Metabolic alkalosis in models of primary and secondary hyperparathyroid states.

H. N. Hulter, R. D. Toto, L. P. Ilnicki, B. Halloran, A. Sebastian

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Abstract

Hyperchloremic metabolic acidosis has been reported in clinical states of primary and secondary hyperparathyroidism (HPT). Acute administration of parathyroid hormone (PTH) decreases renal acidification in humans and dogs, but the renal and systemic acid-base effects of chronic HPT have not been extensively investigated. In chronically thyroparathyroidectomized (TPTX) dogs (group I), bPTH 1-5 U/kg twice daily resulted in sustained hypophosphatemia, hypercalcemia, and Cl- -resistant metabolic alkalosis that was of renal origin at least in part: delta [HCO3-]p + 4.1 +/- 0.8 meq/liter, P less than 0.01; delta [H+]p -4 +/- 1 neq/liter, P less than 0.001, days 10-12. The cumulative change (sigma delta) in net acid excretion (NAE) was +44 meq (day 9, P less than 0.05). Similarly, metabolic alkalosis of renal origin, at least in part, occurred when PTH was administered by chronic continuous intravenous infusion (group II). Since chronic administration of calcitriol in dogs results in metabolic alkalosis, plasma calcitriol concentration was measured and found not to be increased by chronic intravenous PTH administration. In intact dogs (group III), a continuous chronic intravenous infusion of the Ca2+ chelator, Na4EGTA (3.0 mmol/kg daily), substituted for an equimolar amount of prechelated EGTA (CaNa2EGTA), resulted in a model of hypocalcemic HPT and severe Cl- -resistant metabolic alkalosis: delta [HCO3-]p +9.1 +/- 1.9 meq/liter, P less than 0.05; delta [H+]p -5 +/- 1 neq/liter, P less than 0.01, days 6-8. NAE decreased significantly. Thus, whereas metabolic alkalosis induced by PTH administration could be accounted for by increased NAE (group I), EGTA-induced metabolic alkalosis was accounted for by an extrarenal mechanism of base input to extracellular fluid (group III). Neutralization of the extrarenal base input by chronic administration of HCl during the period of EGTA-induced HPT did not preclude the development of metabolic alkalosis (group V), suggesting that a renal component was present in EGTA-induced metabolic alkalosis as well as in models of primary HPT (groups I and II). During the steady state, in this group as in the groups administered PTH, the net endogenous load of acid to the systemic circulation requiring renal excretion was unchanged from control, as indicated by stable values of NAE not significantly different from control. Yet metabolic alkalosis persisted in the steady state.(ABSTRACT TRUNCATED AT 400 WORDS)

Original languageEnglish (US)
JournalThe American journal of physiology
Volume245
Issue number4
StatePublished - Oct 1983

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Alkalosis
Parathyroid Hormone
Egtazic Acid
Acids
Hyperparathyroidism
Kidney
Dogs
Primary Hyperparathyroidism
Calcitriol
Intravenous Infusions
Hypophosphatemia
Secondary Hyperparathyroidism
Extracellular Fluid
Hypercalcemia
Chelating Agents
Acidosis

ASJC Scopus subject areas

  • Medicine(all)

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Metabolic alkalosis in models of primary and secondary hyperparathyroid states. / Hulter, H. N.; Toto, R. D.; Ilnicki, L. P.; Halloran, B.; Sebastian, A.

In: The American journal of physiology, Vol. 245, No. 4, 10.1983.

Research output: Contribution to journalArticle

Hulter, H. N. ; Toto, R. D. ; Ilnicki, L. P. ; Halloran, B. ; Sebastian, A. / Metabolic alkalosis in models of primary and secondary hyperparathyroid states. In: The American journal of physiology. 1983 ; Vol. 245, No. 4.
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abstract = "Hyperchloremic metabolic acidosis has been reported in clinical states of primary and secondary hyperparathyroidism (HPT). Acute administration of parathyroid hormone (PTH) decreases renal acidification in humans and dogs, but the renal and systemic acid-base effects of chronic HPT have not been extensively investigated. In chronically thyroparathyroidectomized (TPTX) dogs (group I), bPTH 1-5 U/kg twice daily resulted in sustained hypophosphatemia, hypercalcemia, and Cl- -resistant metabolic alkalosis that was of renal origin at least in part: delta [HCO3-]p + 4.1 +/- 0.8 meq/liter, P less than 0.01; delta [H+]p -4 +/- 1 neq/liter, P less than 0.001, days 10-12. The cumulative change (sigma delta) in net acid excretion (NAE) was +44 meq (day 9, P less than 0.05). Similarly, metabolic alkalosis of renal origin, at least in part, occurred when PTH was administered by chronic continuous intravenous infusion (group II). Since chronic administration of calcitriol in dogs results in metabolic alkalosis, plasma calcitriol concentration was measured and found not to be increased by chronic intravenous PTH administration. In intact dogs (group III), a continuous chronic intravenous infusion of the Ca2+ chelator, Na4EGTA (3.0 mmol/kg daily), substituted for an equimolar amount of prechelated EGTA (CaNa2EGTA), resulted in a model of hypocalcemic HPT and severe Cl- -resistant metabolic alkalosis: delta [HCO3-]p +9.1 +/- 1.9 meq/liter, P less than 0.05; delta [H+]p -5 +/- 1 neq/liter, P less than 0.01, days 6-8. NAE decreased significantly. Thus, whereas metabolic alkalosis induced by PTH administration could be accounted for by increased NAE (group I), EGTA-induced metabolic alkalosis was accounted for by an extrarenal mechanism of base input to extracellular fluid (group III). Neutralization of the extrarenal base input by chronic administration of HCl during the period of EGTA-induced HPT did not preclude the development of metabolic alkalosis (group V), suggesting that a renal component was present in EGTA-induced metabolic alkalosis as well as in models of primary HPT (groups I and II). During the steady state, in this group as in the groups administered PTH, the net endogenous load of acid to the systemic circulation requiring renal excretion was unchanged from control, as indicated by stable values of NAE not significantly different from control. Yet metabolic alkalosis persisted in the steady state.(ABSTRACT TRUNCATED AT 400 WORDS)",
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AU - Toto, R. D.

