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)

Increased sympathetic tone and adrenal medullary activity in hepatic cirrhosis may promote portal hypertension. We suggest that they may be imperfect homeostatic mechanisms attempting to maintain systemic arterial pressure in response to chronic vasodilatation and that small, endogenous opioid peptides may play a part in this vasodilatation. As initial investigation of this hypothesis, we measured noradrenaline (an indicator of sympathetic tone), adrenaline and methionine enkephalin in the plasma of patients with cirrhosis with oesophageal varices which had or had not bled previously, patients with cirrhosis without varices, patients with acute liver disease and controls. In patients with cirrhosis, noradrenaline, adrenaline and methionine enkephalin were all greatest in those with oesophageal varices which had previously bled. In this group, noradrenaline correlated strongly with the widely used prognostic guide, Pugh's modification of Child's classification. In patients with acute liver disease, methionine enkephalin and adrenaline were increased six- and four-fold respectively. However, noradrenaline was normal, suggesting that increased sympathetic tone in cirrhosis may develop gradually. The use of opioid antagonists may enable determination of whether elevated plasma opioid peptides in cirrhosis stimulate the increase in sympathetic tone and plasma adrenaline, and promote bleeding oesophageal varices.
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PMID:Do increased catecholamines and plasma methionine enkephalin in cirrhosis promote bleeding oesophageal varices? 326 78

In hepatic cirrhosis neurohumoral vasoconstrictor systems are activated to compensate for circulatory disturbances. To study the renin-angiotensin-aldosterone system in more detail, angiotensin converting enzyme in 15 patients with advanced liver disease was inhibited with captopril after moderate sodium restriction. Captopril caused an increase in plasma renin activity (p less than 0.005) and a decrease in plasma aldosterone (p less than 0.025) from an elevated baseline, and a moderate drop in systolic (p less than 0.025) and diastolic (p less than 0.05) blood pressure. Hyperreninaemia after captopril was inversely related to the prevailing plasma sodium level (r = -0.66, p less than 0.01), and the changes in both systolic and diastolic blood pressure were correlated with baseline plasma renin activity (r = 0.49, p less than 0.05 for systolic and r = 0.71, p less than 0.01 for diastolic blood pressure). No change occurred in heart rate or in stimulated plasma noradrenaline and vasopressin levels. The data suggest that in these cirrhotic patients the reactivity of the renin-angiotensin-aldosterone system was still intact, although it occurred at a higher level. They confirm the importance of the renin-angiotensin-aldosterone system in arterial blood pressure regulation in cirrhosis.
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PMID:Effect of captopril on renin and blood pressure in cirrhosis. 331 47

Circulating noradrenaline is increased in patients with cirrhosis, especially in decompensated patients with ascites. Eighty-one patients with alcoholic cirrhosis were followed for up to 8 years in order to establish a possible relationship between plasma catecholamines, haemodynamics, and routine clinical and biochemical variables and survival. Forty-seven (58%) of the patients died during the follow-up period. Univariate analysis showed that plasma noradrenaline and adrenaline concentrations, portal pressure, indocyanine green clearance, serum sodium, bilirubin, and albumin concentrations, and the presence of ascites or cardiovascular disease were of significant prognostic value. In a multivariate analysis (Cox regression model), plasma noradrenaline concentration, portal pressure, serum bilirubin concentration, and the presence of ascites and cardiovascular disease remained significant independent predictors of survival. The results suggest that determination of the circulating level of noradrenaline and portal pressure may add to the prognostic information on survival obtained from routine tests. Thus, the activity of the sympathetic nervous system may indicate the severity of cirrhosis with respect to survival.
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PMID:Plasma catecholamine level and portal venous pressure as guides to prognosis in patients with cirrhosis. 339 85

