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

The "Peripheral Arterial Vasodilation" hypothesis most completely explains the clinical spectrum of cirrhosis ranging from compensated to decompensated to the hepatorenal syndrome (Figure 15-1). As the systemic peripheral vasodilation increases, the neurohumoral responses to arterial underfilling are stimulated with resultant renal vasoconstriction, sodium and water retention. Hypoalbuminemia and portal hypertension, as well as local effects of vasodilation at the capillary level, also contribute to ascites formation and peripheral edema. The suppressed plasma renin activity and aldosterone concentrations and exaggerated natriuresis, which are observed in some patients with early cirrhosis during HWI and the supine position, probably indicate greater central translocation of splanchnic fluid in these volume expanded cirrhotic patients when compared with normal subjects. This interpretation is supported by the greater increases in ANF during HWI in these patients when compared with controls. The neurohumoral responses to arterial vasodilation in cirrhosis combine to decrease distal sodium and water delivery, an event which impairs escape from the sodium retaining effects of aldosterone and causes resistance to the distal tubular effect of ANF (Figure 15-3). As discussed, the peripheral arterial vasodilation of cirrhosis is no doubt multifactorial in nature and the resultant arterial underfilling may be worsened by events that could impair the cardiac response to afterload reduction, including bile salt accumulation, alcoholic cardiomyopathy, and tense ascites decreasing cardiac preload. This pathogenetic schema of cirrhosis is compatible with the unifying body fluid volume hypothesis (Figure 15-3), which we have recently proposed.
 ...
PMID:Pathogenesis of sodium and water retention in liver disease. 129 35

It has recently been shown that ursodeoxycholic acid administration improves liver function tests in patients with chronic liver diseases. Aim of the present study was to evaluate an ursodeoxycholic acid derivative (bis-hemisuccinate bisodic salt Ursodamor, Farmaceutici Damor, Napoli) in patients with chronic hepatitis. Forty patients (15 M, 25 F) with biopsy proven chronic liver disease participated to the study. Patients were randomly allocated to two treatment groups. Twenty patients (4 PBC, 11 CAH/CPH, 5 cirrhosis) received the ursodeoxycholic acid derivate at the dose of 600 mg/day, while 20 patients (1 PBC, 11 CAH/CPH, 8 cirrhosis) received a placebo. For both groups the treatment period was six months. ALT serum levels were significantly reduced in the treated group (from 84 +/- 14 to 62 +/- 14 p less than 0.0005) while no significant change was observed in the placebo group. In the treated group but not in the placebo group alkaline phosphatases and gamma-GT were also significantly reduced (from 268 +/- 56 to 160 +/- 23 p less than 0.0005 and from 79 +/- 21 to 45 +/- 10 p less than 0.0005). In conclusion, our results suggest that the administration of the ursodeoxycholic acid derivate, bis-hemisuccinate, bisodic salt, improves liver function tests in patients with chronic liver hepatitis. Similarly to ursodeoxycholic acid this new derivate probably interferes with bile acid pool composition by replacing the more detergent and probably more toxic endogenous bile acid.
 ...
PMID:[Effects of therapy with bis-hemisuccinate of ursodeoxycholic acid bisodium salt in patients with chronic hepatitis]. 135 68

The retrospective analysis of 3 clinical observations points out the etiopathogenetic, clinical and therapeutical aspects of the diffuse stenotic cholangitis, which can occur after the surgical treatment of the hepatic hydatid cyst. Although rare (2.9% of hydatid cysts, 13% of those which communicate with the bile ducts), the diffuse stenotic posthydatid cholangitis represents a severe postoperative complication in cases of median cysts, exerting a compression upon the convergence of hepatic ducts and communicating with the biliary tract. Its presence should be clinically suspected if a mechanical icterus with septic angiocholitis, sometimes associated with an external biliary fistula (from the residual cavity), occurs in the postoperative course of these patients, especially if the primary operation has excluded the remanance of an obstacle at the level of the main bile duct. The lesional substrate is comparable with that of the primitive sclerosing cholangitis, from which it differs through its clear relation with the primary treatment of the hepatic hydatid cyst, through the rapid course of stenotic lesions which, although diffuse, may become more marked in certain segments, as well as through the constant suprastenotic dilatation of the bile ducts. In the pathogenesis are involved the caustic action of some scolicide solutions (2 per cent formaldehyde solution, hypertonic salt solution) on the wall of the bile duct and the cystobiliary communication which predisposes to the peroperative occurrence o-a migration syndrome and of angiocholitis. It requires an early surgical reintervention in order to solve the cholestasis and angiocholitis: according to the morphological situation, we have the choice between disobstruction and trans-stenotic calibration drainage, on the one hand, and biliodigestive derivations in the hilum, which are more efficient, on the other. The prognosis is burdened with the vital risk of septic angiocholitis and with the early occurrence of a secondary biliary cirrhosis or of stenotic recurrences. Prophylaxis consists in the performance of a primary surgical treatment, adequate in median and communicating hydatid cysts, avoiding the "blind" intracystic administration of scolicide solutions, which exert a caustic action on the bile ducts.
 ...
PMID:[Sclerosing cholangitis in the evolution of a surgical hepatic hydatid cyst]. 136 83

