pituitrin and Hepatic-Encephalopathy

Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and portal hypertension leads to splanchnic vasodilation, and this leads to the activation of compensatory mechanisms such as renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system, and antidiuretic hormone (ADH) to ameliorate low circulatory volume. The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume, resulting in the development of ascites. These compensatory mechanisms lead to impairment of the kidneys to eliminate solute-free water in decompensated cirrhosis. Nonosmotic secretion of antidiuretic hormone (ADH), also known as arginine vasopressin, further worsens excess water retention and thereby hyponatremia. The management of hyponatremia in this setting is a challenge as conventional therapies for hyponatremia including fluid restriction and correction of hypokalemia are frequently inefficacious. In this review, we discuss the pathophysiology, complications, and various treatment modalities, including albumin infusion, selective vasopressin receptor antagonists, or hypertonic saline for patients with severe hyponatremia and those awaiting liver transplantation.

Topics: Acute Kidney Injury; Acute-On-Chronic Liver Failure; Albumins; Antidiuretic Hormone Receptor Antagonists; Ascites; Fluid Therapy; Hepatic Encephalopathy; Hepatorenal Syndrome; Humans; Hypertension, Portal; Hyponatremia; Liver Cirrhosis; Liver Transplantation; Renin-Angiotensin System; Saline Solution, Hypertonic; Splanchnic Circulation; Tolvaptan; Vasodilation; Vasopressins

Acute variceal bleeding is a potentially life-threatening complication of portal hypertension. Management consists of emergent hemostasis, therapy directed at hemodynamic resuscitation, protection of the airway, and prevention and treatment of complications including prophylactic use of antibiotics. Endoscopic treatment remains the mainstay in the management of acute variceal bleeding in combination with pharmacotherapy aimed at reducing portal pressure. This article intends to highlight only the current nonendoscopic treatment approaches for control of acute variceal bleeding.

Topics: Acute Disease; Acute Kidney Injury; Anti-Bacterial Agents; Balloon Occlusion; Blood Transfusion; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Hormones; Humans; Hypertension, Portal; Intubation, Intratracheal; Liver Cirrhosis; Portasystemic Shunt, Transjugular Intrahepatic; Somatostatin; Vasoconstrictor Agents; Vasopressins

A POTENTIALLY SEVERE EVENT: Upper gastrointestinal haemorrhage in a cirrhotic patient is always extremely serious, particularly in the case of rupture of the oesophageal varices, which is the most frequent cause. THE TWO POLES OF TREATMENT: Early vasoactive treatment permits elastic ligature in optimal conditions using an endoscope. The prevention of other complications of cirrhosis is an essential element in the management of these patients.

Topics: Acute Disease; Emergencies; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemostasis, Endoscopic; Hemostatics; Hepatic Encephalopathy; Hormones; Humans; Hypertension, Portal; Ligation; Liver Cirrhosis; Octreotide; Recurrence; Risk Factors; Rupture; Sclerotherapy; Shock, Hemorrhagic; Somatostatin; Vasopressins

Topics: Adrenergic beta-Antagonists; Ascites; Carcinoma, Hepatocellular; Catheterization; Diuretics; Hemorrhage; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Neoplasms; Nitroglycerin; Peritonitis; Somatostatin; Vasopressins

