Continuing Education Activity

Biliary obstruction refers to the impairment of bile flow from the liver to the small intestine due to blockage of the biliary duct system. Bile obstruction affects a large portion of the population worldwide, with significant morbidity and mortality. The most common etiology of biliary obstruction is gallstones causing common bile duct obstruction, which manifests as pain, nausea/vomiting, and jaundice. This activity describes the etiology, pathophysiology, evaluation, and management of biliary obstruction and highlights the interprofessional team's role in caring for affected patients.

Objectives:

• Determine the pathophysiology of biliary obstruction.
• Assess the evaluation in patients with biliary obstruction.
• Intrepret the treatment options available for patients with biliary obstruction.
• Communicate the significance of a coordinated interprofessional team in the early evaluation and management of patients with biliary obstruction.

Introduction

Biliary obstruction commonly refers to blockage of the bile duct system, leading to impaired bile flow from the liver into the intestinal tract. Bile is a substance that contains bile salts, bilirubin, and cholesterol and is continuously synthesized in the liver hepatocytes. Bile is then transported via the bile ducts into the second portion of the duodenum to assist with the metabolism of fats.[1]

Bile formed in the liver flows through the right and left hepatic ducts into the common hepatic duct. The common hepatic duct then joins the cystic duct arising from the gallbladder to form the common bile duct. The common bile duct then joins the pancreatic duct through its course within the head of the pancreas before opening into the duodenum through the major papilla or ampulla. The majority of the bile flows into the gall bladder through the cystic duct, where it is concentrated and temporarily stored, while the rest of the bile flows through the common bile duct into the duodenum through the sphincter of Oddi. The flow of bile into the duodenum is regulated by the release of the hormone Cholecystokinin (CCK) from the duodenum, which controls the release of stored bile from the gallbladder and the relaxation of the sphincter of Oddi.

Biliary obstruction is generally referred to as blockage of the extrahepatic biliary system. Biliary obstruction can occur anywhere along this path and can lead to serious complications such as hepatic dysfunction, renal failure, nutritional deficiencies, bleeding problems, and infections.[2] Disruption in the bile flow due to impairment of the intrahepatic biliary system is generally referred to as cholestasis. Cholestasis can present as abnormalities in serum hepatic enzymes, such as elevated bilirubin and alkaline phosphatase levels, and can lead to jaundice and pruritis.

Biliary obstruction is common and affects a large portion of the world population, causing significant morbidity and mortality. The most common etiology of biliary obstruction is choledocholithiasis or gallstones, causing extrahepatic bile duct blockage. The most serious manifestation of this is the development of infection in the bile ducts called cholangitis, which can be fatal if not treated promptly.[3] 

Etiology

Biliary obstruction can be divided into intrahepatic and extrahepatic etiologies. As described above, intrahepatic biliary obstruction is generally called cholestasis and is not covered here in detail as it is not the scope of this topic. Briefly, intrahepatic cholestasis can be from several disease processes, including certain forms of hepatitis (viral infections, alcohol), drug-induced liver injury (antibiotics, acetaminophen, anti-epileptics, anti-arrhythmic), primary biliary cholangitis, primary sclerosing cholangitis, and infiltrative diseases (sarcoidosis, tumors, abscess, and cysts).[4][5] 

Extrahepatic biliary obstruction, which is the scope of this article, can be divided into various benign and malignant etiologies. These include choledocholithiasis (gall stones in the common bile duct), choledochal cysts (dilation/cysts of bile ducts), Mirizzi syndrome (gall stones in cystic duct pressing on bile duct), benign structuring diseases like Primary sclerosing cholangitis (PSC), fibrotic strictures from gall stone passage or iatrogenic strictures from bile duct cannulation. Neoplastic stricture diseases causing biliary obstruction can include cholangiocarcinoma (bile duct cancer), pancreatic head cancer leading to distal common bile duct stricture, and ampullary carcinoma or adenoma. Other etiologies of biliary obstruction can include infectious diseases like parasitic cholangiopathy (Clonorchis sinensis, Ascaris lumbricoides) causing intra- or extrahepatic obstruction to bile flow, inflammatory and autoimmune diseases like AIDS cholangiopathy, and autoimmune cholangiopathy.[6]

