New approach could reverse liver failure

Liver Disease Survivors Guide

Renowned Health Specialist experienced in working with numerous people with liver disorders share with you and: Explains how the liver works and how liver disorders develop in Simple English without Medical Jargon. Shares the facts about cirrhosis of the liver. Explains complications and treatments in simple language. Talks about Nutrition in Liver Disease. Explains Alternative Treatments available. Talks about the latest research developments in liver disease treatment. Shares resources for Liver disease forums and help-lines. Gives you the true in-depth stories from survivors and how they coped with the challenges of liver disorder. Shares touching stories of family members who had to cope with their loved ones suffering from cirrhosis of the liver, and the strategies they used to cope with them. With Liver Disease Survivors Guide, you will discover : Credible information on Liver disease obtained from detailed interviews with specialist doctors, explained in simple language. Healthy steps in dealing with liver disorders. What to do and what not to do while learning to adapt to the liver disorder. Remarkable stories in patients own words. It gives you a real emotional experience of a person with serious liver disorder and how they view the world. Latest research on liver disorders. Best resources and direct links to forums. Direct links to get professional help and identify the best experts in your area. Alternative treatments and therapies available for liver disorders. No medical jargon or difficult language, the book is written in simple and easy to understand language.

Liver Disease Survivors Guide Summary


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Author: Grace Barrera
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The Use of Diuretics in the Treatment of Ascites and Edema in Hepatic Cirrhosis

Diuretics Right Heart Failure

Cirrhosis of the liver is a major cause of salt and water retention. The tendency for accumulating fluid to localize in the peritoneal cavity is typical of cirrhosis and is far more pronounced than in congestive heart failure or the nephrotic syndrome. Although peripheral edema does occur with cirrhosis, it is generally of lesser magnitude and rarely dominates the clinical picture. In the late stages of cirrhosis, malnutrition and severe hypoalbuminemia may contribute to the development of massive edema. The pathogenesis of the renal salt and water retention in patients with hepatic cirrhosis remains obscure. Two major fluid-retaining hypotheses have been advanced (i) the underfill theory and (ii) the overflow theory. In this chapter we review the evidence in support of these two theories, discuss the indications for dietary salt restriction and diuretic therapy, the specific diuretic options which are available, common complications of diuretic therapy, complications specific to the...

Treatment Of Ascites And Edema In Patients With Hepatic Cirrhosis [35

Salt restriction and diuretics may be used in patients with cirrhosis to reduce mechanical derangements and enhance patient comfort. However, these treatments do not correct or reverse the underlying hepatic abnormalities. The therapeutic goal of such therapy is the reestablishment of salt and water balance at more clinically acceptable levels of ascites and edema. Complete elimination of detectable edema and ascites is rarely possible or desired. Indeed, attempts to eliminate completely edema and ascites may produce circulatory insuffi

Cirrhosis Table

In patients with cirrhosis who are hypoalbuminemic, protein binding is decreased with consequent effects on volume of distribution and clearance. Bioavailability is normal, though the rate of absorption is slowed. Overall, unless renal function is compromised, diuretic delivery into urine is normal (Tables 2 and 3) as such, resistance is pharmacodynamic in nature. The possible mechanisms for such resistance include increased solute reabsorption at the proximal or distal tubule and or alterations in the receptor for loop diuretics. A few studies have shown that some patients with severe cirrhosis have impaired delivery of diuretic into urine, presumably due to mild decreases in renal function. In such patients larger doses will attain adequate amounts of diuretic in the urine. Even including such patients, however, there seems little rationale for administering single intravenous doses of furosemide greater than 40 mg (or the equivalent dose of other agents or formulations).

Aat Deficiency And Disease

Homozygous Z individuals are predisposed to developing childhood cirrhosis 7 and pulmonary emphysema in early hepatocytes. The polymerization results from an intermolecular interaction in which one RCL inserts into a space in the A-sheet. The Z mutation favors polymerization and the accumulated aggregates cause damage to the hepatocytes, which can result in childhood cirrhosis. 10 Only about 3 of PI Z individuals develop severe liver disease that often requires liver transplantation the only effective treatment for them. 11 In a prospective screening study carried out in 200,000 newborns in Sweden, 120 children with PI ZZ were followed up. 12 Eighteen percent of the PI Z children developed clinically recognizable liver abnormalities, 7.3 had prolonged obstructive jaundice with marked evidence of liver disease, 4.1 had prolonged jaundice with mild liver disease, and 6.4 had other abnormalities suggestive of liver disease such as hepatomegaly, splenomegaly, or unexplained failure to...

Clinical Implication Of Drug Transporters

Another important canalicular transport protein for drugs-metabolites, the bile salt export pump BSEP, is involved in progressive familial cholestasis (PFIC-2) in a subgroup of infants and children. The disease is characterized as a cholestatic disorder causing extreme pruritus, growth failure, and can progress to cirrhosis in the first decade of life.38 Mutations on the BSEP gene, such as 890A G (E297G) and 2944G A (G982R), result in a dysfunction of the transport protein, which is characterized by impaired active transport of bile acids across the hepatocyte canalicular membrane into bile.

Surgical Liver Transplant

Cirrhosis is a chronic liver disease that is characterized by destruction of the functional liver cells, which leads to cellular death. Cirrhosis along with other chronic liver diseases result in up to 35,000 deaths each year in the United States and is the ninth leading cause of death. In cirrhosis, the damaged liver cells regenerate as fibrotic areas instead of functional cells, causing alterations in liver structure, function, blood circulation, and lymph damage. The major cellular changes include irreversible chronic injury of the functional liver tissue and the formation of regenerative nodules. These changes result in liver cell necrosis, collapse of liver support networks, distortion of the vascular bed, and nodular regeneration of the remaining liver cells. The classification of cirrhosis is controversial at present. However, most types may be classified by a mixture of causes and cellular changes, defined as follows alcoholic crypto-genic and postviral or postnecrotic biliary...

Gender Ethnicracial And Life Span Considerations

Cirrhosis is most commonly seen in the middle-aged population it is the fourth leading cause of death in the population that is 35 to 55 years of age. It is more common in males than in females. Although the cause is obscure, liver disease appears to be more prevalent in preterm infants who have minimum enteral feedings and who were begun on total parenteral nutrition (TPN) at an early age. Hepatitis C is more common in minority populations, such as African Americans and Hispanic persons, than in other populations. Alcohol dependence and alcoholic liver disease are more common in minority groups, particularly among Native Americans. Primary biliary cirrhosis is more common in Northern Europeans and is less common in populations of African descent.

Primary Nursing Diagnosis

Patients are placed on a well-balanced, high-calorie (2500 to 3000 calories per day), moderate- to high-protein (75 g of high-quality protein per day), low-fat, low-sodium diet (200 to 1000 mg per day), with additional vitamins and folic acid. Accurate fluid intake and output are important to prevent fluid volume overload for most patients, intake should be limited to 500 to 1000 mL per day. Frequently, vitamin K injections are ordered to improve blood clotting factors. If coagulopathies worsen, treatment may require whole blood or fresh-frozen plasma to maintain the hematocrit and hemoglobin. If alcohol is the primary etiologic factor in liver cirrhosis, strongly encourage the patient to cease drinking. Commonly seen in cirrhosis patients are esophageal varices due to portal vein hypertension. Varices can rupture as a result of anything that increases the abdominal venous pressure, such as coughing, sneezing, vomiting, or the Valsalva's maneuver. To remedy bleeding of...

Discharge And Home Healthcare Guidelines

Emphasize to the patient with alcoholic liver cirrhosis that continued alcohol use exacerbates the disease. Stress that alcoholic liver disease in its early stages is reversible when the patient abstains from alcohol. Encourage family involvement in alcohol abuse treatment. Assist the patient in obtaining counseling or support for her or his alcoholism.

