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.

Role of citrate excretion in acid-base balance in diuretic-induced alkalosis in the rat

1985 ◽  
Vol 248 (6) ◽  
pp. F796-F803 ◽  
Author(s):  
A. M. Kaufman ◽  
C. Brod-Miller ◽  
T. Kahn
Keyword(s):  
Base Line ◽  
Acid Excretion ◽  
Acid Base Balance ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Plasma Bicarbonate ◽  
Base Balance ◽  
Furosemide Administration ◽  
Net Acid Excretion

Studies were performed to assess the role of changes in the excretion of citrate, a metabolic precursor of bicarbonate, in acid-base balance in diuretic-induced metabolic alkalosis. Rats on a low-chloride diet with sodium sulfate added were studied during a base-line period, 3 days of furosemide administration, and 4 days post-furosemide. During the period of furosemide administration, net acid excretion and plasma bicarbonate concentration increased. In the post-furosemide period, net acid excretion remained higher than base line but plasma bicarbonate concentration did not increase further. Citrate excretion was significantly higher in the post-furosemide period than in base line. Studies substituting sodium neutral phosphate or sodium bicarbonate for dietary sodium sulfate demonstrated greater increases in net acid excretion post-furosemide and, again, no increase in plasma bicarbonate concentration during this period. Citrate excretion was greater than in the sulfate group. The increment in citrate excretion was proportional to the base “load,” defined with respect to changes in net acid excretion and/or dietary bicarbonate. Thus, in these studies alterations of base excretion in the form of citrate play an important role in acid-base balance during diuretic-induced metabolic alkalosis.

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.

Influence of chronic metabolic acid-base disorders on the acute CO2 titration curve

1983 ◽  
Vol 55 (4) ◽  
pp. 1187-1195 ◽  
Author(s):  
N. E. Madias ◽  
H. J. Adrogue
Keyword(s):  
Titration Curve ◽  
Respiratory Acidosis ◽  
Whole Body ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Hydrogen Ion Concentration ◽  
Plasma Bicarbonate ◽  
Arterial Blood ◽  
Acid Base Equilibrium ◽  
Body Response

Previous studies from this laboratory have characterized the “whole-body” response to acute hypercapnia in normal dog and humans. A more recent investigation has demonstrated that this response is markedly altered by graded degrees of chronic respiratory acidosis. The present studies were carried out to assess the influence, if any, of chronic metabolic acid-base disturbances on the acute CO2 titration curve in the dog. To this purpose we first produced a broad range of chronic plasma bicarbonate concentration of metabolic nature. Metabolic acidosis (n = 14) was produced by prolonged HCl-feeding and metabolic alkalosis (n = 11) by diuretics and a chloride-free diet. Animals with normal acid-base status (n = 4) were also studied. After the establishment of a chronic steady state of acid-base equilibrium, we then performed an acute CO2 titration of the unanesthetized dogs within a large environmental chamber. Three levels of inspired CO2 fraction (FICO2) were employed ranging from 4 to 15%. The results indicate that chronic metabolic acid-base disturbances exert a dramatic influence on the whole-body response to acute hypercapnia. The acute change in plasma bicarbonate for a given change in partial pressure of CO2 in arterial blood (PaCO2) or plasma pH decreases as a function of the chronic level of plasma bicarbonate concentration. Yet the ability of the organism to defend plasma hydrogen ion concentration is progressively strengthened as the chronic level of plasma bicarbonate increases.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effect of growth hormone on renal and systemic acid-base homeostasis in humans

1998 ◽  
Vol 274 (4) ◽  
pp. F650-F657 ◽  
Author(s):  
Anita Sicuro ◽  
Katia Mahlbacher ◽  
Henry N. Hulter ◽  
Reto Krapf
Keyword(s):  
Growth Hormone ◽  
Metabolic Acidosis ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Normal Subjects ◽  
Acid Excretion ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Plasma Bicarbonate ◽  
Net Acid Excretion

