Hepatic encephalopathy or Hepatic Coma is a complex of a central nervous system disorders that were found suffering from liver failure. The disorder is characterized by memory impairment and personality changes.
Hepatic encephalopathy (portal system encephalopathy, hepatic coma) is a disorder in which brain function decline due to toxic substances in the blood, which would normally be discarded by the liver.
Hepatic encephalopathy classification is widely adopted:
1. According to the
a. Hepatic encephalopathy acute type:
Arise suddenly with a short course of the disease, is rapidly deteriorating fell into a coma, often less than 24 hours. These types include fulminant viral hepatitis, hepatitis due to drugs and toxins, Reye syndrome, or can be in cirrhosis of the liver.
b. Hepatic encephalopathy chronic type:
Occurred in a period of time, for months to years. A classic example is that Hepatic encephalopathy occurs in cirrhotic liver with extensive portal collateral system, with signs of mental disorders, emotional or nueurologic disorder that gradually more and more weight.
2. According to the etiology factor
a. Hepatic encephalopathy Primary / Endogenous
Occur without the presence of trigger factors, is the final stage of the damage to liver cells which diffuse widespread liver cell necrosis. In fulminant hepatitis, damage liver cells and diffuse rapidly, so that impaired consciousness, agitation, disorientation arises, screaming, and then quickly fell into a coma, while in siridis liver, caused widespread fibrosis of liver cells and usually there is a collateral system , ascites. Here, the disruption caused by toxic substances that can not be metabolized by the liver. Through the portal system / collateral affects the central nervous system.
b. Hepatic encephalopathy Secondary / Exogenous
Occurred because of the trigger factors in patients who already have heart abnormalities. These factors include:
1. Disorders of fluid balance, electrolyte and blood pH:
o Hepatic encephalopathy Dehydration / hypovolemia
o Parasintesis abdominal
o excessive diuresis
2. gastrointestinal bleeding
3. major surgery
4. severe infections
5. Excessive protein intake
6. Constipation long protracted
7. narcotic / hypnotic
8. Shortcuts porta systemic, either naturally or surgically
There are currently no patagonesis accepted to explain the occurrence of Hepatic encephalopathy. Several hypotheses are most often used as a reference treatment of Hepatic encephalopathy is
(1) Hypothesis of ammonia,
(2) The hypothesis of a synergistic neurotoxic,
(3) false neurotransmitter hypothesis,
(4) Hypothesis GABA / benzodiazepine.
While the factors that are likely to be involved in the occurrence of Hepatic encephalopathy are:
1. Effect of endogenous neurotoxins that are not sufficiently detoxicated by cirrhotic liver.
2. Abnormal function of astroglia with secondary impaired neuronal function.
3. Abnormalities permeability blood-brain barrier.
4. Changes in intracerebral neurotransmitters and their receptors.
In the simplest sense, the Hepatic encephalopathy can be explained as a form of intoxication of the brain caused by intestinal contents that are not in metabolism by the liver. This situation can occur when there is damage to liver cells by necrosis, or the presence of shunt (pathological or due to surgery) which allows the portal blood reaches the systemic circulation in large numbers without passing through the liver.
Metabolites responsible for the onset of Hepatic encephalopathy is not known with certainty. The basic mechanism seems to be due to brain intosikasi by the breakdown of protein metabolism by bacteria in the gut. The results of this metabolism can bypass the liver because of the disease in the liver cells or because the shunt.
Hepatic encephalopathy on chronic liver disease is usually precipitated by conditions such as gastrointestinal bleeding, excessive protein intake, diuretics, paracentesis, hypokalemia, acute infection, surgery, azotemia and administration of morphine, sedatives, or drugs that contain ammonia.
Until now, not yet fully understood pathogenesis of Hepatic encephalopathy, but the knowledge gained by studies of patients and from animal experiments, have revealed some important issues about the pathogenesis. Hepatic encephalopathy is not caused by one single factor but by several factors which also play a role together.
Most research indicates that there is a relationship Hepatic encephalopathy porto systemic circulation directly without passing through the liver, and the presence of liver damage and severe physiological disturbances. Both these conditions cause toxic substances originating from the gut is not metabolized in the liver, and subsequently buried in the brain (blood brain barrier) in patients with Hepatic encephalopathy who facilitate the entry of materials toxic into the central nervous system.
When patients have undergone liver cirrhosis with portal hypertension, opens the possibility for the occurrence of portosystemic shortcuts, which can result in entry of neurotoxins derived from the gastrointestinal tract (mercaptan, ammonia, manganese, etc.) into the systemic circulation.
Porto systemic shunt may also occur due portokaval surgical anastomosis or TIPS (transjugular intrahepatic portosystemic stent shunt) is done to cope with portal hypertension. Neurotoxins that can penetrate the blood brain barrier to accumulate in the brain and cause disturbances in brain metabolism. Barrier permeability of the blood - brain is experiencing changes in patients with decompensated liver cirrhosis, making it more easily penetrated by metabolites such as neurotoxins.
There are five processes that occur in the brain which is considered as the mechanism of the Hepatic encephalopathy / hepatic coma, namely:
1. Increased permeability of brain barrier (BBB).
2. Impaired balance of neurotransmitters
3. Changes (energy) metabolism of the brain.
4. Impaired function of neuronal membranes.
5. Increase in "endogenous benzodiazepines"
Suspected cerebral toxins act through one or more than this mechanism.