Epidemiology

The incidence of gallstones causing biliary obstruction is approximately 5 in 1000 people, whereas 10% to 15% of the adult US population develop gallstones in their lifetime.[6] Gallstones or Cholelithiasis, including gall bladder sludge formation, is the precursor of choledocholithiasis, where gallstones pass through the cystic duct and get lodged into the common hepatic ducts, causing an obstruction. Between 10 and 15% of patients with gallstones are also noted to have common bile duct stones at diagnosis.[7] 

Women are at greater risk of developing gallstones than men and hence increased risk for choledocholithiasis. This is likely secondary to estrogen increasing hepatic uptake of cholesterol, which increases bile production and some degree of cholestasis.[8]

Gallstones are the most common cause of biliary obstruction in Hispanics, Northern Europeans, and Native Americans. Northern Native Americans have the highest reported rates of cholelithiasis at 64% for females and 29% for males. Asian and African Americans have an intermediate prevalence of cholelithiasis, with 13.9% in women and 5.3% in men. The lowest prevalence of cholelithiasis is in sub-Saharan Black Africa, with an overall prevalence of less than 5%. White race North Americans have an overall prevalence of cholelithiasis of 16.6% and 8.6% in females and males, respectively.[9][8]

In developed countries, choledocholithiasis secondary to cholesterol stones is the most common cause of biliary obstruction. In contrast, brown pigment stones from infectious etiologies or hemolysis are the most common etiology in Asia. Other etiologies like recurrent pyogenic cholangiohepatitis are characterized by recurrent bacterial cholangitis, dilatation, and stricture of the biliary tree, the presence of calculi within the intrahepatic bile ducts, and an increased risk for cholangiocarcinoma is common in Asia but rare in the west. Gallbladder malignancy is more common in Central and South America, Central and Eastern Europe, the northern Indian subcontinent, and East Asia.[10][11][8] 

Pathophysiology

The pathophysiology of biliary obstruction is as follows:

1. Catabolism of hemoglobin is a normal function that releases heme molecules, which then convert to biliverdin, a precursor to bilirubin. Biliverdin then transforms into unconjugated bilirubin within the reticuloendothelial system. Since unconjugated bilirubin is lipid-soluble, the renal system does not eliminate it. Unconjugated bilirubin is bound in serum to albumin or exists as free unbound bilirubin. Unbound bilirubin is taken up by hepatocytes and converted to conjugated bilirubin, which is water-soluble. Conjugated bilirubin becomes part of the bile, secreted from the hepatocytes in the liver.
2. Bile formed in the liver flows through the right and left hepatic ducts into the common hepatic duct. Fifty percent of the bile flows into the cystic duct. It is then stored in the gallbladder, with the rest of the bile flowing through the common bile duct and converging and flowing through the main pancreatic duct in the head of the pancreas to empty into the duodenum through the sphincter of Oddi.
3. Biliary obstruction refers to obstruction in the biliary system, leading to blockage of bile flow into the small intestine. It can occur anywhere along the path from the liver to the intestinal tract. Biliary obstruction is common and affects a large portion of the population around the world, with significant morbidity and mortality. Gallstones are the most prevalent cause of biliary obstruction; they commonly manifest by dilating the common bile duct and causing jaundice.
4. Jaundice, a physical exam finding of yellowish discoloration of the skin, conjunctiva, or mucous membranes, is a consequence of obstruction leading to bile stasis and buildup of conjugated bilirubin in the blood.
5. Normal total serum bilirubin values are 0.2 to 1.2 mg/dL. Clinically, jaundice is evident at 3 mg/dl. 
6. Normal urine contains no bilirubin; however, in patients with obstructive jaundice, conjugated bilirubin is excreted, giving it a dark color. Urinary bilirubin is detectable at a lower level than that needed to cause clinical jaundice.
7. The inability of bilirubin to reach the intestinal tract gives a pale color to stools. 
8. Pruritus is common in patients with biliary obstruction, but the cause of this is unknown. The deposition of bile acid into the skin is 1 postulation that could account for these symptoms. Percutaneous biliary drainage was found to decrease pruritis symptoms.[12]

Histopathology

Intrahepatic cholestasis can be diagnosed with a percutaneous or transjugular liver biopsy, which this topic does not cover in detail. Extrahepatic biliary obstruction can also lead to chronic changes to liver histology over prolonged obstruction of bile ducts. However, the etiology of biliary obstruction can be determined through histology from brush cytology or tissue biopsy samples obtained during various procedures like endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiogram (PTC), or endoscopic ultrasound (EUS) directed biopsy. Sometimes, a tissue sample is imperative for accurate diagnosis, especially for workups for the stricture of the biliary tract noted on non-invasive imaging. 

