Severe liver disease can lead to hepatic encephalopathy (HE) with high blood ammonia and altered functioning of the nervous system. Failure to metabolize ammonia from the body may cause altered mental functioning. Treatments are available for HE and the symptoms are reversible. (This paper covers HE caused by chronic liver disease._
The onset of symptoms of HE is variable. Some people start with confusion or coma, but other people start with very mild complaints. Even mild HE should be diagnosed since it can be associated with falling and impaired driving ability.
Elevated ammonia levels are found in HE, but they are only a part of the picture. It is believed that ammonia is produced by bacterial species in the intestine, such as Enterobacteriaceae, Proteus, and Clostridium species. A bacterial enzyme called urease breaks down uric acid into ammonia and carbon dioxide. In addition, cells of the walls of the intestine use their primary food (glutamine) to produce glutamate and ammonia.
While the gut produces ammonia, the liver is responsible for metabolizing it. At the same time, the kidneys can produce and excrete ammonia. The kidneys metabolize glutamine to ammonia, bicarbonate, and glutamate as an acid-base balancing mechanism. Alkalosis can cause a decrease in urinary loss of ammonia, and be one more reason for high ammonia levels. In times of acidosis, the kidneys release more ammonia into the urine. Muscles of the body can convert ammonia into glutamine and, temporarily, make up partially for a failing liver. However, the glutamine is returned to the circulation and turned back into ammonia by the kidneys.
Ammonia causes cerebral dysfunction, possibly by causing cerebral edema. People with acute HE from chronic liver disease can develop high pressures within their skulls, which can result in death.
Treatment of HE includes reduction of ammonia, treatment of the fecal flora, modulation of neurotransmission, and correction of any nutritional deficiencies. The most common precipitating event is an infection, while gastrointestinal bleeding and dehydration are less common causes. Activated charcoal used orally is effective for reducing blood ammonia. Zinc depletion is common in severe liver disease, and a recent study suggests that zinc supplementation may be beneficial.
Fecal flora can be modulated to improve HE since they play a significant role in the development of HE. This can done by using antibiotics, probiotics or prebiotics. Prebiotics are mostly fibers which enhance the growth of beneficial strains (Bifidobacteria and Lactobacilli), reducing harmful bacteria. The beneficial strains show improvements in animal models of HE. Rifaximin is a frequently used prescription antibiotic.
CONCLUSION: Altering bacterial gut flora is one way to treat hepatic encephalopathy, and activated charcoal and zinc supplements are beneficial. Because of the poor long-term survival of patients with hepatic encephalopathy, a liver transplant should be considered.
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