The Role of the Liver in Acid-Base Regulation

Abstract

Traditionally, lungs and kidneys are viewed as sole and principal organs being involved in systemic acid-base homeostasis in mammals, but this view is not entirely compatible with basic principles of chemistry (for review see [1–6]). Recent conceptual developments point to a role of the liver in pH homeostasis in addition to the well-established role of lungs and kidneys [1–6]. 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. A hepatic role in this interorgan team effort is based upon several features. (i) The presence of a quantitatively important and liver-specific pathway for irreversible removal of metabolically generated bicarbonate, i.e. urea synthesis. (ii) A structural-functional organization, which uncouples urea cycle flux control from the vital need to maintain ammonium homeostasis. (iii) A sensitive and complex control of bicarbonate disposal via hepatic ureogenesis by the extracellular acid-base status, suggestive for a feed-back control loop between the acid-base status and the rate of bicarbonate elimination, i.e. a hepatic bicarbonate-homeostatic response. (iv) Inhibition of amino acid uptake into the liver at the level of plasma membrane transport in acidosis, which may result in a shift of amino acid catabolism to extrahepatic tissues under these conditions. Some pathophysiological implications arising from the acid-base regulation of the liver are discussed.