Approach To Biliary
Disease
Objectives
Describe the spectrum of biliary tract diseases.
Describe the classic history and physical exam findings for biliary tract disease.
List the typical laboratory findings for different biliary tract diseases.
Discuss the advantages and limitations of the different radiologic studies utilized in the
diagnosis and differentiation of biliary tract disease.
Describe a diagnostic algorithm for acute cholecystitis in patients with a high pretest
probability of disease.
Discuss the appropriate treatment and disposition decisions for patients with diseases of the
biliary tract.
Background
Diseases of the biliary tract (gallbladder and bile ducts) are common and result in significant
morbidity and mortality.
Cholelithiasis is the term used to refer to the presence of gall stones in the gallbladder. In the
United States, 8% of men and 17% of women have gallstones. If untreated, 20-30% of these
patients will develop serious complications of gallstones such as choledocholithiasis,
cholecystitis, and cholangitis. Pancreatitis is also a common complication of gallstones.
Many people with gallstones are asymptomatic, however the risk for having complications or
developing symptoms is 1-4% per year.
CHOLELITHIASIS
Clinical Features
The most common clinical manifestation of cholelithiasis is biliary colic.
The pathophysiology is related to the passage of small stones from the gallbladder through the cystic
duct into the common bile duct.
The term colic is often misleading; affected patients commonly report steady pain, rather than
intermittent or cramping discomfort.
Associated signs and symptoms include nausea and vomiting, which may be severe enough to lead to
fluid and electrolyte imbalances
Physical Examination
Vital signs and physical findings in asymptomatic cholelithiasis are completely normal.
Physical findings include mild tenderness to palpation, without guarding or rebound in the RUQ
or epigastric region.
In classic cases pain is in the RUQ, however visceral pain and GB wall distension may be only in
the epigastric area.
Once peritoneum irritated, localizes to RUQ.
Patients with biliary colic commonly report similar self-limited occurrences in the past and may
offer an association between symptom onset and eating.
Causes
Fair, fat, female, fertile of course.
High fat diet
Obesity
Rapid weight loss, TPN, Ileal disease, NPO.
Increases with age, alcoholism.
Diabetics have more complications.
Hemolytics
Differentials
AAA
Appendicitis
Cholangitis, cholelithiasis
Diverticulitis
Gastroenteritis, hepatitis
IBD, MI, SBO
Pancreatitis, renal colic, pneumonia
Workup
Labs with asymptomatic cholelithiasis and biliary colic should all be normal.
WBC, elevated LFTS may be helpful in diagnosis of acute cholecystitis, but normal values do not
rule it out.
ALT, AST, AP more suggestive of CBD stones.
Amylase elevation may be GS pancreatitis.
The diagnosis of biliary colic is made clinically in conjunction
with the demonstration of stones in the gallbladder. Ultrasonography
is the procedure of choice for investigating the gallbladder.
Ultrasound of gallbladder
FF
GBW
Stones
Gallbladder with gallstones (Stones), thickened gallbladder
wall (GBW), and pericholecystic fluid (FF). Together these
findings constitute
the sonographic signs of cholecystitis.
Management
Episodes of biliary colic are usually self-limited and can be treated symptomatically with pain control
(NSAIDS and/or narcotic pain medications), fluid resuscitation and antiemetics.
While medical treatments (oral dissolving agents and dietary changes) are available, the definitive
treatment for symptomatic cholelithiasis is surgical removal of the gallbladder (cholecystectomy).
Choledocholithiasis is treated with surgical or endoscopic (ERCP) removal of the stone.
The most common complication of biliary colic is fluid and electrolyte imbalances secondary to
vomiting. Other adverse consequences include Mallory-Weiss tears from uncontrolled emesis and
cholangitis from unrecognized and persistent common bile duct obstruction.
Disposition
Patients with biliary colic whose symptoms are improving may be discharged home with
outpatient referral to a general surgeon for consideration of an elective cholecystectomy. They
should be advised to return immediately for signs of complications of gallstones such as
prolonged symptoms (> 6 hours), and/or symptoms associated with fever (> 100.4 F) or jaundice.
Most patients with choledocholithiasis should be admitted for definitive treatment due to high
rates of associated complications such as cholangitis, pancreatitis, gallbladder perforation and
gangrene. An exception could be considered for the reliable, asymptomatic patient who has
appropriate outpatient follow up.
.
Special Considerations
Biliary colic is an uncommon symptom in children and is usually associated with an underlying
hemolytic disorder (eg, sickle cell anemia, spherocytosis).