The management of both acute and recurrent variceal bleeding continues to be a significant challenge to the clinician. The cause and pathogenesis of portal hypertension has been described. Alcoholic cirrhosis is the most common cause of intrahepatic sinusoidal and postsinusoidal obstruction in the United States. Long term survival depends on rapid institution of an established protocol of surgical management for variceal hemorrhage. A patient who presents with variceal bleeding must be rapidly stabilized with fluid resuscitation, and specific measures, such as the use of vasopressin and balloon tamponade, must be instituted to control hemorrhage so that endoscopy can be used to establish the diagnosis. Sclerotherapy achieves a high rate of success in the acute situation, but if hemorrhage cannot be controlled, percutaneous transhepatic embolization or emergent shunting must be performed, depending on the condition of the patient. Angiography, prior to surgical treatment, is necessary to define venous anatomy and determine portal hemodynamics, both of which provide information vital in choosing the type of shunt. If bleeding is massive and the patient is unstable, H-grafts are most appropriate, for they are technically easier and give excellent short term results. In a stable Child's A or B patient with minor ascites as well as suitable anatomy and hepatopedal flow, DSRS is the procedure of choice because it produces the smallest degree of HE postoperatively and increases the survival rate for nonalcoholics. If this is not feasible or if the surgeon lacks the technical expertise to perform DSRS, PCS is the logical alternative. In view of the data from the series observed in the United States, ablative procedures cannot be recommended at the present for the treatment of variceal bleeding. In the Child's C poor-risk patient, the operative mortality rate is prohibitive, and only nonsurgical means should be used to establish control of bleeding. In the elective situation, the surgical options change. The efficacy of ES as a definitive procedure to control recurrent variceal bleeding is unproved, and rebleeding can be significant; therefore, it cannot be recommended. H-grafts have a prohibitively high rate of long term thrombosis and are also not recommended, and the Linton or proximal splenorenal shunt offers no advantages over conventional portacaval shunting. Moreover, arterialization of the hepatic stumps of the portal vein does not prevent hepatic encephal

Topics: Acute Disease; Clinical Trials as Topic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis, Alcoholic; Portacaval Shunt, Surgical; Radiography; Recurrence; Sclerosing Solutions; Vasopressins

Topics: Acidosis, Renal Tubular; Aldosterone; Ascites; Diuretics; Hepatic Encephalopathy; Humans; Hypokalemia; Kidney Failure, Chronic; Kidney Transplantation; Kidney Tubules, Distal; Liver Cirrhosis; Liver Transplantation; Sodium; Transplantation, Homologous; Uremia; Vasopressins; Water-Electrolyte Imbalance

Topics: Anti-Bacterial Agents; Blood Transfusion; Cryotherapy; Drainage; Esophageal and Gastric Varices; Esophageal Perforation; Gastrointestinal Hemorrhage; Hemostasis; Hepatic Encephalopathy; Humans; Hypertension, Portal; Intubation, Gastrointestinal; Liver Cirrhosis; Myocardial Infarction; Peptic Ulcer; Pneumonia, Aspiration; Portacaval Shunt, Surgical; Sclerosing Solutions; Therapeutic Irrigation; Ulcer; Vasopressins; Vitamin K

Topics: Ammonia; Anti-Bacterial Agents; Antifibrinolytic Agents; Diet Therapy; Exchange Transfusion, Whole Blood; Hepatic Encephalopathy; Humans; Hypothermia, Induced; Vasopressins; Water-Electrolyte Balance

The management of both acute and recurrent variceal bleeding continues to be a significant challenge to the clinician. The cause and pathogenesis of portal hypertension has been described. Alcoholic cirrhosis is the most common cause of intrahepatic sinusoidal and postsinusoidal obstruction in the United States. Long term survival depends on rapid institution of an established protocol of surgical management for variceal hemorrhage. A patient who presents with variceal bleeding must be rapidly stabilized with fluid resuscitation, and specific measures, such as the use of vasopressin and balloon tamponade, must be instituted to control hemorrhage so that endoscopy can be used to establish the diagnosis. Sclerotherapy achieves a high rate of success in the acute situation, but if hemorrhage cannot be controlled, percutaneous transhepatic embolization or emergent shunting must be performed, depending on the condition of the patient. Angiography, prior to surgical treatment, is necessary to define venous anatomy and determine portal hemodynamics, both of which provide information vital in choosing the type of shunt. If bleeding is massive and the patient is unstable, H-grafts are most appropriate, for they are technically easier and give excellent short term results. In a stable Child's A or B patient with minor ascites as well as suitable anatomy and hepatopedal flow, DSRS is the procedure of choice because it produces the smallest degree of HE postoperatively and increases the survival rate for nonalcoholics. If this is not feasible or if the surgeon lacks the technical expertise to perform DSRS, PCS is the logical alternative. In view of the data from the series observed in the United States, ablative procedures cannot be recommended at the present for the treatment of variceal bleeding. In the Child's C poor-risk patient, the operative mortality rate is prohibitive, and only nonsurgical means should be used to establish control of bleeding. In the elective situation, the surgical options change. The efficacy of ES as a definitive procedure to control recurrent variceal bleeding is unproved, and rebleeding can be significant; therefore, it cannot be recommended. H-grafts have a prohibitively high rate of long term thrombosis and are also not recommended, and the Linton or proximal splenorenal shunt offers no advantages over conventional portacaval shunting. Moreover, arterialization of the hepatic stumps of the portal vein does not prevent hepatic encephal