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AU - Halloran, B.

AU - Sebastian, A.

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N2 - Hyperchloremic metabolic acidosis has been reported in clinical states of primary and secondary hyperparathyroidism (HPT). Acute administration of parathyroid hormone (PTH) decreases renal acidification in humans and dogs, but the renal and systemic acid-base effects of chronic HPT have not been extensively investigated. In chronically thyroparathyroidectomized (TPTX) dogs (group I), bPTH 1-5 U/kg twice daily resulted in sustained hypophosphatemia, hypercalcemia, and Cl- -resistant metabolic alkalosis that was of renal origin at least in part: delta [HCO3-]p + 4.1 +/- 0.8 meq/liter, P less than 0.01; delta [H+]p -4 +/- 1 neq/liter, P less than 0.001, days 10-12. The cumulative change (sigma delta) in net acid excretion (NAE) was +44 meq (day 9, P less than 0.05). Similarly, metabolic alkalosis of renal origin, at least in part, occurred when PTH was administered by chronic continuous intravenous infusion (group II). Since chronic administration of calcitriol in dogs results in metabolic alkalosis, plasma calcitriol concentration was measured and found not to be increased by chronic intravenous PTH administration. In intact dogs (group III), a continuous chronic intravenous infusion of the Ca2+ chelator, Na4EGTA (3.0 mmol/kg daily), substituted for an equimolar amount of prechelated EGTA (CaNa2EGTA), resulted in a model of hypocalcemic HPT and severe Cl- -resistant metabolic alkalosis: delta [HCO3-]p +9.1 +/- 1.9 meq/liter, P less than 0.05; delta [H+]p -5 +/- 1 neq/liter, P less than 0.01, days 6-8. NAE decreased significantly. Thus, whereas metabolic alkalosis induced by PTH administration could be accounted for by increased NAE (group I), EGTA-induced metabolic alkalosis was accounted for by an extrarenal mechanism of base input to extracellular fluid (group III). Neutralization of the extrarenal base input by chronic administration of HCl during the period of EGTA-induced HPT did not preclude the development of metabolic alkalosis (group V), suggesting that a renal component was present in EGTA-induced metabolic alkalosis as well as in models of primary HPT (groups I and II). During the steady state, in this group as in the groups administered PTH, the net endogenous load of acid to the systemic circulation requiring renal excretion was unchanged from control, as indicated by stable values of NAE not significantly different from control. Yet metabolic alkalosis persisted in the steady state.(ABSTRACT TRUNCATED AT 400 WORDS)

AB - Hyperchloremic metabolic acidosis has been reported in clinical states of primary and secondary hyperparathyroidism (HPT). Acute administration of parathyroid hormone (PTH) decreases renal acidification in humans and dogs, but the renal and systemic acid-base effects of chronic HPT have not been extensively investigated. In chronically thyroparathyroidectomized (TPTX) dogs (group I), bPTH 1-5 U/kg twice daily resulted in sustained hypophosphatemia, hypercalcemia, and Cl- -resistant metabolic alkalosis that was of renal origin at least in part: delta [HCO3-]p + 4.1 +/- 0.8 meq/liter, P less than 0.01; delta [H+]p -4 +/- 1 neq/liter, P less than 0.001, days 10-12. The cumulative change (sigma delta) in net acid excretion (NAE) was +44 meq (day 9, P less than 0.05). Similarly, metabolic alkalosis of renal origin, at least in part, occurred when PTH was administered by chronic continuous intravenous infusion (group II). Since chronic administration of calcitriol in dogs results in metabolic alkalosis, plasma calcitriol concentration was measured and found not to be increased by chronic intravenous PTH administration. In intact dogs (group III), a continuous chronic intravenous infusion of the Ca2+ chelator, Na4EGTA (3.0 mmol/kg daily), substituted for an equimolar amount of prechelated EGTA (CaNa2EGTA), resulted in a model of hypocalcemic HPT and severe Cl- -resistant metabolic alkalosis: delta [HCO3-]p +9.1 +/- 1.9 meq/liter, P less than 0.05; delta [H+]p -5 +/- 1 neq/liter, P less than 0.01, days 6-8. NAE decreased significantly. Thus, whereas metabolic alkalosis induced by PTH administration could be accounted for by increased NAE (group I), EGTA-induced metabolic alkalosis was accounted for by an extrarenal mechanism of base input to extracellular fluid (group III). Neutralization of the extrarenal base input by chronic administration of HCl during the period of EGTA-induced HPT did not preclude the development of metabolic alkalosis (group V), suggesting that a renal component was present in EGTA-induced metabolic alkalosis as well as in models of primary HPT (groups I and II). During the steady state, in this group as in the groups administered PTH, the net endogenous load of acid to the systemic circulation requiring renal excretion was unchanged from control, as indicated by stable values of NAE not significantly different from control. Yet metabolic alkalosis persisted in the steady state.(ABSTRACT TRUNCATED AT 400 WORDS)

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