Gallstones: Symptoms, Treatment and the Surgical Process

What Are the Gallbladder and Gallstones?

Hello, I am Dr. Emre Geçer. The gallbladder is a pear-shaped organ, approximately 7–10 cm long, located on the undersurface of the liver. Its main function is to store and concentrate bile produced by the liver. When a fatty meal is eaten, cholecystokinin (CCK) is released and the gallbladder contracts, emptying bile through the common bile duct (choledochus) into the duodenum. Bile plays a critical role in the digestion and absorption of fats.

Gallstones (cholelithiasis) are stone-like structures formed by precipitation and solidification of bile components inside the gallbladder. About 10–15% of the adult population has gallstones. They are 2–3 times more common in women than in men. The vast majority (80%) of gallstones are asymptomatic; however, approximately 1–2% per year become symptomatic.

Types of Gallstones

1. Cholesterol Stones (80%)

These are the most common type of stone in Western societies. They form when cholesterol in bile reaches supersaturation and crystallizes. They are yellow-green in color and may be either a single, large stone (1–2 cm) or numerous small stones. Three factors known as Admirand's triangle (the triple defect) play a role in cholesterol stone formation:

• Cholesterol supersaturation of bile: The liver secretes excess cholesterol, or the amounts of bile acids and lecithin (phospholipid) are insufficient.
• Accelerated nucleation: Increased mucin and other pronucleating proteins accelerate the precipitation of cholesterol crystals.
• Gallbladder hypomotility (stasis): Inadequate contraction and delayed emptying of the gallbladder leave bile stagnant and predispose to stone formation.

2. Pigment Stones (20%)

Pigment stones form in disorders of bilirubin metabolism. There are two subtypes:

• Black pigment stones: Composed of calcium bilirubinate and polymer compounds. More common in chronic hemolysis (sickle cell anemia, thalassemia, hereditary spherocytosis), liver cirrhosis and advanced age. Usually small, hard and numerous.
• Brown pigment stones: Associated with biliary tract infections and parasitic infestations (Clonorchis sinensis, Ascaris). More common in East Asian countries. They typically form within the bile ducts (intrahepatic or extrahepatic).

Risk Factors

The 4F Rule and Beyond

The classic mnemonic for gallstone risk factors is the "4F" rule:

• Fat (overweight): Obesity — especially abdominal obesity — increases gallstone risk 2–3-fold. In obesity, liver cholesterol secretion is increased.
• Forty (over forty): Gallstone prevalence rises markedly with age. After 40, the risk increases each decade.
• Female: Gallstones are 2–3 times more common in women than in men. Estrogen increases cholesterol secretion and reduces gallbladder motility.
• Fertile (fertile/pregnant): During pregnancy, high progesterone levels reduce gallbladder contractility, and high estrogen increases biliary cholesterol saturation. Risk is higher in women who have had multiple pregnancies.

Additional Risk Factors

• Rapid weight loss: Very-low-calorie diets (less than 800 kcal/day) or rapid weight loss after bariatric surgery markedly increase gallstone risk. Rapid weight loss increases cholesterol saturation of bile and causes gallbladder stasis.
• Total parenteral nutrition (TPN): Without oral intake, CCK stimulation decreases and gallbladder stasis develops.
• Genetic predisposition: ABCG8 gene variants increase cholesterol stone risk. Prevalence is higher in Pima Native Americans and in Scandinavian countries.
• Medications: Estrogen/hormone replacement therapy, ceftriaxone (precipitates in bile and causes pseudolithiasis), octreotide, clofibrate.
• Chronic hemolytic diseases: Sickle cell anemia, thalassemia (pigment stones).
• Crohn's disease (ileal): Terminal ileum involvement impairs bile acid absorption, shrinking the bile acid pool.
• Spinal cord injury and prolonged immobility.

Symptoms of Gallstones

Asymptomatic Gallstones

Up to 80% of gallstones are asymptomatic and are most often found incidentally on ultrasound performed for other reasons. The vast majority of asymptomatic stones never produce symptoms during a person's lifetime.

