Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This contribution presents data from the literature as well as our own results concerning the mechanisms of hepatic encephalopathy (HE). 1. Blood chemistry: In patients with liver cirrhosis, the plasma levels of ammonia, phenylalanine, tyrosine, phenolic acids, and octopamine correlated with the stages of HE. Methionine and free tryptophan concentrations were increased only in stages 2-4. Further, branched chain amino acids were below the normal range. Experimental findings in animals elucidated some mechanisms of these changes. 2. Effects of administered substances: With ammonia, methionine, methanethiol, tryptophan, phenolic substances, and fatty acids central nervous disturbances were observed. 3. Interactions: Anemia, methanethiol, and fatty acids favored ammonia toxicity. Alkalosis diminished cerebral symptoms. 4. Neurotransmitters: HE was accompanied by an enhanced turnover of serotonin and by increased amounts of false neurotransmitters (like octopamine) in the brain. 5. Oxydative brain metabolism: Disorders of cerebral oxygen and glucose utilization were mainly documented in cases of long term HE with EEG alterations. 6. Structural changes of the brain: Most of them are irreversible.
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PMID:[Pathogenesis of hepatic encephalopathy (author's transl)]. 1 66

Tyrosine (Tyr), tyrosine hydroxylase (TH), tryptophan (Trp), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) were assayed spectrofluorometrically and radioenzymatically in various regions of post-mortem brains of human patients with hepatic, uremic, and diabetic coma, liver cirrhosis without coma, and hepatic coma treated with parenteral administration of L-valine, a branched-chain amino acid. The results were as follows: In both hepatic and diabetic coma Tyr was increased as compared to non-comatose cirrhosis and controls, while TH acitivity was within normal limits, indicating sufficient oxygen supply of the brain in both types of coma. Brain DA showed a mild decrease in all types of metabolic coma. Brain Trp was not considerably changed in non-comatose cases of liver cirrhosis and after L-valine treatment of hepatic encephalopathy, but was significantly increased in hepatic coma, with highest elevation in the brainstem tegmentum. Both 5-HT and 5-HIAA were not significantly changed in non-comatose cirrhosis, while a general increase with prevalence for the brainstem was obvious in all types of metabolic coma. After L-valine treatment of hepatic coma, 5-HT levels were usually decreased below control values, while 5-HIAA levels were at or below controls. These results in human post-mortem brains confirm previous CSF and brain findings in experimental and human hepatic and uremic encephalopathies, indicating derangement of brain monoamine neurotransmitter metabolism which is attributed to imbalance of aromatic and branched-chain amino acids in plasma and brain. Increased cerebral 5-HT turnover, particularly in the ascending serotonergic brainstem systems, due to derangement of brain uptake of Trp is suggested to represent an important biochemical substrate of disorders of consciousness in hepatic failure and other types of metabolic encephalopathies. Clinical improvement of hepatic encephalopathy and of the underlying neurotransmitter derangements by administration of L-valine and the possible role of this competitive amino acid on intermediary metabolism and ammonia detoxification are discussed.
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PMID:Brain monoamines in hepatic encephalopathy and other types of metabolic coma. 3 73

Proline metabolism was prospectively evaluated in patients with surgical sepsis, cirrhosis, and elective surgical procedures. Significant correlations were found in the septic patients. Proline levels were an excellent indicator of mortality and correlated positively with lactate levels. Lactate and proline were inversely related to total peripheral resistance and oxygen consumption. In septic patients who expired: the metabolites involved in the hepatic pathways of proline degradation were elevated in proportion to proline; lactate, glutamate and proline were directly related to pyruvate; lactate/pyruvate ratios were constant; proline, glutamate, ammonia, ornithine, lactate and pyruvate levels were inversely proportional to oxygen consumption and total peripheral resistance. The primary defects in sepsis seem to be metabolic; there are very strong correlations in time between physiology and metabolism; the metabolic abnormality seems to be a progressive energy-fuel deficit, possibly from a progressive inhibition of substrate entry into the Krebs cycle.
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PMID:Proline metabolism in sepsis, cirrhosis and general surgery. The peripheral energy deficit. 11 5

Pulmonary function and oxygen transfer was studied in five patients with cirrhosis of the liver and different degrees of portasystemic encephalopathy. Four patients were restudied after a change in CNS function. The contribution of various parameters of pulmonary gas exchange to the unsaturation found was evaluated employing the graphic analysis described by King and Briscoe. The following results were obtained: (1) there was no inequality of ventilation as judged by a nitrogen washout study; (2) a large true venous admixture was found in all patients; (3) in four patients studied twice venous admixture was larger when mean EEG frequency was lower; (4) besides the true venous admixture a low overall D/Q ratio was an important factor contributing to unsaturation in most cases; (5) in some cases a decreased overall V/Q ratio contributed to the unsaturation. This decreased V/Q ratio appeared to be due to an increase in pulmonary perfusion without a concomitant rise in ventilation. Changes in pulmonary perfusion pathways are suggested as the most likely cause of the defect in oxygen transfer found in patients with cirrhosis.
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PMID:Pulmonary function studies and oxygen transfer in patients with liver cirrhosis and different degree of portasystemic encephalopathy. 23 51

