Metabolic Acidosis in Hyperparathyroidism Role of Phosphate Depletion and Other Factors

1977 ◽  
pp. 301-307 ◽  
Author(s):  
Shaul G. Massry
Keyword(s):  
Metabolic Acidosis ◽  
Phosphate Depletion

Effect of acidosis on PTH-dependent renal adenylate cyclase in phosphorus deprivation: role of G proteins

1990 ◽  
Vol 258 (6) ◽  
pp. F1640-F1649
Author(s):  
E. Bellorin-Font ◽  
R. Starosta ◽  
C. L. Milanes ◽  
C. Lopez ◽  
N. Pernalete ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Adenylate Cyclase ◽  
Maximal Activity ◽  
Phosphate Deprivation ◽  
Adp Ribosylation ◽  
Phosphate Depletion ◽  
Cortical Membranes ◽  
And Function ◽  
Gs Alpha

These studies examine the regulation of adenylate cyclase in renal cortical membranes from phosphate-deprived and phosphate-deprived acidotic dogs. Enzyme stimulation by parathyroid hormone (PTH) was decreased in phosphate deprivation [Vmax 1,578 +/- 169 vs. 2,581 +/- 219 pmol adenosine 3',5'-cyclic monophosphate (cAMP).mg protein-1 x 30 min-1 in controls, P less than 0.01]. Metabolic acidosis further decreased PTH-stimulated activity. Membranes from phosphate-deprived dogs showed a decrease in Gs alpha-content by cholera toxin-dependent ADP-ribosylation (174 +/- 18 arbitrary units vs. 266.4 +/- 13.6 in controls, P less than 0.01). Metabolic acidosis further decreased Gs alpha-content, P less than 0.01. Gi content by pertussis-dependent ADP-ribosylation was also lower in phosphate-deprived and phosphate-deprived acidotic animals. Gs function was examined by its property to protect the catalytic unit from inactivation by N-ethylmaleimide when preincubated with GTP gamma S. In controls, protection of inactivation was 80% of the maximal activity, whereas in phosphate deprivation protection was less than 50%. In conclusion, metabolic acidosis enhances adenylate cyclase resistance to PTH in phosphate deprivation. These alterations are associated with a decrease in the content and function of Gs alpha, suggesting a role of Gs in the renal adaptation to phosphate depletion and acidosis.

scholarly journals Metabolic Acidosis in Patients with CKD: Epidemiology, Pathogenesis, and Treatment

2021 ◽  
pp. 1-16
Author(s):  
Marcin Adamczak ◽  
Stanisław Surma
Keyword(s):  
Metabolic Acidosis ◽  
Sodium Bicarbonate ◽  
Current Knowledge ◽  
Venous Blood ◽  
The Body ◽  
Hydrogen Ions ◽  
Ckd Progression ◽  
New Drug ◽  
Treatment And Prevention

<b><i>Background:</i></b> Metabolic acidosis in CKD is diagnosed in patients with plasma or venous blood bicarbonate concentration lower than 22 mmol/L. Metabolic acidosis occurs in about 20% of patients with CKD. Metabolic acidosis may lead to dysfunction of many systems and organs as well as CKD progression. Currently, sodium bicarbonate is mainly used for pharmacological treatment of metabolic acidosis in patients with CKD. Veverimer is a new drug dedicated to treatment of metabolic acidosis in patients with CKD. Orally given veverimer binds hydrogen ions in the intestines and subsequently is excreted from the body with feces. Clinical studies have shown that veverimer is effective in increasing serum bicarbonate concentrations in CKD patients with metabolic acidosis. Here, we present review of the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients. <b><i>Summary:</i></b> Metabolic acidosis is common in patients with CKD and contributes to CKD progression and many complications, which worsen the prognosis in these patients. Currently, sodium bicarbonate is mainly used in metabolic acidosis treatment. The role of the new drug veverimer in the metabolic acidosis therapy needs further studies. <b><i>Key Message:</i></b> The aim of this review article is to summarize the current knowledge concerning the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients.

