Porth's Essentials of Pathophysiology, 4e

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Gastrointestinal and Hepatobiliary Function

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abnormal, however, and require investigation and treat- ment (see Chapter 13). Intrahepatic or hepatocellular jaundice is caused by disorders that directly affect the ability of the liver to remove bilirubin from the blood or conjugate it so it can be eliminated in the bile. Liver diseases such as hepatitis and cirrhosis are the most common causes of intrahepatic jaundice. Drugs such as the anesthetic agent halothane, oral contraceptives, estrogen, anabolic steroids, isoniazid, trimethoprim-sulfamethoxazole, amoxicillin-clavulanic acid, and chlorpromazine may also be implicated in this type of jaundice. Because intrahepatic jaundice usually interferes with all phases of bilirubin metabolism—uptake, conjugation, and excretion—both conjugated and unconjugated bilirubin are elevated, the urine often is dark because of bilirubin in the urine, and the serum alkaline phosphatase (ALP), an enzyme present in the bile duct epithelium and cana- licular membrane of hepatocytes, is slightly elevated. Posthepatic or obstructive jaundice , also called cho- lestatic jaundice, occurs when bile flow is obstructed between the liver and the intestine, with the obstruction located at any point between the junction of the right or left hepatic duct and the point where the common bile duct opens into the intestine. Among the causes are strictures of the bile duct, gallstones, and tumors of the bile duct or the pancreas. Conjugated bilirubin levels usually are elevated, the stools are clay colored because of the lack of bilirubin in the bile, the urine is dark, the levels of serum ALP are markedly elevated, and the ami- notransferase levels are slightly increased. Blood levels of bile acids often are elevated in obstructive jaundice. As the bile acids accumulate in the blood, pruritus devel- ops. A history of pruritus preceding jaundice is common in obstructive jaundice. Cholestasis Cholestasis represents a pathologic condition of impaired bile formation and bile flow, leading to accumulation of bile pigment in the parenchymal tissues of the liver. As a result, materials normally transferred to the bile, includ- ing bilirubin, cholesterol, and bile acids, accumulate in the blood. 3,4 The condition may be caused by intrinsic liver disease affecting the intrahepatic canaliculi and bile ducts, in which case it is referred to as intrahepatic cho- lestasis. Alternatively, it can by caused by obstruction of the large bile ducts, for example by strictures, gallstones, or neoplasms, a condition known as extrahepatic cho- lestasis. Genetic disorders involving the transport of bile into the canaliculi also can result in cholestasis. The morphologic features of cholestasis depend on the underlying cause. Common to all types of obstruc- tive and hepatocellular cholestasis is the accumulation of bile pigment in the liver. Elongated green-brown plugs of bile are visible in the dilated bile canaliculi. Rupture of the canaliculi leads to extravasation of bile and subsequent degenerative changes in the surround- ing hepatocytes. Prolonged obstructive cholestasis leads not only to fatty changes in the hepatocytes but also to destruction of the supporting connective tissue. 3

FIGURE 30-6. Jaundice in a person with hepatitis A. (From the Centers for Disease Control and Prevention. Public Health Image Library No. 2860. Courtesy ofThomas F. Sellers.)

spherocytosis, in which the red cell membranes are defective, or in hemolytic disease of the newborn. In prehepatic jaundice, there is mild jaundice, the uncon- jugated bilirubin is elevated, the stools are of normal color, and there is no bilirubin in the urine. Because the hepatic mechanisms for conjugating and excreting bilirubin are not fully mature during the first 2 weeks of life, many newborn infants develop a transient and mild unconjugated hyperbilirubinemia, termed neonatal or physiologic jaundice of the newborn . 3 Abnormally high or sustained levels of unconjugated bilirubin are

CHART 30-1  Causes of Jaundice

Prehepatic (Excessive Red Blood Cell Destruction) Hemolytic blood transfusion reaction Hereditary disorders of the red blood cell Sickle cell disease Thalassemia Spherocytosis Acquired hemolytic disorders Hemolytic disease of the newborn Autoimmune hemolytic anemias Intrahepatic Decreased bilirubin uptake by the liver Decreased conjugation of bilirubin Hepatocellular liver damage Hepatitis Cirrhosis Cancer of the liver Drug-induced cholestasis Posthepatic (Obstruction of Bile Flow) Structural disorders of the bile duct Cholelithiasis Congenital atresia of the extrahepatic bile ducts Bile duct obstruction caused by tumors