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Pathogenetische Bedeutung der Gallensäuren

Pathogenic significance of bile acids

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Summary

Because of their amphiphilic properties, bile acids have important physiological functions. However, they can also be pathogenetically active. Some recent findings on the biochemistry and enterohepatic circulation of bile acids are presented. In contrast to the adult liver where the only primary bile acids formed are cholic- and chenodeoxycholic acid, the foetal liver is able to synthesise a variety of “atypical” bile acids. Under certain circumstances, a retrograde differentiation is possible in the adult. The very effective transport systems in gut and in the sinusoidal and canalicular membrane of the liver cell limit the bile acids almost exclusively to the enterohepatic circulation. During transport in blood, through biomembranes and in the liver cell cytosol, bile acids are bound to carrier proteins. The carrier has been detected using photoaffinity labelling. Following biotransformation (sulphation and glucuronidation) pathogenetically active bile acids can be converted into derivatives which can be rapidly eliminated.

Disturbances of these mechanisms result in functional defects and diseases. The pathological significance of bile acids in hepato-biliary diseases is represented with regard to the cholestatic and proliferative effect of individual bile acids. The significance of bile acids in chologenic diarrhea, steatorrhea and enteral hyperoxaluria are presented as examples of the pathogenetic effects of bile acids on the gut. In these diseases it is possible to recognise the specific effects of certain bile acids on the colon mucosa. Recent studies have demonstrated that bile acids are possibly of pathogenetic significance in the case of epidemiologically proven relationship between colon carcinoma and high fat, high cholesterol and low fibre diets.

Zusammenfassung

Gallensäuren haben aufgrund ihrer amphiphilen Eigenschaften wichtige physiologische Funktionen, können aber auch pathogenetisch wirksam sein. Einige neuere Befunde zur Biochemie und enterohepatischen Zirkulation der Gallensäuren werden dargestellt. Während beim Erwachsenen nur Cholsäure und Chenodesoxycholsäure als primäre Gallensäuren in der Leber gebildet werden, ist die fötale Leber zur Synthese verschiedener „atypischer“ Gallensäuren befähigt. Unter besonderen Bedingungen ist beim Erwachsenen eine „Retrodifferenzierung“ möglich. Wirkungsvolle Transportsysteme im Darm und in der sinusoidalen und canaliculären Membran der Leberzellen bewirken, daß die Gallensäuren nahezu ausschließlich im enterohepatischen Kreislauf zirkulieren. Beim Transport im Blut, durch die Biomembranen und im Zytosol der Leberzelle sind Gallensäuren an Carrierproteine gebunden, die mit Hilfe der Photoaffinitätsmarkierung erfaßt wurden. Durch Biotransformation (Sulfatierung, Glukuronidierung) können pathogenetisch wirksame Gallensäuren in rasch eliminierbare Derivate übergeführt werden.

Störungen dieser Mechanismen führen zu Funktionsstörungen und Erkrankungen. Die pathogenetische Bedeutung der Gallensäuren bei hepatobiliären Erkrankungen wird im Hinblick auf den cholostatischen und proliferativen Effekt einzelner Gallensäuren erörtert. Als Beispiele pathogenetischer Effekte der Gallensäuren am Darm werden die Vorgänge bei der chologenen Diarrhoe und Steatorrhoe und bei enteraler Hyperoxalurie dargestellt; diese Erkrankungen lassen spezifische Wirkungen bestimmter Gallensäuren auf die Colonmukosa erkennen. Bei dem epidemiologisch nachgewiesenen Zusammenhang zwischen fett- und chloesterinreicher, faserarmer Kost und Coloncarcinom weisen neuere Untersuchungen auf die pathogenetische Bedeutung der Gallensäuren hin.

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  1. Medizinische Klinik der Universität Freiburg i. Br., Germany

    W. Gerok & S. Matern

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Herrn Prof. Dr. P. Schölmerich zum 65. Geburtstag gewidmet

Erweiterte Fassung der State of the Art-Lecture beim Internationalen Kongress für Gastroenterologie, Hamburg 1980

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Gerok, W., Matern, S. Pathogenetische Bedeutung der Gallensäuren. Klin Wochenschr 59, 575–589 (1981). https://doi.org/10.1007/BF02593847

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