Topics: Acute Disease; Clinical Trials as Topic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis, Alcoholic; Portacaval Shunt, Surgical; Radiography; Recurrence; Sclerosing Solutions; Vasopressins

The aquaporin (AQP) water channel plays an important role in the regulation of water. AQP2 is expressed in the collection duct of the kidney, serving as the final channel that helps to regulate water excretion in the kidneys and affecting the regulation of water and hyponatremia in cirrhotic patients. So far, research on aquaporin expression in cirrhosis has had various results. The purpose of this study is to investigate the factors that affect the regulation of expression of AQP in patients with cirrhosis. The study comprised 81 cirrhosis patients and 18 control subjects. In each group, 24-h urine was collected and nitric oxide and vasopressin levels were measured in the blood. The amount of urinary AQP was measured by Western blot. In this study, the positivity rate and amount of expression of AQP was higher in the cirrhotic group than that of the control group. AQP expression in urine was also compared between the groups with use of diuretics and the groups with no use of diuretics. A 57.4% positivity was observed with the former, whereas a 51.5% was seen in the latter. No significance was found between the groups (P = 0.581). Expression of AQP in compensated cirrhotic patients is significantly higher than decompensated cirrhotic patients and is especially higher in cirrhotic patients with ascites than with no ascites. There is no relationship between the concentration of vasopressin and expression of AQP. Concentration of serum NOx is higher in cirrhotic patients than the control group and there is a positive association between the concentration of serum nitric oxide and AQP in urine. In conclusion, expression of AQP is increased in cirrhotic patients and is significantly higher in patients with ascites. There is a positive association between the expression of AQP and concentration of serum nitric oxide.

Topics: Adult; Aged; Aquaporin 2; Biopsy; Female; Hepatic Encephalopathy; Humans; Liver; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Multivariate Analysis; Nitric Oxide; Vasopressins; Water-Electrolyte Balance

