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)