How To Cure Liver Cirrhosis Naturally

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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The Use of Diuretics in the Treatment of Ascites and Edema in Hepatic Cirrhosis

Salt Poor Albumin For Ascites

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...

Cirrhosis and Complications of End Stage Liver Disease

Emergency Medacine For Liver Disease

Hepatic cirrhosis results from fibrous scarring mixed with hepatocellular regeneration in response to sustained inflammatory, toxic, metabolic, and congestive insults. Over time, the functional anatomy of the liver is replaced by scar tissue isolating nodules formed by foci of regenerating hepatocytes. Normal function of the liver is dependent not only on preservation of hepatocyte number but also on the elaborate microscopic architecture of the functional hepatic units. In addition to progressive loss of synthetic and metabolic function, scarring and degeneration of the liver contribute to increased resistance to blood flow from the splanchnic circulation, contributing to portal-systemic shunting and portal hypertension. Shunting isolates the remaining functional tissue of the liver, further contributing to the metabolic derangements that characterize progressive and end-stage liver disease. Emergent complications of cirrhosis and end-stage liver disease include gastroesophageal...

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

Nutritional Management Acute Liver Failure

The nutritional status of someone with acute liver failure versus chronic liver failure can differ greatly. The primary goal of the nutritional management in acute liver failure is supportive. An increase in nausea, vomiting, and anorexia may be associated with acute liver disease, which may result in decreased oral intake. If normal nutritional status prior to the insult is assumed, the patient will have a much higher nutritional reserve than that of a patient in chronic liver failure. Energy needs can be met by providing the Dietary Reference Intakes for infants and children and approximately 30kcal kg for adults. The provision of adequate protein is crucial in fulminant hepatic failure and encephalopathy. Adequate protein must be provided to minimize catabolism, which may exacerbate any hyperammonemia present. Excessive protein intake should be avoided because it may increase ammonia levels. Protein recommendations for adults and teenagers are 0.5-1.0 g kg day and for infants and...

Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is an enigmatic chronic liver disease characterized by progressive inflammatory obliteration of the intrahepatic bile ducts. Clinical features and laboratory studies of the disease include data suggesting an underlying immunologic basis for pathology. These features There are other theoretical considerations that should be applied to the understanding of the etiology and immunological responses in primary biliary cirrhosis. First, there is scanty data on specific etiology, i.e. environmental insult, toxin or infection. It remains plausible that the mitochondrial autoantigens are cross-reactive with a microbial antigen, but this is yet to be identified with a highly conserved component of an infectious agent. Second, PBC is often viewed as a ductal disease as lesions have been reported in other epithelial glandular tissues, i.e. salivary glands and pancreatic ducts. Third, mitochondrial autoantigens are synthesized in the cytoplasm and then transported...

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).

Acute liver failure

Acute liver failure is the sudden development of liver parenchymal injury resulting in coagulopathy (INR 1.5) in a patient who lacks underlying chronic liver disease. Progression to encephalopathy in such a patient is known as fulminant hepatic failure (FHF). The etiologies of acute liver failure include

Diagnosis And Workup Of Malignant Ascites

Ascites With Pancreatic Cancer

The finding of ascitic fluid in patients with known abdominal malignancy is usually secondary to the tumor itself. Many times, however, patients present with increasing abdominal girth without other sequelae or prior diagnosis of malignancy. Non-neoplastic causes of ascites include congestive heart failure, cirrhosis, renal disease or pancreatic disease, hypoproteinemia, infectious processes such as spontaneous bacterial peritonitis or tuberculosis (Fig. 3.2). In addition, benign gynecologic conditions such as endometriosis may be associated with ascitic collection. A small amount of ascitic fluid noted on imaging studies in the pelvis or lateral gutters of an asymptomatic patient with known intraperitoneal malignancy does not need to be aspirated because in most instances it can be assumed that the fluid collection is secondary to the malignancy itself. Paracentesis is indicated when a definitive diagnosis of malignant ascites is necessary for staging purposes or when planning...

Structure and shape of erythrocytes

Beside these physiologic (reversible) modifications of the red cell shape, some cleavage processes of the membrane or metabolic events may cause a persistent (irreversible) deformation of the cell surface. The variety of the morphologic features of distorted erythrocytes has led to a classification (according to an international Greek nomenclature), which reflects the prominent characteristics of the pathologic cells. The detection of these features offers a key for the interpretation of some underlying disorders in many patients (for example, the presence of acanthocytes in abetalipoproteinemia in liver alcoholic cirrhosis, of codocytes (target cells) in thalassemia, hemoglobinopathies or in hereditary lecithin-cholesterol acyltransferase (LCAT) deficiency, of keratocytes (helmet cells) and schizocytes in microangiopathic hemolytic anemia and disease associated with intravascular deposition of fibrin, of dacryocytes (tear drop cells) in myelofibrosis, of drepanoevtes in sickle cell...

Skin Subdural Hematoma

Putrefactive Bullae Postmortem

In sepsis-related deaths, jaundice of the skin, sclerae, and conjunctivae upon external examination of the body indicate liver failure complicating the septic disease state. The proof of the portal of entry of the pathogenic organism often is difficult to establish because clostridial gas gangrene also may develop in the absence of trauma in individuals with underlying immunocompromise, malignancies, pancreatitis, cholecystitis, liver cirrhosis, diabetes mellitus, radiation colitis, or alcohol abuse.

Coronary Artery Regions

Coronary Arter Bulls Eye

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.)

Causes of Upper Gastrointestinal Bleeding

ESOPHAGEAL AND GASTRIC VARICES Esophageal and gastric varices result from portal hypertension and, in the United States, are most often a result of alcoholic liver disease. Although varices account for only about 6 percent of all cases of upper Gi hemorrhage, they are highly likely to rebleed and carry a high mortality rate. Despite this, many patients with end-stage cirrhosis never develop varices, many patients with documented varices never bleed, and many patients with a documented history of varices presenting with upper GI bleeding will be bleeding from nonvariceal sites.

Pharmacodynamic Mechanisms for Diuretic Antagonism

Pharmacodynamic 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...