History and Physical

History and Presentation

Biliary obstruction can have very varied presentations depending on the underlying etiology. It usually presents as jaundice with clay-colored or acholic stools and dark urine. Patients can have pruritis with chronic biliary obstruction. Depending on the underlying etiology, patients can have right upper quadrant abdominal pain, fever, nausea and vomiting, and weight loss. The onset of these symptoms can be variable, ranging from acute development to over months.

A careful history of symptom duration, if gradual or acute onset, accompanying symptoms like weight loss, loss of appetite, nausea/vomiting is important. Similarly, any right-sided abdominal pain, along with severity and radiation, is important to know. A history of diarrhea, hematochezia, and upper GI bleeding symptoms is also relevant to diagnosing the underlying process. It is imperative to know any pertinent personal and family history like bile duct or pancreatic malignancy, inflammatory bowel disease, or primary liver disease. A careful review of social history related to current and former smoking, alcohol use, and drug abuse is important. Similarly, travel history to parasitic endemic regions is of value in determining the etiology of biliary obstruction. A careful review of medication history can sometimes be significant in determining intrahepatic cholestasis vs. extrahepatic biliary obstruction.

Physical Examination

A detailed and thorough physical exam is of paramount importance. It is imperative to check baseline vital signs, especially for fever and elevated heart rate. A general physical exam is important to assess for any distress, pallor, skin jaundice, scleral icterus, palmer erythema, and signs of malnutrition. A detailed abdominal examination to assess for right upper quadrant tenderness (Murphy's sign), hepatomegaly and splenomegaly, presence of ascites, any palpable mass, and stigmata of cirrhosis (caput-medusae) is very crucial for diagnosis. A cardiac exam to assess for signs of congestive heart failure with jugular venous distension and displacement of heart sounds can be very important to determine underlying etiology. Similarly, a pulmonary exam to assess for pleural effusions, determining whether one-sided or bilateral, helps determine etiology. Assessment for lymphadenopathy in left supraclavicular lymph nodes and other neck lymph nodes can provide helpful information. Looking for lower extremity edema is also important.

Evaluation

Blood Tests

Workup for biliary obstruction includes routine labs and some dedicated labs, including:

• Complete blood count (CBC)
• Comprehensive metabolic profile (CMP)
• Fractionated bilirubin
• Alkaline phosphatase and fractionation
• Gamma-glutamyltransferase
• Viral hepatitis serology
• Antimitochondrial antibody levels
• Antinuclear antibody
• Coagulation studies
• Tumor markers (CA19-9, CEA, AFP) [13][14]

Urine Test

• Urine bilirubin

Stool Test

• Occult blood to rule out GI malignancy 

Radiological and Endoscopic tests - Non-invasive and invasive radiologic tests can help diagnose the underlying etiology of biliary obstruction.[15][16]

• Abdominal ultrasound with doppler can be a starting radiological test due to its low cost, noninvasive nature, and easy availability. It is a good test for evaluating gallstones, extrahepatic bile duct dilations, and blood vessel patency using doppler.
• Based on the ultrasound results, an abdominal CT scan can be the next step. This can help assess for pancreatic head and liver lesions and rule out other intra-abdominal processes.
• Nuclear medicine scans like the HIDA scan can assess for cystic duct obstruction.
• MRCP (magnetic resonance cholangiopancreatography) is a very sensitive test for assessing further intra- and extrahepatic bile duct abnormalities, such as cholangiocarcinoma, strictures, or bile duct stones.
• Endoscopic tests like EUS (endoscopic ultrasound) with needle aspiration and ERCP with cytology and biopsies can be further considered based on noninvasive testing results. ERCP can be diagnostic and therapeutic in cases of biliary obstruction caused by gallstones.
• Sometimes, interventional radiology-based PTCA (percutaneous transhepatic cholangiogram) can be done to obtain biopsies and evaluate for strictures.

