Functional gallbladder disorder is biliary pain from motility disturbance in the absence of gallstones, sludge, or microcrystal disease. In patients with biliary-type pain and a normal US, the prevalence is 8% men and 21% women. We will review the clinical manifestations, diagnosis, and management of patients with suspected functional gallbladder disorder, and also address current evaluation and management of sphincter of Oddi dysfunction.

1. Fun Functional
Gallbladder Disorders:
Update on Hypo and
Hyperkinetic Gallbladder and
Sphincter of Oddi Dysfunction
Patricia L. Raymond MD FACG

2. Dr. Raymond has no relevant relationships
with commercial interest organizations
whose products are related to the program content.
The Society of Gastroenterology Nurses and Associates, Inc. is accredited as a provider of
continuing nursing education by the American Nurses Credentialing Center’s (ANCC)
Commission on Accreditation.
Disclosures

3. Say ‘hello’ to my
little friend

4. From http://i0.wp.com/www.theayurveda.org/wp-content/uploads/2015/09/Anatomy-of-Ga

5. Gallbladder- what does it do?
• Stores bile, aka ‘gall’, needed for the digestion of fats
• Produced by the liver, bile flows through small vessels
into the larger hepatic ducts and ultimately through the
cystic duct into the gallbladder for storage.
• The gallbladder can store 30 to 60 ml of bile
• The gallbladder is an ‘optional organ’
• Name the three solo optional organs

7. The death of Alexander the Great may have been associated with an acute episode of cholecystitis.

8. “You have a lot of gall!”
To have 'gall' is associated with bold behavior
To have 'bile' is associated with bitterness
In the Chinese language, the gallbladder (Chinese: 膽) is
associated with courage (terms such as "a body completely of gall"
describes a brave person, and "single gallbladder hero" describes a
lone hero
In the Zangfu theory of Chinese medicine, the gallbladder not only
has a digestive role, but is seen as the seat of decision-making

9. Single Gallbladder Hero

10. fromhttps://www.healthcareatoz.com/
gallstones-causes-symptoms-and-types/

11. Gallbladder Surgery
First surgical removal of a gallstone
(cholecystolithotomy) was in 1676 by physician
Joenisius, who removed the stones from a
spontaneously occurring biliary fistula after an
abscess burst.
Stough Hobbs in 1867 performed the first
recorded surgical cholecystotomy
German surgeon Carl Langenbuch performed the
first cholecystectomy in 1882 for a sufferer of
cholelithiasis.

13. Boring typical gallbladder disease:
“Calculous cholecystitis”
• Acute cholecystitis
develops in 6-11% with
symptomatic gallstones
over a median follow-up of
7-11 years
• Occurs with cystic duct
obstruction, but the development
of acute cholecystitis is NOT fully
explained by cystic duct
obstruction aloneNatural history of asymptomatic and symptomatic gallstones.
Friedman GD Am J Surg. 1993 Apr;165(4):399-404.
Roles of lithogenic bile and cystic duct occlusion in the pathogenesis of acute cholecystitis.
Roslyn JJ, DenBesten L, Thompson JE Jr, Silverman BF Am J Surg. 1980;140(1):126.

14. Not fully explained by cystic duct
obstruction alone: Lysolecithin
• An additional irritant is required to develop gallbladder inflammation
• Lysolecithin, is produced from lecithin, a normal constituent
of bile
• The production of lysolecithin from lecithin is catalyzed by
phospholipase A, which is present in gallbladder mucosa
• This enzyme is released into the gallbladder following
trauma to the gallbladder wall from an impacted
gallstone
• Lysolecithin (normally absent in bile) is detectable in
gallbladder bile in patients with acute cholecystitis
Natural history of asymptomatic and symptomatic gallstones.
Friedman GD Am J Surg. 1993 Apr;165(4):399-404.
Roles of lithogenic bile and cystic duct occlusion in the pathogenesis of acute cholecystitis.
Roslyn JJ, DenBesten L, Thompson JE Jr, Silverman BF Am J Surg. 1980;140(1):126.

15. Not fully explained by cystic duct
obstruction alone: Prostaglandins
• Inflammatory mediators are released in response to gallbladder
inflammation
• Further propagate the inflammation
• Prostaglandins are involved in gallbladder contraction and fluid
absorption
• Probably play a central role in this process
• The prostaglandin hypothesis is supported by the observation that
prostaglandin inhibitors can reduce intraluminal gallbladder
pressure and relieve biliary colic
• Indomethacin, Sulindac
Treatment of biliary colic with diclofenac: a randomized, double-blind, placebo-controlled study.
Akriviadis EA, Hatzigavriel M, Kapnias D, Kirimlidis J, Markantas A, Garyfallos A
Gastroenterology. 1997;113(1):225.