Cholelithiasis may be encountered in pregnant women. Diagnosis in this population is made more
difficult by the common occurrence of nausea and vomiting, particularly in the first trimester,
and the presence of an enlarged uterus in later pregnancy, which alters anatomic relationships
and interferes with an abdominal examination.
A 40-year-old woman presents with acute onset right upper quadrant pain, nausea and
vomiting. It began 18 hours ago after a fatty meal, and has progressively worsened. She is febrile
and has tenderness in the right upper quadrant. She is not jaundiced. Blood tests are significant
for a leukocytosis but only mildly elevated liver enzymes, bilirubin and amylase. Ultrasound
examination reveals gallbladder wall thickening and pericholecystic fluid. The common bile duct
is patent. Which of the following is the most likely diagnosis?
What is the most sensitive and specific imaging test for
acute cholecystitis?
A. Contrast CT scan
B. Nuclear scintigraphy with iminodiacetic acid (IDA)
C. Serum alkaline phosphatase level
D. Serum bilirubin level
E. Ultrasonography
Answer: B. IDA administered IV is taken up by hepatocytes and
secreted into bile canaliculi. Visualization of the gallbladder and
common duct within 1 hour has a negative predictive value of
98%. Scintigraphy with IDA loses its sensitivity at bilirubin levels
of 5 to 8 mg/dL.
Acute Cholecystitis
Definition: Acute inflammation of the gallbladder
Variant Forms
Acalculous cholecystitis (10% of cases): Inflammation of the gallbladder in the absence of
gallstones or cystic duct obstruction that is more common in older patients and after non-biliary
tract surgery
Emphysematous cholecystitis (1% of cases): Inflammation of the gallbladder along with the
presence of gas in the gallbladder wall. It is more commonly seen in diabetic patients.
Pathophysiology
Cystic duct obstruction is the proximate cause of cholecystitis >Obstruction leads to gallbladder
distension
An inflammatory reaction occurs due to either mucosal ischemia from increased hydrostatic
pressure or cytotoxic effects of bile degradation
Causes:
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Gallstones (95% of patients with cholecystitis)
Fibrosis
Parasitic infection
Tumor
Lymphadenopathy
Differential Diagnosis
Biliary colic
Choledocholithiasis
Mirizzi syndrome (gallstone impaction in the cystic duct or gallbladder neck causing common bile
duct (CBD) or common hepatic duct compression)
Acute Hepatitis
Hepatic abscess
Right lower lobe pneumonia
Cholangitis
Pancreatitis
Pyelonephritis
Presentation
History
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Right upper quadrant (RUQ) pain
History of similar, self-limited pain (biliary colic)
Nausea/Vomiting
Radiation of pain to the tip of the right scapula (referred pain)
Physical Examination
◦ RUQ/epigastric tenderness to palpation
◦ Variable presence of rebound/guarding
◦ Tenderness with an inspiratory pause during palpation of the RUQ during a deep breath (Murphy’s sign)
Murphy’s: Best test for diagnosis of acute cholecystitis (Jain 2017)
(+) LR = 15.64
(-) LR = 0.40
Fever is poorly sensitive (35%) and nonspecific (80%) (Towbridge 2003)
Diagnostics
Laboratory Tests
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Overall, laboratory tests are insensitive and non-specific. They can neither rule in nor out the disease
WBC count: Elevation with a left shift is common but may be absent in up to 40% of patients
AST/ALT: May be mildly elevated but are poorly sensitive (38%) and specific (62%)
Total/Direct Bilirubin: If elevated, it raises suspicion for choledocholithiasis, cholangitis, or Mirizzi
syndrome
Ultrasound (US) Common findings
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Presence of gallstones (absence of stones has a high negative predictive value for cholecystitis)
Thickened gallbladder wall (> 3 mm)
Pericholecystic fluid
Maximal tenderness elicited over the visualized gallbladder by the US probe (Sonographic Murphy’s