Clinical Description

Cystic fibrosis is often considered the most common serious autosomal recessive disease in Caucasians of northern European ancestry. It is a multiorgan condition, characterized by abnormally viscous secretions from epithelial cells in various tissues, leading to duct obstruction and infections. The most prominent and potentially lethal site for these phenomena is the lung, but CF patients also may suffer from pancreatic exocrine insufficiency, intestinal obstruction (called meconium ileus in the perinatal period), diabetes, biliary cirrhosis, growth retardation and failure to thrive, dehydration because of excessive salt loss in sweat, and sinusitis. In addition, virtually all males with classical CF exhibit a congenital malformation, bilateral absence of the vas deferens (CBAVD), causing infertility.

Clinical Features of Infection

Chronic HBV infection is most often asymptomatic ('healthy carriers') and symptomatic chronic active hepatitis with periods of fever, malaise and hepatic pain is much less common. In highly endemic regions of the world such as eastern Asia, most HBV infections occur in newborns or young children and are relatively asymptomatic many of these infections become persistent and remain silent for many years until cirrhosis or HCC develop in middle or old age and become symptomatic with pain, ascites, abdominal mass, etc. In the United States, more primary HBV infections occur in adults and more often result in symptomatic acute hepatitis B, and fewer become persistent.

Erythropoietic protoporphyria

Perioral furrowing, and aged-appearing, thickened, or hyperkeratotic skin of the dorsal hands with sustained, more intense, or frequent exposures, waxy scleroderma-like induration and or weather-beaten or cobblestone textures of the face and dorsal aspects of hands progressive liver failure in rare instances, with hepatosplenomegaly and jaundice

Improvement in Solute Delivery

For many years hypoproteinemic states have been assumed to be associated with reductions in effective intravascular volume. This event has been postulated to play a seminal role in the intense renal sodium retention associated with nephrotic syndrome and cirrhosis through activation of a number of volume sensitive neurohumoral mechanisms stimulating sodium reabsorption. Additionally changes in vascular volume could induce direct increases in peritubular physical forces favoring sodium uptake in the renal proximal tubule. Intravenous infusions of albumin could therefore increase vascular volume, increase filtered sodium load, blunt neurohumoral mechanisms stimulating sodium reabsorption, and directly decrease the fraction of filtered sodium reabsorbed in the proximal tubule. In the presence of a diuretic, the resultant increase in distal delivery would be more effectively excreted. Data from a number of investigators, however, now suggest that most patients with hypopro-teinemia from...

Early Diagnosis Of Hemochromatosis Phenotyping Vs Genotyping

Early diagnosis of hemochromatosis permits treatment of iron overload and thereby prevents premature death due to hepatic cirrhosis (and primary liver cancer) and diabetes mellitus complications.1-1,2-1 Preventing iron overload may also reduce the frequency or severity of arthropathy, hypogonadotrophic hypogonadism and other endocrinopathic disorders, and cardiac abnormalities. 1,2

Cirrhotic Patients Refractory to Combination Diuretics

M. (1994). The nitric oxide hypothesis and the hyperdynamic circulation in cirrhosis. Hepatology 20, 1343-1350. 6. Fuller, R., Hoppel, C., and Ingalls, S. T. (1981). Furosemide kinetics in patients with hepatic cirrhosis with ascites. Clin. Pharmacol. Ther. 30,461 -467. 7. Gabuzda, G.J. (1970). Cirrhosis, ascites and edema. Gastroenterology 58, 546-553. 9. Gines, P., Tito, L. 1., Arroya, V., Planas, R., Panea, J., Rimola, A., Llach, J., Humbert, P., Badala-menti, S., and Jimenez, W. (1988). Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology 94, 1493-1502. 13. Leevy, C. M., Zinke, M., Baber, J., and Chey, W. Y. (1985). Observations on the influence of medical therapy on portal hypertension in hepatic cirrhosis. Ann. Intern. Med. 49, 837-851. 15. Levy, M. (1977). Sodium retention in dogs with cirrhosis and ascites Efferent mechanisms. Am. J. Physiol. 233, F586-F592. 16. Ito, S., and...

Pharmacokinetics in Patients

Pharmacokinetic profiles have been studied in adult and pediatric hemophilia patients, as well as in adults with acquired FVII deficiency (i.e., healthy adult volunteers pretreated with acenocoumarol and patients with liver cirrhosis) 41-45 . The clearance and half-life values (range 2.4 to 3.2 h) after bolus administration of rFVIIa were in the same range in the adult populations studied. However, pediatric patients with hemophilia have been reported to have a shorter half-life (1.3 h) and higher clearance values than the adults with hemophilia 42,44 . A clinical trial to evaluate this possible difference in half-life and clearance between adults and pediatric patients with hemophilia is in progress.

Results from Finalized Trials Outside the Current Indication

The liver is the principal site of synthesis and clearance of coagulation factors, components of the fibrinolytic system, and anticoagulants. The most frequently encountered hemato-logical abnormalities in patients with liver disease include prolonged PT and hyperfibri-nolysis 78,79 . The progressive loss of liver parenchymal cells associated with cirrhosis results in a decreased synthesis of the vitamin K-dependent coagulation factors (FII, FVII most pronounced , FIX, FX), fibrinogen, and proteins C and S. When bleeding occurs, all Variceal bleeding is a medical emergency that has a 6-week mortality in the range of 5 to 50 , depending on the severity of the underlying liver disease, mainly because of the high rate of failure to control bleeding during the first days after the initial onset of bleeding 81 . The treatment modalities available for the patient with advanced cirrhosis and active variceal bleeding remains unsatisfactory in terms of a safe and fast correction of the...

BOX 1 Bleeding Esophageal Varices

Esophageal varices (fragile, distended, and thin-walled veins in the esophagus) occur in patients with liver failure because of portal hypertension. Obstructed blood circulates to low-resistance alternate vessels around the portal circulation in the liver, which is a high-pressure system. One of these routes is through the esophageal veins, which become distended with blood, irritated from pressure, and susceptible to rupture. Treatment of esophageal varices includes develop massive hepatic cystic disease that results in liver failure. Wilson disease is a genetic disorder (autosomal recessive pattern) leading to a large liver accumulation of copper. About 5 of patients suffer from acute liver failure or fulminant hepatitis.

Leading Causes of Death

Figure 10.2 Age-specific acceleration of mortality by cause of death. Data averaged for the years 1999 and 2000 for non-Hispanic white males in the United States from statistics distributed by the National Center for Health Statistics http nchs , Worktable Orig291. The causes of mortality are based on the International Classification of Diseases, Tenth Revision http The diseases are Heart for diseases of the heart CerVas for cerebrovascular diseases Accid for accidents (unintentional injuries) Infl for influenza and pneumonia Suic for intentional self-harm (suicide) Nephr for nephritis, nephrotic syndrome and nephrosis Sept for septicemia Canc for malignant neoplasms ChrRsp for chronic lower respiratory diseases Liver for chronic liver diseases and cirrhosis Diab for diabetes mellitus and Alzh for Alzheimer's disease. From Frank (2004a). Figure 10.2 Age-specific acceleration of mortality by cause of death. Data averaged for the years 1999 and 2000 for non-Hispanic white...

Hepatic Form lethalinfantile

The second form presents as a lethal neonatal multiorgan deficiency of carnitine palmitoyltransferase II. Reduced CPT II activity in multiple organs is observed and reduced concentrations of total and free carnitine and increased concentrations of lipids and long chain acylcarnitine can be found. The accumulation of long-chain acylcarnitines has an arrhythmogenic effect on the heart. The patients presented with hypoketotic hypo-glycaemia, seizures, tachycardia, cardiomegaly, hepatomegaly, liver failure and died within the first two years.