The effects of recombinant human growth hormone (GH, 0.1 U ⋅ kg body wt−1 ⋅ 12 h−1) on systemic and renal acid-base homeostasis were investigated in six normal subjects with preexisting sustained chronic metabolic acidosis, induced by NH4Cl administration (4.2 mmol ⋅ kg body wt−1 ⋅ day−1). GH administration increased and maintained plasma bicarbonate concentration from 14.1 ± 1.4 to 18.6 ± 1.1 mmol/l ( P < 0.001). The GH-induced increase in plasma bicarbonate concentration was the consequence of a significant increase in net acid excretion that was accounted for largely by an increase in renal [Formula: see text]excretion sufficient in magnitude to override a decrease in urinary titratable acid excretion. During GH administration, urinary pH increased and correlated directly and significantly with urinary[Formula: see text] concentration. Urinary net acid excretion rates were not different during the steady-state periods of acidosis and acidosis with GH administration. Glucocorticoid and mineralocorticoid activities increased significantly in response to acidosis and were suppressed (glucocorticoid) or decreased to control levels (mineralocorticoid) by GH. The partial correction of metabolic acidosis occurred despite GH-induced renal sodium retention (180 mmol; gain in weight of 1.8 ± 0.2 kg, P< 0.005) and decreased glucocorticoid and mineralocorticoid activities. Thus GH (and/or insulin-like growth factor I) increased plasma bicarbonate concentration and partially corrected metabolic acidosis. This effect was generated in large part by and maintained fully by a renal mechanism (i.e., increased renal NH3 production and[Formula: see text]/net acid excretion).

scholarly journals A redefinition of normal acid-base equilibrium in man: Carbon dioxide tension as a key determinant of normal plasma bicarbonate concentration

1979 ◽  
Vol 16 (5) ◽  
pp. 612-618 ◽  
Author(s):  
Nicolaos E. Madias ◽  
Horacio J. Adrogué ◽  
Gary L. Horowitz ◽  
Jordan J. Cohen ◽  
William B. Schwartz
Keyword(s):  
Carbon Dioxide ◽  
Carbon Dioxide Tension ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Plasma Bicarbonate ◽  
Base Equilibrium ◽  
Normal Plasma ◽  
Acid Base Equilibrium ◽  
Normal Acid

Role of ion transfer processes in acid-base regulation with temperature changes in fish

1984 ◽  
Vol 246 (4) ◽  
pp. R441-R451 ◽  
Author(s):  
N. Heisler
Keyword(s):  
Ion Transfer ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Fish Tissues ◽  
Model Calculations ◽  
Temperature Changes ◽  
Transfer Processes ◽  
Transfer Mechanisms

The contributions of transmembrane and transepithelial ion transfer processes and of nonbicarbonate buffering to the in vivo acid-base regulation have been evaluated. Model calculations were performed utilizing experimental data on transepithelial transfer of ions relevant for the acid-base regulation, the intracellular buffering properties of fish tissues, and the behavior of intracellular and extracellular pH and bicarbonate concentration with changes of temperature. The results of these studies indicate that the changes in the pK values of physiological nonbicarbonate buffers with changes in temperature support the adjustment of pH to lower values with rising temperature; however, transmembrane and transepithelial ion transfer mechanisms determine the acid-base regulation of intracellular and extracellular compartments.

scholarly journals Nutritional disturbance in acid–base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney

2013 ◽  
Vol 110 (7) ◽  
pp. 1168-1177 ◽  
Author(s):  
Jean-Philippe Bonjour
Keyword(s):  
Fracture Risk ◽  
Bone Mineral ◽  
Bone Growth ◽  
Kidney Diseases ◽  
Buffer System ◽  
Acid Base ◽  
Alkaline Salt ◽  
Nutrition Research ◽  
Acid Base Equilibrium