In 15 patients with acute gastrointestinal bleeding, central hemodynamics were monitored by means of a flow directed thermodilution catheter. Also, the systemic blood pressure, heart rate, blood volume and oxygen saturation in arterial and mixed venous blood were measured. In patients without cardiac insufficiency, the pulmonary artery mean pressure was found to be the hemodynamic parameter giving the most clear and constant evidence of hypovolemia. In patients with left ventricular failure and hypovolemia, the pulmonary artery pressures revealed cardiac insufficiency, and the central venous pressure indicated the degree of hypovolemia. The method has proved useful in observing patients with acute gastrointestinal hemorrhage complicated by cardiac disease, cirrhosis of the liver or the frailty of old age.
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PMID:Central hemodynamics in acute gastrointestinal bleeding. 30 94

Polymorphonuclear leucocyte function was investigated in twenty patients with alcoholic cirrhosis and three patients with cryptogenic cirrhosis. Bacterial ingestion, oxygen-dependent bactericidal capacity, and chemotactic response were measured. Serum dependent abnormalities were common; they included deficiencies of ingestion and of all subsequent oxygen-dependent metabolic events (three patients), all oxygen-dependent metabolic events (one patient), cytochrome c reduction and iodination deficiencies (six patients), isolated cytochrome c reduction deficiency (ten patients), and chemotactic deficiencies (fourteen out of eighteen patients). Serum-independent abnormalities were much less common; they included increased ingestion rate (four patients), decreased stimulated reduction of nitroblue tetrazolium (three patients), and decreased myeloperoxidase content (eight patients). Polymorphonuclear leucocyte abnormalities are frequent in cirrhosis and may account in part for increased susceptibility to infection in that disease.
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PMID:Blood polymorphonuclear dysfunction in patients with alcoholic cirrhosis. 41 78

Splanchnic and systemic hemodynamic observations in eight patients with cirrhosis and refractory ascites were compared to those of 25 patients with cirrhosis and responsive ascites. The refractory ascitic group was characterized by less portasystemic shunting from both the superior mesenteric and splenic vascular beds, a lower cardiac output, a higher systemic vascular resistance, a wider arterial-hepatic venous oxygen difference, and a tendency for a lower HBF and higher postsinusoidal resistance. Portal pressures assessed from hepatic vein catheterization were similar in the two groups. The absence of a well-developed portasystemic collateral bed in patients with refractory ascites could in part be caused by the tense ascites but could also be an important factor in the mechanism of refractory ascites.
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PMID:Splanchnic hemodynamic factors in cirrhosis with refractory ascites. 42 41

Plasma concentrations of alphaxalone have been measured during various rates of continuous infusion of Althesin used to supplement nitrous oxide-oxygen anaesthesia in man. There was an approximately linear relationship between the plasma concentration of alphaxalone and the rate of infusion of Althesin. The rate of uptake of alphaxalone into the liver did not appear to be impaired in the presence of the steroid myoneural blocking agent pancuronium, or in patients with hepatic cirrhosis.
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PMID:Plasma concentrations of alphaxalone during continuous infusion of Althesin. 50 92

Hypoxemia is a frequent occurrence in patients with severe hepatic disease. Multiple mechanisms have been implicated in the production of such hypoxemia. The case of a 35-year-old man with cyanosis, clubbing, and cirrhosis is presented. Physiologic data from this patient revealed normal pulmonary function, except for a low diffusing capacity and a 28 percent shunt while the patient was breathing 100 percent oxygen. A perfusion scan with radioactive 99mtechnetium-labelled macroaggregated albumin revealed 67 percent of the labelled macroaggregated albumin in the systemic circulation. Post-mortem examination demonstrated normal pulmonary parenchyma, markedly dilated intraparenchymal capillaries and arterioles, subpleural angiomata, and cirrhosis. No anatomic arteriovenous connections were demonstrated before or after death. We conclude that the arterial hypoxemia of some patients with hepatic cirrhosis results from dilated gas-exchanging blood vessels. These widened vessels prevent end pulmonary capillary oxygen tension from reaching equilibrium with alveolar gas, perhaps because of the widened distance for diffusion.
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PMID:Alveolar-capillary oxygen disequilibrium in hepatic cirrhosis. 63 Sep 68

Intrahepatic disturbances of circulation following various portasystemic shunting procedures can be monitored by means of the Pt-multiwire surface electorde. The normal liver is capable of compensating for each degree of portal blood deprivation. In the presence of a thioacetamide-induced liver cirrhosis in the rat a side-to-side PCS significantly improves oxygen supply of the liver. Preserving residual portal perfusion of the liver by choice of different portasystemic shunts, the oxygen supply is slightly improved, too. This effect does not correlate with the quantity of residual liver perfusion, but is possibly due to vasocative hormonal substances, from a pancreatico-duodenal source, that regualte liver circulation.
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PMID:[Improvement of the oxygen supply of the cirrhotic rat liver by selection of portacaval shunt method]. 75 86


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