Treatment / Management

Initial Management

Initial management depends on the patient's clinical condition and probable etiology. If the patient is stable, most of the work can be done as an outpatient with regular follow-ups in the gastroenterology clinic. However, if the patient is febrile and showing signs of sepsis and hepatic dysfunction, admitting the patient for evaluation and treatment may be necessary. This is needed in patients with acute cholangitis, cholecystitis, and acute liver failure. 

Treatment

Treatment varies widely depending on the etiology of biliary obstruction. Below are some common etiologies and board management.[17]

Cholelithiasis and Choledocholithiasis

• Gallstones with common bile duct (CBD) stones;

  • CBD size less than 1.5cm with small stones- ERCP and sphincterotomy with cholecystectomy
  • CBD size more than 1.5cm with large stones - ERCP and sphincterotomy with lithotripsy, choledochotomy, choledochoduodenostomy, choledochojejunostomy, or cholecystectomy [18][19]

CBD Stricture

• Benign

  • Endoscopic sphincterotomy and balloon dilatation 
  • Endoscopic stenting with stent removal/exchange at 4 to 6 weeks
  • Biliary-enteric bypass if and when surgery is required
• Malignant

  • Endoscopic drainage with stenting
  • Percutaneous drainage with PTC with internal and external drainage
  • Palliative biliary-enteric bypass in unresectable cases
  • Resection of the tumor with biliary-enteric anastomosis in resectable disease [20]

Parasites

• Medication

  • Albendazole
  • Mebendazole
  • Pyrantel pamoate
• Surgical/endoscopic:

  • ERCP with sphincterotomy and extraction using a basket.
  • In the case of gallbladder invasion, cholecystectomy, CBD exploration, and T-tube placement [21][22]

Choledochal Cysts

• Assessment for malignancy with ERCP and cytology
• Possible Excision and hepaticojejunostomy if required [23]

Neoplasm

• Advanced disease

  • Palliation with endoscopic biliary stenting and chemoradiotherapy or photodynamic therapy
  • Percutaneous transhepatic endobiliary radiofrequency ablation along with biliary stenting
  • Duodenal stenting in ampullary carcinoma
• Resectable disease

  • Excision with clear margins and bilioenteric anastomosis
• Pancreatic head carcinoma

  • Whipple procedure/pylorus-preserving pancreaticoduodenectomy
• Ampullary carcinoma

  • Whipple procedure 
• Gallbladder malignancy

  • Cholecystectomy with liver resection and lymph node clearance [24]

Differential Diagnosis

The differential diagnosis for biliary obstruction is broad, ranging from benign to malignant diseases, as mentioned below.

Benign Diseases

• Acute cholecystitis and biliary colic from gallstones (cholelithiasis)
• Acute pancreatitis
• Alcoholic hepatitis
• Ascariasis
• Bile duct strictures and cholangitis
• Biliary trauma and leaks
• Choledochal cysts
• Chronic pancreatitis
• Cirrhosis from various etiologies 
• Viral hepatitis, including chronic hepatitis B and hepatitis C
• Hepatocellular adenoma and carcinoma
• Mirizzi syndrome
• Primary biliary cholangitis
• Primary sclerosing cholangitis [25]

Malignant Diseases

• Ampullary carcinoma or adenoma
• Bile duct tumors (cholangiocarcinomas)
• Gallbladder cancer
• Pancreatic cancer
• Primary hepatic malignancies
• Enlarged malignant lymph nodes

Prognosis

The prognosis of biliary obstruction is highly dependent on the etiology. If left untreated, it can lead to life-threatening infection and sepsis. If the obstruction is persistent and chronic, it is usually due to a chronic liver pathology, which commonly has a poor prognosis. Most acute cases can be successfully managed with medical, surgical, or endoscopic treatment with full recovery. Obstruction caused by chronic liver disease and malignant etiology usually has a less favorable prognosis.

Complications

Acute Cholangitis

One of the most feared complications of biliary obstruction is acute ascending cholangitis, an infection of the biliary tree caused by obstruction. This can quickly lead to systemic sepsis and resultant multi-organ failure. 

Acute cholangitis can present as Charcot’s triad (right upper quadrant pain, fever, and jaundice) or Reynold’s pentad (Charcot's triad with mental status change and hemodynamic shock). Important and helpful laboratory evaluation includes elevated White blood cell count with leukocytosis, Abnormal liver testing with elevated bilirubin levels, alkaline phosphatase, and gamma-glutamyl transpeptidase. Elevation of bilirubin is generally in the form of conjugated hyperbilirubinemia. Important diagnostic tests include abdominal ultrasound, CT scan of the abdomen, and MRCP.

