Hepatic encephalopathy is a neuropsychiatric condition in which toxins accumulate in the brain due to improper functioning of the liver. Liver is responsible for about 500 plus functions in the body and one of them is detoxification by removing toxins from the body. If liver fails to work properly due to any of the reasons (mostly due to liver cirrhosis and portal hypertension), then the toxins start accumulating in the body including brain. The accumulation of toxins in the brain leads to various changes in personality due to loss of brain function. The individual shows signs of confusion, personality changes, memory loss, concentration trouble, and change in sleep habits, stupor and coma. Persistence of hepatic encephalopathy can even prove to be fatal.
What Are The Causes Of Hepatic Encephalopathy?
The exact cause of hepatic encephalopathy is still unknown. However, it is a serious complication of various diseases such as chronic hepatitis, cirrhosis, liver failure, Reye’s syndrome, portal hypertension and hepatocellular carcinoma. It might also be triggered by an infection (such as pneumonia), kidney problems, dehydration, post-surgery, trauma, hypoxia (low oxygen levels), immunosuppressant medications, consumption of excess amounts of protein, medications that suppress central nervous system (such as barbiturates or benzodiazepines), gastrointestinal bleeding, hypokalemia or electrolyte imbalance, hypoglycemia, excessive alcohol consumption, pain medications and diuretics.
Although, the cause of hepatic encephalopathy is not understood properly, but it has been postulated that the role of certain chemicals and factors including ammonia, manganese, false neurotransmitters, oxidative stress, neurosteroids and inflammation is vital to the causation of hepatic encephalopathy.
Ammonia: It is considered neurotoxic at increased levels, which is formed after the breakdown of nitrogen containing compounds. The liver is responsible for removing most of the ammonia by breaking it down into glutamine and urea as a byproduct and prevents the entry of these byproducts into the systemic circulation. The impairment of liver function and portal congestion might lead to elevated levels of ammonia in blood. As there is increased level of ammonia in brain tissues, there might also be cerebral edema due to deposition of glutamine in brain cells (astrocytes) that also might lead to altered mental state.
False Neurotransmitters: Liver also plays a vital role in the synthesis of proteins as well as breakdown of amino acids and detoxification, the end product being ammonia. It has been hypothesized that due to imbalance between various groups of amino acids and increased permeability of blood brain barrier, there is accumulation of false neurotransmitters (such as octopamine), which may contribute to hepatic encephalopathy.
Neurosteroids: It is hypothesized that there is an increase in benzodiazepine receptors in inflamed astrocytes with patients of hepatic encephalopathy, which leads to increased production of neuroactive steroids by astrocytes.
Manganese: Magnetic resonance imaging (MRI) of various patients suffering from liver cirrhosis has shown deposition of manganese in basal ganglia. The deposition of manganese in patients with cirrhosis elucidates symptoms of tremor in patients of hepatic encephalopathy.
Oxidative Stress: In vitro studies have shown increased production of reactive nitrogen species and reactive oxygen species to the exposure of ammonia, benzodiazepines and inflammatory cytokines. There is an increased evidence of an inter-relation between reactive oxygen species and swelling of astrocytes.
Inflammation: The role of ammonia is not solely responsible for neuropsychiatric symptoms in patients of hepatic encephalopathy. It has been noted that there is an increase in proinflammatory mediators and cytokines such as tumor necrosis factor (TNF) and interleukin-6 (IL-6), which might increase the permeability and diffusibility of brain cells to ammonia leading to inflammation of the cells, thus causing and precipitating hepatic encephalopathy.
This may lead to varying degree of physical as well as mental symptoms ranging from mild to severe encephalopathy depending on the severity and longevity of the underlying etiology. The treatment aimed at decreasing ammonia and the above conditions that trigger hepatic encephalopathy reverses the condition and symptoms associated with it. The last resort is liver transplantation if liver function is completely impaired.
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