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)

Elevated serum ammonia may play a role in central nervous system derangement after transurethral resection of the prostate. Glycine used as a surgical irrigant for prostate resection produces ammonia as a by-product after liver and renal metabolism. The presence of liver dysfunction often leads to an inability to remove generated ammonia from the circulation. To determine whether the presence of cirrhosis allows significant metabolism of glycine and the resulting serum ammonia levels generated, the production of ammonia after glycine infusion was examined in normal and cirrhotic rats. Hepatic microsomal enzyme induction was produced in male Sprague-Dawley rats given sodium phenobarbital, added to the drinking water to hasten the development of cirrhosis, by increasing the toxicity of carbon tetrachloride given intragastrically to one group at weekly intervals for production of cirrhosis. A control group was maintained under similar conditions except for carbon tetrachloride dosing. The end point for production of cirrhosis was the development of ascites. Two weeks after the development of ascites in the cirrhotic rats and the discontinuation of phenobarbital in both groups, both control and cirrhotic rats were anesthetized with IP pentobarbital and glycine (1.25 g/kg; 7.5%) was given intravenously. Venous blood samples were taken at intervals up to 120 min for serum ammonia analysis. After the final serum ammonia sample, lethal pentobarbital injection was given and livers and kidneys removed for histologic analysis. Terminal body weight, glycine dose, and renal histology were not different between groups. Liver weights were greater in cirrhotic rats. Baseline serum ammonia levels were also greater int he cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum ammonia levels in response to glycine infusion in normal and cirrhotic rats. 258 60

In view of the universal metabolic importance of zinc in the organism, it was the purpose of the present work to determine the concentrations of zinc in serum, of amino acids and ammonia in plasma of patients with liver cirrhosis, and investigate that correlations might exist between these substances. The study involved 18 patients with decompensated liver cirrhosis without coma and eleven with coma. The subjects with normal livers were used as controls. While confirming known data (reduced zinc levels, imbalance of plasma amino acids, hyperammonaemia in chronic liver diseases) the findings also revealed correlations between the above substances. A negative correlations existed between zinc and ammonia. Decreases in zinc serum levels were accompanied by increases in plasma ammonia concentrations in hepatic coma (p less than 0.05). Plasma levels of amino acids did not correlate with serum zinc concentrations.
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PMID:Correlations between zinc, amino acids and ammonia in liver cirrhosis. 262 52

The goal of this study was to evaluate the presence of extrahepatic damage and the uniformity and reversibility of the histological findings in CCl4-induced liver cirrhosis in the rat. To verify these findings rats were sacrificed 2 and 10 weeks after a treatment consisting of ten intragastric doses of CCl4, administered weekly. All treated rats developed an irreversible micronodular cirrhosis with no damage to the brain, kidney and pancreas. Moreover, rats sacrificed 2 weeks after the last CCl4 dose showed a number of functional alterations usually observed in man. In particular, low branched chain/aromatic amino acids (BCAA/AAA) plasma ratio, high ammonia, low zinc and high insulin with normal blood glucose were obtained.
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PMID:Carbon tetrachloride-induced experimental cirrhosis in the rat: a reappraisal of the model. 262 82

Ammonia clearance, portal blood ammonia, and amino acid concentrations were studied during induction of cirrhosis by carbon tetrachloride in rats. Exposure to CCl4 vapors twice weekly for 7-16 weeks doubled orotic acid excretion. If exposure was discontinued for 7 days, the orotic acid excretion decreased despite the presence of cirrhosis proven histologically. Replacement of dietary casein with soybean protein eliminated the CCl4-induced orotic aciduria in growing rats but not in adults. Supplementation of casein with 1.5% arginine did not prevent CCl4-induced orotic aciduria. [14C]Orotate uptake into RNA and DNA of liver was not impaired. Perfusion of livers of cirrhotic animals with ammonia concentrations between 0.2 and 3.0 mM revealed no significant decreases in urea synthesis rates due to cirrhosis and no increase in the tendency to make orotic acid at a given ammonia concentration. However, ammonia uptake by cirrhotic livers was significantly reduced, resulting in higher ammonia concentrations in the effluent when there was moderate-to-severe cirrhosis. Portal blood samples taken from rats exposed to CCl4 had higher ammonia concentrations as cirrhosis worsened. The results lend support to the "intact hepatocyte" hypothesis of cirrhosis which attributes metabolic abnormalities to intrahepatic shunts.
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PMID:Orotic acid overproduction in experimental cirrhosis of rats. 272 54