Diuretics have long been used to lower blood pressure in hypertensive patients or to control body fluid and electrolyte homeostasis in diseases such as congestive heart failure, chronic renal failure or cirrhosis. The initial response to diuretics is a negative sodium and fluid balance. The diuretic-induced loss of salt and water activates several hormonal systems such as vasopressin, the renin-angiotensin-aldosterone system or the sympathetic nervous system which tend to compensate for the changes in sodium and water balance. This neurohormonal response may have important clinical implications. Thus, the activation of the renin-angiotensin-aldosterone cascade appears to be partially responsible for the flat dose-blood pressure response curve of thiazides in hypertensive patients. It may also be responsible for the difference between responders and non-responders to diuretic therapy and for the development of side-effects such as hypokalaemia, metabolic alkalosis or hyponatraemia. There are several ways to prevent the undesirable consequences of the neurohormonal responses to diuretics. The first is to use low doses of these agents. It is also possible to combine them with agents that block the activity of the renin-angiotensin-aldosterone system such as ACE inhibitors or in combination with drugs that reduce aldosterone secretion such as calcium antagonists. The development of drugs able to enhance urinary sodium excretion and to reduce simultaneously the activity of the renin-angiotensin-aldosterone system may offer a new interesting alternative. This might perhaps be achieved in the future with the administration of neutral endopeptidase inhibitors which interfere with the enzymatic degradation of atrial natriuretic peptide.
 ...
PMID:Neurohormonal consequences of diuretics in different cardiovascular syndromes. 136 43

The pathogenesis of salt and water retention in cirrhosis remains unclear. Systemic and portal hemodynamic parameters, including cardiac output, portal pressure gradient and systemic vascular resistance, were measured in six patients with untreated ascites and in six patients with hepatic cirrhosis with no history of ascites. Renal blood flow, urinary volume, and humoral factors, including plasma renin, aldosterone, angiotensin II, and urine kallikrein, were measured. Significant differences were seen between the two groups in urine volume, urine sodium and fractional sodium excretion, plasma angiotensin II, and the ratio between plasma renin activity and urinary kallikrein excretion (PRA:UKallV). A strong correlation existed between urinary sodium excretion and the PRA:UKallV ratio. No significant differences were detected between the groups in portal, renal, and systemic hemodynamics. The present results suggest that humoral changes occur early in ascites. Altered relationships between intrarenal hormone systems, such as the renin-angiotensin and kallikrein-kinin systems, may be important in salt and water retention.
 ...
PMID:Portal and systemic hemodynamics and humoral factors in cirrhosis with and without ascites. 141

Ascites formation in patients with cirrhosis of the liver is dependent on local factors that preferentially localize any fluid retention to the peritoneal space and systemic factors that favor renal retention of salt and water. The local factors are largely related to adaptive changes in the hepatic sinusoids and mesenteric capillaries in response to an increase in hydrostatic pressure. The systemic factors reflect the disturbance in volume homeostasis evident in patients with cirrhosis and are largely explained by the neurohumoral consequences of a decreased peripheral vascular resistance.
 ...
PMID:Pathophysiology of ascites formation. 156 74

Perindopril is a non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which requires hydrolysis to its active metabolite, perindoprilat, to produce its effects. Ten cirrhotic patients with mild to severe disease were studied after oral administration of a single 8 mg dose of perindopril as its tert-butylamine salt. Compared with a historical control group of young healthy volunteers receiving the same single oral dose of perindopril, mean AUC values of the prodrug perindopril were double in patients with liver cirrhosis (602 +/- 294 s.d. ng ml-1 h vs 266 +/- 70 s.d. ng ml-1 h) whereas the mean AUC of perindoprilat was found to be similar (134 +/- 139 ng ml-1 h vs 120 +/- 29 ng ml-1 h). The partial metabolic clearance of perindopril to perindoprilat was much lower in the cirrhotics (26 +/- 12 ml min-1 vs 58 +/- 22 ml min-1). The maximum inhibition of plasma ACE activity measured in the cirrhotic patients (87.5 +/- 5.1%) was comparable with that previously reported with perindopril in patients with mild hepatic impairment as well as in patients with essential hypertension. We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindoprilat but that no dosage adjustment of perindopril is required in cirrhotic patients.
 ...
PMID:The pharmacokinetics of perindopril in patients with liver cirrhosis. 157 57

