- Describe the spectrum of biliary tract diseases.
- Describe the classic history and physical exam findings for biliary tract disease.
- List the typical laboratory findings for different biliary tract diseases.
- Discuss the advantages and limitations of the different radiologic studies utilized in the diagnosis and differentiation of biliary tract disease.
- Describe a diagnostic algorithm for acute cholecystitis in patients with a high pretest probability of disease.
- Discuss the appropriate treatment and disposition decisions for patients with diseases of the biliary tract.
Diseases of the biliary tract (gallbladder and bile ducts) are common and result in significant morbidity and mortality. In the United States 20% of all people will suffer from symptomatic gallstones (cholelithiasis) at some time in their lives. If untreated, 20-30% of these patients will develop serious complications of gallstones such as choledocholithiasis, cholecystitis, and cholangitis. Pancreatitis is also a common complication of gallstones but will not be further discussed in this module.
- Cholelithiasis (gallstones) occurs as a result of supersaturation of bile with cholesterol (70%), pigments such as bilirubin (20%), or both (10%) combined with delayed emptying of the gallbladder (stasis).
- Choledocholithiasis refers to the presence of gallstones within the common bile duct.
- Acute Cholecystitis is inflammation of the gallbladder and is related to the presence of gallstones in 90-95% of cases. Acalculous cholecystitis occurs in <10% of cases and is seen more often in patients who are elderly, post-operative, or critically ill from other causes.
- Cholangitis is inflammation of the bile ducts and is most often caused by a polymicrobial bacterial infection. Biliary obstruction – such as from a stone or neoplasm – serves as a major factor in its pathogenesis. The condition is less common than cholecystitis, but has significantly higher mortality (40% vs 15%).
The classic presentation of biliary colic (episodic pain due to gallstone obstruction of the neck of the gallbladder) is right upper quadrant (RUQ) or epigastric pain associated with nausea and vomiting. The pain may radiate to the back, right flank or tip of the right scapula. It is often described as an intermittent or “colicky” pain that is burning, pressure-like, or heavy in nature. The patient may relate a history of prior similar episodes that occur in relation to the ingestion of fatty meals. Most episodes of uncomplicated biliary colic are self-limited and resolve within 4-6 hours with or without treatment.
Persistent pain (> 6 hours) and/or associated complaints of fever or jaundice suggest a more serious cause and should prompt further investigation for complications such as choledocholithiasis, cholecystitis, or cholangitis. Charcot’s triad (RUQ pain, fever, and jaundice) is the classic presentation of cholangitis and is seen in 70% of patients.
The physical exam findings for biliary tract disorders can vary depending on which disease state is present. The examination of patients with biliary colic may only reveal RUQ or epigastric tenderness. The cessation of deep inspiration on palpation over the gallbladder is considered a positive Murphy’s sign which has good sensitivity (63-90%), but low specificity (45-65%) for acute cholecystitis. Jaundice may be present when there is obstruction of the biliary tree as in cholangitis and choledocholithiasis. An elevated temperature suggestive of infection is seen in 1/3 of patients with cholecystitis and > 90% with cholangitis. Signs of sepsis such as hypotension and altered mental status may be present in severe cases.
The table below summarizes the typical laboratory results in select biliary tract diseases. It is important to note that while lab tests are typically normal in uncomplicated cholelithiasis, they can also be normal in acute cholecystitis and thus cannot reliably be used to distinguish between these two disease processes. This is particularly true in patients who are clinically judged to have a high pre-test likelihood of cholecystitis. Conversely, large elevations in bilirubin and alkaline phosphatase should alert the physician to the possibility of bile duct obstruction and the need for further evaluation.
