The Intracellular pH of Human Leucocytes in Response to Acid—Base Changes in Vitro

1976 ◽  
Vol 50 (4) ◽  
pp. 293-299 ◽  
Author(s):  
G. E. Levin ◽  
P. Collinson ◽  
D. N. Baron
Keyword(s):  
Metabolic Acidosis ◽  
Intracellular Ph ◽  
Metabolic Alkalosis ◽  
Venous Blood ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Ph Measurements

1. Viable human leucocytes were isolated from venous blood and suspended in artificial media. Intracellular pH measurements were made by the dimethyloxazolidinedione technique in conditions simulating ‘respiratory’ or ‘metabolic’ acid-base disturbances. 2. Normal intracellular pH was 7·11 ± 0·02 (mean ± 2 sd) at an extracellular Pco2 of 5·8 kPa and a bicarbonate concentration of 25 mmol/l. 3. ‘Respiratory’ and ‘metabolic’ acidosis caused little change in pH1 although increases in Pco2 led to relatively greater falls in pH1 than did reduction in external bicarbonate concentration. 4. ‘Respiratory’ and ‘metabolic’ alkalosis caused similar and relatively greater increases in the pH1 when compared with the response to an external acidosis.

Leucocyte Intracellular pH in Patients with the Metabolic Acidosis of Renal Failure

1977 ◽  
Vol 52 (3) ◽  
pp. 325-328 ◽  
Author(s):  
G. E. Levin ◽  
D. N. Baron
Keyword(s):  
Renal Failure ◽  
Metabolic Acidosis ◽  
Intracellular Ph ◽  
Healthy Subjects ◽  
Venous Blood ◽  
Ph Measurements ◽  
Made In

1. Human leucocytes were isolated from venous blood and resuspended in the subject's plasma. 2. Intracellular pH measurements were made in vitro by the dimethyloxazolidinedione technique in 13 healthy subjects and in 11 subjects with renal failure and metabolic acidosis. 3. The intracellular pH of the healthy subjects was found to be 7·07 (sd 0·04), significantly lower than that of the patients, which was 7·11 (sd 0·03). For all estimations plasma Pco2 was maintained at approximately 5·5 kPa. The methodological and possible metabolic reasons for this difference in intracellular pH are discussed.

Ventilatory response to chronic metabolic acidosis and alkalosis in the dog

1984 ◽  
Vol 56 (6) ◽  
pp. 1640-1646 ◽  
Author(s):  
N. E. Madias ◽  
W. H. Bossert ◽  
H. J. Adrogue
Keyword(s):  
Metabolic Acidosis ◽  
Metabolic Alkalosis ◽  
Ventilatory Response ◽  
Wide Spectrum ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Arterial Pco2 ◽  
Plasma Bicarbonate ◽  
Oral Sodium ◽  
Chronic Change

Systematic data are not available with regard to the anticipated appropriate responses of arterial PCO2 to primary alterations in plasma bicarbonate concentration. In the present study, we attempted to rigorously characterize the ventilatory response to chronic metabolic acid-base disturbances of graded severity in the dog. Animals with metabolic acidosis produced by prolonged HCl feeding and metabolic alkalosis of three different modes of generation, i.e., diuretics (ethacrynic acid or chlorothiazide), gastric drainage, and administration of deoxycorticosterone acetate (alone or in conjunction with oral sodium bicarbonate), were examined. The results indicate the existence of a significant and highly predictable ventilatory response to chronic metabolic acid-base disturbances. Moreover, the magnitude of the ventilatory response appears to be uniform throughout a wide spectrum of chronic metabolic acid-base disorders extending from severe metabolic acidosis to severe metabolic alkalosis; on average, arterial PCO2 is expected to change by 0.74 Torr for a 1-meq/l chronic change in plasma bicarbonate concentration of metabolic origin. Furthermore, the data suggest that the ventilatory response to chronic metabolic alkalosis is independent of the particular mode of generation.

Changes in the plasma anion gap during chronic metabolic acid-base disturbances

1978 ◽  
Vol 235 (4) ◽  
pp. F291-F297 ◽  
Author(s):  
H. J. Adrogue ◽  
J. Brensilver ◽  
N. E. Madias
Keyword(s):  
Metabolic Acidosis ◽  
Metabolic Alkalosis ◽  
Protein Concentration ◽  
Anion Gap ◽  
Acid Base ◽  
Plasma Protein Concentration ◽  
Basic Premise ◽  
Hyperchloremic Metabolic Acidosis ◽  
Large Groups

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.