[2 Phenotype Changes of Fut8 Knockout Mouse Core Fucosylation Is Crucial for the Function of Growth Factor Receptors

Core Fucosylation

GDP-l-Fuc N-acetyl- -d-glucosaminide a1,6-fucosyltransferase (Fut8, E.C. catalyzes the transfer of a fucose residue from GDP-fucose to position 6 of the innermost GlcNAc residue of hybrid and complex types of N-linked oligosaccharides on glycoproteins to form core fucosylation in mammals, as shown in Fig.1A. Fut8 is the only core FucT in mammals, but there are core a1,3-Fuc residues in plants, insects, and probably other species. The Fut8 gene is expressed in most rat organs with a relatively high level expression in brain and small intestine (Miyoshi et al., 1997). a1,6-Fucosylated glycoproteins are widely distributed in mammalian tissues and are altered under some pathological conditions. For example, the level of core fucosylation is elevated in both liver and serum during the process of hepatocarcinogenesis (Hutchinson et al., 1991). The presence of core fucosylation of a-fetoprotein, a well-known tumor marker for hepatocellular carcinoma (HCC), is known to distinguish...

Clinical Features

Jaundice that develops gradually and is accompanied by weakness, peripheral muscle wasting, ascites, spider angiomata, pruritus, and symptoms of portal hypertension is frequently caused by alcoholic liver disease and cirrhosis. A history of sustained, significant alcohol intake should be elicited from the patient or from family and friends. A history of any previous episodes of jaundice, pancreatitis, or hematemesis should be obtained. Fever, vomiting, and right upper quadrant tenderness accompany episodes of alcoholic hepatitis. The presence of asterixis, fetor hepaticus, or encephalopathy indicates advanced disease.

The Overflow Hypothesis

Cirrhosis Edema

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...

Bioethics Perspective I Health Disparities

According to reports from the Centers for Disease Control (CDC), African Americans have higher death rates than whites due to cancers, diabetes, cirrhosis, homicide, AIDS, and cardiovascular diseases. Maternal death is between three and four times higher for black women than for white women. More white women have breast cancer, but the death rate is higher in black women and is increasing.

Antibiotic Prophylaxis

Although antibiotic prophylaxis is commonly employed for patients with comorbid conditions predisposing to wound infection (diabetes, cirrhosis, advanced age, and immunosuppression), there is little supporting evidence for this practice in all circumstances except for the types of wounds described above.

Clinical and Experimental Data

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.

Laparoscopy For Ascites And Peritoneal Malignancyresults

The benefit of laparoscopic evaluation is highlighted especially in patients with ascitic fluid collections that are found clinically to be unassociated with other signs of malignancy. The majority of these collections are from benign sources. Chuet al16 recently reviewed 129 patients having malignant ascites of unknown origin. Seventy-eight (60.5 ) were found to have visual manifestations of peritoneal car-cinomatosis on laparoscopic evaluation. Peritoneal biopsy revealed malignancy in 67 of 76 cases which were biopsied and showed that a majority of these were adenocarcinoma followed by lymphoma and mesothelioma. In 14 of the lap-aroscopic studies, no definitive diagnosis could be made whereas peritoneal tuberculosis accounted for 20 of the cases and cirrhosis in 5 . Overall, laparos-copy with peritoneal biopsy was able to establish the cause of ascites in 86 of cases. Approximately 75 of women who present with malignant ascites of un

Previous abil surgeryNo midline scars

Mechanism Scar Formation

A systematic, thorough and unhurried visual exploration of the abdominal cavity is essential, and all peritoneal surfaces must be carefully examined to detect possible deposits. The undersurface of the diaphragm, the hepatic round ligament and the omentum require particular interest. Using a palpator and tilting the patient, the entire surface and all edges of both liver lobes must be closely scrutinized for evidence of metastatic disease. Lymph nodes in the hepatoduodenal ligament are examined for visible enlargement. Finally, the quality of the liver parenchyma with regard to the degree of cirrhosis or steatosis can be assessed. flexible tip may be useful, we do not find this to be essential. Curved array transducers provide distorted images of target lesions and are generally have a shorter field of view. The 7.5 MHz transducer provides superb resolution and, in our experience, has sufficient penetration depth of the liver parenchyma to allow complete imaging. In large right lobes,...

Membranoproliferative Glomerulonephritis

Subendothelial Deposits

Vague substructure of deposits, with short, curved, vaguely fibrillar deposits (Fig. 3.6) (suggestive of mixed cryoglobulinemia), or rarely microtubu-lar substructure, strongly PAS-positive cryo- plugs in capillary lumina (Fig. 3.9), vasculitis, predominant IgM deposits, sometimes with clonality (13). Cryoglobulinemia is commonly associated with hepatitis C, an RNA virus (14,15). Approximately 150,000 cases of hepatitis C infection occur per year in the United States. Of these, approximately half have liver disease, with 15,000 developing chronic active hepatitis and or cirrhosis. The prevalence of hepatitis C infection is approximately 0.6 in the United States, reaching up to 6 in Africa. In one large series of hepatitis C-positive cases affecting the kidney, 40 patients with an average age of 46 years were studied. The most common risk factors for infection in this series were intravenous drug abuse, and blood transfusion. The mixed type 2 cryoglobulinemia associated with various...

Atrial Natriuretic Peptide and Related 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...

Aat Deficiency And Disease

Aat Deficiency

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...

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

Brain Leucine Glutamate Flux Astrocyte

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...

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...

Radiological Imaging Modalities

By virtue of its simplicity and availability, transabdominal US still plays a crucial role in detecting and evaluating liver malignancies. Variations in contrast within abnormal liver tissues and between solid or cystic tumors are ideally suited to detection with US. It provides multiplanar imaging with excellent spatial resolution, while hepatic vascular anatomy and patency can be accurately displayed using color Doppler flow techniques.15 US is, however, highly operator dependent and easily restricted by patient habitus or interference by bowel gas and the concealing rib cage. Although sensitivity as high as 94 has been reported for the detection of small hepatomas, results are generally much more variable with sensitivities ranging from 20-76 in the detection of colorectal liver metastases.16,17 Nevertheless, US is suitable for the screening of liver metastases during the follow-up of colorectal cancer, and the development of HCC in patients with known cirrhosis or chronic...

Muscle antigens Smooth muscle

Sera from patients with chronic active hepatitis contain antibodies to smooth muscle antigens that are detectable by IIF and bind smooth muscle of all organs. The major antigen of the smooth muscle is actin. The antibodies belong mainly to the IgG class, but they can also be found in the IgM class. The test is performed on unfixed cryostat sections of rodent stomach as substrate. Smooth muscle antibodies arc found in 40-70 of patients with active chronic hepatitis, with lower titers found in 50 of patients with primary biliary cirrhosis, and 28 of patients with cryptogenic cirrhosis. These antibodies are also found at low titer in patients with acute viral hepatitis, infectious mononucleosis, asthma, yellow fever and malignant tumors (carcinomas of the ovary, malignant melanoma). They have been found in less than 2 of the normal population.

