Hepatic encephalopathy

Hepatic encephalopathy is a complication of cirrhosis of the liver and its resultant portal hypertension, toxic substances accumulate in the blood and impair the function of brain cells. Signs can include impaired cognition, a flapping tremor (asterixis), and a decreased level of consciousness. more...

Pathogenesis

Cirrhosis 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 ("shunts") develop, and portal blood (from the intestinal veins), will bypass the liver, and return to the heart via another route without undergoing 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 toxic substances involved are not well understood, but have been felt to 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.

Grading of symptoms

Grading of the symptoms of hepatic encephalopathy is as follows:

• Grade 0 - Clinically normal mental status but minimal changes in memory, concentration, intellectual function, and coordination
• Grade 1 - Mild confusion, euphoria, or depression; decreased attention; slowing of ability to perform mental tasks; irritability; and disordered sleep pattern, such as inverted sleep cycle
• Grade 2 - Drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behavior, and intermittent disorientation, usually regarding time
• Grade 3 - Somnolent but can be aroused, unable to perform mental tasks, disorientation about time and place, marked confusion, amnesia, occasional fits of rage, present but incomprehensible speech
• Grade 4 - Coma with or without response to painful stimuli

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 toxic substances. 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 (Als-Nielsen et al 2004).

Read more at Wikipedia.org