Biliary Colic

The most characteristic symptom of gallstones is biliary colic. It develops when a gallstone temporarily obstructs the gallbladder neck (infundibulum) or cystic duct:

• Character of pain: Sudden-onset, severe, steady (not actually colicky, but constant) pain in the right upper quadrant or epigastrium. It may radiate to the right shoulder or below the scapula (referred pain).
• Duration: Typically lasts 30 minutes to 6 hours. Pain lasting longer than 6 hours suggests progression to acute cholecystitis.
• Trigger: Often starts after a fatty meal. CCK release prompts the gallbladder to contract, and the stone causes obstruction.
• Associated symptoms: Nausea and vomiting are frequent. Fever and jaundice are usually absent in simple biliary colic.

Murphy's Sign

Murphy's sign is an important physical finding. The clinician presses on the right upper quadrant while asking the patient to take a deep breath in. As the liver and gallbladder descend during inspiration, the inflamed gallbladder touches the examiner's hand and the patient halts their breath because of pain. A positive Murphy's sign has 65% sensitivity and 87% specificity for acute cholecystitis.

Complications

1. Acute Cholecystitis

Acute cholecystitis is inflammation of the gallbladder caused by persistent obstruction of the cystic duct by a gallstone. It is the most common complication of biliary colic attacks. Findings include:

• Right upper quadrant pain lasting longer than 6 hours
• Fever (38 °C and above)
• Leukocytosis (elevated white blood cell count)
• Positive Murphy's sign or ultrasonographic Murphy's sign
• Increased gallbladder wall thickness (>4 mm) and pericholecystic fluid on ultrasound

If untreated, it can progress to life-threatening complications such as gangrenous cholecystitis, gallbladder perforation and peritonitis.

2. Choledocholithiasis (Common Bile Duct Stone)

Choledocholithiasis is the migration of a gallstone from the gallbladder into the common bile duct (choledochus). It occurs in 10–15% of patients. Findings include biliary colic, jaundice (conjugated hyperbilirubinemia), dark urine and pale (acholic) stools. Liver enzymes (ALP, GGT, bilirubin) rise. Diagnosis uses MRCP (magnetic resonance cholangiopancreatography) or endoscopic ultrasound (EUS).

3. Acute Cholangitis

Acute cholangitis is a potentially life-threatening condition that develops from obstruction and infection of the biliary tract. Charcot's triad describes the classic findings:

• Right upper quadrant pain
• Fever and chills
• Jaundice

When hypotension and confusion are added to this triad, Reynolds pentad is formed, indicating septic cholangitis. It requires urgent biliary drainage via ERCP and antibiotic therapy.

4. Gallstone Pancreatitis

Acute pancreatitis develops when a gallstone passing through the common bile duct temporarily or permanently obstructs the outflow of the pancreatic duct (duct of Wirsung). It is the most common cause of acute pancreatitis (40%). It is characterized by severe epigastric pain radiating to the back, nausea, vomiting and elevated amylase and lipase.

5. Gallstone Ileus

Gallstone ileus is a rare but serious complication. A large gallstone (usually >2.5 cm) passes into the small bowel through a cholecysto-enteric fistula caused by chronic inflammation and produces mechanical bowel obstruction. The most common site of obstruction is the ileocecal valve. The classic Rigler's triad is seen on abdominal X-ray: signs of bowel obstruction, air in the biliary tree (pneumobilia) and an ectopic gallstone.

Diagnostic Methods

• Abdominal ultrasound: The gold-standard first-line method for diagnosing gallstones. Sensitivity is over 95%. It assesses stone size and number, gallbladder wall thickness, pericholecystic fluid and bile duct width.
• MRCP (magnetic resonance cholangiopancreatography): Visualizes the bile ducts non-invasively. It is the preferred method when choledocholithiasis is suspected. Sensitivity is 90–95%.
• ERCP (endoscopic retrograde cholangiopancreatography): Both diagnostic and therapeutic. It allows endoscopic removal of common bile duct stones (sphincterotomy + stone extraction). Because of complication risks such as pancreatitis, bleeding and perforation, it is reserved for therapeutic indications.
• Hepatobiliary scintigraphy (HIDA scan): Used to diagnose acute cholecystitis. A radioactive isotope is taken up by the liver and excreted into the biliary tree; if the cystic duct is obstructed, the gallbladder is not visualized (positive finding).
• Endoscopic ultrasound (EUS): Superior to MRCP for detecting small common bile duct stones and microlithiasis.