16. Fromhttp://geoffreye-reedlife.blogspot.com/2012/12/gallstones.html
Pink “What about
pus?”

17. Infection is not as common as you’d expect
•Prospective study of 467 subjects divided into seven groups:
•42 control subjects with normal biliary tracts
•221 patients with symptomatic gallstone disease
•12 patients with hydropic gallbladder
•52 patients with acute cholecystitis
•67 patients with common bile duct stones without cholangitis
•49 patients with common bile duct stones and acute
cholangitis
•24 patients with previous cholecystectomy and common bile
duct stones
Simultaneous bacteriologic assessment of bile from gallbladder and common bile duct in
control subjects and patients with gallstones and common duct stones.Csendes A, Burdiles
P, Maluenda F, Diaz JC, Csendes P, Mitru N Arch Surg. 1996;131(4):389.

18. Hydrops of the gallbladder
AKA gallbladder mucocele
• Overdistended gallbladder filled
with mucoid or clear and watery
content
• Usually noninflammatory
• Outlet obstruction of the
gallbladder by an impacted
stone in the neck of the
gallbladder or in the cystic duct.
http://www.imed.ro/chirurgie/P%202/CAZURI%20CLINICE%20P2/BREZEAN
=hidrops=cronic/CTG_0716_AUT35807.JPG
http://surgery.0catch.com/gallbladder/

19. Gallbladder infection is strange…
•Control subjects: no bacteria in gallbladder bile
•Gallstones, acute cholecystitis, and hydropic gallbladder:
22% to 46%
•Significantly higher in patients with common bile duct
stones without cholangitis (58.2%)
•Cholangitis OR previous cholecystectomy had a high
rate of positive cultures of common duct bile (93% to
100%)
Simultaneous bacteriologic assessment of bile from gallbladder and common bile duct in
control subjects and patients with gallstones and common duct stones.Csendes A, Burdiles
P, Maluenda F, Diaz JC, Csendes P, Mitru N Arch Surg. 1996;131(4):389.

20. Fun Infection Facts
•Age > 60 years increased positive bile cultures
•No correlation between the number of stones in the
gallbladder or common bile duct and the percentage
of positive cultures
• In 98% of the patients, the same bacteria were
isolated from gallbladder and common duct bile
Simultaneous bacteriologic assessment of bile from gallbladder and common bile duct in
control subjects and patients with gallstones and common duct stones.Csendes A, Burdiles
P, Maluenda F, Diaz JC, Csendes P, Mitru N Arch Surg. 1996;131(4):389.

21. Ultrasound for diagnosis of traditional cholecystitis
Stones in the gallbladder in a
patient with right upper quadrant
abdominal pain and fever
supports the diagnosis of acute
cholecystitis but is not
diagnostic.
What else can cause RUQ pain?

22. Additional sonographic signs: Murphy’s sign
Gallbladder wall thickening (greater than 4 to 5
mm) or edema (double wall sign)
A "sonographic Murphy's sign" is similar to the
Murphy's sign elicited during abdominal
palpation, except that the positive response is
observed during palpation with the ultrasound
transducer.
More accurate because it can confirm that it is
indeed the gallbladder that is being pressed by
the imaging transducer when the patient catches
his or her breath.

23. Murphy’s sign
videohttps://youtu.be/k
RXScm2UIc4

24. Biliary Colic
• Biliary colic is usually constant and not colicky.
• Intense discomfort located in the right upper quadrant or
epigastrium that may radiate to the back (particularly the right
shoulder blade).
• Associated with diaphoresis, nausea, and vomiting
• Plateaus in less than an hour, ranging from moderate to
excruciating in severity.
• After plateaued, the pain typically lasts at least 30
minutes and then slowly subsides over several hours,
with the entire attack usually lasting less than six hours
The circadian rhythm of biliary colic.
Rigas B, Torosis J, McDougall CJ, Vener KJ, Spiro HM
J Clin Gastroenterol. 1990;12(4):409.

25. Biliary Colic
•Classic biliary colic occurs “one to two hours after
ingestion of a fatty meal”
•Association with meals is not universal
•Many nocturnal, with a peak occurrence
around midnight
•Characteristic pattern and timing for an
individual patient (84% specific clock time)
The circadian rhythm of biliary colic.
Rigas B, Torosis J, McDougall CJ, Vener KJ, Spiro HM
J Clin Gastroenterol. 1990;12(4):409.