Umbilical Hernia In Adults

Pictures Ascites With Navel Hernia

Umbilical hernias are an important complication of cirrhosis and ascites the ascites should be controlled either medically or with a shunt before hernia repair is undertaken. Umbilical herniation is sometimes a consequence of chronic ambulatory peritoneal dialysis (CAPD). In all patients that are to initiate CAPD, any hernia that is found prior to the insertion of the catheter must be repaired.

Laparoscopic Ultrasonography

Exact size and location, the presence of satellite lesions, extension into surrounding structures (e.g., diaphragm, vena cava, duodenum) or intrahepatic vascular invasion (esp. portal vein) and the state of the hepatic parenchyma (cirrhosis) may all be assessed. Evaluation of candidates for liver transplant is another indication.

Zoonotic Infections And Immunocompromised Patients

Immunocompromised patients deserve special consideration and encompass a very large group patients with congenital immunodeficiencies, diabetes mellitus, chronic renal failure, or liver failure splenectomized patients chronic alcoholics cancer patients and HIV-positive patients. Of all of these patients, those undergoing chemotherapy and those with AIDS have the greatest risk of acquiring a zoonotic infection. 7 It is estimated that 30 to 40 percent of immunocompromised patients may own pets.57 Salmonella and Campylobacter are the two most common infections acquired by immunocompromised patients from their pets,7 but the overall risk of transmission of Salmonella and Campylobacter from contact with pets is low. Additionally, Mycobacterium marinum, from aquatic pets, and Bartonella, from cats, are also commonly acquired by immunocompromised patients. Other acquired zoonotic infections that immunocompromised patients are susceptible to include

Laparoscopic Diagnosis and Treatment of Ascites and Peritoneal Malignancies

From its inception, the laparoscope has been an important tool in the assessment of causes of fluid collection in the abdomen as well as in the diagnosis and subsequent management of peritoneal malignancies.1 Although most cases of as-cites result from benign conditions worldwide, it is important to understand that benign and malignant conditions may occur concurrently and that a focused approach to the etiology of ascitic collection is mandatory for appropriate treatment strategies. Among the non-malignant causes of ascites in cancer patients are cirrhosis, nephrosis, congestive heart failure and peritonitis secondary to pyogenic organisms and tuberculosis (Table 3.1). History, physical examination, and diagnostic paracentesis with cell counts, cytology, protein, lactate dehydrogenase determinations, and culture will usually provide the diagnosis. Malignant ascites is seen most commonly in patients with ovarian, endometrial, breast, colon, gastric and pancreatic cancer (Fig. 3.1)....

Laboratory Evaluation

A direct-reacting fraction of at least 30 percent (and usually much higher) is present with conjugated hyperbilirubinemia. Conjugated bilirubin is water soluble and appears in the urine at very low serum concentrations. Urobilinogen will be absent from the urine if significant cholestasis is present. If liver enzyme levels are normal, the jaundice is caused by sepsis or recent systemic infection, in-born errors of bilirubin metabolism (such as Rotor syndrome or Dubin-Johnson syndrome), or pregnancy rather than by primary hepatic disease. If liver enzyme levels are abnormal, which is much more common, the pattern of abnormality suggests the cause. Predominance of aminotransferase elevation is more suggestive of hepatocellular disease, such as viral or toxic hepatitis or cirrhosis, while marked elevations of alkaline phosphatase (two to three times normal) and g-glutamyl transpeptidase suggest intra- or extrahepatic obstruction, such as malignancy or gallstones.

Surgery Of Hepatobiliary Malignancies

Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy, although it is relatively uncommon in Northern Europe. As elsewhere, it is typically recognized at an advanced stage and is generally associated with chronic liver disease. Extensive aggressive surgery is justified as it remains the treatment of choice. Associated cirrhosis (present in over 80 of cases) and chronic hepatitis constitute a significant obstacle to performing major hepatectomy, and only about 20 of all patients with HCC are considered resectable at initial presentation. Although recurrence will develop in approximately 70 of patients after curative resection, a 5-year survival rate of 35 can be achieved.8,9 Early detection by screening high-risk groups and the use of parenchyma-preserving segmental resections are the main reasons for an increase in the number of patients undergoing curative surgery. Specific problems relate to the initial recognition and diagnosis of tumor within cirrhotic liver...

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.

Hazards of Alcohol

In addition to the problems directly related to episodes of acute alcohol intoxication, there is widespread recognition of the harm caused by chronic excessive drinking, commonly referred to as alcoholism. At sufficient doses, the daily or frequent drinker may experience increased tolerance and, eventually, physiological dependence and withdrawal symptoms. Prolonged heavy drinking is implicated in a number of serious and potentially fatal health problems, including cirrhosis, pancreatitis, peptic ulcer, hypertension

Hyponatremia With Increased Total Body Water

Causes of hyponatremia associated with increased total body water are acute water intoxication, the syndrome of inappropriate antidiuretic hormone (SIADH), edema-forming states including nephrotic syndrome, and cirrhosis. In nephrosis and cirrhosis, hyponatremia is usually mild and chronic. Even though whole body water is increased, intravascular volume may be low due to third spacing. Treatment usually consists of diuresis, with a combination of albumin followed by a diuretic. These patients are best managed in consultation with a pediatric nephrologist.

Alcohol and Facial Flushing

This is similar to the disulfiram reaction due to the rise of acetaldehyde after inhibition of ALDH. Disulfiram is used therapeutically to encourage abstinence in alcohol rehabilitation programs. The aversive effects of acetaldehyde may reduce the development of alcoholism and the incidence of cirrhosis in 'flushers.' However, some alcoholics with ALDH2 deficiency and, presumably, higher hepatic acetaldehyde levels develop alcoholic liver disease at a lower intake of ethanol than controls.

