Liver regulation of acid-base balance

Miner Electrolyte Metab. 1997;23(3-6):249-52.


Traditionally, lungs and kidneys have been viewed as the sole and principal organs involved in systemic acid-base homeostasis in mammals, but this view is not entirely compatible with basic principles of chemistry. Recent conceptual developments point to a role for the liver in pH homeostasis in addition to the well-established role of lungs and kidneys. Hepatic and renal nitrogen metabolism are linked by an interorgan glutamine flux, which couples both renal ammoniagenesis and hepatic ureogenesis to systemic acid-base regulation. Hepatic urea synthesis is a major pathway for the removal of metabolically generated bicarbonate. A structural-functional organization in the liver acinus uncouples urea cycle flux control from the vital need to maintain ammonium homeostasis. There is a sensitive and complex control of bicarbonate disposal via hepatic ureogenesis by the extracellular acid-base status, suggestive of a feedback control loop between acid-base status and the rate of bicarbonate elimination, i.e., a hepatic bicarbonate-homeostatic response. Some pathophysiological implications arising from the pH-stat function of the liver are discussed.

Publication types

  • Review

MeSH terms

  • Acid-Base Equilibrium / physiology*
  • Amino Acids / metabolism
  • Animals
  • Bicarbonates / metabolism
  • Biological Transport
  • Feedback
  • Homeostasis
  • Humans
  • Liver / metabolism
  • Liver / physiology*
  • Structure-Activity Relationship


  • Amino Acids
  • Bicarbonates