Laboratory Studies in Biliary Tract Disease
or ↓ (if septic)
or ↓ (if septic)
|Transaminases (AST/ALT)||Normal or slightly ↑||Normal or slightly ↑||Normal or slightly ↑||↑|
|Bilirubin (conjugated)||Normal||↑||Normal or slightly ↑||↑|
|Alkaline phosphatase||Normal or slightly ↑||↑||Normal or slightly ↑||↑|
|Amylase/lipase||Normal||Normal||Normal||Normal or slightly ↑|
US is the initial diagnostic study of choice for evaluation of biliary tract diseases. It is a low risk, non-invasive procedure that is usually readily available. US is quite sensitive (>95%) for the identification of cholelithiasis which is diagnosed by the presence of mobile echogenic material within the gallbladder (GB) that casts posterior shadows. Stones outside of the gallbladder, however, may be missed by US which is significantly less sensitive (<80%) for choledocholithiasis. Dilation of the common bile duct (> 6mm in adults, > 8mm in elderly) indicates the likely presence of biliary duct stone or other obstruction and may be seen in choledocholithiasis and cholangitis.
The sensitivity and specificity of ultrasound for acute cholecystitis is estimated to be between 88-94% and 78-80%, respectively. The important ultrasonographic findings of acute cholecystitis include the presence of gallstones, GB wall thickening (5mm or greater), pericholecystic fluid, and/or a positive sonographic Murphy’s sign (maximum tenderness with pressure from the US transducer directly over the gallbladder). Distention of the GB and increased blood flow to GB on Doppler studies can also be seen. The diagnosis of cholecystitis is supported by a combination of these findings. The positive predictive value (PPV) of the presence of stones and a positive Murphy’s sign has been reported to be 92%. The PPV of stones and GB wall thickening has been reported to be 95%. In terms of excluding cholecystitis, an ultrasound that does not detect any stones in combination with either a normal GB wall or negative Murphy’s sign has a negative predictive value of 95%.
Hepatobiliary imino-diacetic acid scan (HIDA)
HIDA scan is 90-94% sensitive for the presence of acute cholecystitis and is indicated if US is equivocal or negative for cholecystitis in the presence of a high clinical suspicion.
A HIDA scan is a nuclear imaging procedure that utilizes a radioactive tracer, technetium-99m, to evaluate GB function. The tracer is injected intravascularly, circulates to the liver, and is excreted into the biliary system. A normal (or negative) HIDA is visualization of the gallbladder within 1 hour of tracer injection. Lack of visualization of the GB within 4 hours after the injection constitutes a positive study and indicates the presence of cholecystitis or cystic duct obstruction.
As CT is often the initial imaging study of choice in the evaluation of undifferentiated abdominal pain, it also plays an important role in the diagnosis of biliary disease. While it is relatively insensitive (<70%) for gallstones, it has a sensitivity of 92% for the diagnosis of acute cholecystitis due to its ability to detect GB distention, GB wall thickening, and pericholecystic fluid. It is furthermore highly sensitive (>96%) for evidence of biliary obstruction.
In the setting of equivocal ultrasound results, CT can be considered as the next diagnostic step if HIDA scan is unavailable or if a broad differential to the patient’s abdominal pain is still being considered. CT may outperform ultrasound in the detection of rare complications of acute cholecystitis such as emphysematous cholecystitis or GB perforation.
Less than 20% of gallstones will contain sufficient calcium to be visible on X-ray. In general, x-rays are not utilized in the work-up of biliary disease due to their poor sensitivity.
When choledocholithiasis is suspected an ERCP may be indicated. ERCP is used to both diagnose and treat diseases of the biliary and pancreatic ducts. In this technique an endoscope is passed through the GI tract into the biliary system. Fluoroscopy allows visualization of dye injected into the biliary tree and obstructions can be identified. This is an invasive procedure associated with significant risks including pancreatitis (~5%), perforation of the GI tract or ductal system, dye reactions, and bleeding. Due to these risks, its use strictly for diagnosis is decreasing as less invasive diagnostic studies such as magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound become more widely available.
So how do you make the diagnosis?
Diagnosis of biliary tract disease is made based on:
- History and physical examination
- Laboratory studies – CBC, liver function tests (LFT’s), pancreatic enzymes
- Imaging – US, HIDA, CT, ERCP
Listen to the History
A history of similar prior episodes following the ingestion of fatty meals is classic for biliary colic. The persistence of symptoms longer than 6 hours or complaints of fever or jaundice suggest more serious disease.
