Studies on Hypoalbuminemia Produced by Protein-Deficient Diets

Abstract

Plasma transfusions are often used clinically to correct hypoproteinemia resulting from malnutrition although the results are often disappointing in the severe cases. It seemed advisable, therefore, to study experimentally the effect of intravenous plasma in dogs depleted by a non-protein diet which has been shown by Weech (1) and ourselves (2) to produce a rapid fall in the albumin fraction of the blood. Holman, Mahoney, and Whipple (3) were the first to study the metabolic effect of plasma transfusions in the dog and they showed that protein given in this way led to positive nitrogen balance but only when dog plasma was used. These findings were confirmed by later studies (4, 5). More recently Kremen et al. have reported similar findings with human plasma in human beings but not with bovine plasma (6). In protein-depleted dogs Shearburn (7) found that one plasma transfusion calculated to restore the plasma protein deficiency had only a transient influence on plasma volume and no effect on the hypoproteinemia, whereas smaller amounts given once or twice a day for 2 weeks led to a gradual return of the plasma protein to normal. ProceduresThe dietary method used to produce hypoalbuminemia was similar to that devised by Weech (1) except that a solution was used and administered by garage twice daily (2). The energy value was 50 calories per kilo per day and the nitrogen intake due largely to vitamin B complex was under 20 rag. per kilo per day. A period of 3 weeks was used for depletion; the 4th week was used for therapy and the depletion then continued for 2 more weeks. Thus each experiment lasted 6 weeks. Under such a non-protein r6gime hypoalbuminemia rapidly develops except that occasionally it is masked by hemoconcentration which is revealed by a rise in the hematocrit reading (8). However, in the present experiments plasma volumes were measured to circumvent this state of affairs; the method used was described in a previous paper in this series (9).The amount of plasma given during the 4th week was determined by measuring its nitrogen content. A dose of 0.5 gm. of nitrogen per kilo per day was given, which was the same we used in other regeneration experiments in which hydrolyzed protein was used (2). In terms of protein this represented a little over 3 gin. per kilo per day, which is somewhat greater than 2.5 gin. employed by Weech. It was 1 on

Chemical, Clinical, and Immunological Studies on the Products of Human Plasma Fractionation. Xxxiv. Comparative Studies on the Nutritive Value of Orally and Intravenously Administered Human Serum Albumin in Man 123

“…Parenterally injected albumin and plasma proteins disappear rapidly from the blood stream (1,21), but repeated injections are followed by an appreciable and readily detectable increase in the total circulating plasma proteins, as reported here and by others (5,10,12). It is clear that roughly 24 to 46 per cent of the protein retained in our subjects could be accounted for by the albumin increase in the blood plasma (Table II, hydrolysate).…”

Metabolic Studies on Protein-Depleted Patients Receiving a Large Part of Their Nitrogen Intake From Human Serum Albumin Administered Intravenously 12

“…E. G. (see Figure 2) who received slightly more than 8 of the urine began to increase and rose slowly but progressively until the experimental period was terminated. In only one instance, however (the case of G. V.), did the urinary nitrogen become so great as to produce a negative nitrogen balance.…”

“…The opinions and conclusions are those of the authors and do not necessarily reflect the policy of the National Blood Program. 8 Henry C. Buswell Fellow in Internal Medicine.…”

“…It is generally conceded that positive nitrogen balances can be established in both animals and man by the intravenous administration of homologous plasma, provided that the dose is in excess of the minimum protein requirements. It is felt by some investigators (7,8) that the positive balance obtained is an illusory affair and that the actual utilization is poor in some instances. On the other hand, Whipple and coworkers (9) believe that parenteral plasma protein can supply all the requirements for maintenance over a considerable period of time.…”

Metabolic and Cardiovascular Studies of Prolonged Intravenous Administration of Human Serum Albumin

“…Ten years ago, animal studies showed that homologous plasma proteins were retained during the several days of infusion. There was controversy as to whether or not a subsequent loss of equivalent nitrogen occurred (1)(2)(3). Recent studies in Whipple's laboratory (4) have shown, however, that the protein balance of dogs may be maintained for three months with plasma as the sole source of nitrogen.…”