Nitric oxide has been proposed as a mediator of hyperdynamic circulation in cirrhosis. Endotoxin and cytokines induce the synthesis of nitric oxide. The aim of this study was to investigate the relationship between endotoxemia, cytokines, and nitric oxide in patients with cirrhosis, and to correlate these findings with clinical, biochemical, and hemodynamic parameters.. Clinical, biochemical, and hemodynamic parameters were assessed in 66 patients with cirrhosis and 15 controls. Levels of antidiuretic hormone, plasma renin activity, aldosterone, interferon gamma, interleukin-1, interleukin-6, tumor necrosis factor alpha, endotoxin, and nitrates-nitrites were determined.. Mean arterial pressure was lower and interleukin-6, tumor necrosis factor alpha, nitrites-nitrates levels, and endotoxin positivity rates were higher in cirrhotics than in controls (p < 0.005). Mean arterial pressure decreased and interleukin-6 levels increased with worsening of Child score (p < 0.005). Patients with ascites had higher levels of interleukin-6, tumor necrosis factor alpha, and nitrates-nitrites than patients without ascites (p < 0.01). Elevated levels of interleukin-6 were found in patients with encephalopathy grade I, compared with patients without (p < 0.001); this association was independent of the severity of liver disease. In patients with low mean arterial pressure, interleukin-6 levels were higher than in patients with high mean arterial pressure (p = 0.001), whereas tumor necrosis factor alpha and nitrates-nitrites levels were not different. By multivariate analysis, high interleukin-6 levels showed independent associations with the presence of ascites, encephalopathy, and low mean arterial pressure. Only interleukin-6 levels had significant correlations with Child score, plasma renin activity, serum and urinary sodium, and mean arterial pressure (r > or = 0.4, p < 0.005).. Although the activity of the nitric oxide pathway is increased in patients with cirrhosis and might contribute to the hemodynamic alteration, other factors are involved. Interleukin-6, possibly through nitric oxide-independent mechanisms, also might play a role in the vasodilatation of cirrhosis and the pathogenesis of hepatic encephalopathy.

Topics: Aged; Aldosterone; Ascites; Blood Pressure; Endotoxins; Female; Hepatic Encephalopathy; Humans; Interferon-gamma; Interleukin-1; Interleukin-6; Liver Cirrhosis; Male; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Renin; Tumor Necrosis Factor-alpha; Vasopressins

Chronic liver disease may be accompanied by disturbed sodium and water homeostasis. There is usually sodium retention and ascites. However, spontaneous natriuresis has also been reported in humans and experimental animals with liver cirrhosis. Chronic hypercortisolism, which may occur in dogs with advanced liver disease, is known to induce the inhibition of the osmostimulation of vasopressin (AVP) release. We have therefore investigated the osmoregulation of AVP release in 11 dogs with chronic hypercortisolism associated with advanced liver dysfunction and hepatic encepahlopathy and in 10 control dogs. Basal pituitary-adrenocortical activity was investigated by measuring the concentration in multiple plasma samples of adrenocorticotropin (ACTH), alpha-melanocyte-stimulating hormone (MSH), and cortisol and the cortisol:creatinine ratio in 24-hr urine. Urine specific gravity was also measured. The feedback regulation of the system was investigated by measuring these hormones in plasma after an intravenous (iv) injection of 0.01 mg/kg of dexamethasone. The osmoregulation of the release of AVP was investigated by the intravenous infusion of a 20% NaCl solution at a flow rate of 0.03 ml/kg for 2 hr and the measurement of AVP in plasma sampled at 20-min intervals. The AVP release was analyzed in terms of the threshold osmolality at which it commenced and the sensitivity, which reflects the magnitude of the response. All dogs had highly increased urinary cortisol:creatinine ratios, ranging from 21 to 210 x 10(-6) (normally < 10 x 10(-6)). The mean basal plasma concentrations of the three pituitary-adrenocortical hormones were significantly increased. ACTH values were 35 to 146 ng/l (normally, 14 to 68), MSH values were 26 to 118 ng/l (normally, 10 to 36), and cortisol values were 88 to 194 nmol/l (normally, 23 to 112). The feedback inhibition of the secretion of ACTH and cortisol in response to dexamethasone was unaffected. Urine specific gravity was significantly decreased. The regulation of AVP release was found to be abnormal in all dogs with hepatic encephalopathy. The osmotic threshold at which the release of AVP was induced was abnormally high in seven of the dogs with liver disease and in the normal range in one. It could not be determined in three dogs. The sensitivity of AVP release in response to increasing plasma hypertonicity was normal in two dogs and decreased in nine. In three dogs, there was no increase in AVP release. None of the dogs had normal

Topics: Adrenocorticotropic Hormone; Animals; Dexamethasone; Dog Diseases; Dogs; Female; Glucocorticoids; Hepatic Encephalopathy; Hydrocortisone; Liver; Male; Melanocyte-Stimulating Hormones; Natriuresis; Osmolar Concentration; Pituitary Gland, Posterior; Pituitary-Adrenal System; Vasopressins; Water-Electrolyte Balance

Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis; Splenectomy; Splenomegaly; Vasopressins

Topics: Angiography; Barium Sulfate; Counseling; Esophageal and Gastric Varices; Esophagoscopy; Gastrointestinal Hemorrhage; Hemostatic Techniques; Hepatic Encephalopathy; Humans; Hypertension, Portal; Medical History Taking; Physical Examination; Vasopressins; Water-Electrolyte Imbalance

One of the may vital functions of the liver is the biodegradation of foreign substances. The enzyme systems responsible for this liver function are frequently the site of drug interactions, both therapeutic and detrimental. Various substances can alter these enzymes by inducing, inhibiting, or competing with them, thus affecting drug response. In most instances, the liver detoxifies and deactivates chemicals, protecting the body from their harmful effects. In some biotransformation processes, however, toxic metabolites are produced that may be injurious to liver tissue as well as other body organs and systems. The effect of alcohol on the liver is a prime example. Although significant strides have been made in recent years, much is yet to be learned concerning the effect of the liver on drugs, the effect of drugs on the liver, and the pharmacologic management of various liver diseases.

Topics: Acetaldehyde; Alcoholism; Chemical and Drug Induced Liver Injury; Diuretics; Drug-Related Side Effects and Adverse Reactions; Ethanol; Hepatic Encephalopathy; Humans; Inactivation, Metabolic; Lactulose; Levodopa; Liver; Liver Cirrhosis; Liver Diseases; Microsomes, Liver; Neomycin; Oxidation-Reduction; Pharmaceutical Preparations; Spironolactone; Vasopressins

It has been shown, that measurement of total hepatic blood flow is not of great diagnostic value: normal functioning of this organ is dependant on blood flow only to a minor degree and diseases of the liver usually go along with only minor changes of total blood flow. There are two reasons for this phenomenon: 1) liver cells are able to extract oxygen from blood exhaustively 2) regulation of hepatic arterial blood flow is almost autonomous and compensates well for changes of portal venous blood flow and changes of extrahepatic arterial circulation. Thus normal hepatic arterial blood flow is the most important factor as far as prognosis of shunt operations is concerned. The manifestation of portal-systemic encephalopathy in addition depends not only upon the amount of portal-venous blood bypassing the liver, but also upon arterial blood flow, since urea synthesis is located primarily in zone 1 of liver microcirculation, which is supplied in the first line by the hepatic arterial system. Reduction of portal venous blood flow plays a rather minor role as compared to reduction of arterial flow; it does mean however a considerable loss of important nutritive and trophic factors for the liver.

Topics: Ammonia; Hepatic Artery; Hepatic Encephalopathy; Humans; Liver Circulation; Liver Cirrhosis; Microcirculation; Urea; Vasopressins

Topics: Catheterization; Esophageal and Gastric Varices; Gangrene; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Intestinal Diseases; Male; Mesenteric Arteries; Mesenteric Vascular Occlusion; Middle Aged; Portal Vein; Sepsis; Thrombophlebitis; Thrombosis; Vasopressins

Topics: Acute Kidney Injury; Adolescent; Amino Acids; Ammonia; Anti-Bacterial Agents; Arginine; Aspartic Acid; Coenzyme A; Diet Therapy; Exchange Transfusion, Whole Blood; Glutamates; Hepatic Encephalopathy; Humans; Malates; Male; NAD; Ornithine; Prednisone; Prognosis; Renal Dialysis; Thiamine Pyrophosphate; Thioctic Acid; Vasopressins

Topics: Blood Transfusion; Drug Therapy; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Vasopressins

Topics: Arginine Vasopressin; Drug Therapy; Hepatic Encephalopathy; Humans; Liver Cirrhosis; Neomycin; Vasopressins