Intracellular pH measurements in Kidney in vitro — New advantages on single cell diagnosis in the intact organ

2000 ◽  
Vol 118 (4) ◽  
pp. A1109
Author(s):  
Michael J. Sessler ◽  
Christina Baumstark ◽  
Joerg Weik ◽  
Michael Weinlich ◽  
Richard Viebahn ◽  
...  
Keyword(s):  
Single Cell ◽  
Intracellular Ph ◽  
Ph Measurements ◽  
Single Cell Diagnosis

Influence of plasma bicarbonate concentration and pH on citrate excretion

1964 ◽  
Vol 206 (4) ◽  
pp. 875-882 ◽  
Author(s):  
David P. Simpson
Keyword(s):  
Linear Relationship ◽  
Metabolic Alkalosis ◽  
High Plasma ◽  
Alkaline Ph ◽  
Acid Base Balance ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Plasma Bicarbonate ◽  
Close Relationship ◽  
Base Balance

Citrate excretion has been studied in dogs under various conditions of acid-base balance in order to determine which factors are responsible for the increased citrate clearance present in metabolic alkalosis. A close relationship, significantly modified by systemic pH, was found between plasma bicarbonate concentration and citrate clearance. In the presence of an alkaline plasma pH, there was a linear relationship between changes in plasma bicarbonate concentration and changes in citrate clearance. Other experiments also demonstrated the influence of plasma bicarbonate concentration on citrate clearance at alkaline pH. Under acidotic conditions citrate clearances were low and changes in plasma bicarbonate concentration had little effect on citrate excretion. A change in plasma pH from an acidotic to an alkalotic state, with a constant plasma bicarbonate concentration, produced an increase in citrate clearance. Thus the coexistence in metabolic alkalosis of high plasma bicarbonate concentration and high plasma pH results in a markedly increased citrate clearance.

Role of endothelin-1 in renal regulation of acid-base equilibrium in acidotic humans

2012 ◽  
Vol 303 (7) ◽  
pp. F991-F999 ◽  
Author(s):  
Alexandra Pallini ◽  
Henry N. Hulter ◽  
Jurgen Muser ◽  
Reto Krapf
Keyword(s):  
Metabolic Acidosis ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Endothelin 1 ◽  
Plasma Bicarbonate ◽  
Human Volunteers ◽  
Acid Base Equilibrium ◽  
Normal Human ◽  
Mineralocorticoid Activity

Endothelin-1 inhibits collecting duct sodium reabsorption and stimulates proximal and distal tubule acidification in experimental animals both directly and indirectly via increased mineralocorticoid activity. Diet-induced acid loads have been shown to increase renal endothelin-1 activity, and it is hypothesized that increased dietary acid-induced endothelin-1 activity may be a causative progression factor in human renal insufficiency and that this might be reversed by provision of dietary alkali. We sought to clarify, in normal human volunteers, the role of endothelin-1 in renal acidification and to determine whether the effect is dependent on dietary sodium chloride. Acid-base equilibrium was studied in seven normal human volunteers with experimentally induced metabolic acidosis [NH4Cl 2.1 mmol·kg body weight (BW)−1·day−1] with and without inhibition of endogenous endothelin-1 activity by the endothelin A/B-receptor antagonist bosentan (125 BID p.o./day) both during dietary NaCl restriction (20 mmol/day) and NaCl repletion (2 mmol NaCl·kg BW−1·day−1). During NaCl restriction, but not in the NaCl replete state, bosentan significantly increased renal net acid excretion in association with stimulation of ammoniagenesis resulting in a significantly increased plasma bicarbonate concentration (19.0 ± 0.8 to 20.1 ± 0.9 mmol/l) despite a decrease in mineralocorticoid activity and an increase in endogenous acid production. In pre-existing human metabolic acidosis, endothelin-1 activity worsens acidosis by decreasing the set-point for renal regulation of plasma bicarbonate concentration, but only when dietary NaCl provision is restricted.

Bicarbonate: The Alternative Buffer for Peritoneal Dialysis

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 109-113 ◽  
Author(s):  
Jutta Passlick-Deetjen ◽  
Judith Kirchgessner
Keyword(s):  
Peritoneal Dialysis ◽  
Metabolic Acidosis ◽  
Cell Function ◽  
Multicenter Trial ◽  
The Body ◽  
Bicarbonate Concentration ◽  
Promising Alternative ◽  
Technical Problems ◽  
Cell Functions

For a long time bicarbonate, the physiological buffer of the body, was suggested to be the best buffer for peritoneal dialysis. However, since the production of bicarbonate containing solutions is associated with technical problems, lactate was favored. To avoid the well-known disadvantages of lactate solution concerning biocompatibility and possible metabolic side effects, different attempts have been made to use bicarbonate as a buffer in peritoneal dialysis. One of the major approaches was the total replacement of lactate by bicarbonate combined with storage of the fluid in a specially designed double-chamber bag. Further solutions of the above-mentioned problem were the on-line preparation of bicarbonate fluids for intermittent peritoneal dialysis, the addition of bicarbonate just before use, the combination of bicarbonate with organic acids, or its combination with the dipeptide glycylglycine as a stabilizing agent. By now, the beneficial effect of the neutral bicarbonate fluid, for example, on cell viability and cell functions, has been demonstrated in many different in vitro and animal studies. However, only few reports on clinical experience have been published. These investigations demonstrated independently that bicarbonate fluids diminish inflow pain, are well tolerated by the patients, and may correct metabolic acidosis of uremic patients. A controlled randomized multicenter trial using 34 mmol/L bicarbonate for at least three months confirmed that bicarbonate is as efficacious as lactate in equimolar concentrations. Concomitant investigations on energy metabolism and redox state of red blood cells and phospholipid secretion of mesothelial cells additionally demonstrated the improvement of cell function with bicarbonate solutions. For some patients with severe metabolic acidosis the bicarbonate concentration used in the multicenter trial seemed to be too low. Thus, a fluid containing a higher bicarbonate concentration was tested in a pilot study resulting in the expected significant increase of arterial bicarbonate levels. In summary, bicarbonate-containing peritoneal dialysis solutions are a promising alternative to lactate, especially if bicarbonate concentrations are adjusted individually to the patient's need.

