Liver failure hepatic encephalopathy

Hyperammonemias are caused by inborn errors of ureagenesis and organic acidemias, liver immaturity (transient hyperammonemia of the newborn), and liver failure (hepatic encephalopathy). Neonatal hyperammonemias are characterized by vomiting, lethargy, lack of appetite, seizures, and coma. The underlying defects can be identified by appropriate laboratory measurements (e.g., assessment of metabolic acidosis if present and characterization of organic acids, urea cycle intermediates, and glycine). 

The precise pathogenesis of the central nervous system (CNS) signs and symptoms that accompany liver failure (hepatic encephalopathy) in patients such as Percy Veere is not completely understood. These changes are, however, attributable in part to toxic materials that are derived from the metabolism of nitrogenous substrates by bacteria in the gut that circulate to the liver in the portal vein. These materials "bypass" their normal metabolism by the liver cells, however, because the acute inflammatory process of viral hepatitis severely limits the ability of liver cells to degrade these compounds to harmless metabolites. As a result, these toxins are "shunted" into the hepatic veins unaltered and eventually reach the brain through the systemic circulation ("portal-systemic encephalopathy"). 

Crystalline amino acid bulk solutions are supplied by various manufacturers in various concentrations (e.g., 3.5%, 5%, 7%, 8.5%, 10%, 15%, and 20%). Different formulations are tailored for specific age groups (e.g., adults and infants) and disease states (e.g., renal and liver disease). Specialized formulations for patients with renal failure contain higher proportions of essential amino acids. Formulas for patients with hepatic encephalopathy contain higher amounts of branched-chain and lower amounts of aromatic amino acids. However, these specialized formulations should not be used routinely in clinical practice because their efficacy has not been clearly demonstrated. Crystalline amino acid solutions have an acidic pH (pH = 5-7) and may contain inherent electrolytes (e.g., sodium, potassium, acetate, and phosphate). 

End-stage liver disease Liver failure that is usually accompanied by complications such as ascites or hepatic encephalopathy. 

Initially, the patient is asymptomatic or has mild gastrointestinal upset (nausea, vomiting). After 24-36 hours, evidence of liver injury appears, with elevated aminotransferase levels and hypoprothrombinemia. In severe cases, fulminant liver failure occurs, leading to hepatic encephalopathy and death. Renal failure may also occur. 

Six unselected patients (four women), mean age 27 years, with acute liver failure and grade IV hepatic encephalopathy received terlipressin 0.005 mg/kg as a single intravenous bolus (16). There was an increase in cerebral blood flow 1 hour after the bolus, which returned to baseline at 5 hours, and an increase in intracranial pressure at 1 hour, which returned to baseline at 2 hours. The authors speculated that terlipressin could have a deleterious effect on cerebral hemodynamics in patients with severe hepatic encephalopathy. 

Lactitol 40 is a disaccharide that has been used in the management of hepatic encephalopathy, a major neuropsychiatric complication of both acute and chronic liver failure. It has mild laxative properties and is used to reduce the production and absorption of gut-derived neurotoxic substances symptomatic of hepatic encephalopathy. Although long considered a first-line pharmacological treatment, there is a lack of sufficient evidence to support lactitol s efficacy and continued use when weighed against other suitable therapeutic alternatives such as oral antibiotics <2006MI94>. 

Case study level 1 - Alcoholic cirrhosis alcohol withdrawal 338 Case study level 2 - Alcoholic cirrhosis management of bleeding risk and treatment for the maintenance of alcohol abstinence 339 Case study level 3 - Hepatic encephalopathy and ascites 341 Case study level Ma - Pulmonary tuberculosis 342 Case study level Mb - Liver failure 344... 

Drugs that can disturb fluid-electrolyte balance must be used with caution in patients with certain types of liver impairment. Diuretics, for example, are often required to treat ascites but can cause hypo-natraemia, hypo- or hyperkalaemia. A disturbance in electrolyte balance can lead to encephalopathy in susceptible patients such as cirrhotics or those with acute liver failure. Dehydration induced by diuretics is a common precipitant of hepatic encephalopathy. The mechanism is not fully understood, but could possibly be due to the reduced metabolism of hepatic toxins because of hepatic hypoxia [5]. 