26. Functional gallbladder disorder
• Biliary pain in the absence of gallstones, sludge, microlithiasis, or
microcrystal disease.
• Diagnosis requires an evaluation to exclude other organic causes of
pain
• Caused by gallbladder dysmotility
• AKA
gallbladder dyskinesia
gallbladder spasm
acalculous biliary disease
chronic acalculous cholecystitis
chronic acalculous gallbladder dysfunction
cystic duct syndrome

27. Acalculous cholecystitis (hypocontractile)
Acalculous cholecystitis
accounts for about 5 to
10 percent of cases of
painful gallbladder

28. Functional GB disease uncommon
• Rare as compared with other functional gastrointestinal disorders
• Survey completed by 5931 of 6300 adults, UK Canada, US
• 2083 (35 percent) had symptoms compatible with a FGID
Rome IV
• Only 10 (0.2 percent) individuals met the defined criteria for
functional gallbladder disorder
• Functional gallbladder disorder is not an uncommon indication for
surgery
• 2 to 5 percent in adults
• Up to 10 percent in children
The Prevalence and Impact of Overlapping Rome IV-Diagnosed Functional Gastrointestinal Disorders
on Somatization, Quality of Life, and Healthcare Utilization: A Cross-Sectional General Population
Study in Three Countries. Aziz I, Palsson OS, Törnblom H, Sperber AD, Whitehead WE, Simrén M
Am J Gastroenterol. 2018;113(1):86. Epub 2017 Nov 14.

29. FGD is not on the rise
American College of Surgeons National Surgical Quality Improvement Program
Elective cholecystectomies from 2005-2013
• 156,322 patients undergoing cholecystectomy
• 5,161 (3.3%) had FGBD.
• FGB as an indication for cholecystectomy remained stable over time
• 3.4% in 2006 to 3.2% in 2013, P = .29).
• Compared with biliary colic, patients with FGBD were more likely
• <50 years old
• non-Hispanic white
• female
• body mass index < 25 (all P < .001)
Functional gallbladder disease: Operative trends and short-term outcomes.
Thiels CA, Hanson KT, Chawla KS, Topazian MD, Paley KH, Habermann EB, Bingener J
Surgery. 2016;160(1):100. Epub 2016 Apr 26.

30. Why does FGD dysmotility happen?
• Metabolic disorder: bile supersaturated with cholesterol which increases bile
viscosity
• Primary motility disorder in the absence of any abnormalities of bile composition
• Associated with abnormal gastric emptying and colonic transit, suggesting a
possible generalized gastrointestinal motility disorder
• 16 patients with STC (slow transit constipation) and 20 healthy controls, sham
feeding and qHIDA/CCK
• Gall bladder emptying in response to SF was significantly reduced in patients
with STC
• Gall bladder emptying in response to CCK was not different between patients
and controls
• Abnormalities in gastrointestinal motility proximal from the colon in slow
transit constipation, and impaired neural responsiveness
Gall bladder emptying in severe idiopathic constipation.
Penning C, Gielkens HA, Delemarre JB, Lamers CB, Masclee AA
Gut. 1999;45(2):264.

31. qHIDA-false positives and CCK infusion rates
• GBEF < 35 to 40 percent is considered low
• Supportive but not diagnostic of FGBD.
• False-positive results: diabetes, celiac disease, obesity, cirrhosis, and medications,
including calcium channel blockers, oral contraceptives/progesterone, histamine-2
receptor antagonists, opiates, benzodiazepines, atropine, octreotide, and
theophylline
• CCK-stimulated cholescintigraphy should be performed with a slow infusion of CCK
(sincalide) 0.02 mcg/kg given over 45 minutes (30 to 60 minutes)
• Rapid administration of CCK (over two to three minutes) is associated with cramping,
patient discomfort, and highly variable results
• Slower infusion rates lead to less inter- and intra-subject variability and an overall
increase in mean gallbladder ejection fraction compared with rapid infusion
• Variability in CCK administration techniques may account for some of the differences seen in
studies examining the ability of the GBEF to predict a response to cholecystectomy.Gallbladder function: methods for measuring filling and emptying.
Sarva RP, Shreiner DP, Van Thiel D, Yingvorapant N
J Nucl Med. 1985;26(2):140.

32. Treatment: Surgery (but use caution)
• Lap chole for FGBD (EF< 40%) with typical biliary pain if the
symptoms are severe or recur > three months
• Atypical symptoms such as bloating, fullness, or
dyspepsia are unlikely to respond to surgery even with
low GBEF; seek alternate management
•Classic gallbladder symptoms 61 patients, atypical symptoms
32 patients
•Cholecystectomy had helped only 43% of the atypical
patients and 88% of the classic patients at 2 years post op
The treatment of gallbladder dyskinesia based upon symptoms: results of a 2-year,
prospective, nonrandomized, concurrent cohort study.
Carr JA, Walls J, Bryan LJ, Snider DL
Surg Laparosc Endosc Percutan Tech. 2009;19(3):222.

33. Is surgery the right thing to do with FGBD?
• Meta-analysis 10 studies with a total of 615 patients
• Right upper quadrant pain, no gallstones, and a positive qHIDA
scan
• Cholecystectomy was more likely than medical therapy to
achieve complete symptom relief in patients with a low GBEF
(odds ratio 16.3)
• 4% of patients reporting no symptom improvement with
surgery
•Wide variability in data reporting, particularly with respect to
symptom relief and duration of follow-up
Meta-analysis of cholecystectomy in symptomatic patients with positive hepatobiliary iminodiacetic
acid scan results without gallstones.
Mahid SS, Jafri NS, Brangers BC, Minor KS, Hornung CA, Galandiuk S
Arch Surg. 2009;144(2):180.