History and Classification

After serologic screening tests for the detection of hepatitis B and hepatitis A viruses were introduced in the 1970s to eliminate these viruses from human blood supplies, the role of HCVs in causing up to 90 of transfusion-associated hepatitis was recognized. The term hepatitis C virus (HCV) was coined in 1989 after identification of an RNA genome of this virus from cDNA libraries of human serum containing the infectious agent. In humans, infection with HCV commonly evolves into a chronic persistent hepatitis which can lead to progressive hepatic cirrhosis and hepatocellular carcinoma. Lack of a suitable cell culture system for propagating HCV had until only recently been a major impediment to progress in understanding the details of its replication. In addition, studies of HCV pathogenesis have been hampered by the lack of animal model systems, and progress has depended on use of clinical data from human cases, or from the use of a chimpanzee model.

Epidemiology and Clinical Disease

It is estimated that there are at least 170 million chronically infected HCV subjects worldwide, with prevalence varying from 0.1 to as high as 18 (Egypt). In areas where HCV has been eliminated from blood supplies by donor screening, use of illicit injectable drugs remains the most important mode of transmission. Various other forms of exposure, including occupational and sexual exposures, are involved in some cases of transmission. HCV is a primary cause of cirrhosis, a significant cause of hepato-cellular carcinoma, and in the United States is the leading reason for liver transplantation. There is great variability in the spectrum of disease. Acceleration of disease is observed in persons who are older at the time of infection, and in the setting of continuous alcohol exposure, and co-infection with HIV or hepatitis B virus (HBV). Individuals who sustain infection at a younger age tend to have slower progression.

Calciphylaxis Calcific Uremic Arteriolopathy

Patients developing calciphylaxis have end-stage renal disease, but some have milder renal insufficiency. Other cases have occurred in association with Crohn's disease (2), alcoholic cirrhosis (3), acute renal failure (4), metastatic breast cancer (5), and primary hyperparathyroidism (6). Most earlier literature on the subject regarded the disease as a form of metastatic calcification due to secondary hyperparathyroidism of end-stage renal disease. This view is not supported by data that show that only one third of patients with calciphylaxis have an elevated calcium-phosphate product. Additionally, the calcium-phosphate product of calciphylaxis patients and a control group of patients with end-stage renal disease without skin lesions is similar (7). Evidence of hyperparathyroidism is often lacking in patients with calciphylaxis, and treatment by parathyroidectomy results in clinical improvement in only a subset of patients. A group of patients with calci-phylaxis has been described...

Clinical Features and Pathology

In persistent infections, tolerance may break down over time, particularly with a cell-mediated immune response to the virus. Liver damage is attributable especially to the lysis of infected hepatocytes by cytotoxic T cells and peptides derived from the core (C) ORF seem to be a major target. In the long term, chronic active hepatitis may lead to the development of fibrosis, cirrhosis, and ultimately, end-stage liver failure. Cirrhosis also is a high risk for the development of primary liver cancer (hepatocellular carcinoma, HCC). However, almost all HCCs arising in HBV-infected livers contain chromosomally integrated HBV DNA and, in contrast to hepatitis C, in hepatitis B HCC may develop in the absence of cirrhosis and even on a background ofalmost normal liver histology. The rodent hepadnaviruses can also become persistent in their natural hosts and chronic hepatitis, cirrhosis, and HCC may ensue. On the other hand, DHBV infection of ducks results in very little pathology, the...

Hepatocellular Carcinoma

More recently, seroepidemiological evidence was obtained for a correlation between hepatitis C virus (HCV) infections and hepatoma. Antibodies against HCV were detected in between 13 and over 80 of liver cancer patients around the world. Over 60 of acute hepatitis C becomes chronic and may progress to cirrhosis and hepatocellular carcinoma. Latency periods between primary infection and cancer are usually measured in decades but in some cases the intervals are rather short (5 10 years). The cumulative prevalence of hepatoma in cirrhotic HCV-infected patients is over 50 , indicating that HCV substantially increases the risk of hepatocellular carcinoma. HCV is related to flaviviruses and pestiviruses and is the first human tumor-related virus with an RNA genome and no DNA intermediate during replication. The role of the virus in carcinogenesis is not yet clear. Liver injury during chronic hepatitis may be responsible for malignant conversion but there is also some evidence that HCV is...

Clinical Manifestation

The duration of viremia in acute hepatitis C is unpredictable and can vary from 2 to more than 4 months. Some patients even become HCV RNA negative during early convalescence but later on viremia rebounds. Overall 50-80 of HCV infections lead to a chronic carrier state (Figure 1(b)). About 30 of these chronically infected persons progress to liver cirrhosis 10-30 years after primary infection and hepatocellular carcinoma occurs in up to 2.5 of these patients. In contrast to chronic hepatitis B, in case of persistent HCV infection a hepatocellular carcinoma only develops on the basis of prior cirrhosis.

Pathology and Histopathology

Hepatocytes are the primary target of HCV. Therefore, the histological alterations of chronic hepatitis C are hepatocellular injury, portal and parenchymal inflammation, and necrosis. The injury of the hepatocyte is thought to be induced primarily by the immune reaction rather than by viral cytopathogenicity. Liver damage is typically spotty and focal with accompanying chronic inflammatory cells, macrophages, and, eventually, variable degrees of fibrosis. The progression rate of hepatic fibrosis is the major determinant for the outcome of chronic hepatitis C in terms of developing cirrhosis and hepatocellular carcinoma. Unfortunately, there are only a few histologi-cal markers that are more often associated with hepatitis C than with other causes of hepatitis, such as steatosis. Although the liver is the primary target, persistent HCV infection is often associated with extrahepatic symptoms, such as renal complications, lymphoma, and diabetes. A high proportion of patients with...

Vitamin D Calcium and Phosphorous Metabolism Vitamin D

A deficiency in active vitamin D can result from a combination of factors. These include a lack of sunlight exposure, poor dietary intake, gastrointestinal malabsorption, and liver or kidney defects impairing the hydroxylation of vitamin D. Impairment of 1a-hydroxylase can be seen in renal insufficiency failure or vitamin D-dependent rickets, type II. Liver failure impairs the body's ability to make 25(OH)D (96). Many drugs impair the metabolism of vitamin D, espe

Historical Introduction

Wilson disease, also referred to as hepatolenticular degeneration, was first described in 1912 by Samuel A. Kinnier Wilson as a familial progressive disorder of the central nervous system accompanied by liver cirrhosis, and by Bruno Fleischer as a ''pseudosclerosis'' with tremor, liver cirrhosis, and corneal deposits. 1,2 One year later, Rumpel demonstrated an excessive hepatic copper accumulation in Wilson disease. 3 This finding was confirmed by Luthy, who also detected an elevated copper concentration in the basal ganglia. 4 An autosomal recessive inheritance pattern was shown by Bearn, 5 and in 1993 the disease-causing gene was identified as a metal-transporting P-type ATPase designated ATP7B. 6-8

Natural History of the Disease

Natural History Disease Diagram

The incubation period following exposure is 3-6 months. In the week before icterus appears, some patients develop a serum sickness-like syndrome including arthralgia, fever, and urticaria. The clinical picture varies from asymptomatic anicteric infection to protracted icterus and, in some patients (

Posterior Lv Wall Motion Is Dyskinetic Reasons

Coronary Arteries Territories Echo

Pseudo-dyskinesis in 54-yr-old male with end-stage liver disease. Left ventricular walls in this 54-yr-old male with end-stage cirrhosis owing to chronic alcohol use and hepatitis C virus infection was normal during diastole (A-C). Apparent hypokinesis dyskinesis in the postero-inferior walls (B,D, arrows) was a result of external pressure from tense ascites secondary to his end-stage liver disease. (Please see companion DVD for corresponding video.)