Consider the Patient’s Risk Factors
- Female gender
- Age > 40 years
- Family history
- Rapid weight loss
- Sickle Cell or other hemolytic disorders (pigmented stones)
- Diabetes (increased risk of cholecystitis)
Look at the Patient
A well-appearing appearing patient with RUQ pain and/or nausea and vomiting that resolves is likely suffering from uncomplicated biliary colic. Jaundice, fever, and/or a toxic appearance should raise your suspicion for complications such as acute cholecystitis or cholangitis.
Look at the Tests
In patients with suspected biliary disease, the presence of an abnormal white count and/or transaminitis should alert the physician to the possibility of inflammation of the gallbladder. Significant elevations of alkaline phosphatase and bilirubin should raise concern for obstruction of the biliary tract. Conversely, normal labs should not preclude the use of diagnostic imaging when there is a strong clinical suspicion for acute cholecystitis.
Ultrasound serves as the initial imaging study of choice. The diagnosis of acute cholecystitis is supported by the detection of gallstones in conjunction with gallbladder wall thickening, pericholecystic fluid, and/or a positive sonographic Murphy’s sign. The presence of ductal dilatation should raise concern for obstruction of the common bile duct. Normal labs and the presence of gallstones without other findings on US suggest biliary colic. Due to its greater sensitivity, HIDA scanning should be considered in patients with equivocal ultrasound findings or in patients with normal ultrasound results but who have ongoing pain and a high pretest probability of disease.
Episodes of biliary colic are usually self-limited and can be treated symptomatically with pain control (NSAIDS and/or narcotic pain medications), fluid resuscitation and antiemetics. While medical treatments (oral dissolving agents and dietary changes) are available, the definitive treatment for symptomatic cholelithiasis is surgical removal of the gallbladder (cholecystectomy).
Choledocholithiasis is treated with surgical or endoscopic (ERCP) removal of the stone.
Initial treatment of cholecystitis and cholangitis is similar to that for biliary colic – symptom control with fluids, antiemetics and analgesics. In addition, broad-spectrum parenteral antibiotics such as ampicillin/sulbactam, a fluoroquinolone, or a third-generation cephalosporin +/- metronidazole should be administered early. In the presence of sepsis, aggressive fluid resuscitation and blood pressure support may be necessary. Prompt surgical consultation is imperative. Cholecystectomy is indicated in cholecystitis, but may be delayed, especially in the critically ill patient. Immediate surgical or percutaneous decompression (cholecystostomy) may be necessary in either condition.
Patients with biliary colic whose symptoms are improving may be discharged home with outpatient referral to a general surgeon for consideration of an elective cholecystectomy. They should be advised to return immediately for signs of complications of gallstones such as prolonged symptoms (> 6 hours), and/or symptoms associated with fever (> 100.4 F) or jaundice.
Most patients with choledocholithiasis should be admitted for definitive treatment due to high rates of associated complications such as cholangitis, pancreatitis, gallbladder perforation and gangrene. An exception could be considered for the reliable, asymptomatic patient who has appropriate outpatient follow up.
All patients with acute cholecystitis and cholangitis must be admitted to the hospital for IV antibiotics and possible surgical intervention. In the presence of signs of sepsis ICU admission may be required.
Pearls and Pitfalls
- Lab tests alone do not reliably distinguish cholelithiasis from acute cholecystitis.
- Acute cholecystitis should be suspected and a surgical consult and/or HIDA scan obtained in any patient with unexplained RUQ pain and a fever regardless of the WBC count or US findings.
- RUQ pain lasting more than 6 hours should NOT be attributed to benign biliary colic regardless of the presence or absence of significant laboratory or imaging abnormalities. Persistent pain should prompt admission and further evaluation.
- Don’t forget to include non-biliary causes or RUQ pain in your differential diagnosis. These include hepatitis, right lower lobe pneumonia, kidney stone/infection, and acute coronary syndrome with atypical presentation.
- Written By: Suzanne Dooley-Hash, University of Michigan, Ann Arbor, Michigan
- Edited By: David Gordon, Duke University, Durham, North Carolina
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