Severe cases of cholangitis present with:

• Hypotension requiring any vasopressor
• Mental status change
• PaO2/FiO2 less than 300
• Serum creatinine greater than 2.0 mg/dL
• INR greater than 1.5
• Platelet count less than 100000/mm^3 [26]

Treatment

General Principles

• Initial management for acute cholangitis requires admission to the hospital for IVF resuscitation and electrolyte replacement, pain control, and antibiotics with activity against enteric streptococci, coliforms, and anaerobes are generally needed.
• Low-risk community-acquired infections can be treated with ertapenem or piperacillin-tazobactam or combination therapy like ceftriaxone, ciprofloxacin, or levofloxacin with metronidazole.
• High-risk community-acquired infections can be treated with imipenem-cilastatin, meropenem, or piperacillin-tazobactam or combination therapy such as cefepime or ceftazidime with metronidazole.

Drainage ProceduresMost patients with cholangitis eventually require 1 of the following:

• Decompression procedure with ERCP (endoscopic retrograde cholangiopancreatography)
• Endoscopic removal of biliary stones with drainage of bile, often with sphincterotomy, PTC (percutaneous transhepatic cholangiography)
• Insertion of a needle into the biliary tract percutaneously for drainage, removal of stones, and possible placement of the biliary stent or surgical drainage
• Open or laparoscopic surgical intervention with biliary decompression, removal of the obstruction, and cholecystectomy if warranted and the patient is stable

Consultations

Biliary obstruction can result from various etiologies, which could be complex and considered difficult to access anatomy; its management may require a multi-specialty approach, including:

• Gastroenterology and hepatology
• Radiology
• Interventional radiology
• Pathology
• Oncology
• General or hepatobiliary surgery

Deterrence and Patient Education

Biliary Obstruction

• Blockage within the biliary tract leads to obstruction of bile flow to the small intestine.

Most Common Cause

• Gallbladder stones that can obstruct the biliary tract

Symptoms

• Right upper quadrant abdominal pain
• Pain in the back under the shoulder blade
• Nausea and vomiting
• Jaundice (yellowing of the skin)

Testing

• Laboratory evaluation and imaging
• Ultrasound of the abdomen
• Further testing is chosen appropriately depending on the initial testing results.

Treatment

• Treatment for biliary obstruction depends on the cause, but it is likely either surgical or non-surgical, including endoscopic.
• Surgical may include cholecystectomy to remove the gallbladder if the cause is gallstones, along with ERCP with sphincterotomy to remove any gallstones from the biliary tract causing an obstruction.
• Non-surgical treatment may include stabilization, pain control, and medications to help dissolve any gallstones that cause obstruction.
• Patients should eat a low-fat, high-fiber diet. They should avoid fried foods, canned fish, processed meats, full-fat dairy products, processed baked goods, fast food, and most packaged snack foods. Whole fruits and vegetables high in vitamin C, like kiwi and broccoli, and citrus fruits, like orange and grapefruit, may be beneficial.

Prevention of Recurrence

• Maintain a healthy body weight with proper nutrition and exercise

Enhancing Healthcare Team Outcomes

Biliary obstruction encompasses many conditions that result in a typical clinical finding of elevated bilirubin. Patients may first present to their primary care physicians or an emergency department for treatment. A prompt initial diagnosis helps drive therapy and improve outcomes in most patients. Special attention is necessary for timely diagnosis of infection of the bile ducts where patients present with fever, sepsis, and biliary obstruction findings, which can lead to poor prognosis. Initial laboratory and radiographic assessment determine the specialty needed to treat the obstruction, whether general surgery, gastroenterology, oncology, or interventional radiology. Management of biliary obstruction requires an interprofessional healthcare team of clinicians (including PAs and NPs), specialists, nurses, and pharmacists, all collaborating and communicating across disciplinary boundaries to achieve improved patient outcomes.

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Disclosure: Ethan Coucke declares no relevant financial relationships with ineligible companies.

Disclosure: Hina Akbar declares no relevant financial relationships with ineligible companies.

Disclosure: Arslan Kahloon declares no relevant financial relationships with ineligible companies.

Disclosure: Peter Lopez declares no relevant financial relationships with ineligible companies.