The pathogenesis of hepatic encephalopathy

Year 1997, Volume: 10 Issue: 4, 226 - 235, 01.10.1997

C. Yurdaydm

Abstract

A careful reader of manuscripts on the pathogenesis of hepatic encephalopathy (HE) will notice that most of them state in their introduction that its pathogenesis is "poorly understood". This may indeed be the case but progress has been made, and this review will try to provide some new developments in the field as well as recapitulate the classic knowledge on the pathogenesis of HE.

The modern pathophysiological concept of HE comes from the landmark paper by Dame Sheila in the 50's

(1). Accordingly, under normal conditions 'neuroactive' nitrogenous substances derived from the intestine would be efficiently extracted and metabolized by the liver whereas in liver failure, these substances would tend to bypass the liver, as a consequence of impaired extraction and/or portal- systemic collateral venous channels, and accumulate in peripheral blood plasma (Fig. 1). However, credit must be given to William Shakespeare (1564-1616) who in the "Twelfth Night" quite nicely describes the same concept in the following words by one of the characters in the play: " I am a great eater of beef, and I believe that this harms to my wit."

The classical hypotheses of the pathogenesis of HE are listed below:

1. Ammonia Hypothesis

2. Synergistic Neurotoxin Hypothesis and Serotonin

3. False Neurotransmitter Hypothesis

4. Gamma aminobutyric acid (GABA) Hypothesis

5. A Hypothesis implicating Glutamate

Keywords

The pathogenesis of hepatic encephalopathy

References

• Sherlock 5, Summerskill WHJ, White LP, Phear EA. Portal-systemic encephalopathy: neurological complications of liver disease. Lancet 1954; 2:453-457