The potent diuretic and natriuretic properties of atrial natriuretic factor (ANF) suggest that atrial hormones may participate to the regulation of salt and water excretion under physiological conditions. ANF, via the increase of its intracellular second messenger cGMP, has been recently shown to inhibit the apical sodium channel of the inner medullary collecting tubule (IMCD). In addition, ANF inhibits renin and aldosterone synthesis and antagonizes the antinatriuretic effects of angiotensin II. ANF may also contribute to the excretion of free water by inhibiting both the secretion of vasopressin and its antidiuretic action. ANF appears to play an important physiological role in sodium repleted states, or when the effective plasma volume is increased. On the contrary, when the effective plasma volume is decreased or in sodium depleted states, the natriuretic effect of both endogenous and exogenous ANF is severely blunted. That ANF-resistance may be related to the activation of the renin-angiotensin-aldosterone axis, increased circulating catecholamines, renal sympathetic nerve stimulation, changes in renal hemodynamics or increased degradation of ANF. All these factors could explain the lack of significant natriuretic effect of both endogenous and exogenous ANF in some pathological conditions such as heart failure or liver cirrhosis. ANF may also been concerned in water homeostasis. In addition to the well-known osmoregulatory pathways of water metabolism, we recently found that ANF could be involved in the volume adjustment to acute water intake in normal man.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Atrial natriuretic factor and the endocrine control of electrolyte homeostasis. 183 42

Twenty of 320 patients with Wilson's disease initially presented with chemical and laboratory features of chronic active hepatitis, confirmed histologically in 17. When first seen, cirrhosis was present in all 20 and was complicated by ascites and/or jaundice in 11. Within 1 week to 8 years of the onset of over liver disease the diagnosis of Wilson's disease was established, and treatment with D-penicillamine was promptly initiated in 19 patients. One man refused treatment and died 4 months later. Treated patients received D-penicillamine or trientine for a total of 264 patient-years (median, 14 patient-years). Abnormal water retention, for which salt restriction and diuretics were added to penicillamine or trientine, disappeared in all but 1 of the patients so affected. Symptomatic improvement and virtually normal levels of serum albumin, bilirubin, aspartate aminotransferase, and alanine aminotransferase followed within 1 year in the majority of subjects. One woman died after 9 months of treatment. Two patients, who became noncompliant with the therapeutic regimen after 9 and 17 years of successful pharmacological treatment, required liver transplants. These results indicate that the prognosis of specifically treated Wilsonian chronic active hepatitis is very good in spite of the presence of cirrhosis.
 ...
PMID:Prognosis of Wilsonian chronic active hepatitis. 199 98

Previous studies strongly suggest that adenosine receptors on juxtaglomerular cells function to restrain the secretion of renin induced by a variety of stimuli. The clinical significance of this is that caffeine, a widely consumed adenosine receptor antagonist, could augment renin release responses to diseases such as renovascular hypertension, liver cirrhosis and heart failure and to therapeutic maneuvers such as salt restriction, diuretics and vasodilators. Caffeine may be particularly troublesome in this regard because this methylxanthine has central nervous system effects and intracellular actions that also might contribute to the overall ability of caffeine to potentiate renin secretion. The purpose of this study was to document the effects of caffeine on renin release responses to a vasodilator and to investigate what mechanisms were responsible for any augmentation of vasodilator-induced renin secretion. Accordingly, we compared the effects of caffeine vs. 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX; a xanthine that we documented in this study not to significantly enter the brain or penetrate cell membranes) on base-line and hydralazine-induced renin release in both normal and beta adrenoceptor-blocked (propranolol, 15 mg/kg) rats. Both xanthines (at a dose of 10 mg/kg plus 150 micrograms/min) attenuated adenosine-mediated hypotension and bradycardia, and DPSPX was at least as effective as caffeine in antagonizing peripheral adenosine receptors. Caffeine and DPSPX increased base-line plasma renin activity to a similar extent regardless of whether the animals were pretreated with propranolol. In rats with an intact beta adrenergic system, caffeine, but not DPSPX, increased the renin release response to low-dose hydralazine (1 mg/kg). Although both xanthines augmented the renin release response to high-dose hydralazine (10 mg/kg), caffeine was more efficacious in this regard. In beta adrenoceptor-blocked rats, neither caffeine nor DPSPX augmented the renin release response to low-dose hydralazine, whereas both xanthines equally potentiated the renin release response to high-dose hydralazine. These data demonstrate that caffeine increases base-line renin release primarily by blocking peripheral (most likely renal), cell-surface adenosine receptors; however, caffeine potentiates vasodilator-induced renin secretion in part by blocking peripheral (most likely renal), cell-surface adenosine receptors and in part by additional central nervous system and/or intracellular mechanism(s) that involve the beta adrenergic system.
 ...
PMID:Caffeine potentiates vasodilator-induced renin release. 200 84


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>