Acid-base effects of altering plasma protein concentration in human blood in vitro

1986 ◽  
Vol 61 (6) ◽  
pp. 2260-2265 ◽  
Author(s):  
T. H. Rossing ◽  
N. Maffeo ◽  
V. Fencl

We altered the concentration of plasma proteins in human blood in vitro by adding solutions with [Na+], [K+], and [Cl-] resembling those in normal blood plasma, either protein-free or with a high concentration of human albumin. After equilibrating the samples with a gas containing 5% CO2-12% O2–83% N2 at 37 degrees C, we measured pH, PCO2, and PO2; in separated plasma, we determined the concentrations of total plasma proteins and albumin and of the completely dissociated electrolytes (strong cations Na+, K+, Mg2+ and anions Cl-, citrate3-). With PCO2 nearly constant (mean = 35.5 Torr; coefficient of variation = 0.02), lowering plasma protein concentration produced a metabolic alkalosis, whereas increasing plasma albumin concentration gave rise to a metabolic acidosis. These acid-base disturbances occurred independently of a minor variation in the balance between the sums of strong cations and anions. We quantified the dependence of several acid-base variables in plasma on albumin (or total protein) concentration. Normal plasma proteins are weak nonvolatile acids. Although their concentration is not regulated as part of acid-base homeostasis, hypoproteinemia and hyperalbuminemia per se produce alkalosis and acidosis, respectively.

1991 ◽  
Vol 70 (3) ◽  
pp. 1085-1096 ◽  
Author(s):  
L. E. Olson ◽  
A. Pou ◽  
T. R. Harris

A combination of an amphipathic-indicator-dilution (ID) diffusing tracer 1,4[14C]butanediol (B) and a hydrophilic tracer ([14C]urea) (U) was hypothesized to provide a capillary surface area- (S) independent assessment of lung microvascular permeability (P). We performed ID studies on isolated perfused dog lungs and administered randomly two interventions, increasing P by alloxan infusion and reduction in S by lobar ligation. The ratio of PS product of U (PSU) to that for butanediol (PSB) was sensitive to changes in P yet insensitive to changes in S. We performed ID studies in which the dependence of PSU and PSB on flow, hematocrit, and plasma protein binding were examined. Measurements of PSU and PSB after flow and hematocrit were changed suggested that these factors have no significant independent effects. From ID and in vitro studies we also found that no significant binding of B to plasma proteins (albumin) occurred. We concluded that ID techniques using B and U provide a consistent measure of P, despite changes in S, hematocrit, plasma protein concentration, and recruitment.


1939 ◽  
Vol 70 (6) ◽  
pp. 605-613 ◽  
Author(s):  
Charles L. Yuile ◽  
Ralph E. Knutti

By repeated weekly intravenous injections of gum acacia solution in dogs over periods of 4 to 5 months, it has been possible to maintain plasma protein concentration and total circulating protein at very low levels. If sufficient numbers of such injections are given and then discontinued, plasma protein concentration will remain below the normal limits for several more months. Acacia remains in the blood during this time. Reduction of fibrinogen concentration in such animals is out of proportion to and more marked than the changes in plasma protein concentration. This would indicate interference with liver function. Plasma volume when determined at 7 day intervals during injection periods at first diminishes, then rises 20 to 25 per cent above basal levels. The total blood volume does not show such marked changes because of a decrease in red cell volume. Globulins are reduced to a greater extent than albumin after a single injection of gum acacia, although both albumin and the globulins diminish. This cannot be accounted for by a decrease in fibrinogen alone. After 14 to 16 weekly injections, both albumin and globulins are more profoundly reduced. During injection periods in such animals, it has not been possible to control quantitatively the dietary intake, a complication which has made it difficult to ascertain the effect of various protein diets upon the protein-acacia balance. The changes described, however, have taken place regardless of various types of animal protein diets. Following periods of injection, in spite of very low plasma protein concentration and high acacia concentration in the blood, most of the dogs eat well and therefore they can be used during this period for controlled dietary experiments which may be of value in investigating the mechanism of the production and function of the plasma proteins.


2008 ◽  
Vol 295 (4) ◽  
pp. E913-E920 ◽  
Author(s):  
Maureen Keller-Wood ◽  
Charles E. Wood

Pregnancy is characterized by increased plasma adrenocorticotropic hormone (ACTH) and cortisol. Studies suggest that progesterone acts as an antagonist at mineralocorticoid receptors. Therefore, we tested the hypothesis that chronic progesterone, produced by treatment of nonpregnant ewes or during pregnancy, will result in increased plasma ACTH relative to the plasma cortisol concentrations. We studied three groups of ewes: ovariectomized nonpregnant, nonpregnant treated with progesterone, and pregnant ewes. In two series of studies, ewes were adrenalectomized and replaced with 0.35 mg·kg−1·day−1 or 0.5 mg·kg−1·day−1 cortisol. In both studies, aldosterone was infused at 3 μg·kg−1·day−1. In the first study, additional infusions of cortisol over 24 h were used to increase daily replacement doses to 0.5, 1, or 1.5 mg·kg−1·day−1, and intact pregnant and nonpregnant ewes were studied with infusions of cortisol at 0, 0.5, and 1 mg·kg−1·day−1. In adrenalectomized ewes chronically replaced to 0.35 mg·kg−1·day−1 cortisol, plasma ACTH concentrations were decreased significantly in the nonpregnant progesterone-treated ewes compared with the ovariectomized nonpregnant ewes. With 0.5 mg·kg−1·day−1 cortisol, plasma ACTH levels were greater in pregnant ewes than in nonpregnant ewes with or without progesterone. Overall plasma ACTH levels at 0.35 mg·kg−1·day−1 were significantly related to the plasma protein concentration, suggesting that the ACTH levels in the hypocorticoid ewes are most closely related to plasma volume. Across all steroid doses, ACTH was positively related to plasma proteins and progesterone, and negatively related to cortisol. We conclude that increased progesterone does not alter the feedback relation of cortisol to ACTH, but may modulate ACTH indirectly through plasma volume.


