title: Ureagenesis: evidence for a lack of hepatic regulation of acid-base equilibrium in humans.
abstract: Ureagenesis in the liver consumes up to 1,000 mmol of HCO3-/day in humans as a result of 2NH4+ + 2HCO3- --> urea + CO2 + 3H2O. Whether the liver contributes to the regulation of acid-base equilibrium by controlling the rate of ureagenesis and, therefore, HCO3- consumption in response to changes in plasma acidity has not been adequately evaluated in humans. Rates of ureagenesis were measured in eight healthy volunteers during control, chronic metabolic acidosis (induced by oral administration of CaCl2 3.2 mmol.kg body wt-1.day-1 for 11 days), and recovery as well as during bicarbonate infusion (200 mmol over 240 min; acute metabolic alkalosis). Rates of ureagenesis were correlated negatively with plasma HCO3- concentration both during adaption to metabolic acidosis and during the chronic, steady-state phase. Thus ureagenesis, an acidifying process, increased rather than decreased in metabolic acidosis. During bicarbonate infusion, rates of ureagenesis decreased significantly. Thus ureagenesis did not appear to be involved in the regulated elimination of excess HCO3-. The finding of a negative correlation between ureagenesis and plasma HCO3- concentration over a wide range of HCO3- concentrations, altered both chronically and acutely, suggests that the ureagenic process per se is maladaptive for acid-base regulation and that ureagenesis has no discernible homeostatic effect on acid-base equilibrium.
authors.affiliation: Department of Medicine, Kantonsspital Bruderholz, CH 4101 Bruderholz/Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Hosch
authors.forename: Juergen
authors.initials: J
authors.lastname: Muser
authors.forename: Henry N
authors.initials: HN
authors.lastname: Hulter
authors.forename: Reto
authors.initials: R
authors.lastname: Krapf
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology*; D000138:Acidosis / Q000139:chemically induced / Q000503:physiopathology; D000328:Adult; D000471:Alkalosis / Q000139:chemically induced / Q000503:physiopathology; D001639:Bicarbonates / Q000008:administration & dosage / Q000097:blood; D002122:Calcium Chloride / Q000008:administration & dosage; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008099:Liver / Q000502:physiology*; D008297:Male; D014508:Urea / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D014508:Urea; D002122:Calcium Chloride