Biliary disease obstruction

The Group II (biliary tract) enzymes are abnormal usually when the serum bilirubin concentration is also abnormal. Most commonly used is alkaline phosphatase which is a highly sensitive indicator of biliary tract obstruction, perhaps because the enzyme is synthesized as an induced response to obstruction of even small bile ducts. Most techniques used to identify the origin of an elevated serum alkaline phosphatase are not very useful from a clinical viewpoint (23). The simultaneous measurement of GMT activity has been found to be useful in differentiating between the hepatic and bony origin of alkaline phosphatase. An increased GMT activity in a patient with an increased ALP activity is a good indication that there is biliary biliary tract disease (62,63). 

Among the different roles previously described, the liver exerts an excretory function, being involved in the formation of bile, which drains into the small intestine. Bile salts in the bile play an important role as emulsifying agents for the reabsorption of lipids and fatty acids from the intestine. Hepatic and obstructive biliary diseases lead to abnormal metabolism of bile acids (BAs). 

GGT is fouud particularly iu hepatocytes aud biliary epithelial cells. GGT serum levels may be high iu liver disease, but it is particularly a feature of biliary outflow obstruction more so than hepatocellular damage. GGT serum measuremeut provides a very sensitive indicator of the presence or absence of hepatobiliary disease. However, raised GGT levels have also been reported in a variety of other clinical conditions, including pancreatic disease, myocardial infarction, chronic obstructive pulmonary disease, renal failure, diabetes, obesity and alcoholism. It is also a sensitive indicator of liver damage through alcohol iugestion. 

Alkaline phosphatase (ALP) Liver kidney, bone, placenta, intestine, biliary epithelia 30-300 lU/L (higher in children due to increased bone growth) Raised levels may indicate biliary inflammation/ obstruction, malignant infiltration, cirrhosis, bone destruction, Paget s disease... 

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... 

The bile acid sequestrants are contraindicated in patients with known hypersensitivity to the drugs. Bile acid sequestrants are also contraindicated in those with complete biliary obstruction. These drags are used cautiously in patients with a history of liver or kidney disease Bile acid sequestrants are used cautiously during pregnancy (Pregnancy Category C) and lactation (decreased absorption of vitamins may affect the infant). 

Superior mesenteric artery syndrome Enteric infections Inflammatory bowel diseases Pancreatitis Appendicitis Cholecystitis Biliary colic Gastroparesis Postvagotomy syndrome Intestinal pseudo-obstruction Functional dyspepsia Gastroesophageal reflux Peptic ulcer disease Hepatitis Peritonitis Gastric malignancy Liver failure... 

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. 

The presence of LP-X in the plasma of patients with liver disease has been considered as a sensitive indicator of biliary obstruction and, thus, useful in the differential diagnosis of diseases of the liver (S29, Wl). However, the recent demonstration (see Section 8.2) that particles resembling LP-X occur also in the plasma of patients with LCAT deficiency poses serious reservations regarding the specificity of the proposed test. 

Switzer, S., Plasma lipoproteins in liver disease I. Immunologically distinct low-density lipoproteins in patients with biliary obstruction. J. Clin. Invest. 46, 1855-1866 (1967). 

Parenteral Anticoagulant-induced prothrombin deficiency hypoprothrombinemia secondary to conditions limiting absorption or synthesis of vitamin K (eg, obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal resection, cystic fibrosis of the pancreas, regional enteritis) drug-induced hypoprothrombinemias due to interference with vitamin K metabolism (eg, antibiotics, salicylates) prophylaxis and therapy of hemorrhagic disease of the newborn. 

Biliary tract Administer with caution to patients with known or suspected cholelithiasis or biliary tract disease. Contractions of the gallbladder or biliary smooth muscle could precipitate complications including cholecystitis, cholangitis, and biliary obstruction. 

Hepatic disease or biliary obstruction - In general, total daily dosage greater than 4 g should not be necessary. 

Renal function impairment Cephalosporins may be nephrotoxic use with caution in the presence of markedly impaired renal function (Ccr less than 50 mL/min/1.73 m ). Hepatic function impairment Cefoperazone is extensively excreted in bile. Serum half-life increases 2-fold to 4-fold in patients with hepatic disease or biliary obstruction. 

If a patient with liver disease also has ascites and oedema, the Vd of some drugs may be increased and biliary obstruction may impair the excretion of drugs cleared through the bile. 

Biliary cirrhosis, secondary disease this requires elimination of the obstructive cause. Itching associated with bile acid retention can respond to cholestyramine, a bile acid binding resin. 

Dosage in renal and/or hepatic impairment Do not exceed 4 g/day in those with liver disease and/or biliary obstruction. Modification of dose usually not necessary in those with renal impairment. Dose should not exceed 1-2 g/day in those with both hepatic and substantial renal impairment. 

If more cholesterol enters the bile than can be solubilized by the available bile salts and phosphatidylcholine, cholesterol gallstone disease (cholelithiasis) can occur. This is generally caused by gross malabsorption of bile acids from the intestine, obstruction of the biliary tract, or severe hepatic dysfunction, leading to abnormalities in bile or bile salt production. 

A word of comment on the high Cu64 content of the bile seems justifiable, since the exact chemical form of copper excreted in the bile has not been determined. The possibility that ceruloplasmin or some copper-containing metabolite of ceruloplasmin is normally excreted in the bile has not been carefully examined. The abnormal elevation of the serum ceruloplasmin level in acute biliary obstruction (7), and the abnormally low serum ceruloplasmin seen in some cases of advanced liver disease, particularly Wilson s disease (2, 3), are in keeping with the liver being the site of ceruloplasmin synthesis and excretion. 

Codeine and morphine should be used with caution in hypotension, hypothyroidism, asthma (avoid during an attack) and decreased respiratory reserve, shock, prostatic hypertrophy, obstructive or inflammatory bowel disorders, diseases of the biliary tract, pregnancy and breastfeeding. They may precipitate coma in patients with hepatic impairment and as such, they should be avoided or a reduced dose used. In patients with renal impairment, the dose should be reduced or they should be avoided. If used in the elderly and debilitated, the dose should be reduced. 

For oral administration, the water-soluble preparation menadiol sodium phosphate, is used in patients with hepatic disease, especially biliary obstruction. The usual dose is 10 mg daily. Alternatively, phytomenadione tablets may be used in those patients who do not have impaired fat absorption. 

Biliary sludging has been documented in children receiving ceftriaxone. The formation of biliary sludge has been reported to lead to biliary obstruction, cholecystitis, choledocholithiasis and psendolithiasis. Most cases are asymptomatic, transient, reversible, and nsnally only necessitate conservative management. However, greater care is required in patients with pre-existing liver disease, and it is advised that abdominal ultrasound scans are performed when ceftriaxone is initiated [2]. It would seem sensible to consider alternative antibiotic therapy in these types of patient. 

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. 

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)... 

Hepatocellutar Disease. Most forms of acute or chronic hepatocellular disease, including acute viral hepatitis and cirrhosis with jaundice, are associated with decreased levels of Hp, possibly caused in part by altered estrogen metabolism. Increased red cell breakdown secondary to erythrocyte membrane lipid alterations may also play a role, although this has never been documented with turnover studies. In contrast, biliary obstruction is also associated with significant lipid alterations but with increased Hp levels, in the absence of severe hepatocellular disease. 

---