Use Of Albumin And Diuretics For Edema Treatment

Very little information is available on the use of albumin and diuretics for the edema associated with cirrhosis and other hypoproteinemic conditions. In cirrhosis this undoubtedly reflects the recognition that rapid diuresis is unnecessary and potentially hazardous due to the limited rate at which fluid can be reabsorbed from the peritoneal cavity. Furthermore, in circumstances where fluid must be removed rapidly, large volume paracentesis has been reported to be more effective and have fewer complications than diuretic therapy 13 . Thus this latter technique has been used instead of diuretics when vigorous fluid and sodium removal is required. Other hypoproteinemic diuretic resistant conditions do not occur with sufficient frequency to determine whether diuretics combined with albumin are beneficial.

Antithyroid Drug Therapy

An apparent difference between the adult and pediatric populations is the higher incidence of adverse side effects of antithyroid medications in the young. Published studies including 500 children 6, 13, 59, 108, 109 , show that complications of drug therapy include increases in liver enzymes (28 ) and leukopenia (25 ). Up to 0.5 of propylthiouracil (PTU) or methimazole (MMI)-treated children will develop serious complications 6, 10 . By 1998, 36 serious adverse events and two deaths from liver failure (from PTU) due to antithyroid drug therapy of childhood Graves' disease had been reported to the FDA MedWatch Program, which is very prone to under reporting 6 . In addition, at least five other deaths related to antithyroid medication therapy in children have been reported to me by professionals. Other rare and serious adverse effects of thionamide drugs include periarteritis nodosa, other forms of vasculitis, nephrotic syndrome, hypothrombinemia, and aplastic anemia 6 .

Hepatic Encephalopathy Is A Disorder Of Astrocyte Function Resulting In A N E U R O P S Y C H I At R I C Syndrome

Astrocyte Reactive Hyperplasia

Hepatic encephalopathy is observed in patients with severe liver failure. The disease can be in one of two forms an acute form, called fulminant hepatic failure, and (2) a chronic form, portosystemic encephalopathy (Plum and Hindfeld, 1976). The neuropsychiatric symptoms of fulminant hepatic failure are delirium, coma, and seizures associated with acute toxic or viral hepatic failure. Patients having portosystemic encephalopathy may present personality changes, episodic confusion, or stupor, and, in the most severe cases, coma. The current view on the pathophysiology of hepatic encephalopathy is that, owing to liver failure, toxic substances that affect brain function accumulate in the circulation (Norenberg et al., 1992). One of the substances thought to be responsible for the neuropsychiatric toxicity is ammonia. The neuropathological findings are rather striking astrocytes are the brain cells that appear principally affected. In the acute form, astrocyte swelling is prominent and...

Veterinary Uses Of Plants

It is well-known as being severely toxic to animals (Forsyth), causing cirrhosis of the liver, from which the animal cannot recover. The trouble is that animals will not usually eat it, so it flowers and seeds undisturbed, and the effect is eventually to produce more ragwort than grass in a pasture. The condition is known in Canada as the Pictou cattle disease, and the scientific name is seneciosis. The problem is that the plant seems to have been used as a curing agent this is St James's Wort, and St James is the patron saint of horses. The use of Ragwort in veterinary practice seems to be confirmed by other names, such as Staggerwort, that is, the herb that cures staggers in horses. Sir Edward Salisbury, for one, stated clearly that staggers was actually caused by Ragwort. If both views are correct, here is an example of homeopathic magic at work, of like curing like. East Anglian horsemen favoured the use of FEVERFEW on their charges. A way to control unruly...

Role of Complement in Ethanol Induced Liver Injury

Alcoholic liver disease (ALD) develops in approximately 20 of all alcoholics with a higher prevalence in females (Lieber 1994). The development of fibrosis and cirrhosis is a complex process involving both parenchymal and non-parenchymal cells resident in the liver, as well as the recruitment of other cell types to the liver in response to damage and inflammation (Gressner and Bachem 1995). The progression of the alcohol-induced liver injury follows a pattern characteristic to all types of liver fibrosis, regardless of the causative agent. This progression is marked by the appearance of fatty liver, hepatocyte necrosis and apoptosis, inflammation, regenerating nodules, fibrosis and cirrhosis (Martinez-Hernandez and Amenta 1993). Fibrosis is thought to be initiated in response to hepatocellular damage, with inflammatory processes contributing to the progression of the disease (Gressner and Bachem 1995). Interestingly, many of the events involved in the development of fibrosis are...

Alexandra N Heinloth Gary A Boorman and Richard S Paules

We chose acetaminophen (APAP), one of the most popular analgesics worldwide, as a model compound to study genomic responses in liver tissue. This choice was driven by several criteria we believe to be of crucial importance for compound selection. First, APAP is the focus of major health concerns in the US and Europe. Accidental overdoses and ingestions with suicidal intent make APAP the leading cause of drug-induced acute liver failure in the United States (6). Secondly, rodents metabolize APAP similar to humans and are therefore an appropriate model system. APAP is metabolized by several isoforms of cytochrome p450 to the highly reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). At low, therapeutic concentrations, this metabolite is detoxified by conjugation with glutathione (GSH). At high, toxic concentrations, the liver is depleted of GSH and NAPQI is covalently bound to proteins (7). Thirdly, significant information already exists about APAP metabolism and toxicity in the...

Atrial Natriuretic Peptide and Related Peptides

Structure Natriuretic Peptides

Because of its combined effect of counteracting antinatriuretic influences and inhibiting renal salt and water reabsorption, ANP is a potent natriuretic and diuretic. Efforts to apply these properties clinically have centered on infusions of ANP in edematous states. In cirrhosis with attendant ascites, basal ANP levels tend to remain normal. However, following head out water immersion or placement of a La Veen peritoneovenous shunt, there is a rise in circulating ANP levels, an increase in urinary cGMP excretion (denoting ANP action in the kidney) , and an increase in salt and water excretion 11, 20 . These results suggest that an increase in preload in cirrhosis leads to an increase in ANP levels which can augment salt and water excretion. However, infusion of ANP without measures to increase preload has led to severe hypotension which has precluded significant natriuretic responses. In congestive heart failure, ANP levels are high, likely in response to the chronic enlargement of...

The Overflow Hypothesis

Heart Failure Overflow

The underfill hypothesis has been challenged on several fronts. Lieberman, Levy, their co-workers, and others have advanced clinical and experimental data which challenge the early sequence shown in Fig. 1 15,16 . Careful studies of dogs with experimental cirrhosis and patients with early hepatic cirrhosis demonstrate that renal salt and water retention can develop prior to the formation of ascites or edema. The classic underfill hypothesis requires that ascites and or edema develop first, to reduce the EABV and thereby activate neurohormonal cascades which increase renal salt and water retention. (The modified underfill hypothesis which begins with vasodilation and shunting was discussed above. The data are consistent with that modification.) In contrast, the overflow hypothesis begins with hepatic abnormalities which in some way cause the kidneys to retain salt and water. This salt retention precedes detectable ascites or edema. This sequence leads to ECF expansion and ascites and...