34. Rome III Functional GBD
• Episodes of epigastric and/or right upper quadrant pain in a patient with an intact gallbladder
and normal liver chemistries and amylase/lipase that meet all the following criteria
• Episodes of pain lasting 30 minutes or longer
• Recurrent symptoms occurring at varying intervals (not daily)
• Gradual buildup of pain intensity to a steady level
• The pain is severe enough to interrupt the patient's activities and/or lead to an emergency
department visit.
• The pain is not relieved by bowel movements.
• The pain is not relieved by postural changes.
• The pain is not relieved by antacids.
• Structural diseases that could explain the patient's symptoms have been excluded
• The pain might present with 1 or more of the following supportive criteria:
• Pain associated with nausea and vomiting
• Pain radiates to the back and/or right subscapular region.
• Pain awakens patient from sleep in the middle of the night
Right Upper Quadrant Pain and a Normal Abdominal Ultrasound
Ahmed, Furqaan et al.
Clinical Gastroenterology and Hepatology , Volume 6 , Issue 11 , 1198 - 1201

35. Shaky ground

36. Hyperdynamic
Gallbladder
gallbladder ejection fractions of > 80%

37. Hyperdynamic Gallbladder
Retrospective 108 patients during a 1-year period with qHIDA GBEF > 80%
Questionnaires were obtained from primary care providers about patients'
symptoms, whether a cholecystectomy was performed and — if it was performed
— whether symptoms improved, were partially resolved, or completely resolved.
Complete data were obtained for 63 patients.
• 28 (44%) of 63 patients with high ejection fractions received a cholecystectomy
• 27 (97%) of 28 patients indicated that they had improvement in their
symptoms
• 22 (79%) of 28 patients said they had total resolution of their symptoms
• 1 with no improvement
J Nuclear Med. 2009;50:453P. SNM 2009: Patients With High
Gallbladder Ejection Fraction Benefit From Surgery

38. Hypercontractile GB in pediatrics
Children with symptomatic biliary colic and abnormal HIDA scan, specifically
those with high ejection fractions, may benefit from cholecystectomy.
• Patients <18 years old undergoing cholecystectomy from 2008 to 2012
• Patients with a negative US and CCK-HIDA ejection fractions > 80 %
included
• Data extracted from charts, whereas postoperative symptoms were
obtained by phone interviews
• Of 174 patients who underwent cholecystectomy, 12 (7%) met study criteria.
• All patients (12 of 12) had evidence of cholecystitis on the final
pathology note.
• All 11 patients contacted had relief of colic after gallbladder removal
with a mean follow-up of 16 months.
Am Surg. 2013 Sep;79(9):882-4.
Hyperkinetic gallbladder: an indication for cholecystectomy?
Lindholm EB1, Alberty JB, Hansbourgh F, Upp JR, Lopoo J.

39. What about adults?
•Retrospective chart review hyperkinetic gallbladder with
cholecystectomy from July 2014 to February 2018
•Thirty-two patients had laparoscopic cholecystectomy for
symptomatic hyperkinetic gallbladder
•Average GBEF was 92%.
•Chronic cholecystitis 29 (90%) on pathology.
•23 (74%) complete resolution of biliary symptoms
•5 (16%) improved symptoms
•3 (10%) no change in symptoms
Surg Endosc. 2018 Sep 12. doi: 10.1007/s00464-018-6435-2. [Epub ahead of print]
Is hyperkinetic gallbladder an indication for cholecystectomy?
Saurabh S1, Green B2.

40. Nay sayers Pediatrics: Caution!
• Records <21 years and younger who underwent qHIDA within the Indiana
Network for Patient Care from 2004 to 2013
• 2841 HIDA scans on 2558 patients
• 310 patients had a pathology report paired with the HIDA scan.
• GBEF did not correlate with the presence of gallbladder pathology (cholecystitis,
cholelithiasis, or cholesterolosis)
• Hypokinetic gallbladders are no more likely to have gallbladder pathology than
normal or hyperkinetic gallbladders in the setting of a patient with both a HIDA
scan and a cholecystectomy.
• Care should be used when interpreting the results of HIDA scans in children and
adolescents
J Pediatr Gastroenterol Nutr. 2016 Jul;63(1):71-5. doi: 10.1097/MPG.0000000000001065.
Gallbladder Ejection Fraction Is Unrelated to Gallbladder Pathology in Children and Adolescents.
Jones PM1, Rosenman MB, Pfefferkorn MD, Rescorla FJ, Bennett WE Jr.