sign)
Impacted gallstones (in the neck or cystic duct) + sonographic Murphy’s sign have a positive
predictive value of 70% (Rosen 2001) to 92% (Ralls 1985)
Overall sensitivity 88%, specificity 80% (Shea 1994)
Distended gall bladder shows
edematous wall, calculi and sludge with
pericholecystic collection
CT findings
Higher accuracy than US for defining complications related to cholecystitis (gangrene,
emphysematous cholecystitis)
Common findings (Fidler 1996)
◦ Thickened gallbladder wall (> 3 mm)
◦ Increased attenuation of the gallbladder bile
◦ Subserosal edema
Nuclear Scintigraphy with Technetium-99mlabeled hepatobiliary iminodiacetic acid (HIDA)
Gold standard for diagnosis with high sensitivity and specificity
Positive study: Failure of HIDA to outline the gallbladder within 1 hour of administration
Management:
Basic Supportive Care
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IV crystalloids: optimize volume status
Check + replete electrolytes as needed (may be significant losses from vomiting)
Antiemetics
Pain control
Antibiotics
◦ The role of bacterial infection in the pathogenesis of cholecystitis is not completely understood
◦ If the patient exhibits signs of sepsis, administer broad-spectrum antibiotics covering gram
negative/positive pathogens as well as anaerobes
◦ Vancomycin AND an advanced generation penicillin (i.e. piperacillin/tazobactam)
◦ Vancomycin AND a 3rd/4th generation cephalosporin (i.e. cefepime) AND metronidazole
Emphysematous cholecystitis
Likely caused by invasion of gas-producing pathogens (E. coli, Klebsiella, Clostridium perfringens)
Advanced generation penicillin (i.e. piperacillin/tazobactam) +/- metronidazole
Managment
Surgical Consultation for cholecystectomy
Complications
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Gangrene leading to necrosis and perforation
Emphysematous cholecystitis
Pericholecystic abscess
Sepsis
Disposition
Admission for IV antibiotics and pain control
Cholecystectomy is typically performed during the initial hospitalization as early
cholecystectomy appears to have improved outcomes
Patients with gangrene or perforation may undergo immediate cholecystectomy or
cholecystostomy and drainage
A 55-year-old woman with a history of gallstones presents to the ED with right upper quadrant
abdominal pain. Her blood pressure is 98/64 mm Hg, heart rate is 110 beats per minute,
respiratory rate is 22 breaths per minute, and temperature is 39.8C. She has scleral icterus and
appears jaundiced. She is also mildly confused. She is tender in the RUQ with guarding. What is
the most likely diagnosis?
Ascending Cholangitis
Definition: Acute bacterial infection of the bile ducts resulting from common bile duct
obstruction. Also called ascending cholangitis. Mortality rate 5-10%
Pathophysiology
Bile duct develops an obstruction
◦ Obstruction may be incomplete (more common) or complete
◦ Causes: Gallstones (most common), malignancy, benign stricture, iatrogenic (i.e. ERCP), biliary parasites,
primary sclerosing cholangitis (PSC)
Elevated intraluminal pressure in the gallbladder leads to translocation of bacteria
◦ Bacteria may gain access via lymphatics, portal venous blood or retrograde from the duodenum
◦ Common pathogens: E. coli, Klebsiella, Streptococcus, Enterobacter, Pseudomonas Other causes:
HIV/AIDS cholangiopathy, parasitic infections (Ascaris lumbricoides)
Presentation
Charcot’s Triad: Fever, RUQ pain and jaundice (neither sensitive nor specific)
Symptoms
◦ Fever/chills
◦ Nausea/vomiting
◦ Abdominal pain
Physical Exam
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RUQ tenderness to palpation
Peritoneal signs are variable
Jaundice
Frank sepsis (fever, tachycardia, hypotension, tachypnea) is a common presentation
Reynold’s Pentad: Charcot’s triad + sepsis and AMS
Diagnostics
Cholangitis is a clinical diagnosis. There are no diagnostic tests that absolutely clinches or rules
out the diagnosis.