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

Hepatic intestinal and whole body plasma clearance and appearance of noradrenaline (NA) was quantified in patients with alcoholic cirrhosis (n = 12) and in controls (n = 6). As NA may be released as well as removed in the same vascular bed, infusion of tritium labelled NA (3H-NA) was carried out during hepatic vein catheterisation in order to determine both flux rates. In alcoholic cirrhosis plasma concentrations of endogenous NA and adrenaline (A) were significantly above control values (NA: median 2.4 v 1.7 nmol/l, p less than 0.02; A: 0.38 v 0.19 nmol/l, p less than 0.01). Whole body clearance of 3H-NA equal in the two groups (1.6 v 1.7 l/min, ns), while as the overall appearance rate of NA was significantly higher in alcoholic cirrhosis (4.2 v 2.6 nmol/min, p less than 0.02) indicating an enhanced sympathoadrenal activity in this group. The hepatic intestinal clearances of A, NA, and 3H-NA were not significantly different in patients and controls, but the estimated hepatic intestinal spillover rate of NA was 0.24 nmol/min in patients as compared with 0.0 nmol/min in controls (p less than 0.02). As a result of portosystemic shunting in cirrhosis the present estimation of NA spillover represents a minimum value. Our results indicate that the augmented circulating catecholamines in cirrhosis do not result from diminished removal but are contributed to from increased sympathetic nervous activity in the hepatic intestinal area (enhanced mesenteric sympathetic nervous activity).
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PMID:Hepatic intestinal uptake and release of catecholamines in alcoholic cirrhosis. Evidence of enhanced hepatic intestinal sympathetic nervous activity. 342 92

A decrease in plasma noradrenaline--a reflection of sympathetic nervous system activity--by clonidine, a centrally acting alpha 2-agonist, could reduce the hyperdynamic circulation observed in cirrhosis and may thereby decrease portal hypertension. Plasma noradrenaline concentration and plasma renin activity as well as systemic and splanchnic hemodynamics were measured in 12 patients with cirrhosis and ascites before and after administration of either 150 micrograms of clonidine or placebo. Plasma noradrenaline concentration significantly decreased in all patients after clonidine administration, whereas plasma renin activity did not change significantly. There were statistically significant reductions of cardiac output (-17.4%), mean arterial pressure (-12.2%), hepatic venous pressure gradient (-19.7%) and azygos blood flow (-26.6%) after administration of clonidine. No significant correlation was found between the reduction of plasma noradrenaline concentration and changes in systemic or splanchnic hemodynamics. Hepatic blood flow was not changed by clonidine. Placebo administration had no effect on any laboratory or hemodynamic measurement. We conclude that the reduction in sympathetic nervous system activity by clonidine and the subsequent decrease in the hyperdynamic circulation suggests that sympathetic overactivity contributes to the circulatory derangements in patients with cirrhosis.
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PMID:Hemodynamic effects of a clonidine-induced decrease in sympathetic tone in patients with cirrhosis. 354 75

Although an impairment in renal sodium and water excretion is a commonly encountered clinical problem in cirrhotic patients, the mechanisms responsible for this abnormality are uncertain. Norepinephrine (NE) levels are elevated in some patients with decompensated cirrhosis, but a causal relationship between these levels and impaired sodium and water excretion has not been established. Since in normal man, water immersion to the neck (NI) results in a preferential central hypervolemia, and since theoretical considerations suggest that central hypervolemia might suppress NE, we designed the present study to determine if the natriuretic and diuretic responses of cirrhotic patients to NI are mediated by a decrease in NE. 16 cirrhotic patients with ascites were studied on two occasions: during a seated control study and during 4 h of NI: NE, determined by radioenzymatic assay, was measured hourly. 15 of the 16 patients manifested a marked diuresis, and 12 had a natriuresis that equalled or exceeded that documented in normal subjects during NI. NI did not alter mean NE, with 9 subjects manifesting an increase of NE as compared with the prestudy hour. Furthermore, peak urinary sodium excretion and flow rate varied independently of prestudy NE (r = 0.163 and -0.173, respectively), change in NE (r = 0.256 and 0.239), as well as nadir NE levels (r = 0.118 and -0.039). The demonstration of a natriuresis and a diuresis in a majority of the subjects, occurring without concomitant suppression of plasma NE, suggests that NE does not constitute the prepotent determinant in the impaired sodium and water excretion of many patients with advanced liver disease.
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PMID:Effects of water immersion on plasma catecholamines in decompensated cirrhosis. Implications for deranged sodium and water homeostasis. 388 19

