fourth (C4) and third (C3) components in patients with renal allograft rejection and hereditary angioedema (HAE)

“…For each 24 hr period the k. value calculated on the basis of plasma radioactivity was fairly constant, whereas relating urinary excretion to extravascular or whole body radioactivity did not produce a constant catabolic rate. This fact is consistent with the assumption that catabolism of these plasma proteins occurs in or near the plasma space (22).…”

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“…Since the half-life of excretion of free iodide in man is considerably less than 24 hr (19,20), two-thirds of the injected free iodide was arbitrarily subtracted from the first urine collection (usually about 20 hr), and one-third from the second 24 hr collection. When the amount of catabolically released iodide excreted in the urine was expressed as a percentage of the proteinbound iodide in the plasma space at the midpoint of the period of collection, a direct measure of the catabolic rate of the protein was obtained (k.) (21,22). Cumulative excretion of iodide was subtracted from the injected dose and the resulting whole body curve plotted on the same axes as the plasma curve.…”

Albumin and gamma-globulin tracer studies in protein depletion states.

“…Much more difficulty obtains in the interpretation of extravascular and total body albumin mass measurements. The equilibrium time method, which we have used, is not valid where conditions are "unsteady" (10,12 In study A a distinct fall in intravascular albumin pool followed low-protein feeding, a change that was reversed by high-protein diet. At the same time the extravascular pool appeared to fall and then increase.…”

Use of 125I- and 51Cr-Labeled Albumin for the Measurement of Gastrointestinal and Total Albumin Catabolism*

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