Last updated on April 13, 2019 at 12:18
Hepatic encephalopathy is a syndrome that is observed in people with liver failure. It is characterised by personality changes, intellectual impairment and decreased consciousness. Coma may develop in severe cases.
Portal encephalopathy is a related to hepatic encephalopathy. It can be present without liver failure in cases of where portal hypertension occurs without liver failure. It also aggravates and contributes to the hepatic encephalopathy when liver failure with portal hypertension is present.
Portal encephalopathy occurs because nutrient-rich blood from the intestines bypass the liver by entering the systemic circulation through porto-caval anastomoses. Ammonia from food and bacterial by-products reaches the brain and causes problems by mechanisms we’ll see later. Portal encephalopathy isn’t as severe as hepatic encephalopathy. It’s usually made worse by protein-rich meals, as gut bacteria convert proteins into ammonia.
Bleeding from oesophageal varices may occur in portal hypertension. Blood is rich in protein, and this blood will reach the intestines. This mimics the effect of protein-rich meals, and may cause acute worsening of the encephalopathy.
This type of encephalopathy develops on the basis that failing livers can’t detoxify and metabolize properly. Short-chain fatty acids (SCFAs), phenol, mercaptans, ammonia and aromatic amino acids accumulate in the blood and contribute to this condition. Porto-caval anastomoses also allow toxins and ammonia from the intestines to bypass the liver, just like in portal encephalopathy.
For some reason will the permeability of the blood-brain barrier increase, allowing neurotoxins and the aforementioned substances to more easily enter the brain. Aromatic amino acids can therefore enter the brain, where they are metabolized into catecholamine-like substance called false transmitters like phenyletanolamine and octopamine. These substances disrupt the normal function of neurotransmitters. Tryptophan, an aromatic amino acid, is converted into serotonin, causing somnolence.
Ammonia accumulates as the urea cycle in the liver fails. NH3 stimulates the respiratory centre, causing hyperventilation with resulting respiratory alkalosis. Hypocapnia decreases the blood flow to the brain. Ammonia itself is also toxic to the brain.
NH3 exists in an equilibrium with ammonium (NH4+). Intracellular ammonium binds to α-ketoglutarate, thus depleting an important substrate of the TCA cycle. The Na+/K+ ATPase fails as a result of decreased energy production, which causes cytotoxic brain oedema.
Mercaptans are neurotoxins produced by gut bacteria that is usually detoxified by the liver. In liver failure will they accumulate and damage the brain.
Symptoms and treatment
Asterixis, a type of tremor of the hand where the extended hand appears to flap like wings, is common in hepatic encephalopathy. Confusion, somnolence, depression and confusion are also common. Coma is rare.
Treatment includes diet low in aromatic amino acids and proteins. Oral lactulose inhibits intestinal ammonia production. The antibiotic rifaximin may reduce the number of ammonia-producing bacteria. Probiotics that change the gut microbial flora towards bacteria that don’t produce ammonia may also be beneficial.
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