Extrahepatic biliary obstruction

Quinn, R.J., Meredith, Ch., Slade, L. The effect of the Valsalva maneuver on the diameter of the common hepatic duct in extrahepatic biliary obstruction. J. Ultrasound Med. 1992 11 143-145... 

Schandalik, R., Perrucca, E. Pharmacokinetics of silybin following oral administration of silipide in patients with extrahepatic biliary obstruction. Drugs Exp. Clin. Res. 1994 20 37-42... 

In practice, the plasma aminotransferases and ALP are the most useful tests as they allow differentiation of hepatocellular disease from cholestatic disease. The importance of this distinction cannot be overstated failure to recognize cholestatic disease caused by extrahepatic biliary obstruction will result in liver failure if the obstruction is not quickly corrected. It is also important to recognize that there may be a gray zone of mixed hepatocellular and cholestatic disease where the tests do not distinguish one disease from the other. In this case, it is wise to assume that the problem is cholestatic and rule out biliary obstruction. 

Hepatobiliary transporters are affected by both systemic inflammation (e.g., arising from an infection) and inflammation intrinsic to the liver (e.g., acute inflammatory cholestasis caused by drug or alcohol abuse). As described above, endotoxin or turpentine are used to trigger systemic inflammation in rodents. Other rodent models of cholangitis include ethinylestradiol (oral contraceptive-induced cholestasis/cholestasis of pregnancy), alpha-naphthylisocyanate (vanishing bile duct syndrome), and common bile duct ligation (extrahepatic biliary obstruction) [87, 88]. 

In normal, healthy subjects, the fasting level of serum bile acids is low imd is less than 5 p,mol/liter. This level is greatly increased in various hepatobiliary diseases (A9, B6, F2, F3, P9, S34, Til). For example, some liver diseases and their reported range of fasting serum bile acid concentrations (in brackets) are liver cirrhosis (5-100 pmol/liter), viral hepatitis (78—405 p,mol/liter), and extrahepatic biliary obstruction (5-230 p,mol/liter) (P9). An elevated serum bile acid concentration is highly specific for liver disease, but there is no specificity as to the type of liver disease. Determination of the profile of individual bile acids and calculations such as the cholic to che-nodeoxycholic acid ratio have been proposed as useful in the differential diagnosis of liver disease (P9). In practice, however, there is too much overlap between diseases, so that the pattern of serum bile acids does not normally provide useful diagnostic information. 

Patients with this disorder frequently develop h)q)erbilirubinemia and hyperphosphatasemia during exacerbations. As each individual attack subsides, serum bilirubin concentrations return to normal at times when serum alkaline phosphatase values are still elevated. This sequence of events parallels that seen in most patients with extrahepatic biliary obstruction. 

H9. Heilman, L., Zumoff, B., Fishman, J., and Gallagher, T. F., Estradiol metabolism in total extrahepatic biliary obstruction. /. Clin. Endocrinol. 30, 161-165 (1970). 

In extrahepatic biliary obstruction with jaundice, reduced dye clearance is usual (D7, M20). However, there is frequently increased BSP... 

Retention of dyes, such as BSP, is increased in acute and chronic hepatitis and in intra- and extrahepatic biliary obstruction. Gross retention (>60%) occurs more commonly in patients with hepatocellular jaundice than with obstructive jaundice (R5, S42), but there is considerable overlap between the two groups and retention tests are consequently of little value in distinguishing between hepatocellular and obstructive jaundice or in assessing hepatocellular function in the presence of biliary obstruction. Measurements of the fractional disappearance rate (a), the hepatic storage capacity (S), or the maximal biliary excretion (Tm) have likewise not proved helpful in discriminating between the two conditions (S17). 

Separate measurement of free and conjugated BSP has given statistically different results in hepatocellular and obstructive jaundice. In one series of results (H14), the percentage of conjugated BSP in the plasma 40-60 minutes after an injection, was 77 (20-100)% in patients with extrahepatic biliary obstruction and 94 (76-100)% in patients with hepatocellular jaundice. Although there was overlap, 8 out of 10 patients with biliary obstruction had values less than 88% whereas 8 out of 9 patients with hepatocellular jaundice had values equal to or greater than 88%. Similar trends have been noted by others (C6, S15), but all have found some overlap. 

Vitamin K is poorly absorbed in the absence of bile. Thus, hypoprothrombinemia may be associated with either intrahepatic or extrahepatic biliary obstruction or a severe defect in the intestinal absorption of fat from other causes. 

Extrahepatic biliary obstruction occurs due to a myriad of benign and malignant etiologies. The resulting cholestasis may lead to malabsorption, coagulopathy, pruritus, hepatocellular failure, renal dysfunction. 

In 27 patients who received intrahepatic floxuridine, total dose 20-41 mg/kg extrahepatic biliary sclerosis was discovered by CT scan and ultrasound, followed by endoscopic retrograde cholangiopancreatography and/or percutaneous cholangiography in three cases (4). Radiological findings included complete obstruction of the common hepatic duct in one case, common hepatic duct stenosis in two cases, common bile duct obstruction in one case, and intrahepatic bile duct dilatation without identifiable obstruction in one case... 

