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Ammonium and bicarbonate homeostasis in chronic liver disease

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Summary

Whereas traditionally in acid-base physiology one considers just two organs (lungs and kidneys) to be involved in the regulation of systemic acid-base homeostasis, recent developments indicate that also the liver must be viewed as an important organ for pH regulation. This is because urea synthesis is a quantitatively important bicarbonate-consuming process, which in turn underlies a feedback control by the acid-base status at least in vitro. Consequently, renal ammoniagenesis, generally accepted to be a direct bicarbonate-generating process, can be viewed as a pH-controlled ammonium homeostatic response. In view of the controversies regarding the roles of ureogenesis and renal ammoniagenesis in acid-base regulation, their relationships were studied in 28 patients with normal renal functions, but varying degrees of a well-compensated chronic liver disease. Progressive loss of urea cycle capacity (as determined byin vitro incubations of human liver tissue) was parallelled by increasingin vivo plasma bicarbonate levels (and metabolic alkalosis) and an increasing NH +4 excretion into the urine. Accordingly, renal ammoniagenesis rose with the extent of metabolic alkalosis. Neither hypokalemia, hyperaldosteronism, diuretic treatment, or volume contraction were present, and a satisfactory explanation for this unusual behavior of renal ammoniagenesis in terms of traditional acid-base physiology cannot be given. Here, it seems that renal ammoniagenesis is governed rather by the need to eliminate ammonia than by the acid-base status. The data are compatible with a hepatic role in acid-base regulation: hyperbicarbonatemia results from a diminished hepatic HCO −3 disposal when urea synthesis is impaired and NH +4 homeostasis is maintained by the kidney via an increased NH +4 excretion into urine despite the presence of alkalosis.

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Authors and Affiliations

  1. Medizinische Universitätsklinik Freiburg, Deutschland

    D. Häussinger, R. Steeb & W. Gerok

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  1. D. Häussinger
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  2. R. Steeb
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  3. W. Gerok
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This study was supported by Deutsche Forschungsgemeinschaft. Sonderforschungsbereich 154 „Experimentelle und Klinische Hepatologie“ and the Heisenberg Programm

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Häussinger, D., Steeb, R. & Gerok, W. Ammonium and bicarbonate homeostasis in chronic liver disease. Klin Wochenschr 68, 175–182 (1990). https://doi.org/10.1007/BF01649081

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  • DOI: https://doi.org/10.1007/BF01649081

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