41. Octylonium bromide & pinaverium bromide:
Selective Calcium Blockers
Klin Med (Mosk). 2004;82(9):57-9.
[New approaches to diagnosing and treating hyperkinetic biliary dyskinesia
associated with chronic acalculous cholecystitis].
[Article in Russian]
Bartosh LF, Balakina IV, Gridneva LM.
Abstract
Ninety patients aged 21 to 56 years who had chronic non-calculous cholecystitis (CNCC) concurrent with
hyperkinetic dyskinesia (HKD) detectable by a stepwise duodenal probing and sonography, by using a choleretic
breakfast and by determining the relaxation coefficient (RC) that was equal to the ratio of the volume of the
gallbladder (GB) after the use of a spasmolytic to the baseline GB volume. The patients were divided into 3
groups. The authors used as a spasmolytic agent pinaverium bromide (dicetel) in a dose of 50 mg (1 tablet) in
Group 1), octylonium bromide (spasmomen) in a dose of 40 mg (1 dragee) in Group 2, and drotaverine (no-
spa) in a dose of 40 mg (1 tablet). There was a more significant sonographic increase in the size of GB in
Groups 1 and 2 as compared with Group 3. In the acute drug test and during long-term treatment as well, the
highest spasmolytic effect was noted in patients receiving dicetel (Group 1) and spasmomen (Group 2) as
compared with that in Group 3 patients taking drotaverine. With this, RC was 1.25 +/- 0.2, 1.6 +/- 0.15, and 1.08
+/- 0.1, respectively. No adverse reactions occurred in the patients having selective calcium blockers (SCBs)
whereas the patients receiving no-spa were found to have the following side effects: dry mouth (n = 3), transient
constipation (n = 1), and numb tongue (n = 1). Thus, the study has provided evidence for the fact that SCBs have
some advantage over myotropic spasmolytic agents in the treatment of CNCC with the signs of HKD.

42. IBS and gallbladder dysmotility; association?
IBS-D Hypokinetic GB
IBS-C Hyperkinetic GB
We examined gallbladder motility function after intramuscular injection of caerulein (0.2 micrograms/kg)
to the cases of irritable bowel syndrome (IBS) by using ultrasonography. We measured gallbladder area
pre and after caerulein injection (0' 5' 10' 15' 20' 25' 30' 40' 50' 60') and calculated contraction rate of
gallbladder in each time. We applied one way analysis of variance among the four groups [diarrhea
group (N = 9), alternative group (N = 8), constipation group (N = 8), control group (N = 15)].
Gallbladder contraction rate was low in diarrhea group and high in constipation group (p less than 0.05).
And then we classified gallbladder contraction pattern to three groups (hyperkinetic, intermediate,
hypokinetic). These three groups correlated bowel habits and biliary knocked pain.
Therefore, constipation group showed hyperkinetic tendency and diarrhea group showed hypokinetic
tendency (chi 2 analysis: p = 0.004 CMH analysis: p = 0.001). And biliary knocked pain significantly
appeared in constipation group and hyperkinetic type of gallbladder (chi 2 analysis: p = 0.026, CMH
analysis: p = 0.019). Consequently, it was suggested that bowel habits concerned with abnormality of
gallbladder motility function in IBS.
Nihon Shokakibyo Gakkai Zasshi. 1992 Apr;89(4):1185-90.
[A study of the dynamics of gallbladder contraction in irritable bowel syndrome].
[Article in Japanese]
Kanazawa F1, Mine K, Mishima N, Muraoka M, Nakagawa T.

43. Sphincter of Oddi

44. Sphincter of Oddi- Anatomy
The muscle fibers of the sphincter of Oddi
surround the intraduodenal segment of the
common bile duct and the ampulla of Vater.
A circular aggregate of muscle fibers, known
as the sphincter choledochus (or sphincter
of Boyden), keeps resistance to bile flow high,
and thereby permits filling of the gallbladder
during fasting and prevents retrograde reflux
of duodenal contents into the biliary tree.
A separate structure, called the sphincter pancreaticus,
encircles the distal pancreatic duct. The muscle fibers of the
sphincter pancreaticus are interlocked with those of the
sphincter choledochus in a figure eight pattern.
From UpToDate.com

45. SOD
• AKA papillary stenosis, sclerosing papillitis, biliary
spasm, biliary dyskinesia, and postcholecystectomy
syndrome
• Two separate pathologic entities with distinct
pathogenic mechanisms
• Sphincter of Oddi stenosis
• Sphincter of Oddi dyskinesia
• SOD is associated with two clinical syndromes:
• Biliary pain
• Idiopathic recurrent acute pancreatitis
• two or more attacks of acute pancreatitis of
unclear cause (negative w/u) with complete
resolution between attacks
Pathophysiology of the sphincter of Oddi.
Chuttani R, Carr-Locke DL
Surg Clin North Am. 1993;73(6):1311.
Ruggero Oddi: 23-year old medial student Oddi
described a small group of circular and
longitudinal muscle fibers that wrapped
around the end of the bile and pancreatic ducts
in 1887.

