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Gallstone Disease
Jason Ryan, MD, MPH
Cholelithiasis
Gallstones
• Precipitation of components of bile in gallbladder
• Bilirubin, Bile Salts, Cholesterol
• Delicate balance between these components keeps bile fluid
• If balance is upset → precipitation → stones
Cholesterol Gallstones
• Most common type: cholesterol stones
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• Other types:
• Bilirubin stones
• Mixed stones

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Cholesterol Gallstones
Risk Factors
• Classically occurs in 40-year-olds
• Rare in children or elderly
• Three mechanisms can lead to gallstones:
• Excess estrogen → increased cholesterol
• Altered lipid metabolism → excess cholesterol in bile
• Loss of bile salts

Flikr/Public Domain
Cholesterol Gallstones
Estrogen Risk Factors
• Female gender
• Estrogen → increased cholesterol synthesis
• Pregnancy or multiparity
• Estrogen plus progesterone, which slows gallbladder emptying
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Øyvind Holmstad/Wikipedia
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Cholesterol Gallstones
Excess Cholesterol Risk Factors
• Obesity: increased total body cholesterol
• Rapid weight loss: increased cholesterol mobilization
• Both lead to more cholesterol in bile

Tibor Végh
Bile Salts
Enterohepatic Circulation
• Produced in liver → secreted into bile
• Reabsorbed in terminal ileum
• About 95% absorbed and recycled
• Reduced bile salts → cholesterol gallstones
• Underproduction AfraTafreeh.com
• Poor absorption from ileum

BruceBlaus
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Cholesterol Gallstones
Bile Salt Risk Factors
• Cirrhosis - underproduction Cirrhotic Liver
• Crohn’s Disease – poor absorption
• Cystic Fibrosis
• Fat malabsorption → loss of bile acids in stool
• Clofibrate (and other fibrates)
• Inhibit bile acid synthesis
• Bile acid resins
• Old, rarely-used cholesterol drugs
• Prevent intestinal reabsorption bile acids/salts
Pigment Stones
Bilirubin Stones
• Composed of calcium bilirubinate
• Black or brown
• Unconjugated bilirubin insoluble in H2O
• Rise in unconjugated bilirubin in bile → gallstones
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Emmanuelm/Wikipedia
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Pigment Stones
Bilirubin Stones
• Extravascular hemolysis
• Excess bilirubin
• Cirrhosis or chronic liver disease
• Impaired bilirubin conjugation
• Recurrent biliary tree infections
• Bacterial glucuronidases
• Convert conjugated bilirubin → unconjugated
• Brown (not black) stones (↑ calcium/some cholesterol)

Databese Center for Life Science (DBCLS)

Gallstone Disease
• Asymptomatic (discovered incidentally on imaging)
• Biliary Colic
• Acute Cholecystitis
• Choledocholithiasis
• Gallstone ileus AfraTafreeh.com
• Acute pancreatitis
• Cholangitis
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Biliary Colic
• Episodic right upper quadrant pain
• May radiate to right shoulder blade
Ultrasound Showing Gallstones
• Gallbladder contracts against stone in outlet
• Pain lasts ~30 minutes then subsides
• Often after eating, especially fatty meals
• Cholecystokinin stimulates gallbladder contraction
• Diagnosis: RUQ ultrasound
• Treatment: elective cholecystectomy

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Acute Cholecystitis
• Stone in cystic duct → obstruction
• Gallbladder squeezes → constricts blood supply
• Gallbladder dilates and becomes inflamed
• Inflammation of gallbladder
• Risk of rupture/peritonitis AfraTafreeh.com

Wikipedia/Public Domain
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Acute Cholecystitis
Clinical Features
• RUQ pain
• Radiates to right scapula
• Fever
• ↑ WBC
• Murphy’s sign
• Examiner presses RUQ
• Patient asked to inspire
• Patient abruptly stops inspiration due to pain

PxFuel/Public Domain
Acute Cholecystitis
Diagnosis
• Best first test: ultrasound
• Gallbladder wall thickening or edema
• Most accurate test: HIDA scan
• Hepatic iminodiacetic acid
• Used if high clinical suspicion, but negative US
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• Type of cholecystography
• 99mTc-hepatic iminodiacetic acid administered intravenously
• Taken up by hepatocytes → excreted into bile
• Failure to fill gallbladder suggests obstruction

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Acute Cholecystitis
Treatment
• Antibiotics for all patients
• Gram-negatives and anaerobes
• Emergent surgery indications:
• Gangrene or necrosis
• Perforation
• Emphysematous cholecystitis (air in GB wall)

