Cholestasis obstructive

Elevation of serum copper is found in cholestasis, obstructive jaundice, primary biliary cholangitis, malignant tumours, kwashiorkor, exocrine pancreatic insufficiency, during the last trimenon of pregnancy and after administration of oestrogens. A decrease in serum copper is typical of Wilson s disease. In some rare cases, it is caused by familial benign hypocupraemia and nutritional deficiency in neonates. 

Hepatobiliary disease occurs due to bile duct obstruction from abnormal bile composition and flow. Hepatomegaly, splenomegaly, and cholecystitis may be present. Hepatic steatosis may also be present due to effects of malnutrition. The progression from cholestasis (impaired bile flow) to portal fibrosis and to focal and multilobar cirrhosis, esophageal varices, and portal hypertension takes several years. Many patients are compensated and asymptomatic but maybe susceptible to acute decompensation in the event of extrinsic hepatic insult from viruses, medications, or other factors.7... 

Cholestasis Reduced or lack of flow of bile, or obstruction of bile flow. 

Soroka CJ, Lee JM, Azzaroli F, Boyer JL. Cellular localization and up-regula-tion of multidrug resistance-associated protein 3 in hepatocytes and cholangio-cytes during obstructive cholestasis in rat liver. Hepatology 2001 33(4) 783 791. 

Alkaline phosphatase levels and GGT are elevated in plasma with obstructive disorders that disrupt the flow of bile from hepatocytes to the bile ducts or from the biliary tree to the intestines in condition such as primary biliary cirrhosis, sclerosing cholangitis, drug-induced cholestasis, gallstone disease, and autoimmune cholestatic liver disease. 

Denk GU, Soroka CJ, Takeyama Y, Chen WS, Schuetz JD, Boyer JL. Multidrug resistance-associated protein 4 is up-regulated in liver but down-rregulated in kidney in obstructive cholestasis in the rat. J Hepatol 2004 40 585-591. 

Dose-independent, drug-induced liver dysfunction (cholestatic jaundice) is not an unusual adverse reaction. Caused by a number of different, commonly used drugs, cholestasis is a hypersensitivity reaction that primarily affects the biliary canaliculi, causing an intrahepatic obstructive jaundice. An alteration in... 

Toxicity to bile duct epithelial cells also causes cholestasis. Necrosis of these cells can result in sloughing of an obstructive cast into the duct lumen. The experimental chemical a-naphthylisothiocyanate (ANIT) is known to target bile duct epithelial cells in addition to hepatocytes. Bile duct epithelial toxicity is GSFI-dependent and is thought to depend upon concentrative accumulation within bile ducts subsequent to hepatocanalicular transport of the ANIT-GSH conjugate. 

Possible increase in serum conjugated bilirubin Obstruction of bile flow commonly due to common bile duct stone or pancreatic carcinoma Failure of bile secretion Extrahepatic cholestasis Intrahepatic cholestasis... 

Reduced excretion through bile in obstructive cholestasis (use a statin that is partially cleared in the urine). 

They are highly excreted in bile and their pharmacodynamic disposition in obstructive cholestasis is unknown. 

Cholangiodestmctive cholestasis is caused by bile duct obstruction which may be intrahepatic or extrahepatic. Bile duct injury may lead to sloughing of epithelial cells into the lumen, cell edema, and inflammation, which may contribute to obstruction (Treinen-Moslen, 2001 Plumlee, 2004). Chronic lesions associated with cholangiodestmctive cholestasis typically include bile duct prohferation and periductular fibrosis. Vanishing bile duct syndrome, characterized by a loss of bile ducts, has been seen in chronic cholestatic disease in humans (Zimmerman, 1999 Treinen-Moslen, 2001) and has been produced experimentally in dogs (Uchida, 1989). 

In hepatobiliary diseases, the sensitivity and specificity of y-GT is 95%, since y-GT is also located in cholangiocytes. In individuals with a healthy liver, the specificity is 74%, in overall healthy individuals it is 95%. In cholestasis, the sensitivity of y-GT is six times that of AP and nine times that of LAP Obstruction of bile flow can be the cause of isolated y-GT elevation in fatty liver. 

The Increase In AP activity is stimulated by bile acids. A rise in bile acids, which is considered to be the most sensitive and earliest marker of cholestasis, precedes any elevation in AP. The latter derives from enzyme synthesis with increased secretion into the blood. Under pathological conditions, bile duct AP is formed, which is a sensitive marker for hepatobiliary diseases, cholestasis and space-occupying lesions of the liver. The sensitivity is 80-100% in cholestatic diseases. AP activity is usually higher in obstructive jaundice and cholangitis than in intrahepatic obstructions, and it is highest in the vanishing bile duct disease or in complete obstruction. (13, 39, 41) (s. tabs. 5.9 13.2-13.4)... 

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). 

Acute hepatitis Acute hepatic failure Chronic hepatitis, Cirrhosis Obstructive jaundice. Cholestasis, Primary biliary eirrhosis... 

An elevation of AT III activity (> 120%) is found in cholestasis and obstructive jaundice. This leads to hypo-coagulopathy with the danger of bleeding, (s. tab. 5.13)... 

Obstructive jaundice and cholestasis with dilated bile ducts... 

Differentiation between obstructive and parenchymatous cholestasis is possible in > 90% of cases. A serum bilirubin level of up to 30 mg/dl is not seen as a methodological impediment to sequential scintigraphy. In incomplete obstruction with nondilated bile ducts, this technique provides more information than can be obtained using ultrasound. (17, 18)... 

Further intrahepatic forms of obstruction include recurrent intrahepatic cholestasis and recurrent cholestasis in pregnancy, (s. tab. 12.4)... 

Obstructive cholestasis - initially often without jaundice, thereafter generally with jaundice - is caused by a mechanical impediment of the bile flow. Because of this, the bile flow is reduced and biliary stasis is generated, which, depending on the localization of the impediment, subsequently affects the bile ducts of (i.) the entire liver or (2.) only certain subzones of the liver. 

Pathogenetically, non-obstructive cholestasis is a multifactorial process. The factors that cause intrahepatic cholestasis lead to biochemical dysfunctions and/or damage to subcellular structures, with changes in the metabolism of bile acids. 

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)... 

---