Biliary Obstruction

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Background

Disorders of the biliary tract affect a significant portion of the worldwide population, and the overwhelming majority of cases are attributable to cholelithiasis (gallstones). In the United States, 20% of persons older than 65 years have gallstones and 1 million newly diagnosed cases of gallstones are reported each year.

To better understand these disorders, a brief discussion of the normal structure and function of the biliary tree is needed. Bile is the exocrine secretion of the liver and is produced continuously by hepatocytes. It contains cholesterol and waste products, such as bilirubin and bile salts, which aid in the digestion of fats. Half the bile produced runs directly from the liver into the duodenum via a system of ducts, ultimately draining into the common bile duct (CBD). The remaining 50% is stored in the gallbladder. In response to a meal, this bile is released from the gallbladder via the cystic duct, which joins the hepatic ducts from the liver to form the CBD. The CBD courses through the head of the pancreas for approximately 2 cm before passing through the ampulla of Vater into the duodenum.[1]

Pathophysiology

Biliary obstruction refers to the blockage of any duct that carries bile from the liver to the gallbladder or from the gallbladder to the small intestine. This can occur at various levels within the biliary system. The major signs and symptoms of biliary obstruction result directly from the failure of bile to reach its proper destination.

The clinical setting of cholestasis or failure of biliary flow may be due to biliary obstruction by mechanical means or by metabolic factors in the hepatic cells. For the sake of simplicity, the primary focus of this article is mechanical causes of biliary obstruction, further separating them into intrahepatic and extrahepatic causes. The discussion of intracellular/metabolic causes of cholestasis is very complex, the pathogenesis of which is not always clearly defined. Therefore, these causes are mentioned but are not discussed in detail.

Intrahepatic cholestasis generally occurs at the level of the hepatocyte or biliary canalicular membrane. Causes include hepatocellular disease (eg, viral hepatitis, drug-induced hepatitis), drug-induced cholestasis, biliary cirrhosis, and alcoholic liver disease. In hepatocellular disease, interference in the 3 major steps of bilirubin metabolism, ie, uptake, conjugation, and excretion, usually occurs. Excretion is the rate-limiting step and is usually impaired to the greatest extent. As a result, conjugated bilirubin predominates in the serum.

Extrahepatic obstruction to the flow of bile may occur within the ducts or secondary to external compression. Overall, gallstones are the most common cause of biliary obstruction. Other causes of blockage within the ducts include malignancy, infection, and biliary cirrhosis. External compression of the ducts may occur secondary to inflammation (eg, pancreatitis) and malignancy. Regardless of the cause, the physical obstruction causes a predominantly conjugated hyperbilirubinemia.

Accumulation of bilirubin in the bloodstream and subsequent deposition in the skin causes jaundice (icterus). Conjunctival icterus is generally a more sensitive sign of hyperbilirubinemia than generalized jaundice. Total serum bilirubin values are normally 0.2-1.2 mg/dL. Jaundice may not be clinically recognizable until levels are at least 3 mg/dL.[2] Urine bilirubin is normally absent. When it is present, only conjugated bilirubin is passed into the urine. This may be evidenced by dark-colored urine seen in patients with obstructive jaundice or jaundice due to hepatocellular injury. However, reagent strips are very sensitive to bilirubin, detecting as little as 0.05 mg/dL. Thus, urine bilirubin may be found before serum bilirubin reaches levels high enough to cause clinical jaundice.

The lack of bilirubin in the intestinal tract is responsible for the pale stools typically associated with biliary obstruction. The cause of itching (pruritus) associated with biliary obstruction is not clear. Some believe it may be related to the accumulation of bile acids in the skin. Others suggest it may be related to the release of endogenous opioids.

Epidemiology

Frequency

United States

The incidence of biliary obstruction is approximately 5 cases per 1000 people.

Mortality/Morbidity

The mortality and morbidity of biliary obstruction depend on the cause of the obstruction.