Effects on Particular Organs or Organ Systems

Mechanisms that impair the release of triglycerides to the blood. Carbon tetrachloride and ethanol are among the substances that can cause this. Necrosis is caused by carbon tetrachloride, which forms free radicals in the liver, as well as by other halogenated hydrocarbons. Cirrhosis is the formation of scar tissue in the liver. It is also caused by carbon tetrachloride, although ethanol is most commonly associated with this condition. Although there is evidence to the contrary, the effect of ethanol may be related to nutritional deficiency associated with alcoholism. Cholestasis is an inflammation of the ducts carrying bile or a decrease in bile flow by other mechanisms. There are many types of liver cancer, and many chemicals are known to cause cancer in laboratory animals. The role of chemicals in human liver cancer is less clear, except for the notable case of vinyl chloride, which is known as a potent cause of angiosarcoma.

Clinical and Experimental Data

Eabv Liver

If all of the above issues could be resolved and the total blood volume of nephrotic patients accurately determined, it would still be difficult to use these results to prove or disprove one of the salt-retaining hypotheses. The underfill hypothesis requires a reduced EABV. It is possible for a low EABV to coexist with a normal or expanded total blood volume. Normally, EABV and total blood volume expand and contract symmetrically, but some pathologic disorders can dissociate changes in the size of these two volumes. For example, although EABV is usually reduced in patients with CHF or hepatic cirrhosis, their total blood volume is generally expanded. This could also be true in some patients with the nephrotic syndrome.

Pathology and Pathogenesis

In humans, pathologic changes in the liver include swelling and necrosis of hepatocytes in the midzone of the liver lobule, with sparing of cells in the portal area and surrounding the central veins. Viral antigen and RNA are demonstrable by immunocytochemistry and nucleic acid hybridization in cells undergoing these pathologic changes, and cytopathology is mediated by direct viral injury. Hepatocytes may undergo apop-tosis. Inflammatory changes are absent or minimal, and patients with hepatitis who recover do not develop residual scarring or cirrhosis. The kidneys show acute tubular necrosis, probably the result of reduced perfusion of blood rather than direct viral

The Role Of Complement In Liver Regeneration

Complement is also involved in protection of the liver from damage during regeneration, perhaps again through its role in liver cell priming. After PHx, both C3-'- and C5-'- livers display severe damage and, in some animals, liver failure and mortality108. A similar defect in liver regeneration is observed in C5-'-mice after CCl4 injection. Though CCl4 normally induces damage in livers, C5-'-mice have a much more diffuse and extensive pattern of liver necrosis and apop-tosis after injection of CCl4 compared to wild-type mice, along with an increase in lipid content, known to be detrimental to liver regeneration and function109, 110. Thus, both C3 and C5 are necessary to prevent injury during the restoration of liver mass. Figure 1. Complement involvement in liver regeneration. Initiation of liver regeneration signals complement activation. C5a and possibly C3a bind to their receptors (C5aR, C3aR) on Kupffer cells, and, together with LPS signaling through Toll-like receptor (TLR) 4,...

Clinical Presentation

Most patients with Wilson disease present between 5 and 35 years of age. However, Wilson disease should be included in the differential diagnosis in individuals with liver disease of uncertain cause even if they are younger or older. Clinical presentation of liver disease varies from acute fulminant liver failure requiring transplantation to chronic liver disease with cirrhosis and its complications, such as portal hypertension, esophageal varices, and hypersplenism, but also solely steatosis may occur.

Pharmacologic Highlights

The most common problem for patients with liver failure is fluid volume excess. Measure the patient's abdominal girth at the same location daily, and mark the location as a reference point for future measurements. Notify the physician if the girth increases by 2 inches in 24 hours. Provide the required fluid allotment over the three meals and at night. If the patient desires, reserve some fluids to be used as ice chips. Provide mouth care every 2 hours. Because areas of edema are likely to be fragile and prone to skin breakdown, provide skin care. One of the most life-threatening complications of liver failure is airway compromise because of neurological or respiratory deterioration. Keep endotracheal intubation equipment and an oral airway at the bedside at all times. Elevate the head of the patient's bed to 30 degrees to ease respirations, and support the patient's arms on pillows to decrease the work of breathing. It is essential to be at the bedside and to perform serial...

Management Of Hbvinfected Patients

The inactive HBsAg carrier state is characterized by detectable HBsAg and anti-HBe in serum, undetectable HBeAg, low or undetectable levels of HBV DNA, normal ALT, and minimal or no necroinflammation although inactive cirrhosis may be present if transition to an inactive carrier state occurred after many years of chronic hepatitis. 14,15

Pathogenesis and Clinical Disease

HCV causes acute and chronic forms of viral hepatitis. Acute hepatitis resembles that caused by other agents of viral hepatitis, but overt symptoms are not as frequent, despite biochemical evidence of liver disease in most subjects and appearance of HCV RNA in the serum. HCV causes persistent infection in most infected individuals, who then have chronic hepatitis throughout their lives in the absence of treatment and who remain at risk for cirrhosis and hepatocellular carcinoma. The infection is often diagnosed by screening of asymptomatic blood donors, or by the appearance of either chronic fatigue or features otherwise typical of viral hepatitis. Such individuals have persistent viremia and evidence of chronic inflammatory disease on liver biopsy. The mechanism of liver injury associated with persistent HCV infection is believed to be immune-mediated and initiated by virus-specific T-lymphocytes which infiltrate the liver. Such cells are predominantly of a TH-1 phenotype and produce...

Peroxisome Proliferator Activated Receptory Key Regulator of Adipogenesis and Insulin Sensitivity

PPAR-y was first identified as a part of a transcriptional complex essential for the differentiation of adipocytes, a cell type in which PPAR-y is highly expressed and critically involved (6). Homozygous PPAR-y-deficient animals die at about day 10 in utero as a result of various abnormalities including cardiac malformations and absent white fat (7-9). PPAR-y is also involved in lipid metabolism, with target genes such as human menopausal gonadotropin coenzyme A synthetase and apolipoprotein (apo)-A-I (10,11). Chemical screening and subsequent studies led to the serendipitous discovery that thiazolidinediones (TZDs) were insulin sensitizers that lower glucose by binding to PPAR-y. Used clinically as antidiabetic agents, the TZD class includes pioglitazone (Actos) and rosiglitazone (formerly BRL49653, now Avandia) (12,13). Troglitazone (ReZulin) was withdrawn from the market because of idiosyncratic liver failure. Naturally occurring PPAR-y ligands have been proposed, although with...

Rosiglitazone And Pioglitazone

They usually take a few days to work, so you should not expect glucose levels to fall for at least a week or two. The medicine does depend on having enough insulin to be effective. In addition to their glucose-lowering effect, thiazolidinediones lower triglycerides and free fatty acid levels and raise total cholesterol, LDL cholesterol, and HDL cholesterol. Pioglitazone, when compared to rosiglitazone, is more effective in lowering triglycerides and raising HDL cholesterol. It also does not raise LDL cholesterol as much as rosiglitazone does. Since lipid abnormalities are associated with heart disease, it has been proposed that the lipid changes seen with these drugs (especially pioglitazone) might be beneficial. In small research studies these drugs have been shown to prevent the reblockage of coronary arteries after they have been opened with a procedure called coronary angioplasty. These medicines also seem to help fatty liver, an important abnormality found in many people with...

Abnormal Abdominal Murmurs

If a venous hum is present over the xiphoid region or umbilicus and is heard over the chest, suspect hepatic cirrhosis with portal systemic anastomoses (Cruveilhier-Baumgarten syndrome). Systolic accentuation occurs with inspiration or sitting up. Firm pressure at the site of a thrill may cause the murmur to disappear.

Clinical Findings

Classical branching enzyme deficiency most frequently presents during the first few months of life, with hepatosplenomegaly and failure to thrive. Progressive liver cirrhosis, with portal hypertension, ascites, esopha-geal varices, and death, usually occurs before 5 years of age. However, there are patients who have survived without apparent progressive liver disease. The neuromuscular system may also be involved. Severe cardiomyopathy as the predominant symptom has also been reported. 20 The diagnosis of type IV is established by demonstration of abnormal glycogen (an amylopectin-like polysaccharide) and a deficiency of glycogen branching enzyme in liver, muscle, or fibroblasts.

