Stephanie L. Hansel, MD, MS
True/False: The gallbladder empties during fasting.
True. During fasting, 25% of gallbladder contents empty approximately every 120 minutes. This coincides with the phase III component of the migrating motor complex seen in the intestine.
What happens to the gallbladder in the fed state?
Eating initiates gallbladder contraction through both neural (cephalic and local gastroduodenal reflexes) and hormonal (cholecystokinin) influences. This results in the emptying of over 75% of the gallbladder contents.
What are the phases of gallbladder emptying?
Gallbladder emptying after meals consists of three phases: 1) Cephalic phase—stimulated by sham feeding; 2) gastric phase—stimulated by distension of the stomach and the gastroduodenal reflex; and 3) intestinal phase—stimulated by hormones. The bulk of the contractions occur during the gastric and intestinal phases.
True/False: Fat, protein, and carbohydrate lead to gallbladder contraction.
True. Meal composition determines cholecystokinin release and, hence, gallbladder contraction. Protein and fat result in gallbladder contraction via cholecystokinin release, while carbohydrate also causes gallbladder contraction but via an unknown mechanism.
How does motilin affect the gallbladder?
Motilin induces gallbladder contraction indirectly via cholinergic nerves.
True/False: Patients with gallstones have reduced gallbladder emptying.
True. This impairment results from depression of gallbladder contractility and not the gallstones themselves.
What are the Rome III criteria for diagnosis of functional gallbladder disorder (aka, gallbladder dyskinesia)?
• Episodic pain in the right upper quadrant or epigastrium.
• Episodes last ≥ 30 minutes.
• Symptoms recur at different intervals (not daily).
• Pain builds up to a steady level and is of moderate to severe intensity to the point of interrupting daily activities or prompting a visit to the emergency room.
• Pain not relieved by bowel movements, postural changes, or antacids.
• Other structural diseases to explain the symptoms have been excluded.
• The pain may be associated with nausea and vomiting, radiation to the back and/or right subscapular region, or nocturnal awakening.
• Gallbladder is present.
• Normal liver and pancreatic enzymes.
What is the prevalence of gallbladder dyskinesia?
The estimated prevalence is 8% in men and 21% in women.
True/False: The pathophysiology of gallbladder dyskinesia is well established?
False. The pathogenesis is poorly understood. Multiple theories have been proposed including cholesterolosis, microlithiasis, biliary sludge, chronic cholecystitis, gallbladder dysmotility, narrowed cystic duct, cystic duct spasm, and visceral hypersensitivity.
What test should be ordered to support the diagnosis of gallbladder dyskinesia?
Cholecystokinin-cholescintigraphy (CCK-CS), commonly referred to as a “CCK-HIDA scan” since the test utilizes both CCK and 99mtechnicium-labeled hepatoiminodiacetic acid (HIDA). HIDA is a radioisotope that is taken up by the liver and excreted into the biliary system, where it accumulates in the gallbladder, thus allowing for calculation of the gallbladder ejection fraction after stimulating gallbladder emptying.
True/False: The reproduction of the patient’s characteristic pain and/or other symptoms during a CCK-HIDA scan reliably predicts which patients will respond best to cholecystectomy.
False. Pain reproduction with CCK infusion is generally considered to be poorly predictive of outcome following cholecystectomy.
Why is cholecystokinin used?
Cholecystokinin is the most potent stimulus of gallbladder emptying and, in addition, causes relaxation of the sphincter of Oddi via inhibitory nerves.
What is the gallbladder ejection fraction?
It is a quantitative measurement of gallbladder emptying. The cut-off value of an abnormal gallbladder ejection fraction remains unclear due to differences in CCK-CS technique; however, a recent study using a state-of-the-art 60-minute CCK infusion methodology suggests that a value less than 38% should be considered abnormal.
What drugs cause impaired gallbladder emptying?
The most common drugs that cause impaired gallbladder emptying are narcotics and anticholinergic agents.
What is the treatment for gallbladder dyskinesia?
True/False: Patients with suspected gallbladder dyskinesia who have primarily atypical symptoms such as bloating and epigastric fullness respond to cholecystectomy as well as patients with only the classical symptoms of episodic epigastric or right upper quadrant pain.
What are the three components of the sphincter of Oddi?
The three components are the sphincter choledochus, sphincter pancreaticus, and sphincter ampulla, which surround the distal common bile duct, duct of Wirsung, and common channel, respectively.
What is the role of the sphincter of Oddi?
It regulates flow of pancreatic and biliary secretions into the duodenum by its basal pressure and prevents the reflux of material from the duodenum into the duct by its phasic contractions.
What is the normal basal sphincter of Oddi pressure?
The normal mean basal sphincter of Oddi pressure is less than 35 mmHg.
What are the features of the normal phasic contractions of the sphincter of Oddi?
The phasic contractions consist of three components: amplitude, duration, and frequency. The amplitude is less than 220 mmHg with a duration less than 8 seconds and a frequency of less than 10 per minute.
What drugs relax the sphincter of Oddi?
Anticholinergics, nitrates, calcium channel blockers, and glucagon.
What is the gold standard for the diagnosis of functional sphincter of Oddi disorder (aka, sphincter of Oddi dysfunction [SOD])?
Sphincter of Oddi manometry.
What manometric findings are typical in patients with SOD?