The assumption of upright posture by patients with liver cirrhosis leads to striking activation of adrenergic and renin-angiotensin systems. The tilting-induced modifications in renal function of eight healthy controls and 14 untreated patients with liver cirrhosis and ascites were related to plasma concentrations of noradrenaline, renin activity and aldosterone. All patients had preserved renal blood perfusion. All parameters were evaluated during bed rest for two hours and in the sitting posture for one hour. Basal plasma renin activity (0.1 greater than p greater than 0.05), aldosterone and noradrenaline concentrations (p less than or equal to 0.01) were raised in cirrhotics. The renal function tests (creatinine clearance, filtered sodium, tubular rejection fraction, urinary sodium excretion) were significantly reduced in cirrhosis. Under basal conditions, in cirrhotic patients tubular rejection fraction and urinary sodium excretion were inversely related to both noradrenaline and aldosterone concentrations. After tilting, the noradrenaline and aldosterone integrated outputs (sigma delta) were significantly greater in cirrhosis. All renal function tests significantly decreased in cirrhotics, whereas creatinine clearance only significantly decreased in controls. Patient's tubular rejection fraction of sodium and sodium excretion were related to sigma delta aldosteronaemia (r = -0.72; p less than 0.01), but no longer to sigma delta plasma noradrenaline.
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PMID:Renal function impairment induced by change in posture in patients with cirrhosis and ascites. 389 34

Basal sympathetic nervous system activity was assessed in 8 unmedicated patients with alcoholic cirrhosis using a previously developed radiotracer method for measuring total and renal noradrenaline release to, and clearance from, plasma. Compared to the control group total noradrenaline clearance was significantly increased in the patients with advanced alcoholic cirrhosis (Pugh grade C) [1.89 +/- 0.13 vs 1.51 +/- 0.11 l/min, P less than 0.05) indicating that endogenous plasma noradrenaline levels underestimate total sympathetic nervous system activity in these patients. Renal noradrenaline clearance was similar to controls independent of the severity of the liver disease. Both total and renal noradrenaline release were significantly increased in the patients with cirrhosis. The ratio of renal to total noradrenaline release was similar in cirrhotic (26 +/- 7%) and control (23 +/- 5%) groups. Increased arterial plasma adrenaline levels, indicative of adrenal medullary stimulation, were also evident in the patients with cirrhosis and correlated significantly with total noradrenaline spillover (r = 0.732, P less than 0.05). These results strongly suggest that in patients with cirrhosis, rather than a preferential increase in renal sympathetic tone, the increase is part of a pattern of generalized sympathoadrenomedullary activation. Although renal renin secretion was significantly increased in the cirrhotic group no correlation with renal noradrenaline release was seen (r = 0.199), raising the possibility that in cirrhosis renal sympathetic tone is not a major determinant of renal renin secretion. Finally, renal noradrenaline release did not correlate with renal blood or plasma flow but an influence of the sympathetic nervous system on renal function was suggested by the correlation observed between total noradrenaline spillover and impaired salt (r = -0.683, P less than 0.05) and water excretion (r = -0.702, P less than 0.05) demonstrated in the cirrhotic patients.
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PMID:Total and renal sympathetic nervous system activity in alcoholic cirrhosis. 390 56

The concentration of noradrenaline (NA) and adrenaline (A) was measured in arterial, cubital venous and femoral venous plasma in order to determine possible differences in different vascular beds in the peripheral circulation. In patients with cirrhosis, arterial plasma NA (median 2.54 nmol/l, n = 40) was significantly increased compared to controls (median 1.42 nmol/l, n = 17, p less than 0.001). Arterial plasma A was not significantly different (0.41 vs. 0.38 nmol/l). Cubital and femoral venous NA and A were positively correlated to the arterial values in both cirrhosis and controls (r = 0.86 to 0.97, p less than 0.01). In cirrhosis, median cubital venous:arterial NA ratio was significantly above unity (1.14, n = 36, p less than 0.001) as compared to unity in controls (1.00, n = 8), whereas the femoral venous:arterial NA ratio was similar in cirrhosis and controls, and significantly below unity (median 0.86 and 0.87). Cubital venous:arterial and femoral venous:arterial A ratios were significantly below unity in cirrhosis as well as in controls. The results point towards an enhanced sympathetic nervous activity in cirrhosis which may involve, among other organs, the upper limb (especially the skin of forearm and hand). To assess circulating levels of catecholamines, the importance of arterial sampling is stressed as peripheral venous samples may also reflect local factors.
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PMID:Catecholamines in plasma from artery, cubital vein, and femoral vein in patients with cirrhosis. Significance of sampling site. 395 39


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