scholarly journals BLOOD PLASMA PROTEIN GIVEN BY VEIN UTILIZED IN BODY METABOLISM

1934 ◽  
Vol 59 (3) ◽  
pp. 269-282 ◽  
Author(s):  
Russell L. Holman ◽  
Earle B. Mahoney ◽  
George H. Whipple

Large amounts of normal blood plasma can be given intravenously to normal dogs over several weeks without causing any significant escape by way of the urine. There appears to be no renal threshold for plasma protein even with high plasma protein concentration (9.7 per cent). Dogs receiving sugar by mouth and plasma by vein can be kept practically in nitrogen equilibrium and it would seem that the injected protein must be utilized by the body. If this can happen in this emergency we may suspect that normally there is a certain amount of "give and take" between body protein and plasma protein. Plasma protein fed by mouth under identical conditions shows the same general reaction as noted with plasma by vein but the urinary nitrogen is a little higher and suggests that the injected protein is utilized a little more completely to form new protein. The difference may be explained as due to deaminization in the case of protein by mouth. During fasting periods the blood plasma proteins are used up and the total circulating protein may even decrease to one-half the normal level. The plasma protein concentration changes but little and the significant change is a shrinkage of plasma volume. All these facts point to a dynamic equilibrium between tissue protein and plasma protein depending upon the physiological needs of the moment. In the absence of food protein the body can use material coming from one body protein to fabricate badly needed protein material of different character.

1941 ◽  
Vol 73 (5) ◽  
pp. 571-580 ◽  
Author(s):  
S. C. Madden ◽  
A. P. Turner ◽  
A. P. Rowe ◽  
G. H. Whipple

When blood plasma proteins are depleted by bleeding with return of the washed red blood cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal low protein diet. These dogs are clinically normal but their resistance to infection is distinctly below normal. Introduction of variables into this standardized existence gives information relative to plasma protein production. Plasma protein production under these conditions with a plasma protein concentration of 3.5 to 4.2 gm. per cent is relatively constant. As the plasma protein concentration rises the plasma protein removed falls rapidly (Table 1). At 4.6 gm. per cent the protein removed is less than 50 per cent of the amount removed at a plasma protein level of 4.0 gm. per cent. Cystine appears to be an important amino acid for plasma protein formation. This shows in Table 2 and is supported by data coming from published experiments. These experiments related to the factors which control plasma protein production bear on the problems of shock, hemorrhage, and protein wastage and their treatment by plasma injections which hold the attention of surgeons and physiologists at the moment. Again we would emphasize the fluidity of body protein including plasma protein—an ebb and flow between protein depots and plasma protein—a "dynamic equilibrium" of body protein. A discussion of the passage of large protein molecules through cell borders is submitted.


1940 ◽  
Vol 71 (3) ◽  
pp. 283-297 ◽  
Author(s):  
S. C. Madden ◽  
C. A. Finch ◽  
W. G. Swalbach ◽  
G. H. Whipple

When blood plasma proteins are depleted by bleeding with return of the washed red blood cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal low protein diet. These dogs are clinically normal. Introduction of variables into their standardized life gives insight into the production of plasma protein. Casein retested as the basal protein in the ration may show high yield of plasma protein, equal to 33 per cent of the protein fed. This equals the potency of liver protein (17 to 33 per cent) and approaches the utilization of plasma protein by mouth (40 per cent). Zein has no effect upon plasma protein regeneration but when it is supplemented with cystine, tryptophane, lysine, and glycine, there is a doubling of the liver basal plasma protein production and a retention of the fed protein nitrogen. Threonine does not modify the above reaction. Liver protein supplemented with cystine, leucine, glutamic acid, and glycine in the basal diet yields double the amount of new formed plasma protein compared with liver alone. This combination is then as potent as plasma protein itself when given by mouth—40 per cent utilization. Tyrosine or lysine, arginine, and isoleucine do not modify the above responses. Methionine is not as effective as cystine in supplementing gelatin and tyrosine to produce plasma protein. Cystine, leucine, and glutamic acid appear to be of primary importance in the building of new plasma protein in these experiments. Plasma protein formation is dependent upon materials coming from the body reserve and from the diet. Given an exhaustion of the reserve store there is very little plasma protein produced during a protein fast (3 to 6 gm. per week). A turpentine abscess does not modify this fasting plasma protein reaction. Homologous plasma given by vein will promptly correct experimental hypoproteinemia due to bleeding. It will maintain nitrogen equilibrium and replenish protein stores. Even during hypoproteinemia plasma protein may promptly pass out of the circulation to supply body needs for protein. Perhaps the most significant concept which derives from all these experiments is the fluidity of the body protein (including plasma protein)—a ready give and take between the protein depots—a "dynamic equilibrium" of body protein.


