scholarly journals Update on Peripheral Arterial Vasodilation, Ascites and Hepatorenal Syndrome in Cirrhosis

2000 ◽  
Vol 14 (suppl d) ◽  
pp. 112D-121D ◽  
Author(s):  
Mladen Knotek ◽  
Boris Rogachev ◽  
Robert W Schrier
Keyword(s):  
Hepatorenal Syndrome ◽  
Decompensated Cirrhosis ◽  
Arterial Tree ◽  
Salt Diet ◽  
Bacterial Peritonitis ◽  
Low Salt ◽  
Intrahepatic Portosystemic Shunt ◽  
Peripheral Arterial ◽  
Orally Active

In cirrhosis of the liver, according to the peripheral arterial vasodilation hypothesis, relative underfilling of the arterial tree triggers a neurohumoral response (activation of renin-angiotensinaldosterone system, sympathetic nervous system, nonosmotic release of vasopressin) aimed at restoring circulatory integrity by promoting renal sodium and water retention. Evidence has accumulated for a major role of increased vascular production of nitric oxide as the primary cause of arterial vasodilation in cirrhosis. Ascites is a common complication in cirrhosis. Treatment of ascites consists of a low salt diet with diuretics, and paracentesis together with plasma volume expanders in diuretic-resistant patients. Progression of cirrhosis may result in hepatorenal syndrome, a state of functional renal failure that carries an ominous prognosis. Orthotopic liver transplantation has remained the only curative treatment for patients with advanced liver disease; other modalities such as transjugular intrahepatic portosystemic shunt or vasopressin analogues may serve as a bridge to transplantation. Another complication of decompensated cirrhosis is spontaneous bacterial peritonitis, the incidence of which can be reduced by primary or secondary antibiotic prophylaxis by using orally active antibiotics.

scholarly journals SAT-006 A New Concept for the Endocrinology of Pre-Eclampsia: The Role of Spiral Steroids

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Fred I Chasalow ◽  
Ron Bochner
Keyword(s):  
Type A ◽  
Structural Features ◽  
Type B ◽  
Salt Diet ◽  
Breast Cyst ◽  
High K ◽  
Epithelial Na Channels ◽  
Low Salt

Abstract Background: In 1987, Graves observed that during the 3rd trimester, some patients with pre-eclampsia had high levels of unknown materials that could be detected with assays for digoxin (DLM). In 2018, we characterized a new candidate for the DLM, Ionotropin. It is a phosphocholine (PC) ester of a novel steroid with 23 carbon atoms. As Ionotropin shares structural features (a) with spironolactone (both have spiral lactones in the E-ring) and (b) with digoxin (E-ring lactone and 3α-5β configuration), we have proposed that Ionotropin may function as a potassium (K+) sparing diuretic. This suggestion is supported by the observations that [1] patients who cannot make Ionotropin (7-dehydrosterol reductase deficiency) are K+ wasting and [2] breast cyst fluids with high K+ levels also have high Ionotropin levels. Hypothesis: During the 3rd trimester, fetal requirements for K+ reach a maximum, fetal blood pressure increases and aldosterone signaling is blocked. This blockage leads to fetal sodium (Na+) wasting and is essential for formation of amniotic fluid. These events are consistent with a normal role for an unknown endogenous K+ sparing hormone and would be the basis for a modest elevation of maternal DLM during the 3rd trimester. Our hypothesis is that if any of the functions were inadequate, then the fetal-placental unit would synthesize excess PC-spiral steroids; the woman would exhibit symptoms of K+ sparing hormone excess (hypertension and proteinuria) and would be diagnosed with pre-eclampsia. Experimental Results: We have just reported a pilot study associating elevated PC esters of spiral steroids in women with pre-eclampsia. In brief, 12 of 19 women had elevated levels of at least one of the PC steroids (Z-score > 2) when compared to the levels in 20 pregnant women matched for gestational age and fetal sex. There are two basic mechanisms for this dichotomy: (a) there may be episodic secretion with of a DLM with a short half-life or (b) there may be two different underlying biochemical causes. In prior studies, there has been no indication of episodic secretion of DLM similar to that observed with glucocorticoids, Ionotropin or other PC spiral steroids. Discussion: There are two basic types of K+ sparing diuretics. Type A: Spironolactone functions by regulating the NaK-ATPase. Type B: Triamterene functions by blocking synthesis of epithelial Na+ channels. Thus, Type A would have high levels of spiral steroids and Type B would have low levels of spiral steroids. Type A patients would be expected to have higher risk of long-term consequences when compared to the Type B patients. Conclusion: The recognition of the division of pre-eclampsia into two separate diseases might be the key observation for developing Type-specific diagnosis and therapy. For example, a Type A patient might benefit from a low salt diet but that diet would not be expected to benefit a patient with Type B disease.

