Plasma Protein Metabolism—normal and Associated With Shock

Abstract

The use of heavy nitrogen to label protein should enable the investigator to approach the study of protein exchange in the body with some prospect of success. These experimerlts are directed toward a better understanding of the behavior of the blood plasma proteins in health and disease. We hope ~is paper is but one in a series to be completed as emergencies and time permit.Some of us for several years have been interested in the production and utilization of plasma proteins in the dog. Our understanding of the flow of plasma protein out of the circulation into the tissues and the reverse, we have described as a "dynamic equilibrium." We have shown that all nitrogen requirements of the dog can be supplied by dog plasma given by vein (1,7,14). The dog can be kept in positive nitrogen balance, weight balance, and in health for "weeks while receiving carbohydrate, fat, minerals and accessories by mouth, and plasma protein in suitable amounts by vein. These plasma proteins under such conditions are utilized without significant nitrogen loss (8). No hyperproteinemia of significance is observed in spite of large injections of plasma. Moreover, these long continued plasma injections do not changesignificantly the albumin:globulin ratio. If albumin or any other plasma protein was particularly suited for tissue protein supply or maintenance, one would anticipate a change in the pattern of protein make-up of the plasma. Such changes have not been observed. The fact that no surplus of any plasma protein piles up in the blood plasma of these injected dogs would indicate that all plasma proteins can be utilized in the internal body protein metabolism under these conditions. Schoenheimer, Rittenberg, and their collaborators (18) have found that on feeding to rats various amino acids labeled with deuterium or heavy nitrogen

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

“…Of the protein present in the plasma on day 2, 37 and 67 per cent (average 52 per cent) had disappeared by day 7. Although neither the disappearance from the plasma of labeled plasma protein injected into dogs (26) nor of antibody protein injected into rabbits (27) appeared to be logarithmic, in contrast to the apparent logarithmic disappearance of the retained plasma albumin in our subjects (Figure 6), the similarity is apparent in the rate of disappearance of albumin, plasma protein, and antibody protein from the plasma after intravenous injection. The rate of disappearance of albumin retained in the plasma of our subjects should be a measurable index of the disappearance of the albumin retained in the lymphatic system as well, for their fall will coincide since they are in equilibrium.…”

“…Others have observed that injected plasma protein and injected antibody protein disappeared from the plasma at a similar rate. Thus Fink et al (26) injected plasma protein labeled with radioactive lysine into normal dogs. After an initially rapid disappearance from the plasma during the first day, approximately 50 per cent of the remaining labeled plasma protein disappeared in the next 5 days.…”

Effects of Infusion of Hyperoncotic Dextran in Children with the Nephrotic Syndrome1

“…For example, the existence of a pool of mobile plasma protein in tissue about as large as that in the plasma was suggested some time ago (28). An extravascular "pool" of plasma proteins in nuclei and cytoplasm of many organs and in the interstices of connective tissue has recently been demonstrated (29).…”

Nutritional Factors Affecting Wound Healing

“…The use of protein hydrolysates has recently been reviewed (Elman, 1943;Martin and Thompson, 1943;Gaunt, 1944; J. P. Peters, 1944;Cuthbertson, 1944). The general consensus of opinion is that an enzymic hydrolysate of casein can be obtained almost, if not entirely, free of pyrogens, and that this material can be injected intravenously without inducing untoward reactions.…”

“…During short and moderate periods of illness it is probably not necessary to supplement hydrolysates with vitamins but, if this type of therapy has to be continued over a period of time, daily doses can be given of 2 mg. aneurin, 2 mg. riboflavin, 20 mg. nicotinic acid, and 50 mg. ascorbic acid. Shohl and Blackfan (1940)) Madden, Carter, Kattus, Miller and Whipple (1943), and Bassett, Woods, Shull and Madden (1944) have demonstrated that mixtures of pure amino-acids are suitable for injection in conditions where parenteral administration is necessary for protein nutrition. Preliminary accounts would indicate that they can be given in higher concentration and with greater rapidity than hydrolysates without causing untoward reactions.…”