Updated: 10/25/07 11:31 AM
HOME HEAL EDUCATE RESEARCH DIRECTORY OUTREACH


Authors: W. Volwiler, R.A. Willson, A.M. Larson, and J.D. Ostrow
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T. Hepatic Encephalopathy (HE)

1. Definition of Hepatic Encephalopathy.

Acute vs. chronic HE   A disturbance of the central nervous system (CNS) secondary to hepatic insufficiency and/or porto-systemic shunts. HE can mimic virtually any neurological condition. It can occur in both acute (fulminant) hepatic failure as well as in chronic liver disease (cirrhosis), and it is potentially reversible if liver dysfunction can be improved.

2. Etiology of Hepatic Encephalopathy

CNS toxicity of gut-derived nitrogenous metabolites   a. Many neurotoxins may contribute to the disturbance in CNS function. Paramount importance, however, is given to nitrogenous substances, derived from metabolism of proteins in the intestine. These reach the systemic circulation due to porto-systemic shunts, or decreased hepatic function. These nitrogenous substances, especially ammonia and glutamine, alter neurotransmission in the CNS.

Ammonia is the prime toxin.



Multiple sources of ammonia 		  b. Ammonia is accepted as the prime factor in the pathogenesis of HE. The concentration of NH3 is highest in portal venous blood; portal NH3 is derived from the urease activity of colonic bacteria, and the deamination of glutamine in small bowel mucosa. Other major sources of blood ammonia are metabolism of urea and glutamine by the kidney and of glutamine by skeletal muscles.

Decreased hepatic ammonia removal in liver diseases   Normally, the liver extracts about 80% of portal-venous NH3 (first pass metabolism), and converts it to urea. In liver disease, arterial NH3 levels can increase, due to both decreased metabolism by hepatocytes and increased porto-systemic shunting around the liver. If renal failure is present also, the increased levels of urea in the intestine promote increased formation of NH3.

Ammonia leads to astrocyte swelling & ↓ glutamate, a neuro-excitor   Entry of NH3 into astrocytes leads to increased formation of the osmolyte, glutamine, causing astrocyte swelling and brain edema. Depletion of neuro-excitatory glutamate depresses brain function.



Role of other toxins and drugs that are CNS depressants 		  c. Other putative gut-derived neurotoxins include: short-chain fatty acids, mercaptans, benzodiazepine-like substances.

d. Many sedatives and tranquilizers are metabolized more slowly in liver disease and may add to CNS depression. Avoid their use!

3. Clinical Stages of Hepatic Encephalopathy

Asterixis (flapping tremor): intermittent lapse of posture of the outstretched hands   0. (subclinical). No grossly evident changes in personality or behavior, except by special tests of CNS function; no asterixis

1. Shortened attention span. Impaired memory, handwriting and ability to perform simple arithmetic. Impaired sleep and memory. Altered mood. May have asterixis.

2. Lethargy and/or apathy. Disorientation. Inappropriate behavior. Slurred speech. Obvious asterixis.

3. Gross disorientation. Semi-stuporous or stuporous. Asterixis may be difficult to elicit.

4a. Frank coma. (Seizures may occur in fulminant liver failure)

4b. Fatal herniation of swollen cerebrum through foramen magnum.

4. Treatment of Hepatic Encephalopathy

  a. Improve liver and kidney function (withdraw toxic drugs, toxins, alcohol; treat infections, shock, dehydration; correct acid-base status)

b. Decrease nitrogenous sources in intestine (control GI bleeding, laxatives to clear bowel of blood and bacteria, low-protein diet)

c. Decrease formation and absorption of ammonia in the gut (neomycin to diminish intestinal bacteria; lactulose to increase fecal nitrogen excretion)

d. Stop treatment with sedatives and tranquilizers

e. Benzodiazepine antagonists may mitigate chronic encephalopathy

Next Section (U): Overview of
Some Other Common Hepatic Diseases »



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