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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review examines current understanding about the patient with moderately advanced cirrhosis of the liver and his or her transition to hepatorenal syndrome (HRS). Special emphasis is given to three areas of ongoing research. Atrial natriuretic factor's role in the pathogenesis of salt and water retention is examined, as well as its role in determining volume status in these patients. The current literature regarding prostaglandins (PGs) is reviewed, with emphasis on how vasodilatory PGs appear first to help maintain homeostasis in advanced cirrhosis and how vasoconstrictor thromboxane may then be involved in the transition to HRS. Finally, new findings regarding the liver hormone glomerulopressin are examined, and how deficient release of this may lead to the decrease in glomerular filtration rate seen in HRS.
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PMID:Pathogenesis of the hepatorenal syndrome. 295 1

Malnutrition is frequently associated with advanced cirrhosis. To investigate the role of portal hypertension in nutritional impairment, we developed an animal model to isolate and characterize the effects of chronic intestinal venous hypertension on intestinal nutrient absorption. We performed mesenteric arteriovenous anastomosis combined with portal vein banding in rats. Hepatic architecture and excretory function (bile flow and bile salt output) were unaltered, while severe and persistent intestinal venous hypertension was produced. We then measured in vivo absorption rates of three test nutrients (vitamin D3, valine, and tryptophan) and water. Vitamin D3 absorption was significantly impaired by intestinal congestion, while amino acid absorption was unaffected. Splanchnic hypertensive rats absorbed less water than controls. We conclude that chronic intestinal venous hypertension alone selectively impairs nutrient absorption.
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PMID:Selective impairment of nutrient absorption from intestines with chronic venous hypertension. 300 45

The renin-angiotensin-aldosterone system plays an important role in the development and maintenance of high blood pressure in several forms of hypertension. In hypertensive patients with primary aldosteronism, antimineralocorticoids are, as expected, very effective in reducing blood pressure and correcting metabolic disturbances. In patients with essential hypertension, an abnormal relationship between angiotensin II and aldosterone can occur. Aldosterone secretion in these patients is often too high relative to circulating levels of angiotensin II. Antimineralocorticoids effectively lower blood pressure in a large number of these patients. The reactive hyperreninemia caused by salt depletion is a factor limiting the antihypertensive effect of natriuretic agents including that of antimineralocorticoids. The enhanced aldosterone secretion resulting from treatment with a diuretic other than an antimineralocorticoid may diminish the natriuretic action of that diuretic. Therefore, antimineralocorticoids given in addition to a diuretic enhance natriuresis. The renin-angiotensin-aldosterone system is also involved as a compensatory mechanism in cardiovascular and body fluid homeostasis of patients with severe congestive heart failure or liver cirrhosis with ascites. Antimineralocorticoids are very effective in such conditions. In patients with congestive heart failure treated with digitalis, these natriuretic agents are particularly useful because of their potassium-sparing properties. The risk of developing hyperkalemia during antimineralocorticoid administration is negligible unless renal function is impaired. Antimineralocorticoids have the advantage of exerting no deleterious effect on carbohydrate and lipid metabolism. The use of these agents seems therefore rational in a variety of diseases concerned with blood pressure and body fluid volume regulation.
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PMID:Clinical applications of antimineralocorticoids. 305 64

The present review concentrates on environmental factors which influence the outcome of peptic ulcer disease by acting from the outside. Endogenous risk factors, such as acid output, pepsin secretion and serum pepsinogen, gastritis and mucosal defense, blood group, and secretor status, are only dealt with when they help to explain the mechanism by which exogenous risk factors affect the upper gastrointestinal mucosa. After outlining the wax and wane of peptic ulcer, it is concluded that these changes resulted from similar temporal patterns of occupational workload in the general population. Cross sectional studies also support the contention of occupational workload being a risk factor in peptic ulcer, explaining several characteristic features of peptic ulcer, such as its sex, race, and social class distribution, increased incidence in immigrant workers, seasonal variation, healing by bed rest, and urban versus rural distribution. Susceptible subjects may react to a rise in occupational workload and acute exposure to stressful life events by increased gastric secretion which, in turn, leads to ulceration and symptoms. Cigarette smoking, intake of aspirin and related drugs, dietary salt, and alcohol abuse represent additional environmental risk factors, which form the etiologic link of the association of peptic ulcer with chronic lung disease, rheumatoid arthritis, hypertensive disease, and liver cirrhosis, respectively.
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PMID:Factors which influence the incidence and course of peptic ulcer. 307 62