1924 ◽  
Vol 39 (6) ◽  
pp. 887-920 ◽  
Author(s):  
G. C. Linder ◽  
C. Lundsgaard ◽  
D. D. Van Slyke

In nephrosclerosis (Volhard and Fahr classification of nephritis) there was no decrease in the plasma proteins. With heart failure the ratio of albumin to globulin fell from the normal 1.7 ± 0.3 to about 1. There is a sharp difference between the two types of glomerulonephritis in the effect on plasma proteins. In the vascular-interstitial type the effect was the same as in nephrosclerosis. There was no decrease in the plasma proteins until shortly before death. In the glomerulotubular or nephrotic type, active or recently active, the total plasma proteins were less than 5 gm. per 100 cc. This decrease from the normal 5.5 to 7.5 occurred whether edema was present or absent. The decrease affected chiefly the albumin, the globulin being usually diminished but little, and sometimes slightly increased. Consequently the ratio of albumin to globulin was reduced to less than 1, and occasionally to 0.6. In nephrosis similar changes were found in the total protein concentration but in severe cases the decrease in albumin was greater than in nephrotic glomerulonephritis while the globulin was either very slightly reduced or was increased. The albumin : globulin ratio was therefore lower than in nephrotic glomerulonephritis, ranging down to 0.26. With the disappearance of edema there was usually an increase in the plasma protein concentration, but this was not invariable, and concentrations of 4.5 per cent or less were compatible with the persistent absence of edema. The ratio of albumin to globulin showed an irregular tendency to rise. Whenever the total concentration was less than 4 per cent there was some edema present, but it was sometimes slight in amount. With recovery in acute cases, and remission with decrease of proteinuria in chronic cases, normal concentrations were regained. The albumin : globulin ratio remained low in some instances for a longer period on account of an absolute increase in globulin concentration. In "functional proteinuria" no change in plasma proteins was found. Low plasma protein concentrations were always associated with considerable losses of protein in the urine, but these losses did not provide an explanation for all our observations. A disturbance in the production of the plasma proteins appears probable.


1978 ◽  
Vol 235 (4) ◽  
pp. F291-F297 ◽  
Author(s):  
H. J. Adrogue ◽  
J. Brensilver ◽  
N. E. Madias

A basic premise in the utilization of the plasma anion gap in the assessment of acid-base disorders is that this parameter remains constant during hyperchloremic metabolic acidosis and metabolic alkalosis. Experimental data under in vitro conditions, however, cast serious doubt on this premise. The purpose of the present study was to characterize the plasma anion gap, estimated as (Na + K) - Cl + HCO3), in two large groups of dogs with graded degrees of chronic, HCl-induced metabolic acidosis or chronic, diuretic-induced metabolic alkalosis. The data indicate that the plasma anion gap decreases significantly in HCl acidosis and increases significantly in metabolic alkalosis; the predicted mean anion gap in animals with a plasma bicarbonate concentration of 10, 21 (normal), and 40 meq/liter approximated 13, 18, and 26 meq/liter, respectively. The observed variation in the plasma anion gap is interpreted as originating mainly from directional changes in the net negative charge of plasma proteins; these changes result from the titration process secondary to the altered plasma acidity and, in the case of metabolic alkalosis, from the additional effect of an increased plasma protein concentration.


1985 ◽  
Vol 248 (3) ◽  
pp. F347-F353 ◽  
Author(s):  
B. Zimmerhackl ◽  
C. R. Robertson ◽  
R. L. Jamison

Fluid uptake by vasa recta was determined by two independent methods, videomicroscopy and the micropuncture technique, in the exposed papilla of nine antidiuretic rats to reconcile differences in values previously obtained by the two techniques. Erythrocyte velocity (Vrbc) and diameter (D) in descending vasa recta (DVR) (n = 22) and ascending vasa recta (AVR) (n = 31) near the "base" of the papilla were measured. Using a conversion function determined in vitro, Vrbc was transformed into mean blood velocity (Vblood). From D and Vblood, mean blood flow (Q) in DVR and AVR was calculated. In DVR, mean Vrbc, D, and Q were 1.06 +/- 0.01 mm/s, 16.3 +/- 0.4 micron, and 10.6 +/- 1.4 nl/min, respectively. In AVR, each corresponding value differed significantly, 0.47 +/- 0.06 mm/s (P less than 0.001), 19.8 +/- 0.8 micron (P less than 0.001), and 5.65 +/- 1.3 nl/min (P less than 0.025), respectively. Blood samples from DVR and AVR were obtained by micropuncture from the same location. Plasma protein concentration (g/dl) was 5.1 +/- 0.6 in DVR, 4.0 +/- 0.4 (P less than 0.05) in AVR, and 3.6 +/- 0.3 (P less than 0.025) in the renal vein. Assuming no net transcapillary loss of protein, total plasma outflow exceeded inflow by 29%, the excess representing fluid uptake; and to reconcile the blood flow and plasma protein concentrations found, functioning AVR should outnumber functioning DVR by a ratio of 2.1-2.4 to 1, depending on local hematocrit. Given the total number of AVR + DVR = 2,944 (at the base), capillary fluid uptake was calculated to range between 1.5 and 2.6 microliter/min.


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.


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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