Targeting the gut-liver-immune axis to treat cirrhosis

Gut ◽  
2020 ◽  
pp. gutjnl-2020-320786 ◽  
Author(s):  
Thomas Henry Tranah ◽  
Lindsey A Edwards ◽  
Bernd Schnabl ◽  
Debbie Lindsay Shawcross
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Bacterial Infections ◽  
Hepatorenal Syndrome ◽  
Intestinal Barrier ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Barrier Dysfunction ◽  
Bacterial Peritonitis ◽  
Gut Barrier Function

Cirrhotic portal hypertension is characterised by development of the decompensating events of ascites, encephalopathy, portal hypertensive bleeding and hepatorenal syndrome, which arise in a setting of cirrhosis-associated immune dysfunction (CAID) and define morbidity and prognosis. CAID describes the dichotomous observations that systemic immune cells are primed and display an inflammatory phenotype, while failing to mount robust responses to pathogen challenge. Bacterial infections including spontaneous bacterial peritonitis are common complications of advanced chronic liver disease and can precipitate variceal haemorrhage, hepatorenal syndrome and acute-on-chronic liver failure; they frequently arise from gut-derived organisms and are closely linked with dysbiosis of the commensal intestinal microbiota in advanced chronic liver disease.Here, we review the links between cirrhotic dysbiosis, intestinal barrier dysfunction and deficits of host-microbiome compartmentalisation and mucosal immune homoeostasis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies targeted at restoring intestinal eubiosis, augmenting gut barrier function and ameliorating the mucosal and systemic immune deficits that characterise and define the course of decompensated cirrhosis.

scholarly journals DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels

2020 ◽  
Vol 295 (18) ◽  
pp. 5970-5983 ◽  
Author(s):  
Nataliya Gorinski ◽  
Daniel Wojciechowski ◽  
Daria Guseva ◽  
Dalia Abdel Galil ◽  
Franziska E. Mueller ◽  
...  
Keyword(s):  
Chloride Channels ◽  
Bartter Syndrome ◽  
Post Translational Modification ◽  
Salt Diet ◽  
Type Iv ◽  
Low Salt ◽  
Accessory Subunit ◽  
Palmitoyl Acyltransferase

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.

scholarly journals The use of vasoconstrictors in patients with liver cirrhosis: how, when, why

2012 ◽  
Vol 6 (3) ◽  
pp. 105-115
Author(s):  
Claudio Puoti
Keyword(s):  
Blood Flow ◽  
Liver Cirrhosis ◽  
Hepatorenal Syndrome ◽  
Portal Blood Flow ◽  
Decompensated Cirrhosis ◽  
Enos Activity ◽  
Enhanced Production ◽  
Massive Gastrointestinal Bleeding ◽  
No Release

Portal hypertension (PH) is a severe complication of liver cirrhosis. Patients with PH run the risk of developing gastro-esophageal varices and massive gastrointestinal bleeding, ascites, hepatorenal syndrome, and hepatic encephalopathy. Portal blood flow in its turn increases because of enhanced production of vasodilators, increased eNOS activity and NO release, systemic and splanchnic vasodilation, hyperkinetic circulation, and hyposensitivity to vasoconstrictors. Thus, it is now widely recognized that this hyperkinetic (hyperdynamic) circulation that characterizes liver cirrhosis is the main cause of the complications of the disease. This review is aimed at addressing the role of vasoconstrictor treatment in patients suffering from complications of decompensated cirrhosis, offering practical suggestions for the management of this treatment at bedside. In particular, the management of terlipressin in patients with cirrhosis, its side effects and the efficacy of this vasoconstrictor will be examined.