1950 ◽  
Vol 91 (4) ◽  
pp. 425-431 ◽  
Author(s):  
R. E. Knutti ◽  
J. B. Goetsch ◽  
R. A. Warrick

Dogs were made hypoproteinemic by repeated injections of gum acacia, and the acacia injections were discontinued. Diets of varying protein content were then given. When a high protein diet is provided the plasma protein concentration increases; with a low protein diet, or under conditions of fasting, the plasma protein concentration diminishes. Similarly, plasma acacia concentration shows increases and decreases which are reciprocal to the protein variations. Total circulating plasma protein and total circulating plasma acacia show similar changes. In all instances total circulating colloid (acacia plus protein) concentration adds up to an amount within normal limits for protein alone. The results indicate that under these conditions, acacia stored in the body (principally in the liver) can be removed from its site of deposit and returned to the blood. The data also show that dogs in which acacia is deposited in large quantities, require a larger amount of protein in the diet to maintain a constant plasma protein content than do normal dogs. It appears that the mechanism for maintenance of peripheral colloidal material may be dependent on differences in intracellular and extracellular colloidal osmotic pressure. The experiments also support the idea that plasma protein molecules, as well as gum acacia, may pass in and out of cells through the cell membranes.


1963 ◽  
Vol 205 (3) ◽  
pp. 527-532 ◽  
Author(s):  
Carleton H. Baker

Altered hemodynamics following hemorrhage causing extended mixing time of indicators, fluid shifts, and changes in indicator disappearance slopes were studied in 17 anesthetized splenectomized dogs. Fibrinogen-I131, T-1824, and red cell-Cr51 spaces were determined simultaneously and the animals were bled 11.3 ml/kg. There was a significant decline in concentration of the three indicators that could not be accounted for on the basis of hematocrit or plasma protein concentration changes. After 20 min stabilization, the spaces were again measured, and the animals were bled an average of 17.7 ml/kg (to an arterial pressure of 60 mm Hg). The decline in indicator concentration was again observed. After allowing the animals to stabilize for 20 min, the spaces were again measured. There was a mobilization of red cells following the first hemorrhage and a trapping of red cells following the second hemorrhage. Fibrinogen-I131 and T-1824 spaces agreed closely with the expected spaces calculated from changes in hematocrit or plasma protein concentration. The fibrinogen space was consistently less than the T-1824 space. The ratio BVcells/ BVfibrinogen significantly increased from 0.92 to 0.99 following the hemorrhages. This suggested a possible redistribution of "extra plasma" or a smaller involvement of extravascular space in the plasma volume determination. BVcells/ BVT-1824 did not change following the hemorrhages. Possible causes for the decline in indicator concentration following hemorrhage are discussed.


1948 ◽  
Vol 87 (6) ◽  
pp. 561-573 ◽  
Author(s):  
Roger Terry ◽  
David R. Hawkins ◽  
Edwin H. Church ◽  
G. H. Whipple

Proteinuria in normal dogs can be produced at will by parenteral injections of dog plasma. As the plasma injections are continued the plasma protein concentration rises and at some point protein begins to appear in the urine. The level of plasma protein concentration at which proteinuria appears in normal dogs ranges from 9.6 to 10.4 gm. per cent. This may be termed the renal threshold for proteinuria. Repeat experiments in the same dog show threshold levels to be practically identical. An interval of days (4 to 26 days) has been noted between the start of plasma protein injections and the appearance of the proteinuria. Larger doses of plasma shorten this interval and the critical plasma protein level is attained sooner. Considerable amounts of protein may appear in the urine—298 gm. protein during a 52 day period in one instance studied—yet the urine clears in 1 to 4 days after cessation of protein injections. Autopsy shows undamaged kidneys. Maximal levels of plasma protein concentration range from 10.0 to 11.5 gm. per cent. The highest levels are usually associated with maximal output of protein in the urine. It seems clear that plasma proteins readily pass cell barriers (or membranes) within the body, including the endothelium and epithelium of the renal glomerulus.