The nutritional acid load hypothesis of osteoporosis is reviewed from its historical origin to most recent studies with particular attention to the essential but overlooked role of the kidney in acid–base homeostasis. This hypothesis posits that foods associated with an increased urinary acid excretion are deleterious for the skeleton, leading to osteoporosis and enhanced fragility fracture risk. Conversely, foods generating neutral or alkaline urine would favour bone growth and Ca balance, prevent bone loss and reduce osteoporotic fracture risk. This theory currently influences nutrition research, dietary recommendations and the marketing of alkaline salt products or medications meant to optimise bone health and prevent osteoporosis. It stemmed from classic investigations in patients suffering from chronic kidney diseases (CKD) conducted in the 1960s. Accordingly, in CKD, bone mineral mobilisation would serve as a buffer system to acid accumulation. This interpretation was later questioned on both theoretical and experimental grounds. Notwithstanding this questionable role of bone mineral in systemic acid–base equilibrium, not only in CKD but even more in the absence of renal impairment, it is postulated that, in healthy individuals, foods, particularly those containing animal protein, would induce ‘latent’ acidosis and result, in the long run, in osteoporosis. Thus, a questionable interpretation of data from patients with CKD and the subsequent extrapolation to healthy subjects converted a hypothesis into nutritional recommendations for the prevention of osteoporosis. In a historical perspective, the present review dissects out speculation from experimental facts and emphasises the essential role of the renal tubule in systemic acid–base and Ca homeostasis.

Acid-Base Balance with Different Capd Solutions

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 126-129 ◽  
Author(s):  
Mariano Feriani ◽  
Claudio Ronco ◽  
Giuseppe La Greca
Keyword(s):  
Acid Production ◽  
Dwell Time ◽  
Lactate Concentration ◽  
The Body ◽  
Plasma Lactate ◽  
Acid Base Balance ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Plasma Bicarbonate ◽  
Base Balance

Our objective is to investigate transperitoneal buffer fluxes with solution containing lactate and bicarbonate, and to compare the final effect on body base balance of the two solutions. One hundred and four exchanges, using different dwell times, were performed in 52 stable continuous ambulatory peritoneal dialysis (CAPD) patients. Dialysate effluent lactate and bicarbonate and volumes were measured. Net dialytic base gain was calculated. Patients’ acid-base status and plasma lactate were determined. In lactate-buffered CAPD solution, lactate concentration in dialysate effluent inversely correlated with length of dwell time, but did not correlate with plasma lactate concentration and net ultrafiltration. Bicarbonate concentration in dialysate effluent correlated with plasma bicarbonate and dwell time but not with ultrafiltration. The arithmetic sum of the lactate gain and bicarbonate loss yielded the net dialytic base gain. Ultrafiltration was the most important factor affecting net dialytic base gain. A previous study demonstrated that in patients using a bicarbonate-buffered solution the net bicarbonate gain is a function of dwell time, ultrafiltration, and plasma bicarbonate. By combining the predicted data of the dialytic base gain with the calculated metabolic acid production, an approximate body base balance could be obtained with both lactate and bicarbonate-buffered CAPD solutions. The body base balance in CAPD patients is self-regulated by the feedback between plasma bicarbonate concentration and dialytic base gain. The level of plasma bicarbonate is determined by the dialytic base gain and the metabolic acid production. This can explain the large interpatient variability in acid-base correction. Bicarbonate-buffered CAPD solution is equal to lactate solution in correcting acid-base disorders of CAPD patients.

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.

Practical Evaluation of Acid-Base Balance

1957 ◽  
Vol 3 (5) ◽  
pp. 631-637
Author(s):  
Herbert P Jacobi ◽  
Anthony J Barak ◽  
Meyer Beber
Keyword(s):  
Respiratory Acidosis ◽  
Respiratory Alkalosis ◽  
Acid Base Balance ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Plasma Bicarbonate ◽  
Practical Evaluation ◽  
Base Balance

Abstract The Co2 combining power bears a variable relationship to the in vivo plasma bicarbonate concentration, depending upon the type and severity of acid-base distortion. In respiratory alkalosis and metabolic acidosis the Co2 combining power will usually be greater than the in vivo plasma bicarbonate concentration; whereas, in respiratory acidosis and metabolic alkalosis the Co2 combining power will usually be less. Co2 content, on the other hand, will always parallel the in vivo plasma bicarbonate concentration quite closely, being only slightly greater. These facts, together with other considerations which are discussed, recommend the abandonment of the determination of CO2 combining power.

Sign in / Sign up

Export Citation Format

Share Document