Flikr/Public Domain
Acute Cholecystitis
Treatment
• Low-risk patients:
• Healthy or few comorbidities
• Laparoscopic cholecystectomy
• Usually done during hospitalization
• High risk patients
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• Surgical risk excessive
• Percutaneous gallbladder drainage

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Chronic Cholecystitis Porcelain Gallbladder

• Long-standing, untreated cholecystitis

• Chronic inflammation
• Causes a porcelain gallbladder
• Risk of gallbladder carcinoma
• Treatment: surgery

Herbert L. Fred, MD, Hendrik A. van Dijk

Choledocholithiasis
• Common bile duct stone
• RUQ pain
• Biliary obstruction
• Hyperbilirubinemia
• Jaundice AfraTafreeh.com
• ↑ Alk Phos >> ↑AST/ALT
• Usually non-inflammatory
• No fever

Wikipedia/Public Domain
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Choledocholithiasis
Diagnosis and Treatment
• Best first test: RUQ ultrasound
• Dilated common bile duct
• May see common duct stone
• Treatment: ERCP Ultrasound Imaging of Bile Ducts
• If US non-diagnostic:
• Endoscopic ultrasound
• MRCP

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ERCP
Endoscopic retrograde cholangiopancreatography
• Combination of endoscopy and fluoroscopy
• Imaging and therapy of biliary disorders
• Can remove bile duct stones
Cholangiogram
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Cancer Research UK
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Gallstone Ileus
• Massive gallstone erodes through gallbladder wall
• Creates fistula with small intestine
• Large stone → bowel obstruction at ileocecal valve
• Diagnosis: CT scan Pneumobilia
• Pneumobilia: air in the biliary tree
• Biliary structures normally filled with bile (no air)
• Air from intestine fills biliary tree in gallstone ileus
• Treatment: surgery
• Enterolithotomy (removal of stone from bowel)
• Cholecystectomy

James Heilman, MD
Gallstone Pancreatitis
• Obstruction of common bile duct by stone
• Leads to acute pancreatitis

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Wikipedia/Public Domain
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Acalculous cholecystitis
• Acute cholecystitis not due to gallstones
• Caused by gallbladder ischemia and stasis
• Usually occurs in critically-ill patients
• May present as fever, RUQ mass
• Can cause RUQ pain and Murphy’s sign
• Diagnosis: ultrasound
• Thickened walls, edema, “sludge”
• Treatment:
• Antibiotics
• Percutaneous drainage

Ringer21/Slideshare.net
Ascending Cholangitis
• Stone blocks flow of bile
• GI bacteria able to “ascend” in biliary tree
• Cholestasis plus signs of infection

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Sheldahl
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Ascending Cholangitis
Clinical Features
• Charcot’s triad
• Fever, abdominal pain, jaundice
• Reynolds’ pentad
• Fever, abdominal pain, jaundice, confusion, hypotension
• Indicates sepsis and shock from infection
• Labs
• ↑ WBC
• Cholestasis: ↑Alk Phos >> ↑ AST/ALT
• ↑ conjugated bilirubin (and total)
• Usually no Murphy’s sign
Ascending Cholangitis
Microbiology
• Gram-negative bacteria: E. coli, Klebsiella, Enterobacter
• Rare cause: Clonorchis sinensis
• Chinese liver fluke
• Helminth found in infected fish
• Ascends in biliary tree
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• Causes peripheral eosinophilia
Clonorchis sinensis

Banchob Sripa et al/Wikipedia

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Ascending Cholangitis
Diagnosis
• Fever, abdominal pain, jaundice, abnormal LFTs
• Can proceed directly to ERCP
• Uncertain diagnosis: RUQ ultrasound
• Common bile duct dilatation or stones
• Alternative tests: CT scan or MRCP
Ultrasound Imaging of Bile Ducts
Ascending Cholangitis
Treatment
• Antibiotics
• Gram-negative and anaerobic coverage
• Ampicillin-sulbactam
• Ciprofloxacin-Metronidazole
• Biliary drainage by ERCP
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• Endoscopic sphincterotomy with stone extraction
• Sometimes stent insertion
• Rarely surgery (replaced by drainage techniques)
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Gallstone Disease

Disorder Features Diagnosis Treatment

Cholelithiasis Biliary Colic Ultrasound Elective Cholecystectomy
Cholecystitis Fever, Murphy’s sign Ultrasound Cholecystectomy/drainage
Choledocholithiasis Jaundice Ultrasound/MRCP/ERCP ERCP
Cholangitis Fever, jaundice, RUQ pain Ultrasound/CT/MRCP Antibiotics + ERCP