1938 ◽  
Vol 67 (5) ◽  
pp. 675-690 ◽  
Author(s):  
S. C. Madden ◽  
W. E. George ◽  
G. S. Waraich ◽  
H. Whipple

When blood plasma proteins are depleted by bleeding, with return of the washed red cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal low protein diet. These dogs are clinically normal with normal appetite, no anemia and normal nitrogen metabolism. These dogs become test subjects by which various factors relating to plasma protein production may be tested. The normal dog (10 to 13 kg.) has a substantial reserve store of plasma protein building material (10 to 60+ gm.) which requires 2 to 6 weeks plasmapheresis for its complete removal. After this period the dog will produce uniform amounts of plasma protein each week on a fixed basal diet. Dogs previously depleted by plasmapheresis and then permitted to return to normal during a long rest period of many weeks, may show much higher reserve stores of protein building material in subsequent periods of plasma depletion (see Table 1). Under uniform conditions of low protein diet intake when plasmapheresis is discontinued for 2 weeks the plasma protein building material is stored quantitatively in the body and can subsequently be recovered (Table 4) in the next 2 to 3 weeks of plasmapheresis. Given complete depletion of plasma protein building reserve stores the dog can produce very little (2± gm. per week) plasma protein on a protein-free diet. This may be related to the wear and tear of body protein and conservation of these split products. Abscesses produced in a depleted dog during a fast may cause some excess production of plasma protein which is probably related to products of tissue destruction conserved for protein anabolism. Gelatin alone added to the basal diet causes very little plasma protein production but when supplemented by tryptophane gives a large protein output, while tryptophane alone is inert.


1948 ◽  
Vol 87 (6) ◽  
pp. 547-559 ◽  
Author(s):  
Roger Terry ◽  
William E. Sandrock ◽  
Robert E. Nye ◽  
G. H. Whipple

Proteinuria in normal dogs can be produced at will by parenteral injections of dog plasma. As the plasma injections are continued the plasma protein concentration rises and at some point protein begins to appear in the urine. The level of plasma protein concentration at which proteinuria appears in normal dogs ranges from 9.6 to 10.4 gm. per cent. This may be termed the renal threshold for proteinuria. Repeat experiments in the same dog show threshold levels to be practically identical. An interval of days (4 to 26 days) has been noted between the start of plasma protein injections and the appearance of the proteinuria. Larger doses of plasma shorten this interval and the critical plasma protein level is attained sooner. Considerable amounts of protein may appear in the urine—298 gm. protein during a 52 day period in one instance studied—yet the urine clears in 1 to 4 days after cessation of protein injections. Autopsy shows undamaged kidneys. Maximal levels of plasma protein concentration range from 10.0 to 11.5 gm. per cent. The highest levels are usually associated with maximal output of protein in the urine. It seems clear that plasma proteins readily pass cell barriers (or membranes) within the body, including the endothelium and epithelium of the renal glomerulus.


1924 ◽  
Vol 39 (6) ◽  
pp. 921-929 ◽  
Author(s):  
G. C. Linder ◽  
C. Lundsgaard ◽  
D. D. Van Slyke ◽  
E. Stillman

1. We have not observed gross increases in plasma volume in glomerulonephritis, nephrosis, or nephrosclerosis, even when the concentration of plasma proteins was much below normal. Our results indicate the probability that "hydremic plethora" does not occur. 2. The low protein concentration frequently observed in the plasma in nephritis is not due to increased plasma volume but to a decrease of the total amount of plasma protein in the body. 3. Changes in plasma volume showed no constant relationship to changes in edema.


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