_ The actual cause of HE is very complex and not completely defined but it is clear that nitrogenous wastes, particularly ammonia, derived from the gut play a major role in the observed disruptions of brain function. Bacteria residing in the large bowel (colon) produce ammonia and toxins that are absorbed into the bloodstream leading to the liver. Importantly, although ammonia plays a central role in the development of HE, several other toxins also contribute to HE.
Under normal circumstances, toxins are broken down in the liver so that relatively little escapes into the blood system and eventually the brain. However, with advanced liver disease, whether acute or chronic, the detoxification of ammonia and other toxins by the liver does not occur and tends to accumulate in the blood resulting in HE. This failure results in part from a loss of normally functioning liver cells but also from a blood tending to “short circuit” around the liver.
HE is one of the most frequent complications of a Transjugular Intrahepatic Portosystemic Shunt (TIPS) procedure, a device sometimes placed in patients with cirrhosis to control severe gastrointestinal bleeding or ascites. With TIPS placement, blood from the portal vein containing relatively high levels of ammonia and other toxins passes through the shunt placed within the liver rather than percolating through the liver itself, as it normally does.
There are a number of other triggers that may make HE worse. It is important to identify and treat any of these triggers. Such precipitants are important to rapidly identify and treat because without specific and effective intervention, the patient’s encephalopathy may not improve. Common precipitants that may trigger an episode of severe HE in patients with otherwise stable liver disease include:
Infection: Although infection involving any part of the body, including the urinary tract and lungs, many trigger HE in patients with advanced cirrhosis. Infection of ascites (abdominal fluid) - called spontaneous bacterial peritonitis (SBP) - is one of the most frequent triggers of encephalopathy.
Gastrointestinal Bleeding:Patients with cirrhosis frequently suffer from bleeding in the digestive tract, usually from dilated veins in the esophagus (esophageal varices). Digested blood represents a large protein load in the gut, which can lead to higher levels of ammonia and other toxins and, not surprisingly, HE is frequent in this setting.
Medications: Drugs that suppress the central nervous system, particularly opiate pain medications (e.g., codeine) and benzodiazepines (e.g. diazepam, lorazepam), may trigger HE.
Electrolyte Problems:Low serum sodium (hyponatremia) and potassium (hypokalemia) are common in cirrhotic patients treated with diuretics and both conditions can worsen HE. Hypokalemia appears to make encephalopathy worse in part by stimulating ammonia production from the kidneys.
Dietary Indiscretion: Excessive consumption of protein, particularly from large red meat meals, seems to occasionally increase the effects HE in some patients, but this appears to represent a relatively rare trigger of severe encephalopathy.
Constipation: Slow transit of stool through the gut appears to increase the time for bacteria digest foodstuffs and make ammonia and other toxins, potentially triggering HE.
Kidney Failure: Dehydration from diuretic therapy, diarrhea, infection, some medications, and progression of liver disease can all lead to kidney failure, which in turn leads to decreased clearance of urea, ammonia, and other toxins that can contribute to encephalopathy.
Other Factors:A rise of blood pH (alkalosis), which often results from diuretics and resulting dehydration, may facilitate entry of toxins into the brain worsening instances of encephalopathy.