Lasix Induced Bicarbonate Alterations

Loop Diuretics Metabolism The Liver

Metabolic alkalosis is not a typical baseline feature of the clinical conditions in which loop diuretics are most commonly used. Nevertheless, these conditions are commonly associated with the development of metabolic alkalosis once diuretic therapy is initiated. In addition, the alkalosis tends to develop rapidly and can be large in magnitude. For example, cirrhosis, congestive heart failure, and nephrotic syndrome are all characterized by a contracted effective arterial blood volume. In the basal state, circulating aldosterone levels are already increased but distal sodium delivery is low. Initiation of diuretic therapy allows for the increased circulating levels of aldosterone to be coupled to increased distal sodium delivery, resulting in stimulated distal acidification. Newly generated bicarbonate is readily reclaimed in the proximal nephron as these patients already have a contracted effective arterial blood volume.

Liver in Specific Hepatobiliary Disorders Hepatocellular Diseases

Alcoholic liver disease The term 'alcoholic liver disease' refers to a spectrum of types of hepatic injury associated with continuous alcohol ingestion, ranging from alcoholic fatty liver to alcoholic stea-tohepatitis, fibrosis, and cirrhosis. Nutritional disturbances in alcoholics are an important cause of morbidity and mortality all classes of nutrients are affected. Anorexia leads to decreased food intake and subsequent protein-calorie malnutrition. Maldigestion and malabsorption can occur secondary to chronic alcohol injury to small intestinal mucosa. Alcohol consumption is often associated with chronic pancreatic insufficiency, which results in steatorrhea and decreased absorption of dietary protein, fat, and fat-soluble vitamins. Chronic alcohol ingestion also results in impaired hepatic amino acid uptake and protein synthesis. Many studies have examined the effect of oral or enteral nutritional supplementation in patients with alcoholic cirrhosis. Results are summarized in...

Physiology and function

Portal hypertension can be divided into three main causes presinusoidal, intrasinusoidal, or postsinusoidal. The most common causes of each respectively are portal vein thrombosis, cirrhosis, and hepatic vein occlusion (Budd-Chiari syndrome). Complications of portal hypertension the include esophageal and gastric varices, encephalopathy, and ascites. Ascites (or accumulation of intraabdominal fluid) is thought to be secondary to the effects of portal hypertension on increasing splanchnic blood volume as well as the increased secretion of aldosterone.6

Pathophysiology of Stone Formation

There are three kinds of gall stone cholesterol, black pigment, or brown pigment stones. Cholesterol stones constitute 75-90 of all gall stones. They are composed purely of cholesterol or have cholesterol as the major chemical constituent. Most cholesterol gall stones are of mixed composition. Pigmented stones get their color and their name from precipitated bilirubin. Increased production of unconjugated bilirubin causes black pigmentation. Formation of black pigment stones is typically associated with chronic hemolysis, cirrhosis, and pancreatitis. Brown pigment stones are usually associated with infection. Cytoskeletons of bacteria can be seen microscopically in brown pigment stones, Rapid weight loss Total parenteral nutrition Diabetes Other conditions Immobility Cirrhosis Spinal cord injury Other conditions predisposing to gall bladder disease Insulin-resistant diabetes predisposes to cholelithiasis. A Swedish study showed that the prevalence of gall stones in Crohn's disease was...

Pathology and dysfunction

The previous paragraphs stressed the normal anatomy and function, and touched on the problems one might encounter with hepatobiliary disease. The systematic review of all liver diseases is beyond the scope of this chapter however, our focus will be on surgical pathologic states and the most commonly encountered problems on clinical rotations. What soon will be apparent is that many diseases converge in common pathways. Infectious diseases such as hepatitis B and C lead to hepatocytes damage and subsequent destruction of the liver architecture. Cholestasis as a result of obstructing stone disease, but also secondary to tumors, autoimmune disease or cystic disease leads to destruction of hepatocytes and liver architecture as well. With the loss of normal hepatic architecture and function, characteristic signs of liver failure surface can easily be understood based on the anatomy and function as discussed previously. For the sake of this chapter, we will divide liver disease in four...

TABLE 234 Etiology of Syndrome of Inappropriate Antidiuretic Hormone SIADH

Hypervolemic hyponatremia is described as TBW in great excess. These patients present with manifestations of volume overload, such as peripheral and or pulmonary edema. They usually have impaired ability to excrete a water load. This allows for water retention in excess of Na + retention. These patients can be further categorized into two groups (Iabje,,2 3. .3) The first of these is generalized edematous states without advanced renal insufficiency. These patients have urinary Na + of less than 20 meq L. They include patients with cirrhosis and or ascites, congestive heart failure, and nephrotic syndrome. The second category is advanced acute or chronic renal insufficiency. These patients have urinary Na + in excess of 20 meq L.

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...

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...

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...

Assessment of Manganese Status

Slightly higher than normal in individuals consuming manganese supplements. Lymphocyte MnSOD activity and blood arginase activity are increased in individuals who consume manganese supplements however, their value as biomarkers for manganese status may be complicated due to the number of cytokines and disease states that may also increase their expression. Urinary manganese excretion has not been found to be sensitive to dietary manganese intake. With respect to the diagnosis of manganese toxicosis, the use of MRI appears to be promising because the images associated with manganese tox-icity are relatively specific. Whole blood manganese concentrations can be correlated with MRI intensity and Ti values in the globus pallidus even in the absence of symptoms of neurological damage. Thus, although it is relatively expensive, MRI may be particularly useful as a means of identifying susceptible individuals in, or around, manganese-emitting factories. In addition, the method may be useful...

Injury Pattern Patterned Injury

Tatuajes Mar

Chronic alcoholics, when intoxicated, fall repeatedly. They are predisposed to bleeding because of abnormal coagulation caused by cirrhosis (Fig. 7). Multiple blunt trauma injuries (e.g., contusions) on the extremities, torso, and face suggest assault (Fig. 14 ref. 30). There may be associated internal injuries that heighten concern. The finding of external and internal trauma of different ages, supported by toxicological analysis and investigation of the circumstances of the death, provides reassurance.

Alcoholic Liver Disease

Alcoholic liver disease is among the top ten causes of mortality in the US with somewhat higher mortality rates in western European countries where wine is considered a dietary staple, and is a leading cause of death in Russia. Among the three stages of alcoholic liver disease, fatty liver is related to the acute effects of alcohol on hepatic lipid metabolism and is completely reversible. By contrast, alcoholic hepatitis usually occurs after a decade or more of chronic drinking, is associated with inflammation of the liver and necrosis of liver cells, and carries about a 40 mortality risk for each hospitalization. Alcoholic cirrhosis represents irreversible scarring of the liver with loss of liver cells, and may be associated with alcoholic hepatitis. The scarring process greatly alters the circulation of blood through the liver and is associated with increased blood pressure in the portal (visceral) circulation and shunting of blood flow away from the liver and through other organs...