scholarly journals Hemolytic Anemia following Stent-Graft Transjugular Intrahepatic Portosystemic Shunt Creation

2019 ◽  
Vol 36 (02) ◽  
pp. 072-075
Author(s):  
Andrew Kuei ◽  
Adam E. Mikolajczyk ◽  
Matthew M. Niemeyer
Keyword(s):  
Hemolytic Anemia ◽  
Stent Graft ◽  
Transjugular Intrahepatic Portosystemic Shunt ◽  
Hepatorenal Syndrome ◽  
Portosystemic Shunt ◽  
Refractory Ascites ◽  
Invasive Technique ◽  
Chiari Syndrome ◽  
Intrahepatic Portosystemic Shunt

AbstractTransjugular intrahepatic portosystemic shunt (TIPS) creation is a minimally invasive technique aimed at managing the complications of portal hypertension. Initially performed in the setting of variceal bleeding, the role of TIPS has expanded to treatment of medically refractory ascites, portal hypertensive gastropathy, hepatic hydrothorax, Budd-Chiari syndrome, portal vein thrombus, and hepatorenal syndrome. Potential complications from TIPS are well documented, and include hepatic encephalopathy, hepatic failure, and TIPS dysfunction. Hemolytic anemia is a lesser known complication related to TIPS creation. In this article, a case of hemolytic anemia following TIPS creation using a Viatorr stent-graft in described.

scholarly journals Ascitic Interleukin 6 Is Associated with Poor Outcome and Spontaneous Bacterial Peritonitis: A Validation in Critically Ill Patients with Decompensated Cirrhosis

2020 ◽  
Vol 9 (9) ◽  
pp. 2865
Author(s):  
Ulrich Mayr ◽  
Marina Lukas ◽  
Mayada Elnegouly ◽  
Christine Vogt ◽  
Ulrike Bauer ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Interleukin 6 ◽  
Spontaneous Bacterial Peritonitis ◽  
Polymorphonuclear Neutrophils ◽  
Decompensated Cirrhosis ◽  
Diagnostic Ability ◽  
Bacterial Peritonitis ◽  
Rule Out

Decompensated cirrhosis predisposes to infectious diseases and acute-on-chronic liver failure (ACLF) in critically ill patients. Infections like spontaneous bacterial peritonitis (SBP) are frequently associated with multi-organ failure and increased mortality. Consequently, reliable predictors of outcome and early diagnostic markers of infection are needed to improve individualized therapy. This study evaluates the prognostic role of ascitic interleukin 6 in 64 patients with cirrhosis admitted to our intensive care unit (ICU). In addition, we analysed the diagnostic ability of ascitic interleukin 6 in a subgroup of 19 patients with SBP. Baseline ascitic interleukin 6 performed well in predicting 3-month mortality in patients with decompensated cirrhosis (area under curve (AUC) = 0.802), as well as in patients fulfilling ACLF-criteria (AUC = 0.807). Ascitic interleukin 6 showed a moderate prognostic advantage compared with common clinical scores and proinflammatory parameters. Moreover, ascitic interleukin 6 had a sufficient diagnostic ability to detect SBP (AUC = 0.901) and was well correlated with ascitic polymorphonuclear neutrophils in SBP (p = 0.002). Interestingly, ascitic interleukin 6 revealed a high predictive value to rule out apparent infections on admission to ICU (AUC = 0.904) and to identify patients with “culture-positive SBP” (AUC = 0.856). Ascitic interleukin 6 is an easily-applicable proinflammatory biomarker with high prognostic and diagnostic relevance in critically ill patients with liver cirrhosis.