46. SO- How does it work?
• SO functions independently from the duodenal musculature
• Coordinates timing and volume of up to 3 liters of bile and pancreatic juice into the
duodenum daily
• Fasting: sphincter of Oddi motility is integrated with the migrating motor complex (MMC)
• MMC is the pattern of gastrointestinal motor activity, three phases
• Phase I (quiescent period) lasts 45 to 60 minutes
• Phase II (random intermittent contractions) lasts approximately 30 minutes
• Phase III (period of bursts of rapid, evenly-paced, uninterrupted peristaltic
contractions) lasts for 5 to 15 minutes.
• Myoelectrical potentials within the sphincter of Oddi increase during phase I of the MMC,
reach a maximum during phase III, and then decrease rapidly
• Fed: myoelectrical potentials within the sphincter of Oddi vary depending upon the type
and quantity of nutrients ingested and may be influenced by endogenous hormones
(cholecystokinin)
Motility of Oddi's sphincter: recent developments and clinical applications.
Coelho JC, Wiederkehr JC
Am J Surg. 1996;172(1):48.

47. Biliary SOD
• Most common in patients who have undergone cholecystectomy (postchole syndrome)
• Unmasks pre-existing SOD due to removal of the gallbladder,
• Reservoir to accommodate increased pressure in the biliary system during
sphincter spasm
OR
• Alteration of sphincter of Oddi motility because of the severing of nerve fibers that pass
between the gallbladder and the sphincter of Oddi via the cystic duct
BUT
• SOD also occurs in patients whose gallbladders are intact, suggesting other
mechanisms
• SOD is an uncommon occurrence following cholecystectomy
• Survey of 454 patients post cholecystectomy, the prevalence of SOD <1 %
• Among patients complaining of symptoms following cholecystectomy 14%
Influence of cholecystectomy on sphincter of Oddi motility. Luman W, Williams AJ, Pryde A,
Smith GD, Nixon SJ, Heading RC, Palmer KR Gut. 1997;41(3):371.
Sphincter of Oddi dysfunction in patients with intact gallbladder: therapeutic response to
endoscopic sphincterotomy. Choudhry U, Ruffolo T, Jamidar P, Hawes R, Lehman G
Gastrointest Endosc. 1993;39(4):492.

48. Pancreatic SOD
• One of the most common diagnoses found in patients with idiopathic
recurrent acute pancreatitis
• ERCP, manometry, crystal analysis for idiopathic recurrent acute
pancreatitis
• N=126, 41/126 (33%) with SOD
• Papillary stenosis in 26 (21%)
• Pancreas divisum in 9 (7%)
• Choledocholithiasis in 6 (5%)
• Microcrystals in 27 (50%) with gallbladder
• Sphincter dysfunction in 17 (31%) with gallbladder
• Sphincter dysfunction in 24 (47%) without gallbladder
ERCP, biliary crystal analysis, and sphincter of Oddi manometry in idiopathic
recurrent pancreatitis. Kaw M, Brodmerkel GJ Jr
Gastrointest Endosc. 2002;55(2):157.

49. Diagnosis of Biliary SOD
• Suspected based upon
• Biliary-type pain
• Abnormal liver tests (aminotransferases, bilirubin or alkaline
phosphatase > 2 times normal values) that normalize
between attacks
• Dilation of the common bile duct
• Definitive diagnosis requires SOM
BUT…

50. SOD Type I, II, III
• Two abnormals (Type I)
• Abnormal liver tests AND dilated common bile duct
• No manometry; ERCP and sphincterotomy
• One abnormal(Type II)
• Either abnormal liver tests OR dilated common bile duct
• Sphincter of Oddi dysfunction suspected, undergo SOM (controversial)
• Some recommend empiric sphincterotomy , supported by a cost-
effectiveness analysis
• ERCP with manometry $2790 per patient
• ERCP with "empirical" biliary sphincterotomy $2244
• Normal liver tests and bile duct (Type III)
• Other disease
• Duodenal hyperalgesia
• Somatosensory hypersensitivity following cholecystectomy
Suspected sphincter of Oddi dysfunction type II: empirical biliary sphincterotomy
or manometry-guided therapy? Arguedas MR, Linder JD, Wilcox CM
Endoscopy. 2004;36(2):174.
Postcholecystectomy pain syndrome: pathophysiology of abdominal pain in sphincter
of Oddi type III. Desautels SG, Slivka A, Hutson WR, Chun A, Mitrani C, DiLorenzo C, Wald A
Gastroenterology. 1999;116(4):900.