There can be a pronounced increase in methionine and its derivatives in acute liver failure or in serious cases of cirrhosis. From these substances, mercaptans are formed in the colon (e. g. methandiol, ethandiol, dimethyldisul-phide). The cause of the sweetish aromatic smell of the expiratory air ( fresh-raw liver ) known as hepatic foetor (F. Umber, 1926 L. Schiff, 1946) is deemed to be volatile dimethylsulphide. (38) Its concentration does not correlate with the degree of encephalopathy or hepatic insufficiency, but with the intensity of the portosystemic shunts. Trimethylamine is also suspected of being a causative factor. (22) (s.pp 267, 379)... 

While hepatic encephalopathy is nearly always found in acute liver failure, it can only be expected in some 25-40% of patients with a portosystemic shunt. When these two preconditions coincide, as in the case of liver cirrhosis, manifest hepatic encephalopathy is witnessed in 30-50% of patients and a subclinical course of disease in 50-70%. In other words, the frequency, the degree of severity and the course taken by HE depend on the underlying conditions. 

The expression hepatic encephalopathy (HE) is a collective term covering five clinical forms of disease (H.O. Conn, 1989) (7.) Reyc s syndrome, (2.) enzyme deficiency of the urea cycle, (i.) pseudoportosystemic encephalopathy, (4.) fulminant liver failure, and (J.) portosystemic encephalopathy. It is not known whether the pathogenic mechanisms of these various clinical forms are identical, (s. tab. 15.3)... 

Complications The possible outcome of oesophageal haemorrhage can take the following forms (7.) haemorrhagic shock, (2.) acute liver or kidney failure, (S.) hepatic encephalopathy (culminating in hepatic coma), (4.) consumptive coagulopathy, and (5.) aspiration pneumonia. 

The decompensated stage, i.e. manifest liver insufficiency, can present as cellular decompensation (e. g. in the case of acute liver failure due to toxic or inflammatory mass necrosis) or be expressed only in the form of portal decompensation (e.g. in cases of postsinusoidal intra-hepatic portal hypertension). As a rule, chronic liver insufficiency is accompanied by a combined decompensation with a loss in function of the liver cells and, at the same time, the sequelae of portal decompensation (collateral varicosis, encephalopathy, ascites, hepatorenal syndrome, variceal bleeding), (see chapters 15 19 and 35)... 

Clinically, there are three different courses of disease following the onset of jaundice .) fulminant or hyperacute liver failure (= occurrence of hepatic encephalopathy in the 1 week), (2.) acute liver failure (= occurrence of hepatic encephalopathy between the and 4 week), and (5.) subacute liver failure (= occurrence of hepatic encephalopathy between the 5 and 8 week). Surprisingly, however, it could be shown that 30-40% of the hyperacute forms survived in spite of the development of hepatic coma and cerebral oedema. As opposed to this, the subacute forms displayed a survival rate of only 10-20%, despite a lower frequency of cerebral oedema and better liver function, (s. tab. 20.1)... 

Complications such as variceal bleeding, hepatic encephalopathy, ascites and infections as well as reduced renal function also influence the mortality rate of liver cirrhosis (in Germany some 25,000/year). The main causes of death are hepatic coma or liver failure (25-40%), bleeding (20-30%), infections (about 10%) and HCC (about 5%). Spontaneous bacterial peritonitis is fatal in 50-70%, and with liver dysfunction even in 90% of cases. Occurrence of the hepatorenal syndrome is almost invariably fatal. 

