Porth's Essentials of Pathophysiology, 4e

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Gastrointestinal and Hepatobiliary Function

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The differential diagnosis includes measures to exclude other causes of liver disease, including hepatitis B and C. A characteristic laboratory finding is that of a marked elevation in serum gamma globulins. A biopsy is used to confirm the diagnosis. Corticosteroid and immunosuppressant drugs are the treatment of choice. Although some persons remain in remission after drug treatment is withdrawn, most require long-term mainte- nance treatment. Liver transplantation may be required for persons who are refractory to or intolerant of immu- nosuppressive therapy and in whom end-stage liver dis- ease develops. Acute Fulminant Hepatitis Acute fulminant hepatitis or hepatic failure is hepatic insufficiency that progresses from onset of hepatitis symptoms to hepatic encephalopathy within 2 to 3 weeks in persons who do not have chronic liver disease. 3 Viral hepatitis is responsible for about 10% of cases of fulminant hepatitis, with about 8% of those being caused by HBV and the rest by HAV. 3,21 Acetaminophen (Tylenol) toxicity (to be discussed) is the most common cause, accounting for at least 46% of cases in the United States. 21 Other causes include idiosyncratic drug reac- tions (now the second most common cause), poisonous mushrooms, fatty liver of pregnancy, and other disor- ders of fatty acid oxidation. Acute fulminant liver failure often presents with gas- trointestinal symptoms, signs of the systemic inflam- matory response (see Chapter 20), and hemorrhagic phenomenon. Jaundice may be absent or minimal early, but laboratory tests show severe hepatocellular damage. The blood ammonia level is typically elevated and corre- lates with the development of encephalopathy and cere- bral edema. Survival of more than a week may permit replication of residual hepatocytes. The treatment for acute liver failure is directed toward correcting the underlying liver abnormality and providing supportive care. Liver transplantation is the only option for persons who do not succumb to second- ary infections or other organ failure. The mortality rate of fulminant hepatitis is about 85% without transplant and about 35% with transplant. 3 Intrahepatic Biliary Disorders Intrahepatic biliary diseases disrupt the flow of bile through the liver, causing cholestasis and biliary cirrho- sis. Among the causes of intrahepatic biliary disease are primary biliary cirrhosis and secondary biliary cirrhosis. Primary Biliary Cirrhosis Primary biliary cirrhosis is a chronic disease of the liver characterized by the autoimmune destruction of the medium-sized intrahepatic bile ducts with cholestasis and eventual development of cirrhosis and liver failure. 3,22 Cirrhosis develops only after many years; thus, the name primary biliary cirrhosis is somewhat misleading for per- sons diagnosed early in the precirrhotic stage. 3

The disease is seen most commonly in women 40 to 60 years of age. Both the incidence and prevalence are increasing, and geographic clustering of the disease has been reported, suggesting genetic and environmental factors are important in its pathogenesis. Family mem- bers of persons with the disease have increased risk of developing the disease. The disease may be associated with other autoimmune disorders such as Sjögren syn- drome (sicca complex of dry eyes and mouth), autoim- mune thyroid disease, rheumatoid arthritis, Raynaud phenomenon, and celiac disease. The disorder is characterized by an extremely insidi- ous onset, and persons may be symptom-free for many years. Morphologically, there is progressive scarring and destruction of liver tissue. The liver becomes enlarged and takes on a green hue because of the accumulated bile. The earliest symptoms are unexplained pruritus (itching), weight loss, and fatigue, followed by dark urine and pale stools. Vitamin D malabsorption–related osteoporosis occurs in up to one third of persons with the disorder. 22 Jaundice is a late manifestation of the dis- order, as are other signs of liver failure. Serum alkaline phosphatase (ALP) levels are elevated in persons with primary biliary cirrhosis. Treatment for primary biliary cirrhosis is ursodeoxy- cholic acid (ursodiol), a drug that increases bile flow and decreases the toxicity of bile contents, and has been shown to decrease the rate of clinical deterioration. Cholestyramine, a bile acid–binding drug, or rifampi- cin can be beneficial for treatment of pruritus. Liver transplantation, however, remains the only treatment for advanced disease. Primary biliary cirrhosis does not recur after liver transplantation if appropriate immuno- suppression is used. Secondary Biliary Cirrhosis Secondary biliary cirrhosis results from prolonged obstruction of the extrabiliary tree. 3 The most common cause is cholelithiasis (gallstones). Other causes of sec- ondary biliary cirrhosis are malignant neoplasms of the biliary tree or head of the pancreas and strictures of the common duct caused by previous surgical procedures. Extrahepatic biliary cirrhosis may benefit from surgical procedures designed to relieve the obstruction. Drug- and Alcohol-Induced Liver Disease By virtue of its many enzyme systems that are involved in biochemical processes, the liver has an important role in the metabolism of many drugs and chemical substances. The liver is particularly important in the metabolism of lipid-soluble substances that cannot be directly excreted by the kidney. Drug Metabolism There are two major types of reactions involved in the hepatic detoxification and metabolism of drugs and other chemicals: phase 1 and phase 2 reactions. 23