Chapter References

Avgerinos A, Armonis A, Manokakopoulos S, et al Endoscopic sclerotherapy versus variceal ligation in the long-term management of patients with cirrhosis after variceal bleeding A prospective randomized study. J Hepatol 26 1034, 1997. 21. Avgerinos A, Rekoumis G, Klonis C, et al Propranolol in the prevention of recurrent upper gastrointestinal bleeding in patients with cirrhosis undergoing endoscopic sclerotherapy A randomized controlled trial. J Hepatol 19 301, 1993.

Therapeutic Misadventure

Forty-four cases classified as therapeutic misadventure, comprising 0.46 of 9497 deaths reported to the Office of the Coroner in Dayton, OH, had the following breakdown surgery, 36 (most common intraoperative vascular or visceral trauma with fatal hemorrhage other causes cardiorespiratory arrest, complications of tra-cheostomy, air embolism, poor surgical risk owing to severe natural disease, coagu-lopathy with exsanguination, aspiration of blood) anesthetic complications, 30 (most common acute reaction with cardiorespiratory arrest during induction other causes aspiration during induction, respiratory arrest during a procedure or in the postoperative period, delayed liver failure, overdose) therapeutic procedures, 18 (most common viscus perforation, cardiac arrest following electroconvulsive therapy other causes improper dialysis solution, therapeutic vascular overload, aspiration of blood, vascular laceration) diagnostic procedures, 14 (most common vascular or cardiac lacerations...

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

Hepatitis B Virus Infection And Immunity

Damaged Hgv Tyre Pictures

Hepatitis B virus (HBV) infection is a major public health problem, infecting approximately 300 million people worldwide, and is a major cause of chronic liver disease and hepatocellular carcinoma (HCC). The majority of adults infected have a transient hepatitis from which they completely recover and clear the virus. Rarely the disease becomes fulminant and the patient may die. Between 5 and 10 of adults become persistently infected and develop chronic liver disease. In the majority of cases of vertical transmission the virus is not eliminated and the child becomes chronically infected, greatly increasing its risk of developing cirrhosis and HCC.

Mitochondrial antigens

Autoantibodies to mitochondrial antigens, detectable by IIF on rat kidney sections, are primarily associated with patients with primary biliary cirrhosis. The major antigen is reported to be a component of the pyruvate dehydrogenase enzyme complex. The antibodies belong to the IgG, IgA and IgM classes. The mitochondrial antibodies stain the cytoplasm of cells from different organs, such as thyroid or kidney, that varies with the mitochondrial content of the cells. Distal tubules of kidney and gastric parietal cells show a bright, uniform, cytoplasmic fluorescence, whereas renal proximal tubules show a characteristic coarse, granular, duller staining. Mitochondrial antibodies are detected in 87-98 of patients with primary biliary cirrhosis. They are also observed in 25-28 of patients with active chronic hepatitis and in 25-30 of patients with cryptogenic cirrhosis. They are only seldom observed in patients with extrahepatic biliary tract obstruction and occur very rarely in normal...

General features of CAH

Chlamydia Trachomatis

Chronic hepatitis ranges from an asymptomatic disease recognized only by biochemical abnormalities to one that is severe and progressively cirrhotogenic. Some cases of autoimmune hepatitis can have a long asymptomatic preclinical course, as pertains for other autoimmune disorders. Likewise, an insidious onset and clinical latency is usual for CAH associated with infection with HCV and, in many instances, with HBV. Cases of chronic active hepatitis will have some common general features related to liver dysfunction or cirrhosis, whatever the cause, and other features related to the individual etiological agent or process. The general features include symptoms of hepatitis, including nausea, anorexia, jaundice, hepato-splenomegaly, and biochemical evidence of liver parenchymal damage, in particular high levels of transminase enzymes in serum. The biopsy of the liver may show either of two histological lesions, named as chronic persistent hepatitis which is indolent and nondestructive,...

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.

Metabolic Complications Liver Disease

Although PN may be life sustaining, long-term use may be detrimental to the liver. The severity of injury ranges from reversible transaminase elevations to severe cholestasis and cirrhosis, especially in infants with short bowel syndrome. It is not clear whether this is due mainly to a nutrient deficiency, toxicity, or some physiological process missing because of the lack of enteral feeding. Prevention and treatment strategies continue to include minimizing or preventing episodes of sepsis, providing enteral feedings, moderating energy intake to provide for adequate growth but not to overfeed, cycling parenteral nutrition infusion, reduction of copper and manganese, use of an amino acid solution developed for infants, treatment prophylaxis for bacterial overgrowth, and the use of ursodeoxy-cholic acid. Another drug that has been studied but is not available for clinical use is cholecystokinin, which promotes gallbladder contraction. A recent and controversial recommendation is the...

Diseasespecific diets

Specifically formulated disease-specific diets have been developed for patients with disorders such as encephalop-athy associated with chronic liver disease, and respiratory failure. Malnourished patients with cirrhosis who present with encephalopathy, or who have a previous history of episodes of encephalopathy, present a difficult problem of nutritional management. Branched-chain amino acid-enriched diets have been advocated to normalize plasma amino acid profiles with the aim of improving nutritional state and preventing worsening of encephalopathy. Patients with respiratory failure on ventilators are adversely affected by diets with high carbohydrate loads which increase CO2 production. Diets with a higher fat energy component allow earlier weaning from artificial ventilator support as a result of decreased CO2 production and reduced respiratory quotient.

TABLE 827 Diagnosis and Treatment of Spontaneous Bacterial Peritonitis

Hepatorenal Syndrome Hepatorenal syndrome is characterized by acute renal failure in the cirrhotic patient in the presence of histologically normal kidneys. The exact pathophysiology is elusive but is tied in with the metabolic derangments of end-stage liver failure, decreased effective circulating blood volume, and elevated aldosterone and antidiuretic hormone secretion. GFR drops, as does urine sodium secretion, and azotemia worsens with blood urea nitrogen-creatinine ratios usually greater than 20. This characteristic and refractory form of renal failure complicates cirrhosis with ascites and can be precipitated by any acute illness resulting in dehydration and or sepsis or as a complication of overzealous diuresis or high-volume paracentesis. The ill cirrhotic patient with evidence of acute or worsening renal insufficiency should be hospitalized for appropriate consultation and carefully monitored intravenous fluid administration and diuretic therapy adjustment. 29 Hepatic...