Effects of acid-base disturbances on renal handling of magnesium in the dog

1986 ◽  
Vol 70 (3) ◽  
pp. 277-284 ◽  
Author(s):  
Norman L. M. Wong ◽  
Gary A. Quamme ◽  
John H. Dirks
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Indirect Effect ◽  
Metabolic Alkalosis ◽  
Distal Tubule ◽  
Acid Base ◽  
Renal Handling ◽  
Chronic Metabolic Acidosis ◽  
Magnesium Transport

1. Clearance and micropuncture studies were performed in four groups of acutely thyropara-thyroidectomized animals to study the effects of alkalosis and acidosis on the renal handling of magnesium. 2. Our results indicate that chronic metabolic acidosis reduces, whereas acute metabolic alkalosis enhances, magnesium reabsorption. 3. The site within the nephron where absorption of magnesium increases or decreases during acid-base disturbances was beyond the late proximal tubule. 4. Tubular fluid bicarbonate was also measured in these experiments, and the results indicated that magnesium reabsorption in the distal tubule correlated to bicarbonate delivery. However, whether this was a direct or an indirect effect of bicarbonate on magnesium transport could not be delineated.

Bicarbonate Therapy and Intracellular Acidosis

1997 ◽  
Vol 93 (6) ◽  
pp. 593-598 ◽  
Author(s):  
D. J. A. Goldsmith ◽  
L. G. Forni ◽  
P. J. Hilton
Keyword(s):  
Carbon Dioxide ◽  
Metabolic Acidosis ◽  
Sodium Bicarbonate ◽  
Intracellular Ph ◽  
Extracellular Fluid ◽  
Intracellular Acidification ◽  
Intracellular Acidosis ◽  
Bicarbonate Therapy ◽  
Intracellular Alkalinization

1. The correction of metabolic acidosis with sodium bicarbonate remains controversial. Experiments in vitro have suggested possible deleterious effects after alkalinization of the extracellular fluid. Disequilibrium of carbon dioxide and bicarbonate across cell membranes after alkali administration, leading to the phenomenon of ‘paradoxical’ intracellular acidosis, has been held responsible for some of these adverse effects. 2. Changes in intracellular pH in suspensions of leucocytes from healthy volunteers were monitored using a fluorescent intracellular dye. The effect in vitro of increasing extracellular pH with sodium bicarbonate was studied at different sodium bicarbonate concentrations. Lactic acid and propionic acid were added to the extracellular buffer to mimic conditions of metabolic acidosis. 3. The addition of a large bolus of sodium bicarbonate caused intracellular acidification as has been observed previously. The extent of the intracellular acidosis was dependent on several factors, being most evident at higher starting intracellular pH. When sodium bicarbonate was added as a series of small boluses the reduction in intracellular pH was small. Under conditions of initial acidosis this was rapidly followed by intracellular alkalinization. 4. Although intracellular acidification occurs after addition of sodium bicarbonate to a suspension of human leucocytes in vitro, the effect is minimal when the conditions approximate those seen in clinical practice. We suggest that the observed small and transient lowering of intracellular pH is insufficient grounds in itself to abandon the use of sodium bicarbonate in human acidosis.

Plasma, Extracellular and Muscle Electrolyte Responses to Acute Metabolic Acidosis

1956 ◽  
Vol 186 (1) ◽  
pp. 131-138 ◽  
Author(s):  
Richard B. Tobin
Keyword(s):  
Metabolic Acidosis ◽  
Hydrochloric Acid ◽  
Intracellular Ph ◽  
Extracellular Ph ◽  
Acid Base ◽  
Extracellular Acidosis ◽  
Acid Load ◽  
Acute Metabolic Acidosis ◽  
Volumes Of Distribution

Nephrectomized cats were infused with hydrochloric acid in loads of from 3.5–9.6 mEq/kg. Extracellular moderation of the acidosis calculated from concentrations of electrolytes in plasma and inulin volumes of distribution was proportioned as follows: 35% by Na and 5% by K entering the ECS, and 20% by Cl and 24% by CO2 leaving the ECS. Calculated from changes in the chloride spaces, Na shift moderated 58%, CO2 22% and K 6% of the acid load. Sodium rather than potassium appeared to be the main extracellular moderator of acidosis under the conditions of these experiments. Direct muscle analyses showed a fall in intracellular Na and probably of K in response to extracellular acidosis. It is suggested that K i is not inversely related to extracellular ph. Calculated intracellular ph remained constant during the acidosis, indicating that cells may maintain a constant acid-base environment despite marked fluctuations of extracellular ph and that unmeasured mechanisms are responsible.

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