Role of PCO2 as determinant of CSF [HCO3−] in metabolic acidosis

1979 ◽  
Vol 36 (2) ◽  
pp. 155-166 ◽  
Author(s):  
S. Javaheri ◽  
E.A. Nardell ◽  
H. Kazemi
Keyword(s):  
Metabolic Acidosis

Acidosis inhibits osteoblastic and stimulates osteoclastic activity in vitro

1992 ◽  
Vol 262 (3) ◽  
pp. F442-F448 ◽  
Author(s):  
N. S. Krieger ◽  
N. E. Sessler ◽  
D. A. Bushinsky
Keyword(s):  
Alkaline Phosphatase ◽  
Metabolic Acidosis ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Collagen Synthesis ◽  
Calcium Flux ◽  
Osteoclastic Activity ◽  
Glucuronidase Activity

Metabolic acidosis induces net calcium flux (JCa) from cultured neonatal mouse calvariae through physicochemical and cell-mediated mechanisms. To determine the role of osteoblasts in acid-induced JCa, collagen synthesis and alkaline phosphatase activity were assessed in calvariae incubated in reduced pH and bicarbonate medium, a model of metabolic acidosis (Met), and compared with controls (Ctl). Collagen synthesis fell from 30.5 +/- 1.1 in Ctl to 25.1 +/- 0.4% with Met, and alkaline phosphatase decreased from 403 +/- 25 in Ctl to 298 +/- 21 nmol Pi.min-1.mg protein-1 with Met. During acidosis JCa was correlated inversely with percent collagen synthesis (r = -0.743, n = 11, P = 0.009) and with alkaline phosphatase activity (r = -0.453, n = 22, P = 0.034). To determine the role of osteoclasts in acid-induced JCa, osteoclastic beta-glucuronidase activity was determined in Ctl and Met in the absence or presence of the osteoclastic inhibitor calcitonin (CT, 3 x 10(-9) M). Met increased beta-glucuronidase (5.9 +/- 0.2) compared with Ctl (4.6 +/- 0.3 micrograms phenolphthalein released.bone-1.h-1), whereas CT inhibited beta-glucuronidase in both Ctl and Met (3.1 +/- 0.2 and 3.5 +/- 0.3, respectively). During acidosis JCa was correlated directly with beta-glucuronidase activity (r = 0.683, n = 42, P less than 0.001). Thus the cell-mediated component of JCa during acidosis in vitro appears to result from a combination of inhibited osteoblastic and stimulated osteoclastic activity.

Influence of dietary magnesium in experimental phosphate depletion: bone and soft tissue mineral changes.

1979 ◽  
Vol 237 (2) ◽  
pp. E152
Author(s):  
N Brautbar ◽  
D B Lee ◽  
J W Coburn ◽  
C R Kleeman
Keyword(s):  
Soft Tissue ◽  
Weanling Rats ◽  
Dietary Magnesium ◽  
The Face ◽  
Growing Rat ◽  
Phosphate Depletion ◽  
Mg Content ◽  
Mineral Changes ◽  
Group 1

We studied weanling rats fed 0.06% (group 1) and 0.10% (group II) magnesium (Mg) during phosphate depletion (PD) in order to evaluate the role of Mg in the bone, soft tissue, and serum changes of PD. The following results were obtained: 1) serum Mg remained stable in the face of a negative Mg balance; 2) the hypercalcemic and hypercalciuric response to PD was the same in both groups; 3) bone Mg content was decreased with PD in both groups and was associated with a significant decrease in bone calcium and phosphorus. We conclude that: 1) the hypomagnesemia of PD is dependent mainly on the dietary intake of Mg; 2) the hypercalcemia and hypercalciuria of PD are not caused by primary changes in Mg homeostasis; 3) low-dietary Mg during PD may cause a defect in soft tissue utilization of P in the growing rat.

Basolateral membrane H-OH-HCO3 transport in the proximal tubule

1989 ◽  
Vol 256 (5) ◽  
pp. F751-F765
Author(s):  
P. A. Preisig ◽  
R. J. Alpern
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Basolateral Membrane ◽  
Respiratory Acidosis ◽  
Cell Voltage ◽  
Transport Mechanisms ◽  
Transport Capacity ◽  
Chronic Metabolic Acidosis

This review focuses on the basolateral membrane mechanisms of H-OH-HCO3 transport in the proximal tubule. The mechanism that has the greatest transport capacity and mediates most of transepithelial H-HCO3 transport is the electrogenic, Na-3HCO3 cotransporter. This transporter has been extensively characterized in the salamander, rat, and rabbit proximal tubule, and has now been found in a number of other epithelia that effect transepithelial NaHCO3 transport. Transporter rate is sensitive to intra- and extracellular [Na], intra- and extracellular [HCO3]/pH, and cell voltage. Adaptations in transporter activity have been demonstrated in chronic metabolic acidosis and alkalosis, chronic respiratory acidosis and alkalosis, and chronic hyperfiltration. In addition to the Na-3HCO3 cotransporter, the basolateral membrane possesses both Na-dependent and -independent Cl-HCO3 exchangers, a H leak, and in the S3 proximal tubule an Na-H antiporter. The role of these H-OH-HCO3 transport mechanisms in transcellular HCO3 and Cl absorption and pHi defense is discussed.

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.

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