51. Sphincter of Oddi manometry
• Gold standard for diagnosing of SOD
• Basal pressure and phasic wave contractions are recorded from the common
bile duct and pancreatic duct segments of the sphincter of Oddi
• The mechanical and electrical activity is similar between the two segments
• Measurement of basal pressures from the biliary or pancreatic duct alone may
miss up to one-quarter of patients with abnormal sphincter pressures
• Recommend measurements taken from both the biliary and pancreatic ducts
• Patients with SOD have been divided into two groups based upon manometric
findings:
• Structural alterations of the sphincter of Oddi (stenosis)
• Functional abnormalities (dyskinesia)
Sphincter of oddi manometry: is it necessary to measure both biliary
and pancreatic sphincter pressures?Aymerich RR, Prakash C, Aliperti G
Gastrointest Endosc. 2000;52(2):183.

52. Sphincter of Oddi manometry
• Sphincter of Oddi stenosis
• Elevated basal sphincter of Oddi pressure (>40 mmHg)
• Elevated sphincter of Oddi pressure does not relax following administration of smooth
muscle relaxants
• Sphincter of Oddi dyskinesia
• May also have elevated basal sphincter of Oddi pressure
• Elevated pressure decreases dramatically post amyl nitrite inhalation or glucagon bolus
injection
• Smooth muscle relaxation
• Other manometric characteristics
• Rapid sphincter of Oddi contraction frequency (>7/min) or ‘tachyoddia’,
• Excess in retrograde phasic contractions (>50 percent)
• Substantial basal sphincter of Oddi pressure increase (paradoxical response) following
administration of cholecystokinin-octapeptide (CCK-8)Sphincter of oddi manometry: is it necessary to measure both biliary
and pancreatic sphincter pressures?Aymerich RR, Prakash C, Aliperti G
Gastrointest Endosc. 2000;52(2):183.

53. SOM: Gold Standard but Cautions
• Invasive, technically demanding, and has several limitations:
• The cut-off point for elevated basal sphincter pressure based upon a single study of 50
South American subjects
• The procedure has been associated with an increased risk of pancreatitis
• The technique, equipment, and method of sedation used can affect the results
• The interpretation of results can vary among observers depending in part upon
experience
• ERCP pancreatitis 5%
• ERCP SOM pancreatitis 17%
• 16% SOD II
• 18% SOD III
• Normal SOM 13% Abnormal SOM 22%
• SOM alone 9% ERCP/SOM 26%
Incidence of pancreatitis in patients undergoing sphincter of Oddi manometry (SOM).
Maldonado ME, Brady PG, Mamel JJ, Robinson B
Am J Gastroenterol. 1999;94(2):387.

54. Biliary SOD; how to manage
• Type I SOD: biliary-type pain, abnormal liver tests, and a dilated common bile duct
• Type II SOD: biliary-type pain, either abnormal liver tests OR dilated common bile duct
• Type III SOD: biliary-type pain but normal liver tests and common bile duct diameter
• Type I SOD refer directly for endoscopic sphincterotomy, without preprocedure
manometry (Grade 2C).
• Type II SOD refer for sphincter of Oddi manometry, endoscopic sphincterotomy be
performed if there is evidence of sphincter of Oddi stenosis (Grade 2B).
• Endoscopic sphincterotomy should be avoided in patients with type III SOD (Grade
2B). Symptoms may be better explained by a functional disorder.

55. RightUpperQuadrantPainandaNormalAbdominalUltrasound
Ahmed,Furqaanetal.
ClinicalGastroenterologyandHepatology,Volume6,Issue11,1198-1201

56. RightUpperQuadrantPainandaNormalAbdominalUltrasound
Ahmed,Furqaanetal.
ClinicalGastroenterologyandHepatology,Volume6,Issue11,1198-1201

57. So what if you have Type III SOD
• Drugs that cause smooth muscle relaxation may be beneficial in patients with sphincter of Oddi
dysfunction (SOD).
• Calcium channel blockers and nitrates
• side effects are common
• ineffective in approximately 50 percent of patients
• In patients at increased risk for post-ERCP pancreatitis
• Trial of pharmacologic treatment; however, it is infrequently successful for long-term management.
• Calcium channel blockers (Nifedipine)
• Placebo-controlled crossover trial N=28 patients with recurrent biliary pain with elevated AP and SO
pressures
• Nifedipine given in the maximal tolerated dose
• Significant decreases in a cumulative pain score, number of pain episodes, oral analgesic tablets
consumed, and emergency department visits in 21
• A response to nifedipine could not be predicted by any clinical, radiographic, or manometric criteria
[Management of Oddi sphincter dyskinesis. Results of drug therapy and sphincterotomy].
Döbrönte Z, Simon L, Patai A Orv Hetil. 1995;136(40):2165.
Efficacy of nifedipine therapy in patients with sphincter of Oddi dysfunction: a prospective,
double-blind, randomized, placebo-controlled, cross over trial.
Khuroo MS, Zargar SA, Yattoo GN Br J Clin Pharmacol. 1992;33(5):477.