Degree and Direction of Force and Cause of Death

Exsanguination Traumatic Bleed

Contusions can be extensive yet arise from minimal trauma. If an individual is taking medications (e.g., aspirin, anticoagulants) or has a bleeding diathesis (e.g., cirrhosis, hemophilia), then there is a predisposition to hemorrhage (see Subheading Fig. 7 and refs. 8 and 13). Children bruise more easily because of their loose, delicate skin (8,13). Elderly individuals, because of dermal atrophy and decreased capillary support, Fig. 7. Alcoholic found dead in home. Acute ethanol intoxication (240 mg dL). Cirrhosis seen at autopsy. (A) Evidence of considerable bleeding at scene. (B) Exsanguination from laceration on left eyebrow. Hematoma, upper eyelid. Fig. 7. Alcoholic found dead in home. Acute ethanol intoxication (240 mg dL). Cirrhosis seen at autopsy. (A) Evidence of considerable bleeding at scene. (B) Exsanguination from laceration on left eyebrow. Hematoma, upper eyelid.

Branched Chain Amino Acids Isoleucine Leucine Valine

In liver failure the plasma concentrations of the aromatic amino acids (AAAs) tyrosine, phenylala-nine, and tryptophan increase, probably because they are predominantly broken down in the liver, whereas the plasma levels of BCAAs decrease while they are degraded in excess in muscle as a consequence of hepatic failure-induced catabolism. As AAAs and BCAAs are all neutral amino acids and share a common transporter across the blood-brain barrier (system L carrier), changes in their plasma ratio are reflected in the brain, subsequently disrupting the neurotransmitter profile of

Hepatic Disorders And Hepatic Failure

Cirrhosis, and .Complications of., End-Stage.Liver Disease This chapter will briefly highlight important issues regarding the epidemiology, pathophysiology, and clinical features of acute and chronic liver disease. A rational approach to the interpretation of liver function serologies will be outlined. Specific presentations of hepatobiliary disease will be reviewed, including jaundice, cirrhosis, and complications of end-stage liver disease (ESLD), gallbladder and biliary tract disease, and vascular liver disease. Content will be limited primarily to immediate diagnostic and therapeutic concerns, avoiding discussion of the science of hepatopathology so as to focus on issues most pertinent to the practice of emergency medicine.

Patient Selection And Technique

On the information to be gained from the study. In patients with significant cardiac and respiratory disease who would not be candidates for open abdominal procedures because of the requirements for general anesthesia, laparoscopy may in fact prove hazardous because of the need for both general anesthesia and a significant pneumoperitoneum. Distention of the abdomen may in fact reduce cardiac output and enhance arrhythmias and may be considered a contraindication in those with severe coronary artery disease.10 Similarly, profound problems in coagulation should encourage either correction of clotting problems preopera-tively or abandonment of techniques that would increase bleeding. In patients with ascitic collection from both cirrhosis and hepatoma for instance, (Fig. 3.4) these coagulation problems must be corrected with fresh frozen plasma or vitamin K prior to any diagnostic procedure. In any patient with ascitic collections, a thorough history and physical examination are...

Estimating renal function

Kidney Nephron Structure Diagram Simple

Figure 8.2 The nephron (the functional unit of the kidney). A, afferent arteriole where ACE inhibitors act (angiotensin ll plays a role in autoregulation of renal blood flow by constricting the afferent blood vessels when there are low pressures) CD, collecting duct DCT, distal convoluted tubule E, efferent arteriole where NSAIDs act (prostaglandins play a role in regulation of renal blood flow and increase cortical flow in a person on ACE inhibitors and NSAIDs who is admitted with vomiting and diarrhoea - or hypovolaemia of any cause - both these drugs should be temporarily stopped the combination of hypovolaemia, lack of constriction in the afferent vessels, and lack of vasodilatation in the efferent vessels reduces GFR in cirrhosis and congestive cardiac failure where prostaglandins are recruited to increase renal blood flow, NSAIDs are more potent) F, thick ascending limb of the loop of Henle where frusemide blocks active sodium-potassium-chloride cotransport (despite documented...

Principles of Treatment of Protein Deficiency

However, in states of metabolic adaptation, care should be used in increasing protein intakes. For example, in cases of cirrhosis, the protein intake should be restricted to 20 g day-1 to reduce the risk of precipitating hepatic encephalopathy.

Relative Pyrogenicity

In the early use of the pyrogen assay, no attempt was made to quantitate the amount of endotoxin needed to produce a pyrogenic response in rabbits. Because they are part of one of the most endotoxic families (Enterobacteriaceae) of bacteria, Escherichia coli and Salmonella were later chosen to determine and quantify the amount of endotoxin by weight considered to be pyrogenic. In 1969, Greisman and Hornick (17) performed a study using healthy male inmates (volunteers) and found the threshold pyrogenic response (TPR) level to be about 1 ng kgb for E. coli and Salmonella typhosa (approximately 0.1-1.0) and 50 to 70 ng kg for Pseudomonas. The same study revealed that the rabbit and human TPRs are approximately the same. Therefore, the amount of purified E. coli needed to initiate pyrogenicity in both man and rabbits is approximately 1 ng kg, which represents about 25,000 E. coli bacterial cells (18). In terms of whole cells, the injection of an estimated 1000 organisms per milliliter...

Fulminant Hepatic Failure

NAC also appears to be beneficial in the treatment of acetaminophen-induced fulminant hepatic failure. When compared with controls, NAC therapy was associated with increased survival (48 vs 20 percent), decreased cerebral edema (40 vs 68 percent), and decreased vasopressor requirements (40 vs 80 percent). 12 NAC appears to be beneficial in the treatment of other forms of hepatic failure, too, including viral hepatitis and alcoholic cirrhosis. 16

Tissue Contents and Kinetics of Lycopene Turnover

Patients with alcoholic cirrhosis of the liver have greatly reduced hepatic lycopene concentrations indeed, hepatic lycopene seems to offer a sensitive index of hepatic health. Studies of organ concentrations (Table 3), suggest a gradient from circulating levels in plasma to different ones in specific tissues. The different carotenoid ratios between organs (not shown) also indicate selective transport and accumulation. However, the mechanisms involved are poorly understood. No lycopene is detectable in the retina or lens of the eye, where lutein and zeax-anthin are found however, lycopene is present in the ciliary body.