Pathogenesis of the above is a uniform concept, but the commas on the PSE and FHF there are some differences. For example on the PSE, cerebral toxins accumulate slowly, if accompanied trigger the occurrence of coma. In contrast, the Hepatic encephalopathy / coma induced FHF, because the process is so acute, the factors that contribute to the entry of toxic material into the brain of a sudden, the disappearance of protective material, and the integration of cellular changes permeability blood vessels of the brain and cerebral edema.
Some toxic materials suspected of a role:
Ammonia is the most widely investigated material. This substance is derived from the decomposition of nitrogen by bacteria in the gut, in addition to that produced by the kidneys, peripheral muscle tissue, brain and stomach.
In theory ammonia interfere with physiology of the brain through a direct influence on the membrane of neurons and influencing brain metabolism through increased synthesis of glutamine cycle and ketoglutarate, both these materials affect the Krebs cycle, causing the loss of ATP molecules necessary for cell oxidation.
Other researchers found that high levels of ammonia are not in line with the severity of abnormal EEG recordings. Reported that the role of ammonia in the Hepatic encephalopathy do not stand alone. But together other substances such as mercaptans and short chain fatty acids. Anticipated increase in ammonia levels in Hepatic encephalopathy only a nonspecific indicator of brain metabolism is impaired.
2. Neurotoxic amino acids (tryptophan, methionine, and mercaptans)
Triptopan and serotonin metabolites are toxic to the CNS. Methionine in the intestine had become mercaptan metaolisme by a toxic bacteria to the CNS. In addition, mercaptans and free fatty acids work synergistically to disrupt the detoxification of ammonia in the brain, and ammonia together cause coma.
3. Impaired balance of amino acids
Aromatic Amino Acids (AAA) is increased in Hepatic encephalopathy because of the failure of deamination in the liver and decreased Asan Branch Chain Amino (AARC) due to protein catabolism in muscle and kidney hyperinsulinemia that occurs in chronic liver disease AAA is competing with the AARC to pass through the brain barrier, the permeability change in Hepatic encephalopathy. Including AAA is methionine, phenylalanine, tyrosine, while including the AARC is valine, leucine, and isoleucine.
4. Short-chain fatty acids
In Hepatic encephalopathy there are increased levels of short chain fatty acids such as butyric acid, valerate, octanoate, and kaproat, suspected as one cause of cerebral toxin Hepatic encephalopathy. These materials work by suppressing the brain reticular system, saving the detoxification of ammonia.
5. Neurotramsmitter false.
Neurotrasmitter fake that has been known is gamma aminobutyric acid (GABA), octapamine, histamine, feniletanolamin, and serotonin. False neurotransmitter inhibitor of true kompepetif neurotrasmitter (dopamine and norephinephrine) at the synapse in the nerve endings, whose levels are decreased in patients with PSE and FHF.
Research shows that GABA works synergistically with benzodiazepines form a complex, occupies a chloride ionophore receptor in the brain, called GABA receptor / BZ. Binding of these receptors will lead to hyperpolarization of brain cells, in addition to that also suppress the function of cortical and subcortical, a series of events that cause impaired consciousness and motor coordination. This hypothesis opens the way for further research purposes.
The increase in Hepatic encephalopathy AAA / hepatic coma has close ties with high levels of glucagon. Glucagon elevation contributed for the increase in nitrogen load. Because this hormone release from the protein aromatic amino acids to stimulate liver gluconeogenesis. Glucagon levels rise due to hypersecretion or hypometabolism in liver disease, especially when there is collateral circulation.
7. Changes in blood-brain barrier
The blood vessels of the brain under normal circumstances is not permeable to various substances. There is a strong relationship between brain capillary endothelial, this is a barrier that regulates a variety of substances spending and restrain some essential substances such as neurotrasmitter original. In hepatic coma FHF found particularly capillary damage, endothelial damage relationships, cerebral edema, so the material is usually removed from the brain will fit easily in large numbers are like phenylalanine, so that other woods amino acid levels increased in the brain.
Hepatic encephalopathy is very broad clinical spectrum completely asymptomatic until hepatic coma. Symptoms that are often encountered in clinical Hepatic encephalopathy include personality changes, irritability, apathy, dysphasia, and drowsiness accompanied by clinical signs such as asterixis, irritability, restlessness, and loss of consciousness (coma). Hepatic encephalopathy’s clinical manifestations are usually preceded by hepatic decompensation and the presence of precipitating factors in the form of ammonia agenic circumstances such as eating excess protein, gastrointestinal bleeding or sedation program.
Hepatic encephalopathy manifestation is a combination of mental and neurologic disturbances. Hepatic encephalopathy clinical picture varies, depending on the progression of this disease, causes, and presence or absence based on mental status, presence of asterixis, and EEG abnormalities, neuropsychiatric manifestations in Hepatic encephalopathy can be divided into several stages. Beyond that there is a group of patients who are asymptomatic, but showed abnormalities in the EEG and / or psychometric. Examples of popular test is the NCT psychometric (Number Connection Test). This group is classified as subclinical or latent Hepatic encephalopathy. The researchers found that the proportion of Hepatic encephalopathy is much larger than the Hepatic encephalopathy clinical (acute or chronic), which reached 70-80% of all cases of liver cirrhosis with portal hypertension.
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