Treatment

Asymptomatic Gallstones: Watchful Waiting

The vast majority of asymptomatic gallstones do not require treatment, and a "watchful waiting" strategy is applied. However, in some special circumstances, prophylactic cholecystectomy may be considered even when the stones are asymptomatic:

• Porcelain gallbladder (wall calcification — malignancy risk)
• Gallstones larger than 3 cm (increased risk of gallbladder cancer)
• Patients with sickle cell anemia
• Patients scheduled for bariatric surgery (controversial)

Laparoscopic Cholecystectomy: The Gold-Standard Treatment

The definitive treatment of symptomatic gallstones is laparoscopic cholecystectomy (closed surgical removal of the gallbladder). It has been the gold standard since 1987:

• Surgical procedure: Performed under general anesthesia through 3–4 small trocars (5–10 mm) placed in the abdomen. The abdomen is insufflated with carbon dioxide (pneumoperitoneum). The camera and instruments are introduced through the trocars. The cystic artery and cystic duct are clipped and divided; the gallbladder is dissected from its liver bed and removed.
• Critical View of Safety (CVS): The most important step to prevent bile-duct injury is the unambiguous identification of the cystic artery and cystic duct. Calot's triangle must be cleared and the hepatocystic triangle clearly seen (CVS).
• Recovery: Most patients are discharged the same or the next day. They can return to normal activities within 1–2 weeks and to full activity within 4–6 weeks.
• Complications: Overall, this is a safe operation. Bile-duct injury (0.3–0.5%), bleeding, infection and bowel injury are rare complications.

Treatment of Common Bile Duct Stones: ERCP

Stones in the common bile duct are removed endoscopically with ERCP. The endoscope is advanced to the duodenum, the ampulla of Vater is cannulated, sphincterotomy is performed and the stone is extracted with a balloon or basket catheter. ERCP is usually done before or at the same time as cholecystectomy.

Gallbladder Polyps

Gallbladder polyps are projections extending from the gallbladder wall into the lumen, as seen on ultrasound. The majority are cholesterol polyps and are benign. Indications for surgery include:

• Polyp size >10 mm (increased malignancy risk)
• Polyp size 6–9 mm with risk factors (over 50 years of age, accompanying gallstones, sessile polyp, rapid growth)
• Symptomatic polyps

Asymptomatic polyps smaller than 10 mm are followed with ultrasound every 6–12 months.

Life After Surgery

Quality of life without a gallbladder is generally very good. The liver continues to produce bile, and bile flows directly into the intestine. In a small proportion of patients (10–15%), transient digestive complaints such as diarrhea, bloating or gas may appear after surgery (postcholecystectomy syndrome). These usually settle within a few weeks to months. Starting with a low-fat diet and gradually transitioning to normal eating is recommended.

Conclusion

Although gallstones are a common health problem, they are often asymptomatic. When they become symptomatic, laparoscopic cholecystectomy offers a safe and definitive solution. Urgent medical evaluation is required when symptoms such as biliary colic, fever, jaundice or severe abdominal pain are present. Complications such as acute cholecystitis, cholangitis and gallstone pancreatitis can be life-threatening and require immediate intervention. Maintaining a healthy weight, eating a balanced diet and avoiding rapid weight-loss diets are the most effective ways to reduce the risk of gallstones.

Wishing you healthy days.
Dr. Emre Geçer

References

• Sabiston Textbook of Surgery, 21st Edition — Chapter: Gallbladder and the Extrahepatic Biliary System
• Harrison's Principles of Internal Medicine, 22nd Edition — Chapter: Diseases of the Gallbladder and Bile Ducts
• Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 11th Edition — Chapter: Gallstone Disease
• SAGES Guidelines for the Clinical Application of Laparoscopic Biliary Tract Surgery, 2010
• EASL Clinical Practice Guidelines on the Prevention, Diagnosis, and Treatment of Gallstones, 2016