Diffuse Liver Diseases

Diffuse liver diseases such as fatty infiltration, iron deposition and cirrhosis produce changes in mor phology and signal characteristics which can be characterised by MRI. Although these do not represent malignant disease processes cirrhosis in particular is of importance since it is a common association with hepatocellular carcinoma. Cirrhosis does not significantly alter the T1 or T2 relaxation times of liver although it will produce the classic morphological changes of caudate and left hepatic lobe enlargement and distortion and compression of intrinsic hepatic vessels. Extrahepatic findings such as ascites, splenomegaly and enlargement of the hepatic portal vein and its tributaries may indicate portal hypertension and collateral varices are easily detected.

Malignant Liver Tumours 14621

Hepatocellular carcinoma is the commonest primary hepatic malignancy (80 -90 ) representing over 5 of all cancers . There are 500,000 to one million new cases each year worldwide (Bruix et al. 2001). It is commoner in developing countries but its incidence is rising in the West. It is commonly associated with liver cirrhosis particularly secondary to high alcohol consumption. HCC develops from dysplastic nodules and there are three steps in development regenerative nodule dysplastic nodule (low grade high grade with focus of HCC) and small HCC (Wanless 1996). The lesions have been classified as expanding, spreading or multifocal and can be classified from grade I to IV based on histological criteria (Edmondson and Steiner 1954). Normal contrast enhanced MRI shows non-specific variable signal intensity changes although most (80 ) are hyperin-tense on T2 weighted images. Signal intensity on T1 weighted images correlates with histological grade with high signal intensity seen more...

Enterohepatic Bile Acid Transporters In Liver Disease

Chronic cholestatic liver diseases such as primary biliary cirrhosis and primary sclerosing cholangitis are characterized by an impairment of bile formation or of bile flow. Altered expression or function of bile acid transporters can be either a cause or a consequence of cholestasis, thus leading to hepatotoxicity due to accumulation of bile acids and cholephilic toxins in hepatocytes. Among the genes encoding transporters that are involved in bile acid transport or bile formation are several that have been identified or proposed as disease genes in the pathogenesis of cholestasis. No mutations in the SLC10A1 gene encoding NTCP leading to clinically manifest defects in hepatic bile acid uptake have been characterized thus far. However, a recent study identified ethnicity-dependent single-nucleotide polymorphisms in the SLC10A1 gene that were associated with a considerable decrease in transport function in vitro.39 Thus, genetic heterogeneity in the SLC10A1 gene may play a role in the...

For Diuretic Antagonism

Hemodynamic mechanisms potentially important in the attenuation of diuretic response by NSAIDs include reductions in glomerular filtration rate (GFR) and alterations in total renal blood flow or in intrarenal blood flow distribution. The first limits solute delivery to the tubule, while the second alters peritubular physical factors to favor sodium reabsorption. Reductions in GFR and, thus, reductions in filtered sodium load have been inconsistently reported in NSAID treated animals and humans during administration of loop and thiazide diuretics. Because of the magnitude of the daily filtered sodium load (approximately 20,000 mEq day), a reduction in GFR undoubtedly plays a major role in attenuating the natriuretic response to diuretics in circumstances where it occurs. Although decreases in GFR are inconsistently observed in normal individuals during NSAID administration, reductions in GFR following prostaglandin synthesis inhibition are not infrequent in conditions associated with a...

Progress On New Hepatitis C Virus Targets Ns2 And Ns5a

Hepatitis C virus (HCV) is a major global health problem, affecting about 170 million people worldwide. Chronic infection can lead to cirrhosis and liver cancer. The replication machine of HCV is a multi-subunit membrane associated complex, consisting of nonstructural proteins (NS2-5B), which replicate the viral RNA genome. The structures of NS5A and NS2 were recently determined. NS5A is an essential replicase component that also modulates numerous cellular processes ranging from innate immunity to cell growth and survival. The structure reveals a novel protein fold, a new zinc coordination motif, a disulfide bond and a dimer interface. Analysis of molecular surfaces suggests the location of the membrane interaction surface of NS5A, as well as hypothetical protein and RNA binding sites. NS2 is one of two virally encoded proteases that are required for processing the viral polyprotein into the mature nonstructural proteins. NS2 is a dimeric cysteine protease with two...

Effects of Disease

Few studies have assessed the pharmacokinetics and pharmacodynamics of thiazide diuretics in the clinical conditions in which they are used. In general, changes seem to be similar to those discussed with loop diuretics. No studies have assessed pharmacodynamics. Patients with decreased renal function have slowed elimination of tizolemide and trichlormethiazide with an inverse correlation of elimination half-life with creatinine clearance. This effect would presumably result in a diminished peak diuresis and a prolonged response compared to healthy subjects. No studies have assessed this hypothesis, probably because thiazides are relatively ineffective in patients with decreased renal function. One study showed no difference from normal in the time at which the peak concentration of chlorothiazide occurred in patients with cirrhosis.

Other Keratin Disorders

Recent studies have revealed that mutations in keratins expressed in simple epithelia may be involved in the pathogenesis of a number of gastrointestinal diseases. 20 Cryptogenic cirrhosis is a diagnosis of exclusion applicable to an individual with cirrhosis who does not carry a hepatitis B or C virus who does not test positive for serological markers associated with autoimmune hepatitis or primary biliary cirrhosis who has normal iron, ceruloplasmin, and aj-antitrypsin levels and who has no history of alcohol or toxin ingestion. Recurrent mutations in human K8 K18 genes have been shown to predispose individuals to cryptogenic cirrhosis, chronic pancreatitis, and inflammatory bowel disease. 20,34,35 How K8 K18 mutations cause liver disease is still a matter of debate. Animals deficient in K8 K18 are highly susceptible to proapoptotic signals, suggesting that keratins may play a cytoprotective role in the gastrointestinal tract. 20

Hydrocarbons Solvents Pahs And Similar Compounds

Alcohols, including glycols, are much stronger CNS depressants than aliphatics are and slightly more irritating. As carbon chain length increases, irritation decreases but lipophi-licity increases, as does systemic toxicity. Methanol is less inebriating than ethanol but has the unusual property of destroying the optic nerve. Fifteen milliliters can cause blindness. As with ethanol, it is metabolized by a zero-order rate mechanism, but at one-seventh the rate. Ethanol acts as an irritant by dehydrating protoplasm. An initial stimulant effect is caused by depression of control mechanisms in the brain. Pain sensitivity is greatly reduced. Cutaneous (skin) blood vessels become dilated. The resulting increased heat loss can be dangerous in cold weather. It increases gastric secretion, which can aggravate stomach ulcers. It causes fat accumulation and cirrhosis in the liver. The latter can be fatal itself or can cause progression to cancer. Ethanol increases urine flow through a mechanism...

Improvement in Diuretic Delivery

Loop diur tics as well as thiazides are highly bound to albumin in the plasma. This bind .ng confines the drug to the vascular space and facilitates diuretic delivery t the peritubular space surrounding the proximal tubule. From this location t ie diuretics are secreted into the proximal tubule lumen. Albumin also plays a role in regulating the rate of secretion of anionic loop diuretics into the proximal tubule. This effect is independent of its function as a carrier molecule. Thus albumin is essential in determining the concentration of loop diuretic reaching its active site. The importance of these events in determining diuretic response has been shown by Inoue and associates using an analbumi-nemic rat model 7 . Thirty minutes following furosemide administration, these rats had a ninefold greater increase in the volume of furosemide distribution and a urinary furosemide excretion that was 74 less than that found in normal rats. Mixing furosemide with an equimolar concentration in...