58. Caution from possums
• Studies in the Australian brush-tailed possum
• Calcium channel blockers have greater
effects on blood pressure at low doses than
they do on sphincter of Oddi motility
• Same in humans was noted in a small (N=5)
placebo-controlled crossover trial assigned to
slow-release nifedipine or placebo during a six-
month period
• Active treatment was associated with
frequent vascular side effects
• Active treatment was no more effective than
placebo at controlling symptomsRelative effects of dihydropyridine L-type calcium channel antagonism on biliary, duodenal,
and vascular tissues: an in vivo and in vitro analysis in Australian brush-tailed possum.
Craig AG, Tottrup A, Toouli J, Saccone GT Dig Dis Sci. 2002;47(9):2029.
Slow release nifedipine for patients with sphincter of Oddi dyskinesia: results of a pilot study.
Craig AG, Toouli J Intern Med J. 2002;32(3):119.

60. What if you have Type III SOD
• Nitrates
• Relaxation of the SO in animal models and in humans
• Limited data, case reports
• Not yet established by well-designed controlled trials
• Ursodeoxycholic acid
• Biliary microlithiasis in postcholecystectomy pain
• A randomized, crossover study involving 12 patients found to have microlithiasis
• Identified from a total of 118 patients with postchole pain
• Significant improvement in pain with urso 300 mg BID compared
with untreated controls
• Treatment was continued for six months
• During a mean of 29 months of follow-up, all patients except one
continued to remain free of biliary pain after discontinuing
therapy.
• This was a single center study, small number of patients
• Cautioned about the incorporation of seeking microcrystals
into the diagnostic algorithm of postcholecystectomy pain
evaluation
Nitrate therapy in a patient with papillary dysfunction.Bar-Meir S, Halpern Z, Bardan EAm J Gastroenterol. 1983;78(2):94.
Ursodeoxycholic acid treatment for patients with postcholecystectomy pain and bile microlithiasis.Okoro N, Patel A,
Goldstein M, Narahari N, Cai Q Gastrointest Endosc. 2008;68(1):69.

62. Electroaccupuncture at GB34
• N=11 (M:F = 5:6) with various kinds of biliary disorders were
enrolled.
• SO motility was monitored at ERCP (n = 9) or via percutaneous
transhepatic cholangioscopy (n = 2).
• After baseline monitoring for phasic wave contractions of SO,
electroacupuncture was applied at a specific acupoint GB 34
• A nonspecific acupoint 5 cm away from GB 34 was selected
as a control
• Manometric parameters of the SO were also measured in 6
subjects during stimulation of the control acupoint.
• CCK plasma levels were measured during electroacupuncture
stimulation.
Electroacupuncture may relax the sphincter of Oddi in humans.
Lee SK, Kim MH, Kim HJ, Seo DS, Yoo KS, Joo YH, Min YI, Kim JH, Min BI
Gastrointest Endosc. 2001;53(2):211.

63. Electroaccupuncture at GB34
• Basal pressure, amplitude, frequency, and duration of phasic wave
contractions of the SO were significantly decreased (p<0.05) during
electroacupuncture stimulation
• Inhibition of SO contractility was accompanied by increased CCK
plasma levels.
• After discontinuation of electroacupuncture stimulation,
restoration of amplitude and duration to basal conditions was
noted.
• A tendency toward return of SO basal pressure and contractile
frequency to baseline was also observed
• Stimulation of the control acupoint did not affect SO contractility
Electroacupuncture may relax the sphincter of Oddi in humans.
Lee SK, Kim MH, Kim HJ, Seo DS, Yoo KS, Joo YH, Min YI, Kim JH, Min BI
Gastrointest Endosc. 2001;53(2):211.

65. “Gallbladders”
to the tune of the
Ghostbusters theme
Time for a song?

66. Oh, who you gonna blame?
Gallbladders!
Mmm, if you've had a stinker
Of an Oddi sphincter
Type 1
Just cut it!
Let me tell you somethin'
Sphincteroplasty makes you feel good!
I ain't afraid of 'no stones'!
Have right quadrant pain after fatty food?
Who ya gonna blame?
Gallbladders!
Get a HIDA scan, but it don't
squeeze good
Who ya gonna blame?
Gallbladders!
I ain't afraid of 'no stones'!
When she comes through your suite
Now you know how to treat
Oh, what you gonna blame?
Gallbladders!
Ah, think you better blame?
Gallbladders
I can't hear you- What you gonna blame?
Gallbladders!
Louder!
Gallbladders!
What you gonna blame?
You get belly pain when you eat some
cheese…
Who ya gonna blame?
Gallbladders!
On your HIDA scan, got a mighty
squeeze
Who ya gonna blame?

67. Sally forth and become a
Single Gallbladder Hero

68. Questions?
plraymond@rxforsanity.com
Slide deck available for viewing on
slideshare.net/patriciaraymond