The diuretic effect of the supine position was evaluated in six patients with cirrhosis and ascites and six with congestive cardiac failure. After fasting overnight in bed the patients received bumetanide 1 mg intravenously and were then immediately randomly assigned to either bed rest in the supine position or normal daily activity in the upright position for the next six hours. Two days later the procedure was repeated, the patients being assigned to the other posture. The diuretic response was similar in patients with heart failure and cirrhosis, and was significantly greater in the supine than in the upright position: mean 1133 v 626 ml/6 h (p less than 0.01). The natriuresis was similarly larger during recumbency: mean sodium 96 v 45 mmol(mEq)/6h (p less than 0.01), and the excreted potassium in six hours was similar in both postures. The glomerular filtration rate was 100 and 66 ml/min (p less than 0.01) and heart rate 76 and 83 beats/min (p less than 0.01) in the supine and upright positions respectively. Plasma concentrations of noradrenaline, renin, and aldosterone were all raised even when the patient adopted the supine position, and a further significant rise was observed during the upright position. The results suggest that the attenuated response to intravenous bumetanide in the upright position and during normal daily activity may be due to the activation of several homeostatic mechanisms that may reduce the excretion of water and salt.
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PMID:Diuretic treatment in decompensated cirrhosis and congestive heart failure: effect of posture. 308 44

Increased levels of octopamine in adrenergic nerve terminals and plasma have been implicated in the circulatory and renal disturbances of chronic hepatic failure. Little is known about its renal actions in normal animals. In the present study, DL-octopamine was administered both i.v. and into one renal artery of anaesthetized dogs in doses ranging between 25-200 micrograms/min (1.6-20 micrograms/kg/min). Octopamine was hypertensive in doses of 100 micrograms/min and more and this change was associated with a significant decrement in GFR and renal perfusion. This amine also exerted a direct tubular effect since decreased excretion of sodium and water occurred in the absence of blood pressure or renal perfusional changes when given i.v. When given into one renal artery octopamine produced only an ipsilateral antidiuresis and antinatriuresis, in the absence of any change to GFR or renal perfusion. Lithium clearances suggest that octopamine acts beyond the proximal tubule in altering the tubular reabsorption of salt and water. Because octopamine was found to increase blood pressure in the presence of a hypertensive infusion of noradrenaline, it is likely that this amine exerts a primary pharmacological effect rather than liberating noradrenaline from nerve terminals. Saline expansion (7% body weight), acute biliary obstruction, chronic cirrhosis with ascites, and chronic thoracic caval constriction with the production of ascites all abolish the effect of octopamine when administered at 100 micrograms/min. Though octopamine may directly influence renal perfusion, its possible role in liver disease remains uncertain.
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PMID:Effects of octopamine on renal function in anaesthetized dogs. 314 28

Different aspects of biliary physiology were studied in rat model of liver cirrhosis induced by CCl4/phenobarbitone. We measured bile flow, bile salt secretion, biliary secretion pressure and bile-to-plasma ratios of inert solutes under basal conditions and during infusion of taurocholate (0.4 and 0.8 mumol.min-1.100 g body wt.-1) in 11 cirrhotic and 10 control male Sprague-Dawley rats. Bile flow and biliary bile salt secretion did not differ between the two groups. Analyzing the relationship between bile salt secretion and bile flow, however, we found an increased slope (P less than 0.02) in the cirrhotic animals, suggesting a higher apparent osmotic activity of the bile salts secreted. Maximal biliary secretion pressure was maintained in cirrhotic animals (22.5 +/- 2.5 vs. 25.0 +/- 2.9 cmH2O) in the absence of exogenous bile salt. During taurocholate infusion it decreased to a lesser extent (P less than 0.001) in cirrhotic animals (13.5 +/- 3.4 vs. 19.3 +/- 3.8 cmH2O). Bile-to-plasma ratios of [3H]sucrose and [14C]ferrocyanide were markedly increased in cirrhotic rats. Biliary [14C]erythritol clearance was equal to bile flow in both groups. In the cirrhotic group, the [3H]sucrose bile/plasma ratio was positively correlated with spleen weight (r = 0.744, P less than 0.01), serum concentration of alkaline phosphatase (r = 0.583, P less than 0.05) and basal maximum biliary secretion pressure (r = 0.801, P less than 0.001). We conclude that chronic portal hypertension is associated with increased permeability of the blood/bile barrier. Nevertheless, bile flow and bile salt secretion are maintained in cirrhotic rats, giving support to the intact cell hypothesis for this important hepatocellular function.
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PMID:Canalicular bile flow and bile salt secretion are maintained in rats with liver cirrhosis. Further evidence for the intact cell hypothesis. 318 52