Thalassemia Major

The clinical picture of p-thalassemia major is characterized by presentation with pallor and spleen and liver enlargement at 6-24 months of age. Typical skeletal changes resulting from expansion of the bone marrow are evident only in patients in whom transfusions were initiated late or are undertransfused. At the age of 10-11 years, regularly transfused thalassemia major patients are at risk of developing severe complications related to iron overload. These complications include growth retardation, failure of sexual maturation, dilated myocardiopathy, liver fibrosis or cirrhosis, diabetes mellitus, and insufficiency of parathyroid, thyroid, and pituitary glands. Other complications are hypersplenism, B or C virus chronic hepatitis, HIV infection, venous thrombosis, and osteoporosis. Survival of well-transfused patients treated with appropriate chelation extends beyond the third decade. 2,3

Side Effects

Rarely, people taking metformin can develop a serious medical condition called lactic acidosis, which can lead to death and so requires immediate hospitalization. The symptoms of lactic acidosis include nausea, vomiting, abdominal pain, rapid breathing, and feeling very unwell. People with liver failure, kidney failure, or severe heart failure are at a higher risk for lactic acidosis and therefore should not take this medicine.

Nephrotic Syndrome

The most extreme example of the effects of hypoalbuminemia is the an-albuminemic rat. This strain of rat has no albumin whatsoever. If furosemide is administered to this strain of rat, its volume of distribution is 10 times higher than in control animals, because there is no binding to circulating albumin, which in control animals restricts the diuretic to the intravascular space. In turn, less drug is delivered to proximal tubular secretory sites, and thereby less diuretic reaches intratubular sites of action in these rats. Diuretic response is concomitantly decreased. In these animals, administration of furosemide mixed with albumin predictably results in retention of the diuretic in the intravascular space, a return of volume of distribution toward normal, greater delivery of diuretic into the urine, and restoration of diuretic response. These findings, coupled with anecdotal reports, have raised the question as to whether administration of a mixture of loop diuretic and albumin is...


Drugs that act along the collecting duct, such as amiloride and spironolactone, can be added to a regimen of loop diuretic drugs, but their effects are generally less dramatic than those of DCT diuretics, at least acutely. The combination of spironolactone and loop diuretics has not been shown to be synergistic, but these drugs have an important role in preventing hypokalemia while maintaining renal Na excretion. The setting in which collecting duct diuretics are used most commonly is in treating patients with cirrhosis of the liver in whom hypokalemia must be avoided because it can predispose to hepatic encephalopathy. Cortical collecting duct diuretics also reduce magnesium excretion, relative to other diuretics, making hypomagnesemia less likely than when loop diuretics are combined with DCT diuretics. Although the use of angiotensin converting enzyme inhibitors for patients with compromised left ventricular systolic function has improved the prognosis of patients dramatically,...

Liver disorders

Acute fatty liver of pregnancy (AFLP) is a serious but rare liver condition arising in pregnancy which can be very non-specific at time of presentation. It is associated with nausea, vomiting, abdominal pain and jaundice. Diagnosis is normally confirmed by a moderately elevated aspartate amino transferase (AST), and no direct evidence of pre-eclampsia. The diagnosis may be supported by imaging suggestive of fatty change. Manifestations of liver failure include coagulopathy, haemodynamic instability and hypoglycaemia. Hypoglycaemia is a common feature, especially in labour, and may be profound and requires immediate correction. Serial assessment of blood clotting is also important. Delivery must be achieved prior Liver dysfunction in pregnancy can also be caused by incidental viral or autoimmune hepatitis. Where it is unexplained, serology for acute hepatitis must be sent and medical help requested. It is often difficult to determine whether liver dysfunction is due to a pregnancy...


In the uncommon patient who does not respond to the above therapies, there are several additional lines of therapy (i) demeclocycline, which indues a nephrogenic diabetes insipidus 11 (ii) dietary modification to increases the production of urinary solutes (primarily protein, sodium, and potassium), thereby allowing more water to be excreted 15 (iii) urea infusion to increase solute excretion (iv) aquatic agents such as V2 AVP receptor antagonists that produce a selective water diuresis. In the past, lithium has been used to produce a nephrogenic diabetes insipidus. However, demeclocycline is preferred because it is more effective and less toxic than lithium 11 . Dietary modification and urea infusions will work in the patient with relatively fixed ADH levels, and hence fixed urinary osmolality, since the main determinant of urine volume is the rate of solute excretion. For example, a patient producing 1 liter of 600 mOsm urine will be excreting 600 mOsmols day. On a high salt, high...


(Senecio jacobaea) Severely toxic to animals (Forsyth - Ragwort alone probably causes more annual loss to the livestock industry, than all the other poisonous plants put together ). It causes cirrhosis of the liver, from which no recovery is possible. The condition is known in Canada as the Pictou cattle disease, and it is known scientifically as seneciosis. The trouble is that the animals will not normally eat it, so it flowers and seeds undisturbed, and the effect is eventually to produce more ragwort than grass in a pasture (Long).

Use of Diuretics

A number of conditions lead to decreased Na+ delivery to the distal nephron and impaired acidification by limiting the distal absorption of Na+ and the negative lumenal potential. Under conditions such as diarrhea and cirrhosis, where impaired distal acidification has been described, furosemide and etha-crynic acid have been reported to correct the defect 9, 20 by enhancing the delivery of Na+ to the distal nephron. However, furosemide has been shown only in a few patients with distal RTA to lower urine pH 4 .


The development of metabolic acidosis makes acetazolamide particularly useful in the treatment of patients with metabolic alkalosis who require diuretic therapy. In edematous states such as congestive heart failure, cirrhosis, and nephrotic syndrome use of loop diuretics is often complicated by the development of metabolic alkalosis. Normally, the initial approach to correcting alkalosis induced by diuretic therapy is the administration of isotonic saline. In these patient groups, however, saline may be ineffective in correcting the alka-lotic state as a result of an inability to correct the hemodynamic factors maintaining the alkalosis. In addition, further volume expansion will increase the severity of edema and possibly precipitate pulmonary edema in those patients with borderline cardiac function. The diuretic and bicarbonaturic effects of acetazolamide make this diuretic particularly attractive in this setting.


Enhancing bile duct walls that are more than 5 mm in width suggests a diagnosis of CCA, but is not a sensitive indicator of malignancy. Wall thickening and enhancement can be present in various infectious and inflammatory disorders of the biliary tract, including ascending cholangitis and primary sclerosing cholangitis. It is difficult to differentiate benign and malignant disease, but performance of MRCP can be improved by the use of Tl- and T2-weighted and gadolinium-enhanced sequences to detect features such masses, abscesses, or cirrhosis that may help distinguish among the different entities. One should consider performing MRI MRCP in the evaluation of suspected CCA prior to intervention, as inflammation related to stent placement can subsequently result in wall thickening and enhancement and lead to overestimation of the extent of disease. In patients with inconclusive MRCP, ERCP or before bile duct brushing, positron emission tomography (PET) could be considered to potentially...

