What is the possible cause of right upper quadrant (RUQ) pain in a patient with normal anatomical structures?

RUQ Pain with Normal Anatomical Structures: Functional Gallbladder Disorders

When all anatomical structures appear normal on imaging, the most likely cause of RUQ pain is functional gallbladder disease, specifically biliary dyskinesia (low ejection fraction) or biliary hyperkinesia (high ejection fraction), which requires hepatobiliary scintigraphy (HIDA scan) for diagnosis. 1, 2

Primary Diagnostic Consideration

• Functional gallbladder disorders account for a significant proportion of RUQ pain when standard imaging is unremarkable, as ultrasound has 96% accuracy for structural gallbladder pathology but cannot assess gallbladder function 3, 4
• Over one-third of patients with RUQ pain do not have acute cholecystitis or structural abnormalities, requiring evaluation beyond standard anatomical imaging 5, 4

Algorithmic Diagnostic Approach

Step 1: Confirm Adequate Initial Workup

• Verify that right upper quadrant ultrasound was performed as the first-line study, which is rated 9/9 for appropriateness by the American College of Radiology 1, 6
• Ensure complete metabolic panel including liver function tests (AST, ALT, alkaline phosphatase, GGT, bilirubin) was obtained to exclude hepatobiliary pathology 1, 3
• Confirm beta-hCG was checked in all women of reproductive age to exclude ectopic pregnancy 1

Step 2: Order Hepatobiliary Scintigraphy (HIDA Scan)

• The American College of Radiology recommends cholescintigraphy when ultrasound findings are negative or equivocal, as it evaluates gallbladder function rather than just anatomy 1, 3
• HIDA scan with cholecystokinin (CCK) stimulation measures gallbladder ejection fraction (GBEF) to diagnose functional disorders 3, 2
• Biliary dyskinesia is defined as GBEF <35% at 1 hour, representing inadequate gallbladder contractility 3
• Biliary hyperkinesia is defined as GBEF >80-85% at 1 hour, representing excessive gallbladder contractility and is an overlooked cause of RUQ pain 2

Step 3: Consider Alternative Functional Causes

Colonic Causes with Referred Pain

• Pain specifically triggered by bowel movements suggests hepatic flexure pathology or splenic flexure syndrome rather than primary hepatobiliary disease, which typically presents with postprandial pain 1
• Biliary colic can be triggered by increased intra-abdominal pressure during Valsalva maneuvers while defecating if functional gallbladder disease is present 1

Non-GI Causes to Exclude

• Musculoskeletal pain from thoracic wall muscles can mimic RUQ pain and should be assessed by palpation and reproduction of pain with movement 7
• Pulmonary causes including lower lobe pneumonia or pleurisy can present as RUQ pain 7
• Esophageal or gastric pathology may refer pain to the RUQ 7

Treatment Algorithm Based on HIDA Results

If GBEF <35% (Biliary Dyskinesia)

• Laparoscopic cholecystectomy provides significant symptomatic relief in patients with biliary dyskinesia and should be considered as definitive treatment 2
• Surgical intervention is appropriate when pain causes significant distress and impairs quality of life 2

If GBEF >80-85% (Biliary Hyperkinesia)

• Laparoscopic cholecystectomy has been shown to provide complete resolution of symptoms in biliary hyperkinesia, though this remains a poorly understood and underrecognized entity 2
• Reproducible RUQ pain 40 minutes after consuming a fatty meal supports the diagnosis 2

Critical Clinical Pitfalls

• Do not assume negative ultrasound excludes gallbladder pathology—ultrasound only evaluates structure, not function, and functional disorders require HIDA scan for diagnosis 1, 3
• Never skip ultrasound and proceed directly to CT, as CT has only 75% sensitivity for gallstones compared to ultrasound's 96% accuracy and exposes patients to unnecessary radiation 3, 6
• Many patients with normal baseline investigations remain undiagnosed or are managed medically due to lack of understanding of functional gallbladder disorders, leading to prolonged symptoms and impaired quality of life 2
• Recognize that biliary hyperkinesia is a rare but real entity that is frequently overlooked in clinical practice 2
• If HIDA scan is also normal, consider CT abdomen/pelvis with IV contrast to evaluate for colonic pathology, which has >95% sensitivity for detecting alternative diagnoses 1