Hepatic encephalopathy - Definition and Overview

Hepatic encephalopathy is a condition (usually caused by liver cirrhosis and its resultant portal hypertension) where toxins from the gut damage cells of the brain. Signs can include impaired cognition, a flapping tremor (asterixis), and a decreased level of consciousness.

Pathogenesis

Cirrhosis (as seen in chronic alcoholism or chronic hepatitis) will obstruct the passage of blood through the liver causing portal hypertension. This means it is difficult for blood from the intestines to go through the liver, to get back to the heart. Portal-systemic anastamoses develop, and portal blood (from the intestinal veins), will by-pass the liver, and return to the heart via another route.

This means that blood, containing toxins from the gut, will enter the systemic circulation without first-pass detoxification by the liver. Furthermore, the liver (damaged from the cirrhosis) will not be functioning as well as it should be, so blood that does travel through the liver, may not be as detoxified as it otherwise would be.

The toxins in the gut include ammonia (NH₃) and mercaptans. Ammonia is normally converted to urea by the liver, and, as with mercaptans, is produced by the bacterial breakdown of protein in the intestines.

Ammonia can cross the blood-brain barrier, where it causes the support cells of the brain (astrocytes) to swell. The swelling of the brain tissue increases intracranial pressure, and can lead to coma or death via herniation of the brainstem.

Treatment

It is important to remove excess protein from the lumen of the gut. If there is a gastrointestinal bleed (for instance, ruptured oesophageal varices) this should be stopped, as it serves as a protein supply for bacteria. Dietary intake of protein should be minimised. Special enteral feeding formulations with a high concentration of branched-chain amino acids are sometimes used in therapy, as is parenteral nutrition.

Lactulose is a compound that will cause osmotic diarrhoea, lessening the time bacteria have to metabolise proteins and produce toxins. As well as this, it acidifies the bowel, causing ammonia (NH₃) to be converted to ammonium (NH₄⁺) which is less readily absorbed. Recent evidence suggests it is not very effective.

Antibiotics (such as metronidazole) may be given to kill bacteria present in the gut.