Causes of Severely Diminished Gallbladder Ejection Fraction
A severely diminished gallbladder ejection fraction (GBEF <38%, particularly values as low as 2%) is caused by either gallbladder hypomotility (impaired contractility of the gallbladder muscle itself) or dyskinesia (partial structural or functional obstruction distal to the gallbladder), both resulting in functional gallbladder disorder. 1
Primary Pathophysiologic Mechanisms
The two main mechanisms that cause severely reduced GBEF are:
Gallbladder hypokinesia: Impaired gallbladder contractility where the smooth muscle of the gallbladder fails to contract adequately in response to cholecystokinin (CCK) stimulation 1
Gallbladder dyskinesia: Partial obstruction (either structural or functional) distal to the gallbladder, including at the cystic duct or sphincter of Oddi, preventing adequate emptying despite attempted contraction 1
Discoordination between gallbladder contraction and sphincter of Oddi relaxation: The gallbladder may contract, but if the sphincter of Oddi fails to relax simultaneously, bile cannot exit effectively 1
Clinical Context and Diagnosis
When evaluating a severely diminished GBEF, the underlying pathophysiology remains poorly understood despite these proposed mechanisms 1. The condition is part of functional gallbladder disorder (FGBD), which has been called by multiple names including gallbladder dyskinesia, chronic acalculous gallbladder dysfunction, and biliary dyskinesia 1.
Key diagnostic considerations:
Normal GBEF is defined as ≥38% when measured using standardized CCK-cholescintigraphy with 0.02 μg/kg sincalide infused over 60 minutes 1, 2
A GBEF of 2% is substantially below the normal threshold and indicates severely impaired gallbladder contractility 2
The diagnosis requires biliary-type pain meeting Rome III criteria: episodes lasting ≥30 minutes, occurring at different intervals (not daily), building to steady level, severe enough to interrupt activities, and not relieved by bowel movements, postural change, or antacids 1
Potential Underlying Etiologies to Exclude
Before attributing symptoms solely to low GBEF, rule out these structural causes:
Cystic duct syndrome or mild biliary strictures: Non-obstructive strictures in the common bile duct or cystic duct can present with reduced GBEF and may respond to ERCP with sphincterotomy rather than cholecystectomy 3
Sphincter of Oddi dysfunction: This can coexist with or mimic gallbladder dysfunction and should be considered, particularly if symptoms persist after cholecystectomy 2, 4
Chronic acalculous cholecystitis: Pathologic examination after cholecystectomy reveals chronic cholecystitis in approximately 95% of patients with biliary dyskinesia 5
Critical Methodologic Considerations
Ensure the test was performed correctly to avoid false results:
Verify the standardized protocol was used (0.02 μg/kg sincalide over 60 minutes) as different infusion rates significantly affect results 6, 2
Rapid CCK infusion (<30 minutes) can cause non-specific abdominal symptoms and artificially low GBEF measurements 6, 2
Confirm proper patient preparation including adequate fasting and avoidance of medications affecting gallbladder contraction 2
Common Pitfalls
Do not assume all low GBEF values indicate primary gallbladder disease: Alternative diagnoses including sphincter of Oddi dysfunction, functional gastrointestinal disorders, GERD, and peptic ulcer disease must be investigated and treated before attributing symptoms to the gallbladder 2, 5
Symptom provocation during CCK infusion is not a reliable diagnostic indicator of gallbladder disease and should not be used to guide management 7
In patients without typical biliary pain or with atypical symptoms, the false positive rate increases substantially, making alternative diagnoses more likely 1