Effects of Alcohol on Liver Function

Continued alcohol consumption may lead to cirrhosis. However, not all alcoholics progress to cirrhosis. The reason for this is unclear. It has been suggested that genetic factors and differences in immune response may play a role. In alcoholic cirrhosis there is fibrocollagenous deposition, with scarring and disruption of surrounding hepatic architecture. There is ongoing necrosis with concurrent regeneration. Alcoholic cirrhosis is classically said to be micronodular, but often a mixed pattern is present. The underlying pathological mechanisms are complex and are the subject of debate. Induction of the MEOS and oxidation of ethanol by catalase result in free radical production. Glutathione (a free radical scavenger) is reduced in alcoholics, impairing the ability to dispose of free radicals. Mitochondrial damage occurs, limiting their capacity to oxidize fatty acids. Peroxisomal oxidation of fatty acids further increases free radical production. These changes eventually result in...

Interventions and operations

For uncomplicated gallstone disease, the laparoscopic approach for removal has become standard in most patient populations. While previous surgery is not always a contraindication for laparoscopy, inability to adequately visualize the arterial and biliary anatomy during the procedure is an absolute indication to convert to an open procedure. Cirrhosis, ascites, chronic obstructive pulmonary disease (COPD), previous biliary surgery, and portal hypertension are a few absolute contraindications for laparo-scopic cholecystectomy. If a bile duct injury occurs during a cholecystectomy, and is recognized at the time of the procedure, repair by a trained colleague familiar with techniques of biliary reconstruction is recommended. Frequently, the biliary injury occurs as a result of thermal conduction from the electrocautery. Biliary reconstruction via a Roux-en-Y hepaticojejunostomy is usually indicated and preferred. A hepaticojejunostomy is an anastomosis between the side of bowel (usually...

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.

Liver Disease Applied Physiology

Different conditions cause differing patterns of dysfunction. Excessive red cell turnover causes jaundice by overloading the pathways of haem breakdown even though other liver functions may remain relatively normal. Obstructive and cholestatic jaundice causes major disruption to metabolic pathways and to the absorption of fats and fat soluble vitamins, causing further problems. Hepatocellular dysfunction may be toxic or infective in origin but will result in the same picture of unconjugated bilirubinaemia, fat malabsorption and metabolic disturbance. In the end stage of hepatic failure, virtually all the body's metabolic processes are disturbed. Clinical features include clotting failure, coma from ammonia toxicity because of disturbed protein metabolism, hypoglycaemia because of poor glycogen metabolism, water overload and major electrolyte imbalance. There is usually portal hypertension that causes the formation of collateral circulation including oesophageal varices. If these bleed...

Improvement in Solute Delivery

Klappenst Tze Messing

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...

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...

Alcohol and Nutrition

The nutritional status of alcoholics is often impaired. Some of the pathophysiological changes seen in alcoholics are direct consequences of malnutrition. However, in the 1960s, Charles Lieber demonstrated that many alcohol-induced pathologies, including alcoholic hepatitis, cirrhosis, and myopathy, are reproducible in animals fed a nutritionally adequate diet. Consequently, the concept that all alcohol-induced pathologies are due to nutritional deficiencies is outdated and incorrect.

Chronic liver disease

Superimposed acute hepatic failure also occurs in patients with chronic liver disease. Often times an event such as a new infection (spontaneous bacterial peritonitis) or GI bleed will tip a previously stable cirrhotic into fulminant liver failure. Treatment is supportive as described above. Generally such

Clinical Assessment Of Volume Status

Volume overload is most often encountered in disease states where excretion of free water is impaired. Most of these conditions are related to renal disease, diseases that impair blood flow to the kidneys (resulting in Na + retention), diseases that diminish intravascular osmolality (liver failure and low-protein states), or diseases that cause undesirable Na+ retention by various mechanisms. Decreased intravascular osmolality results in a functional intravascular contraction, with expanded interstitial and cellular volume. These are discussed elsewhere in this chapter.

Neuroendocrine Effects of Alcohol

The development of female secondary sexual characteristics in men (e.g., gynaecomastia and tes-ticular atrophy) generally only occurs after the development of cirrhosis. In women, the hormonal changes may reduce libido, disrupt menstruation, or even induce premature menopause. Sexual dysfunction is also common in men with reduced libido and impotence. Fertility may also be reduced, with decreased sperm counts and motility.

Protein Binding And Free Phenytoin Fractions

Phenytoin is extensively (90 percent) bound to plasma proteins, especially albumin. The free, unbound, form is the biologically active moiety responsible for the drug's clinical effect and toxicity. The free phenytoin fraction normally constitutes 10 percent of the plasma level. The unbound fraction of the drug is greater in the following groups of patients neonates the elderly pregnant women individuals with uremia, hypoalbuminemia (cirrhosis, nephrosis, malnutrition, burns, trauma, or cystic fibrosis), and hyperbilirubinemia and individuals taking drugs that displace phenytoin from binding sites (salicylate, valproate, phenylbutazone, tolbutamide, and sulfisoxazole).

Introduction Toxicogenomics

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...

TABLE 824 Differential Diagnosis of Hyperbilirubinemias

Emergency Medicine Differentials

A patient with fulminant liver failure (acute hepatic necrosis) presents as acutely ill with jaundice and often complications related to impaired hepatic function, including encephalopathy, coagulopathy, and water, electrolyte, and acid-base metabolic disorders ( TabJ.e,.8.2. .5). Progression of disease to complete liver failure often occurs in 8 weeks or less. The appropriate emergency response to such patients involves recognizing the severity of the illness, instituting appropriate resuscitation, assembling an appropriate database including liver serologies and toxicology screens, and arranging for appropriate inpatient care as indicated by the acuity of the presentation. Appropriate guidelines for inpatient management should be based on age, underlying medical conditions, hemodynamic stability on presentation, and response to initial resuscitation measures. General hospital admission is indicated for management of refractory nausea, vomiting, and dehydration intensive care unit...