Most adenomas of the extrahepatic biliary tract (EHBT) occur in the gallbladder and are usually detected incidentally." In contrast, those in the extrahepatic bile ducts (EHBDs) present with signs and symptoms of obstruction. They can be multifocal, especially those with a papillary architecture. On the basis of the growth pattern, they have been classihed traditionally as tubular, papillary, or tubulopapillary, although the relevance of this classihcation independent of the degree of dysplasia is debatable. ... 

A 47-year-old HIV-positive woman who had taken atazanavir 400 mg/day and abaca-vir-l-lamivudine 600/300 mg/day for 6 weeks developed right epigastric pain and raised liver enzymes and total bilirubin. Ultrasonography showed obstruction due to gallstones, with intrahepatic and extrahepatic biliary dilatation. The stones were removed at... 

Intrahepatic rupture can result in hemobilia with or without biliary obstruction. These patients can present with right upper quadrant pain, jaundice, fever, melena, or hematemesis. Extrahepatic rupture usually presents acutely and can lead to exsanguination due to massive intraperitoneal hemorrhage. They can erode into adjacent structures such as the stomach, common bile duct, duodenum, or portal vein. Due to the high mortality from rupture, elective treatment of small asymptomatic aneurysms has been advocated. 

Richer A, Brambs HJ (1997) Metallic stents in malignant biliary obstruction. Cardiovasc Interv Radiol 20 43-49 Robledo R, Muro A, Prieto ML (1996) Extrahepatic bile duct carcinoma US characteristics and accuracy in demonstration of tumors. Radiology 198 869-873 Ros PR, Buck JL, Goodman ZD, et al (1988) Intrahepatic cholangiocarcinoma radiologic-pathologic correlation. Radiology 167 689-693... 

The term cholestatic jaundice is used to include all cases of extrahepatic obstructive jaundice. It also covers those cases of jaundice that exhibit conjugated hyperbilirubinemia due to micro-obstruction of intrahepatic biliary ductules by swollen, damaged hepatocytes (eg, as may occur in infectious hepatitis). 

Elevation of cholesterol is found in fatty liver, particularly under diabetic metabolic conditions. A rather marked increase in cholesterol can be observed in all forms of cholestasis differentiation between intra- or extrahepatic cholestasis, however, is not possible. This elevation of cholesterol in obstruction is due to an enhanced synthesis of cholesterol in hepatocytes and intestinal walls as well as to the retention of bile lipids. Marked elevations of cholesterol are detectable in primary biliary cirrhosis and in cholesterol storage disease. A pronounced increase in cholesterol is also found in Zieve s syndrome (L. Zieve, 1958). 

The bile flow is interrupted in its passage from the porta hepatis to the duodenum as a result of (i.) intraluminal obstruction, (2.) obliterating disease of the biliary duct walls, or (3.) compression of the extrahepatic efferent bile ducts. This form of cholestasis can be sudden in onset or progress slowly, may be transient or persistent, and occurs either as incomplete or complete obstruction with jaundice, (s. tab. 13.2) (s. figs. 8.12, 8.13 25.8)... 

The response of the liver to any form of biliary tree obstruction induces the synthesis of ALP by hepatocytes. Some of the newly formed enzyme enters the circulation to increase the enzyme activity in serum. The elevation tends to be more notable (greater than threefold) in extrahepatic obstruction (e.g., by stone or by cancer of the head of the pancreas) than in intrahepatic obstruction and is greater the more complete the obstruction. Serum enzyme activities may reach 10 to 12 times the upper reference limit and usually return to normal on surgical removal of the obstruction. A similar increase is seen in patients with advanced primary liver cancer or widespread secondary hepatic metas-tases. Liver diseases that principally affect parenchymal cells, such as infectious hepatitis, typically show only moderately (less than threefold) increased or even normal serum ALP activities (Table 21-3). Increases may also be seen as a consequence of a reaction to drug therapy. Intestinal ALP... 

Conjugated hyperbilimbinemia is rare during the neonatal period. It can result from impaired hepatocellular function or extrahepatic obstmction. Hepatocellular defects can be caused by bacterial, viral, or parasitic infections, cystic fibrosis, a -antitrypsin deficiency, Dubin-Johnson and Rotor s syndromes, and other genetic disease. Extrahepatic obstruction can be congenital (biliary atresia) or acquired. 

Intrahepatic and Extrahepatic Sepsis. Bacterial infection of the liver, with microscopic or macroscopic abscess formation, results in hyperbilirubinemia and a rise in serum alkaline phosphatase (B53). Hyperphosphatasemia is greater in patients with microabscesses, particularly in cases of biliary tract obstruction, than in patients with macroscopic abscesses, who show only modest serum alkaline phosphatase elevation (R32). 

On percutaneous transhepatic cholangiography (PTC), extensive filling defects in the biliary tree may be seen with or without obstruction of the extrahepatic bile ducts. PTC can be performed in cases of RMS without biliary dilation and is very useful if there is an obstructive jaundice (Gazelle etal. 1998). 

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