Metabolic alkalosis in models of primary and secondary hyperparathyroid states

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: Δ[HCO₃^-](p) +4.1 ± 0.8 meq/liter, P < 0.01; Δ[H⁺](p) -4 ± 1 neq/liter, P < 0.001, days 10-12. The cumulative change (ΣΔ) in net acid excretion (NAE) was +44 meq (day 9, P < 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: Δ[HCO₃^-](p) +9.1 ± 1.9 meq/liter, P < 0.05; Δ[H⁺](p) -5 ± 1 neq/liter, P < 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. Thus, both hyper- and hypocalcemic HPT result in an increase in the set point at which [HCO₃^-](p) is regulated by the kidney. These studies also demonstrate that chronic hypocalcemic HPT in conscious animals can induce a substantial delivery of alkali into the systemic circulation from an extrarenal source on a chronic basis.