Gallstones (Cholelithiasis): Causes, Pathogenesis, and Management

Gallstones, or cholelithiasis, are crystalline concretions that form in the biliary tract, most often within the gallbladder. They affect an estimated 10–20% of adults in developed countries and can lead to biliary colic, inflammation, and severe complications if left untreated.

Epidemiology and Risk Factors

• Prevalence increases with age; up to 25% in adults over 60.
• Risk factors (the “Four Fs”):
• Female
• Fat (obesity)
• Fertile (multiparity)
• Forty (age >40)
• Additional factors:
• Rapid weight loss or fasting
• Total parenteral nutrition
• Hemolytic disorders
• Diabetes mellitus
• Cirrhosis and cholestatic liver disease
• Ethnicity (Native American, Mexican–American)

Types of Gallstones

1. Cholesterol Stones (75–90%):
2. Yellow-green, form when bile is supersaturated with cholesterol.
3. Pigment Stones:
4. Black Pigment Stones: Associated with hemolysis; composed of calcium bilirubinate.
5. Brown Pigment Stones: Related to infection; contain calcium salts of unconjugated bilirubin.
6. Mixed Stones:
7. Contain cholesterol, calcium salts, bilirubin, and phospholipids.

Pathogenesis

Gallstone formation is driven by three key factors:

1. Cholesterol Supersaturation:
2. Imbalance in bile composition (bile acids, phospholipids, cholesterol) leads to precipitation of cholesterol crystals.
3. Gallbladder Hypomotility (Stasis):
4. Prolonged bile stasis from obesity, pregnancy, prolonged fasting, or sphincter of Oddi dysfunction promotes stone nucleation.
5. Nucleation and Crystal Growth:
6. Mucins, inflammatory proteins, and bacterial beta-glucuronidase accelerate crystal aggregation and stone formation.

Additional Contributory Factors

• Bacterial Infection: E. coli and anaerobes deconjugate bilirubin, forming pigment stones and promoting inflammation.
• Parasitic Infection: Ascaris lumbricoides or liver flukes can serve as nidus for stone formation in endemic regions.
• Metabolic and Genetic Influences: Variations in cholesterol metabolism and gallbladder contractility.
• Role of Metal Ions: Elevated calcium and magnesium levels in bile may enhance nucleation.

Clinical Features

• Many patients are asymptomatic (“silent stones”).
• Biliary Colic: Episodic RUQ or epigastric pain radiating to the back or right shoulder, often postprandial.
• Acute Cholecystitis: Persistent pain, fever, leukocytosis, and Murphy’s sign.
• Complications:
• Choledocholithiasis and cholangitis (Charcot triad).
• Gallstone pancreatitis.
• Gallbladder empyema or perforation.

Diagnosis

1. Transabdominal Ultrasound: First-line; high sensitivity for gallstones and gallbladder wall thickening.
2. HIDA Scan (Cholescintigraphy): Assesses cystic duct patency in acute cholecystitis.
3. MRCP/ERCP:
4. MRCP noninvasive imaging of biliary tree.
5. ERCP for diagnosis and therapeutic stone extraction in choledocholithiasis.
6. Laboratory Tests: Elevated liver enzymes and bilirubin in complicated stones; leukocytosis in cholecystitis.

Management

Asymptomatic Gallstones

• Observation; elective cholecystectomy for high-risk (elderly, immunosuppressed).

Symptomatic Gallstones and Complications

Cholecystectomy

• Laparoscopic Cholecystectomy: Gold standard unless contraindicated.
• Open Cholecystectomy: For complex anatomy or peritonitis.

Endoscopic and Percutaneous Interventions

• ERCP: Stone extraction and stenting for common bile duct stones.
• Percutaneous Cholecystostomy: Temporary drainage in critically ill patients.

Medical Therapy

• Ursodeoxycholic Acid (UDCA): For cholesterol stones in patients unfit for surgery; prolonged therapy required.
• Extracorporeal Shock Wave Lithotripsy: Rarely used; for select patients with solitary stones.

Prevention and Patient Education

• Maintain healthy weight via balanced diet and regular exercise.
• Avoid rapid weight loss; follow gradual calorie-restricted programs.
• Manage underlying metabolic conditions and avoid prolonged fasting.
• Educate patients on recognizing biliary colic and seeking prompt care for complications.

References

1. Portincasa P, Di Ciaula A, de Bari O, et al. Cholesterol gallstone pathogenesis: new insights into the role of nuclear receptors and the gut microbiota. Gastroenterology. 2020.
2. Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut Liver. 2012.
3. Lammert F, Gurusamy K, Ko CW, et al. Gallstones. Nat Rev Dis Primers. 2016.
4. Mann DV. The aetiology of gallstones in adults. Br J Surg. 2019.