Brain tryptophan perturbation in hepatic encephalopathy: implications for effects by neuropsychoactive drugs in clinical practice.

Abstract

The syndromes encountered within the term metabolic encephalopathy may be defined as “any metabolic disease that disrupts normal cerebral function” (Conn and Bircher, 1988). In the case of liver dysfunction, the terms hepatic encephalopathy (HE) or portal-systemic encephalopthy (PSE) are frequently used. In the human and clinical situation, these HE/PSE disorders are recognized as acute, chronic or, most commonly, acute-on-chronic events. The central nervous system (CNS) processes accompanying the patient suffering from HE/PSE probably include a mixture of reversible as well as irreversible changes of euronal function (Victor et al. 1965; Victor 1974, 1979; see also Conn and Lieberthal, 1979). Thus, clinical HE/PSE, which almost inexclusively have included previous or even ongoing exposure to e.g. liver affecting agents, like those related to a variety of acute or chronic infectious or immunological processes, as well as intake of liver toxins such as ethanol. Since the chronic abuse of alcohol is not an uncommon major cause for a subsequently appearing liver cirrhosis, in turn related to the etiology chronic PSE in many clinical cases by blood vessel collateral development bypassing the liver parenchyma, it should be kept in mind that this type of abuse will most certainly exert effects of its own on the CNS in patients with chronic PSE involving aspects of acute, chronic as well as acute-on-chronic CNS effects of ethanol concomitantly to the encephalopathy component provided by the “isolated” PSE per se. Of course, in the clinical setting the isolated effects on the brain of chronic PSE is almost impossible to purify in scientific terms whereas, however, this pure type of chronic PSE may be identified in experimental in vivo models available such as most prominently evidenced by the advent of the surgically induced end-to-side portacaval shunt (PCS) in the rat (Lee and Fisher, 1961).KeywordsHepatic EncephalopathyQuinolinic AcidKynurenine PathwayHepatic ComaPortacaval ShuntThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.