Hepatic dysfunction after portacaval shunting (PCS) has been attributed to loss of portal perfusion to the liver. Proponents of selective systemic shunting state that reduced encephalopathy and hepatic dysfunction with this procedure result from the maintenance of portal perfusion to the liver through the hypertensive mesenteric venous circulation. We questioned the importance of maintaining the diminished portal flow to the cirrhotic liver because hepatofugal flow is known to develop in many of these patients. We sought to further define mechanisms that may contribute to the maintenance of critical flow to the liver in compensated hepatic cirrhosis. We demonstrated a primary relationship between mesenteric venous hypertension (MVH) and increased hepatic arterial blood flow after diversion of portal blood flow. Fifteen dogs had vena caval stenosis above an end-to-side PCS to establish MVH and deprive the liver of portal blood flow. Another 15 dogs had end-to-side PCS alone. A half hour after shunting, hepatic arterial blood flow had increased significantly in all dogs. Hemodynamic parameters remained stable throughout. Six weeks later, mesenteric pressure increased 98% +/- 3% with intracaval stenosis (from 9.6 +/- 0.1 to 19.0 +/- 0.3 cm H2O). Mesenteric pressure was unchanged with PCS alone (9.0 +/- 0.1 cm H2O). Increased hepatic arterial flow was significantly elevated in all dogs above pre-shunt values by 6 weeks postshunt. With MVH, however, further augmentation in hepatic arterial flow was noted in the chronic state (1.5 +/- 0.1 vs 0.9 +/- 0.1 ml/min/gm, p less than 0.05). There was significant correlation between MVH and increased hepatic arterial flow in the chronic state (r = 0.79, p = 0.05). Hepatic arterial flow 6 weeks after PCS with MVH was associated with lower blood ammonia and improved hepatocellular function compared with animals with PCS alone. These results support the hypothesis that MVH is important in maintaining blood supply--beyond providing driving force for sustained portal flow to the liver. This is an important consideration in the medical and surgical management of portal hypertension, a condition in which profound reduction in portal pressure may negatively affect compensatory hepatic arterial blood flow.
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PMID:Mesenteric venous hypertension: importance after portal systemic shunting? 274 Sep 86

To clarify the clinical significance of specific plasma amino acid abnormalities occurring in liver disorders with portal-systemic shunting, plasma amino acids and insulin levels were measured in idiopathic portal hypertension (IPH), extrahepatic portal occulusion (EHPO), and liver cirrhosis (LC). Three branched chain amino acids (BCAA: valine + leucine + isoleucine) were decreased in all three diseases in comparison with controls. Since plasma insulin measured during oral glucose tolerance tests did not specifically rise in LC, reduction of BCAA is not merely ascribed to hyperinsulinemia. Either portal-systemic shunting or some extent of liver damage may contribute to a fall in BCAA. Two aromatic amino acids (AAA: phenylalanine + tyrosine), which were within the normal range in EHPO and IPH, showed a marked increase in LC. Thus, changes of AAA probably mainly reflect the severity of the liver disease. The molar ratio of BCAA/AAA (MR) significantly correlated with ICG k, ICG R15, PT and the sum of blood ammonia in an oral ammonia tolerance test which may reflect the degree of hepatic disorder. MR diminished in the following decreasing order: controls, EHPO, IPH and LC.
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PMID:Plasma amino acid abnormalities in liver disease: comparative analysis of idiopathic portal hypertension, extrahepatic portal occlusion and liver cirrhosis. 277 20

Cerebral blood flow (CBF), measured by the non-invasive 133-Xenon inhalation method, plasma levels of ammonia (NH3) and free tryptophan (fTRP) were determined in 30 cirrhotic patients without overt encephalopathy. Psychometric evaluation detected subclinical hepatic encephalopathy (SHE) in 20 of them, and was normal in the other 10. A significant CBF difference (p less than 0.05) was found between the SHE and the non-SHE patients. fTRP levels were significantly (p less than 0.05) higher in patients with SHE than in those without SHE, and a significant negative correlation (p = 0.003) was found between CBF values and fTRP in the whole group of patients. NH3 did not differ in the two subgroups and did not correlate with CBF values. It is concluded that CBF could have some implications in SHE, although its relevance is still unclear. The negative correlation between CBF and fTRP prompts further investigation concerning the relationships between plasma fTRP, brain serotonin, cerebral metabolism and blood flow in the development of brain derangement during cirrhosis.
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PMID:Cerebral blood flow and plasma free tryptophan in cirrhotics with and without hepatic encephalopathy. 279 14