Manometric criteria include: 1) elevated basal sphincter pressure, 2) increased frequency of phasic contractions, 3) increased proportion of phasic contractions propagated in the retrograde direction, and 4) paradoxical sphincter response to CCK-OP (cholecystokinin-octapeptide) injection. In clinical practice, a basal sphincter pressure > 40 mmHg is the single most useful parameter in which to make this diagnosis.
What type of catheter is most commonly used in biliary manometry?
A triple-lumen, water-perfused catheter. The use of one lumen for aspiration may reduce the risk of procedure-related pancreatitis. The use of a solid-state, nonperfused catheter is available; however, further studies are needed before its routine use can be recommended.
True/False: Glucagon affects sphincter of Oddi manometry.
True. Glucagon causes a relatively brief period of relaxation of the sphincter and so a waiting period of 8–10 minutes is suggested before measuring the basal sphincter pressure if glucagon was used to aid in cannulation.
True/False: Benzodiazepines affect sphincter of Oddi manometry.
False. Benzodiazepines do not affect the sphincter and can be used as a sedative for patients undergoing sphincter of Oddi manometry.
True/False: Anticholinergics affect sphincter of Oddi manometry.
True. Anticholinergics should be avoided as they inhibit sphincter of Oddi motor activity.
True/False: The use of meperidine should be avoided during sphincter of Oddi manometry.
False. Meperidine at a dose of < 1 mg/kg does not alter basal sphincter pressure although it does influence phasic activity.
What are the indications for sphincter of Oddi manometry?
Patients with idiopathic pancreatitis and patients with unexplained pancreaticobiliary pain with or without abnormal liver or pancreatic enzymes.
What are the four clinical criteria for the diagnosis of SOD type I?
1) Typical biliary-type pain, 2) elevated aspartate aminotransferase or alkaline phosphatase > 2 times normal and measured on more than two occasions, 3) delayed drainage of contrast more than 45 minutes at the time of ERCP, and 4) dilated common bile duct more than 12 mm. The third criterion is seldom used in routine clinical practice.
What is SOD type II?
Patients with typical biliary-type pain and one or two of the previously mentioned criteria.
What is SOD type III?
Patients with typical biliary-type pain and no other abnormalities. The clinical relevance of this category remains controversial.
True/False: Sphincter of Oddi manometry is always indicated in type I SOD.
False. It is not necessary before endoscopic sphincterotomy since these patients appear to benefit from sphincterotomy regardless of findings on manometry.
True/False: Sphincter of Oddi manometry is always indicated in type II or III SOD.
True. Sphincter of Oddi manometry is mandatory in these patients to confirm the presence of SOD and to predict the subset that will benefit from sphincterotomy. Those with elevated basal pressures more predictably experience improvement of pain after sphincterotomy.
How does SOD cause pain?
It is postulated that, by impeding the flow of pancreatic and biliary secretions, there is a resulting increase in the ductal pressure (ductal hypertension), causing pain.
What is the estimated frequency of SOD in patients with biliary-type pain following cholecystectomy?
What is the best predictor of pain relief in patients with SOD after sphincterotomy?
Elevated basal sphincter pressure (> 40 mmHg).
What are the indications for surgical sphincter of Oddi ablation?
1) Recurrent stenoses after repeated endoscopic sphincterotomies, 2) when an experienced therapeutic endoscopist is not available, and 3) when endoscopic sphincterotomy is not technically feasible.
What pharmacological agents have been used in the treatment of SOD?
Nitrates and nifedipine. There has also been recent interest in the use of botulinum toxin injections into the sphincter of Oddi.
What is the Nardi test?
A positive result occurs when the injection of morphine, 10 mg subcutaneously, or neostigmine, 1 mg subcutaneously, causes typical biliary-type pain with an associated fourfold increase in aminotransferases, alkaline phosphatase, amylase, or lipase. A positive test may occur in patients with SOD; however, it can also occur in patients with choledocholithiasis. This test is neither sensitive nor specific. Morphine causes sphincter of Oddi contraction, whereas neostigmine increases the pancreatic flow of secretions.
What is a positive secretin stimulation test?
A positive result occurs when secretin administration leads to dilatation of the common bile duct and main pancreatic duct, as detected by ultrasound or magnetic resonance imaging. This may occur when the sphincter of Oddi is dysfunctional causing obstruction. Secretin normally results in sphincter of Oddi relaxation.
What is the role of magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of SOD?
MRCP can be used instead of ERCP to noninvasively assess for alternative etiologies of the patient’s symptoms such as biliary stone disease or pancreatic disease. The use of a provocative MRCP (eg, secretin-stimulated MRCP) to stimulate bile flow and measure ductal diameter changes with MRCP is available but remains poorly validated in the setting of SOD and the clinical utility remains uncertain.
What is a positive hepatobiliary scintigraphy test?
This test assesses bile flow through the biliary tract and into the duodenum. A positive test is defined as a duodenal arrival time greater than 20 minutes and a hilum to duodenal time greater than 10 minutes. This test is not widely performed and remains of uncertain clinical utility in the diagnosis of SOD.
• • • SUGGESTED READINGS • • •
Hansel SL, DiBaise JK. Functional gallbladder disorder: gallbladder dyskinesia. Gastroenterology Clinics of North America. 2010 Jun;39(2):369-379.
Petersen BT. Functional gall-bladder and sphincter of Oddi disorders. In: Talley NJ, Lindor KD, Vargas HE, eds. Practical gastroenterology and hepatology. Liver and biliary disease. Chichester, Hoboken: Wiley-Blackwell; 2010:365-373.