Laboratory Tests
◦ Lab tests are generally neither sensitive nor specific for ruling in or ruling out cholangitis. Below are
common findings
◦ WBCs – usually elevated but may be depressed in severe infection
◦ Hepatic panel
◦ Elevated aminotransferases (i.e ALT/AST)
◦ Elevated alkaline phosphatase
◦ Hyperbilirubinemia
◦ Lipase – useful to evaluate for concomitant pancreatitis
◦ Blood gas may be useful in patients who appear septic to record lactate level
◦ Blood cultures
Imaging
Imaging is helpful in supporting the diagnosis and aids in identifying the cause. Many patients
will have concomitant acute cholecystitis that will be identified on imaging
Ultrasound with Dilated Common Bile Duct (CBD)
Ultrasound
Common findings
◦ Intrahepatic biliary ductal dilation (see video below)
◦ Thickening of the bile duct walls
◦ Obstructing gallstones
Concomitant cholecystitis findings
◦ 4 sonographic signs of cholecystitis: Gallstones, gallbladder wall thickening >3mm, pericholecystic fluid,
sonographic murphy’s
Useful to distinguish between intrahepatic and extrahepatic obstruction
CT Scan
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Classic finding: non-homogenous liver enhancement during arterial phase
Can identify dilated intra- and extrahepatic ducts
Gallstones are poorly visualized
Findings non-specific
Can identify other pathologies or complications of cholangitis (perforation, abscess)
Nuclear scintigraphy: may be more sensitive than US in identifying early obstruction
◦ Useful when ultrasound results are equivocal and the diagnosis is suspected
◦ Cannot visualize the biliary tree with complete obstruction
Endoscopic Retrograde Cholangiopancreatography (ERCP)
◦ Procedure is both diagnostic + potentially therapeutic
◦ Allows removal of obstructing stone, biopsy of mass, culture of bile and decompression or stent
placement
Magnetic resonance cholangiopancreatography (MRCP)
◦ Most sensitive noninvasive method
◦ Requires patient to be stable to obtain study
Management:
Basics:
ABCs, IV, Cardiac Monitor
Unstable patients due to sepsis or septic shock should be aggressively resuscitated per general
sepsis/septic shock algorithms (IV fluids, airway management as necessary, vasoactive substances
etc.)
Broad spectrum antibiotics
◦ Antibiotics should cover gram positive, anaerobic gram negative aerobic andenteric organisms (see above)
◦ Common regimens
◦ Piperacillin/tazobactam (Zosyn®)
◦ Imipenem/Meropenem
◦ Ampicillin/sulbactam (Unasyn®) + metronidazole
Correct electrolyte abnormalities and coagulopathies if present
Biliary tract decompression
◦ Percutaneous drainage via interventional radiology
◦ ERCP via gastroenterology
◦ Should be performed emergently if the patient fails to improve with aggressive resuscitation
◦ In resuscitation responders, should be performed within 24 hours
◦ Surgical drainage
Disposition:
All patients with cholangitis will require admission and many will require a high-resource setting
(ICU or step down unit)
RUG PAIN CASE
Mrs. Stone
41 year-old woman in the ER presenting with 12 hours duration of
progressively worsening right upper quadrant discomfort associated with
nausea and vomiting. She reports chills.
History
What other points of the history do
you want to know?
History, Mrs. Stone
Consider the following:
•Characterization
of Symptoms
•Associated signs/symptoms
•Pertinent PMH
•Temporal sequence
•ROS
•Alleviating / Exacerbating factors
•MEDS
•Relevant Family Hx
•Relevant Social Hx
History Mrs. Stone
Characterization of Symptoms
•
•
•
Epigastric and RUQ pain radiating to the back
Nausea and bilious vomiting followed the onset
Pain constant in nature
Temporal sequence
•
Symptoms started 40 minutes after a meal
of pain
History Mrs. Stone
Alleviating / Exacerbating factors:
Nothing makes this pain better
◦ Breathing and movement makes pain worse
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Associated signs/symptoms:
Similar symptoms in the past – never lasted long
◦ Denies history of jaundice
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History Mrs. Stone
Pertinent PMH: Obesity, G4P4
PSH: Hysterectomy
ROS: no change in bowel habits, no weight loss, no BRBPR, no melena, no
diarrhea, not sexually active
MEDS : None, NKDA
Relevant Family Hx: Mother had cholecystectomy
Relevant Social Hx: non-smoker, no ETOH, divorced
What is your Differential
Diagnosis?
Differential Diagnosis
Based on History and Presentation
Acute Cholecystitis
Rectus Sheath Hematoma
Chronic Cholecystitis
Hepatitis
Choledocholithiasis
Liver Tumor
Pulmonary Embolism
Cholangitis
Pyelonephritis
Colon Tumor
Peptic Ulcer Disease
Colitis/ Typhlitis
Myocardial Infarction
Gastritis
Pancreatitis
Appendicitis
Bowel Obstruction
Pneumonia
PID, Ectopic
Physical Examination
What specifically would you look for?
Physical Examination Mrs. Stone
Vital Signs: T: 100.5, HR: 115, BP: 132/84, RR: 22
Appearance: obese woman in mild distress
Relevant Exam findings for a problem focused assessment
HEENT: no scleral icterus, dry
mucous membranes
Neuromuscular: non focal exam,
good strength
Chest: CTA Bilaterally, shallow
breathing
Skin/Soft Tissue: no rashes, no
jaundice
CV: tachy, no murmurs, gallops,
rubs
Genital-rectal: heme negative, no
masses, no cervical motion
tenderness
Abd: soft, non distended, RUQ
tenderness with positive Murphy’s
sign, bowel sounds normal, no
palpable masses
Remaining Examination
findings non-contributory
Laboratory
What would you obtain?