Effects of Acetaldehyde

Acknowledgement Network Packet

Adduct formation leads to retention of protein within hepatocytes, contributing to the hepatomegaly, and several toxic manifestations, including impairment of antioxidant mechanisms (e.g., decreased glutathione (GSH)). Acetaldehyde thereby promotes free radical-mediated toxicity and lipid peroxidation. Binding of acetaldehyde with cysteine (one of the three amino acids that comprise GSH) and or GSH also reduces liver GSH content. Chronic ethanol administration significantly increases rates of GSH turnover in rats. Acute ethanol administration inhibits GSH synthesis and increases losses from the liver. Furthermore, mitochondrial GSH is selectively depleted and this may contribute to the marked disruption of mitochondria in alcoholic cirrhosis.

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.

Occurrence and Toxicology

Fumonisins have been shown to have diverse biological and toxicological effects. The mechanism of fumonisin toxicity is not well understood. Studies have shown that fumonisins inhibit ceramide synthase. Fumonisins have been shown to be hepatotoxic and carcinogenic in rats resulting in liver cirrhosis and hepatic nodules, adenofibrosis, hepato-cellular carcinoma, ductular carcinoma, and cholangio-carcinoma (Gelderblom et al. 1988 1991 1992b 1993 1994 Marasas 1996). Studies on rats by Riley et al. (1996) suggested that fumonisin B1 (FB1) might act primarily as a tumor promoter. The tumor promoting activity of fumonisins has also been proposed by Huang et al. (1995), Wattenberg et al. (1996) to have been resulted from the stimulation or

Primary Aldosteronism

Primary aldosteronism (Conn syndrome) is a syndrome of HTN and hypo-kalemia caused by hypersecretion of the mineralocorticoid aldosterone. This uncommon syndrome previously accounted for less than 1 percent of unse-lected patients with HTN. However, recent data examining routine screening suggest that aldosteronism may be the cause of up to 15 percent of cases of HTN. An aldosterone-producing adrenal adenoma (APA) is the cause of primary aldosteronism in two-thirds of cases and is one of the few surgically correctable causes of HTN. Idiopathic bilateral adrenal hyperplasia (IHA) causes 30-40 percent of cases of primary aldosteronism. Adrenocortical carcinoma and autosomal dominant glucocorticoid-suppressible aldosteronism are rare causes of primary aldosteronism. Secondary aldosteronism is a physiologic response of the renin-angiotensin system to renal artery stenosis, cirrhosis, congestive heart failure, and normal pregnancy. In these conditions, the adrenal gland functions normally.

Bone Marrow To Other Cell Types

The ability to change a cell's phenotype will greatly facilitate the design of therapies for diseases such as diabetes, liver failure, and neurodegenerative disorders (e.g., Parkinson's disease). We suggest six steps to follow to try and change a cell's phenotype experimentally.

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.

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

Improvement in Diuretic Delivery

Loop diui 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 re 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...

Dietary and Nutritional Management of Secondary Undernutrition

Acids or keto-analog amino acids has been devised to compensate for the metabolic defects of nitrogen handling in hepatic or renal failure states. The objective of nutritional support in patients with liver failure is to provide adequate macronutrients to ensure the specific substrates for energy and protein synthesis and integrity of normal hepatic tissue function, without inducing or accentuating encephalopathy or otherwise aggravating hepatic insufficiency.

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.

Alcohol and Mortality Amount of Alcohol

Some have explained the J shape as an artefact due to misclassification or confounding. Prevailing beliefs among these researchers is that abstainers comprise a mix of former heavy drinkers, underreporting drinkers, ill people who have stopped drinking, and people with an especially unhealthy lifestyle apart from abstaining. However, most researchers attribute the 'J' to a combination of beneficial and harmful effects of ethanol. This is based on findings from population studies of alcohol-related morbidity and cause-specific mortality that show a decreased relative risk of coronary heart disease, and an increased risk of certain cancers and cirrhosis, with increased alcohol intake. Further evidence derives from studies in which people who were ill at baseline were excluded, and these confirmed the previously mentioned findings.

Other polyendocrine autoimmunity syndromes

Rarely, diabetes mellitus results from a decreased biological response to a normal amount of insulin. In type A insulin resistance, the problem lies in the insulin receptor, which is quantitatively or qualitatively abnormal, but in the type B syndrome autoantibodies to the insulin receptor produce diabetes mellitus. In vitro, using short-term culture experiments, these antibodies mimic the action of insulin, which may account for the occurrence of hypoglycemia in some patients. More typically, however, there is massive insulin resistance, so that even 15 000 units of insulin per day may not lower blood glucose, and prolonged in vitro experiments reveal the antagonistic properties of the antibodies. About one-third of these patients have other autoimmune diseases, including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, primary biliary cirrhosis,

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.

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

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

Secondary Diabetes Mellitus Other Specific Types

Secondary diabetes can result from extreme insulin resistance induced by glucocorticoids (Cushing's syndrome) growth hormone (acromegaly) adrener-gic hormones (pheochromocytoma) other medical conditions, such as uremia, hepatic cirrhosis, or polycystic ovary syndrome or medications (diuretics or exogenous glucocorticoids).

Hepatitis C Virus Infection And Immunity

Hepatitis C virus (HCV) was first characterized in 1989, following successful cloning from copy DNA extracted from infectious chimpanzee plasma. The natural route of infection is unknown, but HCV is blood borne, and therefore high-risk groups for infection include intravenous drug users and recipients of unscreened blood and blood products (e.g. hemophiliacs). Sexual transmission does not appear to be a major route of spread of infection. Vertical transmission from carrier mothers is around 2-10 . Estimates of the prevalence of infection vary between 0.1 and 1 of the population of Europe and the USA. There may be significant fluctuations from this in other countries - for example, rates of 15-20 anti-HCV positivity have been reported in Egypt. The majority (possibly 75 ) of HCV infections result in chronic carriage of the virus. The percentage of chronic carriers who will progress to clinically significant liver disease (chronic hepatitis, cirrhosis, hepatocellular carcinoma) is...

Inactivation of pathogens and spoilage bacteria

Listeria monocytogenes is one of the key foodborne pathogens of concern for modern food processors and a 'zero tolerance' policy is mandated for food processing plants in the United States and elsewhere. L. monocytogenes relies on a potent lippopolysaccharide toxin (LPS) to sensitize erythrocytes, leading to what is generally characterized as a granulomatosis in the host, also known as listeriosis. Listeriosis has a variable incubation period with onset usually within a few days and up to 28 days following ingestion of infected foods. The disease in humans is of particular concern to pregnant women, immuno-compromised individuals (such as persons undergoing chemotherapy or those suffering from diabetes, cirrhosis of the liver or AIDS).