Abstract 294: Evaluation of the Role of the NAD(P)H Oxidase Subunit p67phox in the Regulation of Glomerular Filtration Rate in Dahl Salt-sensitive Rats

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Louise C Evans ◽  
Robert P Ryan ◽  
Terry Kurth ◽  
Meredith Skelton ◽  
Allen W Cowley
Keyword(s):  
Nadph Oxidase ◽  
Pressor Response ◽  
High Salt ◽  
Null Mutation ◽  
High Salt Diet ◽  
Salt Diet ◽  
Low Salt ◽  
Species Production ◽  
Stable Control

Studies were performed in male Dahl salt-sensitive (SS) rats with a null mutation in the p67 phox gene (SSp67 phox -/-) and wild type littermates (SS-WT) aged 10-12 weeks (n=5/6 /group). In previous studies we have shown that this important subunit of NADPH oxidase is upregulated in the SS rat. A new method for sequential measurement of GFR in conscious rats was applied during the consumption of a high salt diet. Utilizing a miniaturized device, disappearance curves of fluorescein isothiocynate (FITC)-sinistrin were determined by transcutaneous excitation and real time detection of the emitted light through the skin. The rats were surgically prepared with femoral venous catheters for the administration of (FITC)-sinistrin and carotid catheters for MAP measurement by telemetry. Baseline measurement of GFR and MAP were made daily to obtain 2 stable control days on low salt (LS, 0.4% NaCl). High salt (HS, 4.0% NaCl) measurements were made on day 2,5,7,14 and 21. In SS-WT rats, HS resulted in a progressive and significant increase in MAP (from 126±2 mmHg during LS to 158±11 mmHg by d21 HS). GFR decreased significantly from 1.50±0.03 ml/min/100g bwgt during LS to 1.26±0.02 by d21 HS. Notably, a significant increase in blood pressure was observed at d7 HS in the SS-WT preceeding the reduction in GFR which did not occur until d14 HS. In rats with the null mutation of the p67 phox gene, the pressor response to HS was blunted, MAP averaged 131±5 mmHg by d21, and there was no significant change in GFR (LS values 1.54±0.07 ml/min/100g bwgt comparable to d21 HS values of 1.41±0.04). In summary, when p67 phox is not functional in the SS rat, the hypertensive response to HS is blunted and GFR is maintained. We conclude that reactive oxygen species production via NADPH oxidase plays a major role in the eventual reduction of GFR in SS rats following the development of hypertension.

scholarly journals Role of the gonads in hypertension-prone rats.

1975 ◽  
Vol 142 (3) ◽  
pp. 748-759 ◽  
Author(s):  
L K Dahl ◽  
K D Knudsen ◽  
E V Ohanian ◽  
M Muirhead ◽  
R Tuthill
Keyword(s):  
Blood Pressure ◽  
Growth Hormone ◽  
Opposite Effect ◽  
Ovarian Function ◽  
Pressure Effect ◽  
High Salt Diet ◽  
Salt Diet ◽  
Pituitary Growth Hormone ◽  
Low Salt

In a genetically hypertension-prone (S) strain of rats it was observed previously that males generally developed hypertension more rapidly on a high salt diet than did females although final pressure ultimately were similar in both sexes. A genetic study had shown that there was no sex-linkage involved in setting blood pressure levels, so it was thought that the gonads might be involved. In the present work, castration of males had no effect on blood pressure but in the females it caused a rise in pressure that could not be distinguished from that in males, both on a high and low salt diet. Castration resulted in greater growth in females than in controls, whereas it had the opposite effect in males. It was speculated that these changes were due to influences on pituitary growth hormone with castration increasing the net output of growth hormone (or enhancing receptor sensitivity to it) in the female and the opposite in the male. From the work of others, there are some data compatible with such an interpretation. Experimentally, growth hormone will induce hypertension in rats. Therefore, it is conceivable that growth hormone is involved in the increment in hypertension observed in these castrate females. Because the effect on blood pressure was observed in castrate females on both high and low NaCl diets, it was considered unlikely that the blood pressure effect was simply due to increased NaCl intake in the food associated with greater growth. It was suggested that this rise in blood pressure with cessation of ovarian function might bear on the unsettled question of "menopausal" hypertension in women: in the genetically susceptible individual an increase in growth hormone associated with declining ovarian funtion in the menopause could provide the stimulus for the appearance of hypertension some years earlier than would otherwise have been the case.

scholarly journals Regulation of cardiac NO bioactivity in response to low salt diet: A time course study on the role of NADPH oxidase.

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Yester Skayian ◽  
Arthur Yu He ◽  
Caroline Ojaimi ◽  
Thomas H Hintze
Keyword(s):  
Nadph Oxidase ◽  
Time Course ◽  
Salt Diet ◽  
Low Salt ◽  
Time Course Study
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