Labs ordered, Mrs. Stone
CBC: Hb/Hematocrit, WBC, Platelets
Electrolytes
Liver Function Tests
Amylase /Lipase
PT/PTT
Urinalysis
B-HCG
Cardiac Enzymes, EKG
ABG
Labs Mrs. Stone
CBC: Hb, Hematocrit
WBC
Electrolytes :
LFT’s :
Amylase, Lipase:
PT/PTT:
U/A and b-HCG:
ABG:
Cardiac Enzymes, EKG:
13.2 mg/dl, 39%
13,000
normal
Bili: 1.8, AST:110,
ALT:140, AlkPhos: 170
normal
normal
negative
normal
normal
Lab Results Discussion
Labs point out that a cardiac, pulmonary or urinary source of symptoms is highly unlikely
Patient has no pancreatitis
Elevated WBC raises the suspicion for an infection
Mild elevation in liver function tests may point towards the diagnosis
Differential Diagnosis
Would you like to update your differential?
Differential Diagnosis
Would you like to update your differential?
Acute Cholecystitis
Appendicitis
Chronic Cholecystitis
Pneumonia
Choledocholithiasis
Liver Tumor
Peptic Ulcer Disease
Cholangitis
Bowel Obstruction
Colon Tumor
Gastritis
Interventions at this point?
Interventions at this point?
Start IV with Lactated Ringers or similar isotonic crystalloid solution for
rehydration
Pain medication administration
Proceed with confirmatory studies of suspected differential diagnoses
Studies (X-rays, Diagnostics)
What would you obtain?
Studies ordered Mrs. Stone
Acute Abdominal Series
Ultrasound Right Upper Quadrant
Acute Abdominal Series
Imaging Results
Abdominal Series is Negative
What information will the US report
provide that may help confirm your
diagnosis?
RUQ US
Information
Presence of gallstones or sludge
Presence of pericholecystic fluid
Gallbladder wall thickening
Presence of sonographic Murphy’s sign
Intra- or extrahepatic ductal dilation
Liver, pancreas, right kidney abnormalities
US Mrs. Stone
Ultrasound demonstrating air in the wall of
the gallbladder and sludge in the lumen.
What is your Diagnosis?
Diagnosis
Acute Emphysematous Cholecystitis
What additional treatment would you
now institute?
Interventions at this point?
Administer IV antibiotics
◦ What type?
Admit the patient to the hospital
Bring the patient to the OR
◦ When?
◦ What operation would you do?
OR Findings
Acute gangrenous cholecystitis
with contained perforation
Mrs. Stone underwent a difficult laparoscopic
cholecystectomy with intraoperative cholangiogram. A drain
was left under the liver
Intraoperative cholangiogram
Normal intraand extrahepatic
biliary tree
without filling
defects, normal
flow into the
duodenum
CT SCAN Abdomen/Pelvis
What are you looking for with a CT
SCAN in this patient?
CT SCAN Indications
Rule out other causes of abdominal pain besides cholecystitis (especially in
the face of normal RUQ US and/ or HIDA)
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Pancreatitis
Perforated hollow viscus
Bowel obstruction
Intra-abdominal or Retroperitoneal masses
Liver pathology
Biliary tract disease: tumors
CT SCAN Mrs. Stone
Study demonstrates emphysematous cholecystitis
(arrow points at the air in the wall of the gallbladder)
Discussion
Acute cholecystitis is a common disease that can be treated with minimal
morbidity if diagnosed early
Typical, unrelenting symptoms of more than 6 hours duration is highly suggestive
of the disease
A RUQ US is the first test of choice as it is highly sensitive in diagnosing gallstones
and may demonstrate findings of acute cholecystitis
Discussion
The absence of acute cholecystitis findings on US does not exclude the diagnosis
It should also be kept in mind that acute cholecystitis can occur in the absence
of gallstones (acalculous form of the disease)
The gold standard for the diagnosis of acute cholecystitis is a HIDA scan but in
most patients the diagnosis can be made without it
 Percutaneous drainage should be considered in very high risk patients
Summary
Acute cholecystitis should be treated
operatively when recognized. It is best to
do this as soon as possible as it may result
in severe complications. Alternatives to
surgery for simple uncomplicated cases of
acute cholecystitis include antibiotic
treatment and percutaneous drainage in
medically unfit patients.