Race

The racial predilection depends on the cause of the biliary obstruction.

Sex

The sexual predilection depends on the specific cause of the biliary obstruction.

History

Physical

Causes

Causes of biliary obstruction can be separated into intrahepatic and extrahepatic.

Laboratory Studies

Imaging Studies

Procedures

Medical Care

Treatment of the underlying cause is the objective of the medical treatment of biliary obstruction. Do not subject patients to surgery until the diagnosis is clear. Thus, make every effort to visualize the biliary tree in patients who are jaundiced, with appropriate use of noninvasive and invasive techniques. Importantly, however, a delay in moving on to more invasive therapeutic modalities in a patient who does not initially respond to medical and supportive care increases the risks of an adverse outcome (see Workup).

Surgical Care

As with medical care, the need for surgical intervention depends on the cause of biliary obstruction.

Consultations

Diet

Obesity, excess energy intake, and rapid weight loss can lead to stone formation, with potential biliary obstruction as a consequence. Gradual and modest weight reduction may be of value in patients who are at risk.

Activity

Regular exercise may reduce the risk of gallstones and gallstone complications.

Medication Summary

Bile acid – binding resins and ursodeoxycholic acid are used to treat cholelithiasis when surgery is refused or is inappropriate. Normal gallbladder function must be established by oral cholecystography findings prior to the initiation of drug therapy.

Ursodiol (Actigall)

Clinical Context:  Used to treat biliary stasis and dissolve gallstones.

Class Summary

Ursodeoxycholic acid (ursodiol) is a naturally occurring bile acid present in small quantities in human bile. Suppresses liver synthesis and secretion of cholesterol. Inhibits intestinal cholesterol absorption.

Naloxone (Narcan)

Clinical Context:  Prevents or reverses opioid effects (eg, hypotension, respiratory depression, sedation, pruritus), possibly by displacing opiates from their receptors.

Class Summary

Endogenous opioids may effect pruritic development associated with cholestasis. Treatment with narcotic antagonists may attenuate pruritus.

Rifampin (Rifadin, Rifadin IV, Rimactane)

Clinical Context:  Inhibits DNA-dependent bacterial by binding to the beta subunit of DNA-dependent RNA polymerase, blocking RNA transcription.

Class Summary

Rifampin, in particular, has been suggested as a treatment for cholestasis in certain patients. By reducing intestinal flora, it slows conversion of primary to more toxic secondary bile salts. Has also been shown to decrease serum levels of bilirubin and ALP, perhaps in part contributing to its effectiveness in minimizing associated pruritus.

Cholestyramine (Questran)

Clinical Context:  Acts as a cholesterol-lowering agent. Forms a nonabsorbable complex with bile acids in the intestine, which inhibits enterohepatic reuptake of intestinal bile salts.

Colestipol (Colestid)

Clinical Context:  Binds bile acids in the intestine, facilitates partial removal of bile acids from enterohepatic circulation, and prevents their reabsorption.

Class Summary

Inhibit enterohepatic reuptake of intestinal bile salts.

Further Inpatient Care

Further Outpatient Care

Inpatient & Outpatient Medications

Transfer

Deterrence/Prevention

Complications

Prognosis

Author

Jennifer Lynn Bonheur, MD, Attending Physician, Division of Gastroenterology, Lenox Hill Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Peter F Ells, MD, Associate Professor, Division of Gastroenterology-Hepatology, Albany Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Anil Minocha, MD, FACP, FACG, AGAF, CPNSS, Professor of Medicine, Director of Digestive Diseases, Medical Director of Nutrition Support, Medical Director of Gastrointestinal Endoscopy, Internal Medicine Department, University of Mississippi Medical Center; Clinical Professor, University of Mississippi School of Pharmacy

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

James L Achord, MD, Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP, Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor Flavio R Kamenetz, MD, PhD, to the development and writing of this article.

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