The indication for administering BCAA in patients with hepatic encephalopathy to compensate amino-acid imbalance was proposed by J.E. Fischer et al. in 1974, and implemented parenterally. However, oral application of BCAA for an adequate treatment period also has beneficial effects on cirrhosis and HE (7.) improvement in protein tolerance and the nutritional condition, (2.) improvement in cerebral functions (II8, 122), probably due to an amelioration of liver function, (2.) stimulation of ammonia detoxification with a positive nitrogen balance (118), (4.) reduction in or normalization of AAA levels, and (5.) promotion of glutamine synthesis with a favourable effect on the cells of the immune system and on renal function. By means of BCAA, it was possible to prolong the survival time and delay the occurrence of liver failure in rats with CC -induced cirrhosis. (123, 126) However, there are diverging results, which need further clarification. In principle, the use of BCAA is considered to be a necessary form of supplementary treatment for catabolic metabolism in cirrhosis (124,125, 127, 128, 130-132), in (also latent) HE and after curative resection of hepatocellular carcinoma. (I2l) (s. p. 280)... 

Two cases of serious or fatal toxicity have been described in two infants who had been treated with herbal tea containing pennyroyal oil (4). One infant developed fulminant liver failure with cerebral edema and necrosis the other infant developed hepatic dysfunction and a severe epileptic encephalopathy. 

Valproate-induced fatal liver failure developed in a 29-year-old woman with Friedreich s disease (78). The first symptoms (apathy during febrile upper airways infection) occurred after 2 months of therapy at a dosage of 20 mg/kg. The drug was withdrawn 10 days later, when she had hepatic encephalopathy and a severe bleeding diathesis supportive treatment was provided but she died after 4 weeks. 

Hepatic encephalopathy is a metabolic disorder characterized by a wide spectrum of neuropsychiatric dysfunction. It may occur as an acute syndrome in patients with acute hepatic failure from viral or drug-induced hepatitis or as a chronic syndrome associated with liver failure and cirrhosis. 

Nitrogen requirements for the patient with liver failure are not unlike those of normal subjects, but intolerance to protein is common, and protein restriction has been used successfully as part of the therapy. A dilemma arises when the diet becomes so restrictive that malnutrition results, and the patient becomes susceptible to infection and other comphcations. Overzealous use of protein to correct nutritional deficits invariably results in hepatic encephalopathy. 

The major controversy in nutritional support of the patient with liver failure has centered around the use of protein products. Modified amino acid solutions for PN (HepatAmine, others) are marketed for patients with liver failure and hepatic encephalopathy. They are enriched with BCAAs and have reduced amounts of AAAs and methionine. The products are formulated on the basis of the false neurotransmitter hypothesis, which concludes that hepatic encephalopathy may be due to increased AAA concentrations in the central nervous system. 

Several strategies to treat alcoholic liver disease have been evaluated. Prednisolone may improve survival in patients with severe alcoholic hepatitis and hepatic encephalopathy. Nutrients such as S-adenosylmethionine and polyunsaturated lecithin have been found to have beneficial effects in nonhuman primates and are undergoing clinical trials. Other medications that have been tested include oxandrolone, propylthiouracil, and colchicine. At present, none of these drugs is approved for use in the U.S. for the treatment of alcoholic liver disease. The current primary treatment for liver failure is transplantation in conjunction with abstinence from ethanol. Long-term outcome studies suggest that patients who are alcohol-dependent have survival rates similar to those of patients with other types of liver disease. Alcoholics with hepatitis C may respond to interferon-2a (see Chapter 52). 

The absolute level of ammonia and its metabolites, such as glutamine, in the blood or cerebrospinal fluid in patients with hepatic encephalopathy correlates only roughly with the presence or severity of the neurologic signs and symptoms. y-Aminobutyric acid (GABA), an important inhibitory neurotransmitter in the brain, is also produced in the gut lumen and is shunted into the systemic circulation in increased amounts in patients with hepatic failure. In addition, other compounds (such as aromatic amino acids, false neurotransmitters, and certain short-chain fatty acids) bypass liver metabolism and accumulate in the systemic circulation, adversely affecting central nervous system function. Their relative importance in the pathogenesis of hepatic encephalopathy remains to be determined. 

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