Diagnostic Approach for Gallbladder Disease
The diagnosis of gallbladder disease requires a combination of clinical assessment (particularly Murphy's sign and right upper quadrant tenderness), laboratory testing (elevated white blood cell count, C-reactive protein, and neutrophil count), and imaging with transabdominal ultrasonography as the initial test of choice. 1, 2
Clinical Evaluation
Key Symptoms to Identify
- Right upper quadrant or epigastric pain that lasts at least 30 minutes, builds to a steady level, and is severe enough to interrupt activities 1, 3
- Recurrent episodes occurring at different intervals (not daily) 1
- Associated features: nausea and vomiting, pain radiating to the back or right infrascapular area, pain that awakens the patient from sleep 1, 3
- Food intolerance and possible palpable gallbladder mass in advanced cases 2
Physical Examination Findings
- Murphy's sign (inspiratory arrest during deep palpation of the right upper quadrant) has a positive likelihood ratio of 2.8, though the confidence interval includes 1.0 1, 4
- Right upper quadrant tenderness with a negative likelihood ratio of 0.4 1
- Murphy's sign is more characteristic of acute rather than chronic cholecystitis, and its absence is unreliable if the patient has received pain medication 4
Important caveat: No single clinical sign or laboratory test has sufficient diagnostic power to establish or exclude acute cholecystitis on its own 2. The combination of history, physical examination, and laboratory tests yields better diagnostic accuracy, with one study showing a positive likelihood ratio of 25.7 when findings are combined 1.
Laboratory Testing
Essential Tests
- White blood cell count and C-reactive protein are associated with cholecystitis 2
- Neutrophil count shows the strongest association with acute cholecystitis, with 70% sensitivity and 65.8% specificity 1, 2
- Liver function tests (transaminases, alkaline phosphatase, bilirubin) to assess for common bile duct stones 1
- Amylase and lipase to evaluate for gallstone pancreatitis 3
Imaging Studies
First-Line Imaging
Transabdominal ultrasonography is the initial imaging test of choice due to its availability, lack of radiation exposure, high sensitivity for detecting gallstones, and ability to evaluate alternative diagnoses 4, 3, 5.
Key ultrasound findings include:
- Presence of gallstones 4
- Sonographic Murphy's sign (tenderness reproducing the patient's pain when the probe compresses directly on the gallbladder) 4
- Gallbladder wall thickening 1
- Pericholecystic fluid 1
Diagnostic accuracy: The presence of gallstones plus a positive sonographic Murphy's sign has a 92% positive predictive value for acute cholecystitis 4. Conversely, the absence of stones combined with either a normal gallbladder wall or negative Murphy's sign has a 95% negative predictive value 4.
Second-Line Imaging
When ultrasound is equivocal or negative but clinical suspicion remains high:
- Hepatobiliary iminodiacetic acid (HIDA) scan (cholescintigraphy) can evaluate for acute cholecystitis and functional gallbladder disorder 1, 3
- Magnetic resonance cholangiopancreatography (MRCP) is accurate and noninvasive for identifying choledocholithiasis, biliary obstruction, and certain malignancies 1, 3
- Contrast-enhanced ultrasound (CEUS) can differentiate tumefactive sludge from true gallbladder masses when available 1
- Computed tomography is less interpreter-dependent than ultrasound but has inferior diagnostic accuracy compared to CEUS or MRI for characterizing gallbladder lesions 1
Important consideration: Endoscopic retrograde cholangiopancreatography (ERCP) should be reserved for therapeutic purposes only, not purely diagnostic evaluation, due to complication rates including pancreatitis (3-5%), bleeding (2%), cholangitis (1%), and procedure-related mortality (0.4%) 1. When extrahepatic obstruction is suspected but therapeutic intervention is uncertain, MRCP or endoscopic ultrasound should be performed first 1.
Follow-Up Imaging
Short-interval follow-up ultrasound within 1-2 months with optimized technique and patient preparation may help differentiate tumefactive sludge from true gallbladder masses or polyps when initial imaging is challenging 1.
Risk Stratification for Common Bile Duct Stones
Patients should be stratified for risk of common bile duct stones based on clinical, laboratory, and imaging findings 2:
- High-risk patients should undergo preoperative ERCP 2
- Moderate-risk patients should undergo second-level examinations such as MRCP, endoscopic ultrasound, or intraoperative cholangiography 2
Special Diagnostic Considerations
Functional Gallbladder Disorder
For suspected functional gallbladder disorder, patients should meet Rome III criteria (biliary-type pain with normal liver and pancreatic enzymes, intact gallbladder without stones on ultrasound) and undergo cholecystokinin-cholescintigraphy (CCK-CS) to measure gallbladder ejection fraction 1. Upper endoscopy should be performed to exclude other causes before CCK-CS 1.
Gallbladder Polyps
For incidentally detected gallbladder polyps, ultrasound characteristics guide management, with CEUS or MRI helpful for further characterization of lesions larger than 10 mm 1.
Acalculous Cholecystitis
In critically ill patients, diagnosis relies more heavily on imaging findings (gallbladder wall thickening, pericholecystic fluid, gallbladder distension) as clinical signs may be masked by underlying illness 1.