Adenovirus Incidence

At present there is no specific therapy for adenovirus infection. Treatment consists in aggressive support. There are anecdotal reports of successful management of disseminated adenovirus infection with immunoglobulin, ribavirin, gancyclovir or with adoptive transfer of immune lymphocytes (see EBV disease above). One patient, after undergoing liver transplant, developed adenovirus hepatitis and liver failure and was successfully retransplanted. Undoubt


Likely differences between genotypes in relation to pathogenesis and response to antiviral treatment are beginning to emerge. Genotype C is more frequently associated than B with abnormal liver function tests, lower rates of seroconversion to anti-HBe, higher levels of serum HBV-DNA, cirrhosis, and HCC. Moreover, there is a better sustained response to interferon treatment in patients with genotype B than those with C, and in patients with genotype A than those with D. Genotype A infection appears to be associated with biochemical remission and clearance of HBV-DNA more frequently than genotype D, and has a higher rate ofHBsAg clearance compared with genotype D.

Reduced Excretion

The most common cause of reduced excretion is renal failure, where large amounts of loop diuretics are given to treat volume overload. Similar reductions in excretion are found in patients with cirrhosis. Neonatal kidneys have Reduced renal excretion Renal failure Cirrhosis Neonates Rapid administration

Diet and Bed Rest

Traditionally, the first diuretic used in patients with cirrhosis is the aldosterone antagonist, spironolactone, at an initial dose of 50-100 mg day. This competi tive inhibitor of aldosterone is rapidly metabolized to a number of compounds which undergo slower metabolism and excretion. Several of these spironolactone metabolites also have aldosterone blocking and diuretic activity. In fact, the aldosterone metabolite potassium canreneate is available as a diuretic in Europe. As a result of these metabolites, the biologic diuretic activity of spironolactone is prolonged hepatic dysfunction causes an accumulation of these metabolites and longer periods of activity 28 . Spironolactone and its active metabolites bind to the mineralocorticoid receptors in the cytoplasm of the cortical and medullary collecting tubule cells (and other mineralocorticoid sensitive tissues) and block the mineralocorticoid effects of aldosterone. In general, 7 to 10 days of spironolactone therapy is required to...

Hepatitis Viruses

Hepatitis, or inflammation of the liver, can be caused by many different viruses and chemical substances. Viruses may cause acute infection (hepatitis A virus) or acute infection with the possibility for chronic liver infection leading to cirrhosis and hepatocellular carcinoma. Two major causative agents of acute and chronic disease are hepatitis B (HBV) and hepatitis C (HCV) viruses. The World Health Organization estimates the worldwide population of HBV carriers at about 350 million, with 75 of these living in the Far East. While less than 0.5 of the population of the USA and about 1 of that of Europe may carry HBV, lOand 12 may be carriers in Southeast Asia and Africa, respectively. With the identification of HCV as the cause of most of the non-A, non-B hepatitis, and with the development of immunoassays for detection of antibody to HCV, it has become clear that HCV is a major worldwide problem. The CDC estimate that there are about 150 000 new cases in the USA each year, with 1.5...


The most serious complication of hepatitis is fulminant hepatitis, which occurs in approximately 1 of all patients and leads to liver failure and hepatic encephalopathy and, in some, to death within 2 weeks of onset. Other complications include a syndrome that resembles serum sickness (muscle and joint pain, rash, angioedema), as well as cirrhosis, pancreatitis, myocarditis, aplastic anemia, or peripheral neuropathy.


Diabetes mellitus Chronic alcoholism Malnutrition Obesity Liver cirrhosis Poor personal hygiene Immunosuppression Chronic steroid use Organ transplantation Chemotherapy for malignancy HIV AIDS Tuberculosis Syphilis Chronic alcoholism, malnutrition, liver cirrhosis, poor personal hygiene, and personal neglect are quite common in patients with Fournier's gangrene (Benizri et al. 1996 Hejase et al. 1996 Yeniyol et al. 2004). Other conditions causing depressed immunity that may predispose to the development of Fournier's gangrene include chronic steroid use, organ transplantation, chemotherapy for malignancies such as leukemia, as well as HIV infection (Paty and Smith 1992 Elem and Ranjan 1995 Heyns and Fisher 2005).

Hepatitis D Virus

HDV was first discovered in Italy and is found in the Mediterranean area, reportedly with a declining prevalence, and also in the Far East and South America. The virus may be acquired as a coinfection with HBV or by super-infection of someone already HBsAg-positive. In both cases, disease may be more severe than with HBV alone, and chronic delta hepatitis may progress to cirrhosis more frequently, and more rapidly, than chronic hepatitis B. The hepatitis B vaccine also protects against coinfection but there is no licensed vaccine to protect hepatitis B carriers against HDV infection.

Specific History

A careful medication history is essential, and any medication reported to cause an LP-like eruption should be discontinued. The features of these drug eruptions are sometimes strikingly similar to the idiopathic disease both clinically and microscopically, and offending drugs will be uncovered only by careful history. The list of medications that cause these reactions continues to grow and any agent should be suspect. These drug-induced eruptions are slow to clear and it is not unusual for improvement to take 2 or 3 months. LP has also been associated with an increased incidence of autoimmune diseases (Sjogren's syndrome, sicca syndrome, alopecia areata, vitiligo, ulcerative colitis, myasthenia gravis, and diabetes mellitus), chronic dermatophyte infections, and chronic liver disease (primary biliary cirrhosis, alcoholic cirrhosis, chronic active hepatitis B and C). The presence of a fungal infection is usually significant the authors have seen many cases of LP that clear and...

Respiratory Motion

The main application of dynamic contrast enhanced imaging in the liver has been for the study of liver perfusion in normal and pathological liver tissue. Much of this work has been done by the Brussels group who have a particular interest in liver perfusion changes occurring in cirrhosis. It has been shown previously that changes in hepatic vascular resistance occur as a result of chronic liver diseases and particularly in the cirrhotic liver. This increase in vascular resistance decreases the portal fraction of liver perfusion and changes in hepatic perfusion contribute directly to the deterioration of hepatic function by decreasing blood-hepatocyte exchange. The decrease in portal perfusion is partially compensated by an increase of arterial inflow and morphological changes occur with capillarisation of the sinusoids, deposition of collagen in the extra vascular spaces and the formation of basal lamina. Reliable non-invasive methods for the measurement of hepatic perfusion may...


Bronchial Drug Transporter Localisation

ABCC3 is localized in the basolateral membrane of hepatocytes,47'48 cholangi-ocytes,48 and polarized cells from the gallbladder,192 colon, pancreas, kidney, spleen, and adrenal cortex.200 Hepatic ABCC3 expression is inducible but appears to be constitutive in other organs. This was observed initially in mutant rats with chronic conjugated hyperbilirubinemia,201 which are unable to secrete bilirubin glucuronosides into bile because they lack a functionally active Abcc237'40 (Section 11.7.1). In humans, ABCC3 levels may vary up to 80-fold among individuals,202 and several factors may play a role in hepatic ABCC3 induction. Hereditary and acquired liver disorders, including Dubin-Johnson syndrome,47 progressive familial intrahepatic cholestasis type 3,200 icteric primary biliary cirrhosis,203 and obstructive cholestasis,204 lead to increased ABCC3 protein levels. These liver disorders are associated with elevated serum concentrations of bilirubin glucuronosides, which are normally...


The second issue involved the clinical efficacy of Q D on the outcome of VREF bacteremia in surgical patients with comorbidities of shock, dialysis, mechanical ventilation, liver failure, and immunocompromised state. Mortality was high in both the Q D treated patients and the control group. However, the Q D-treated cohort was less likely to die as a direct consequence of VREF infection, which suggested a beneficial effect of Q D. However, larger clinical trials are needed to determine the true efficacy of Q D treatment. In this context, much discussion centered on the proper identification of VREF bacteremia. Specifically, blood cultures obtained from contaminated intravascular lines and defined as serious VREF bacteremia was considered an inappropriate definition for true VREF bacteremia because it would interfere with proper efficacy studies, not only of Q D treatment but also for any new antimicrobial agent. We all agreed that proper technique was to obtain blood cultures from a...