A 67-year-old, non-alcoholic Japanese female case with liver cirrhosis, in the course of admission due to ascites and rupture of the rectal varix, was affected by an unusual type of acute progressive encephalopathy, presenting inattentiveness and slurred speech as initial symptoms. Her consciousness was increasingly clouded. Variable symptoms such as saccadic eye movement, nystagmus, weakness, hyperreflexia, dysmetria, adiadochokinesis and painful dysesthesia were also noted. Laboratory examination disclosed abnormal liver functions, hyponatremia, respiratory alkalosis and normal blood ammonia. Cerebrospinal fluid was xanthochromic and contained slightly increased protein. On CT scan, bilateral symmetrical low density areas were demonstrated in the diencephalon, brainstem and cerebellum. A week after the onset, she was comatose with rigidity of the extremities. Hyperbilirubinemia and severe hyponatremia developed. On the second CT, low density areas extended to the cerebral deep white matter. Her respiration became irregular, and she expired 16 days after the onset. Autopsy disclosed edematous lesions with dark brown discoloration in the medial basal ganglia, ventral diencephalon and mesencephalic tegmentum. Less severely affected lesions with pale yellow discoloration extended into the cerebral white matter, pontine and medullar tegmentum and cerebellar dentate nuclei. In the central lesions, diapedesis of erythrocytes and serum-plasma was marked, with necrosis of the neurons. In the peripheral lesions, diapedesis of less proteinaceous fluid was noted, with less severe neuronal damages. Neither capillary prominence nor gliosis was remarkable. The clinical and pathological features of the present case bore some similarity to those of Wernicke's and Leigh's encephalopathies. However, the patient's age, habitus or clinical course was atypical for the latter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Acute encephalopathy with symmetrical, widespread, edematous and necrotic lesions--an autopsy case report]. 280 34

A 40-yr-old man presented with encephalopathy and was found to have hepatocellular carcinoma without cirrhosis. A large vascular hepatic mass was defined by CT scan and angiography; laparoscopy with biopsy confirmed the absence of chronic liver disease. A definitive tissue diagnosis of hepatocellular carcinoma was made at laparotomy; the tumor was unresectable. Peripheral arterial and selective portal and hepatic venous ammonia levels were high, and this finding suggested that the encephalopathy was nitrogenous and hepatic in origin. The proposed mechanisms of the encephalopathy are generation of ammonia from tumor breakdown and portosystemic shunting, a result of partial tumor occlusion of the hepatic veins. An unusually high urinary excretion of orotic acid was found similar to that seen in hereditary orotic aciduria.
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PMID:Hepatic encephalopathy and orotic aciduria associated with hepatocellular carcinoma in a noncirrhotic liver. 282 14

The aim of this study was to evaluate the contribution of gluconeogenesis from amino acids in the development of fasting and absorptive hyperammonemia in cirrhosis. Somatostatin (SRIF), which is known to inhibit the hepatic disposal of gluconeogenic amino acids, was administered in a continuous infusion (500 micrograms/h) for 90 min before and 5 h after a protein meal (240 g of meat) in 11 overnight fasting patients. Plasma glucagon, insulin, gluconeogenic amino acids (GAA: alanine, serine, glycine, and threonine) and ammonia (NH3) were evaluated before the infusion, immediately before, and at 1, 3, and 5 h after the meal. As control study, the same protocol was randomly repeated in a different day with saline infusion. During the latter, a direct correlation was found between fasting glucagon and ammonia (r = 0.68; p less than 0.05). Fasting glucagon, insulin, and NH3 did not change, whereas alanine (p less than 0.05) and the GAA sum decreased (p less than 0.01). When SRIF was infused, fasting glucagon (p less than 0.05), insulin (p less than 0.05), and NH3 (p less than 0.05) decreased. Alanine did not change, and GAA sum increased (p less than 0.02). No correlations were found by plotting changes in glucagon or GAA sum and NH3. After the meal, SRIF infusion abolished the plasma response of glucagon and markedly reduced that of insulin, so that their area under the curve (AUC0-5) were reduced (p less than 0.005, for both), with respect to control study. Moreover, the AUC0-5 of alanine (p less than 0.005) and GAA sum (p less than 0.005) were increased, suggesting a reduced disposal of these compounds. In spite of this, the meal-induced early increase and the AUC0-5 of plasma NH3 observed during SRIF and saline infusion did not differ. Our results do not confirm the importance of gluconeogenesis from alpha-amino-nitrogens in determining the fasting ammonemia of cirrhosis, and suggest that this metabolic pathway does not significantly influence the protein meal-induced exacerbation of plasma ammonia.
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PMID:Role of gluconeogenesis from amino acids in determining fasting and absorptive levels of plasma ammonia in cirrhosis. 289 85


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