Epidemiologic evidence shows a strong relationship between gastric cancer and cerebrovascular disease. It was speculated that salt intake might be the linking factor causing hypertension and vascular damage as well as damage to the gastric mucosa. This study tested whether hypertensive diseases, such as ischemic heart disease and cerebrovascular disease, occurred more frequently in patients with gastric cancer and gastric ulcer than expected by chance alone. In addition, it was studied whether gastric and duodenal ulcer coincided more frequently with other diseases that in the past have been associated with peptic ulcer, such as liver cirrhosis, chronic lung disease, and rheumatoid arthritis. The German statistics of rehabilitation were used to assess the frequency of coincidences. The statistics include a description of the primary, secondary, and tertiary diagnoses leading to rehabilitation. This study confirms the presence of a high coincidence of both ulcer types with liver cirrhosis. In patients with rheumatoid arthritis, both ulcer types also occurred more frequently than expected from their general distribution. Gastric but not duodenal ulcer coincided more frequently with ischemic heart disease than expected. Gastric cancer occurred more frequently in patients who had concomitant ischemic heart disease or cerebrovascular disease. Duodenal ulcer was not associated with an increased risk for any disease related to hypertension. The results of the study support the contention that gastric diseases and diseases related to hypertension share a common etiologic factor.
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PMID:Concordant occurrence of gastric and hypertensive diseases. 337 23

Regional (kidney, lower limb) and whole-body kinetics of endogenous noradrenaline (NA) and tritium-labelled L-noradrenaline (3H-NA) were determined in patients with alcoholic liver disease (one alcoholic hepatitis, 12 cirrhosis) and in control subjects (n = 6) in order to get information on the sympatho-adrenal system in liver disease. Arterial NA was significantly elevated in ascitic patients (median 2.5 nmol/l, n = 9, P less than 0.05) as compared to non-ascitic patients (1.6 nmol/l) and controls (1.7) nmol/l). NA spillover per unit NA inflow was increased in the kidney in patients with ascites (0.69 vs. 0.45 pmol/min.g per pmol/min.g in controls, P less than 0.005) but not in the lower limb (0.23 vs. 0.49 in controls, P less than 0.01). In patients with ascites the spillover rate of NA from the kidney into plasma (1.9 pmol/min.g) was significantly increased (P less than 0.02) compared to controls and non-ascitic patients (1.2 and 1.0 pmol/min.g, respectively. Patients and control kidneys and limbs extracted almost the same fraction of 3H-NA (0.34 vs. 0.32 NS and 0.34 vs. 0.37 NS, respectively). Whole-body clearance of 3H-NA was not significantly different in cirrhotics and controls (median 0.89 vs. 0.91 l/min.m2), indicating that the raised NA in decompensated cirrhosis reflects enhanced sympatho-adrenal activity rather than decreased metabolism of this amine. Our results do not point towards a uniform sympatho-adrenal overactivity in decompensated cirrhosis, but rather indicate regional differences with different order of NA spillover. The renal sympathetic overactivity, as indicated by the increased renal NA overflow, is likely to be important to the decreased renal perfusion and increased salt-water retention characteristic of this clinical condition.
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PMID:Kidney, lower limb and whole-body uptake and release of catecholamines in alcoholic liver disease. 340 82

The in vivo formation of the sulfate ester of glycolithocholate is a critical step in the elimination of this hepatotoxic bile salt. Rhesus monkeys fed chenodeoxycholate or ursodeoxycholate, the precursors of lithocholate, develop frank cirrhosis in association with accumulation of nonsulfated glycolithocholate in bile. An enzyme catalyzing the formation of glycolithocholate-3-sulfate has been isolated from hepatic cytosol of adult female rhesus monkeys and has been purified 146-fold. When reduced it appears as a 30 kD band on an SDS-polyacrylamide gradient gel. It has a pH optimum of 7.0 and is stimulated by low concentrations of Mg2+ (up to 2 mM), but does not have an absolute requirement for this metal ion. The kinetics of this enzyme have been investigated to ascertain whether its reaction mechanism can account for the poor in vivo rate of glycolithocholate sulfation. Inhibitor studies with an oxidized metabolite of lithocholate, 3-keto-5 beta-cholanoate, showed that the latter is a competitive inhibitor of glycolithocholate and is noncompetitive with the active form of sulfate, 3'phosphoadenosine-5'-phosphosulfate. The monophosphonucleotide 3'-AMP is a competitive inhibitor of 3'phosphoadenosine-5'-phosphosulfate, and is noncompetitive with glycolithocholate. These observations are consistent with a sequentially ordered Bi Bi reaction mechanism in which the bile salt is the first substrate to bind to the enzyme. Such a reaction mechanism for bile salt:3'phosphoadenosine-5'-phosphosulfate:sulfotransferase would be, therefore, the first time in which the sulfate acceptor (the bile salt) is the initial substrate to bind to a sulfotransferase. These studies have shown that although rhesus monkeys have a liver enzyme capable of forming the sulfate ester of glycolithocholate, its reaction mechanism and the potent inhibition caused by simple metabolites, such as 3-keto-5 beta-cholanoate, may serve to under-express the activity of the enzyme in vivo.
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PMID:Evidence for an ordered reaction mechanism for bile salt: 3'phosphoadenosine-5'-phosphosulfate: sulfotransferase from rhesus monkey liver that catalyzes the sulfation of the hepatotoxin glycolithocholate. 347 Apr 20


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