This section looks at gallstone disease in general. For info on cholecystitis specifically click here.

Overview

Gallstones, also called cholelithiasis, are solid deposits formed from components of bile, most commonly cholesterol or bilirubin. They usually develop within the gallbladder but may migrate into the biliary ducts. Gallstones range from very small particles to large stones and may be single or multiple.

Most gallstones remain asymptomatic and are discovered incidentally. Symptoms and complications occur when a stone obstructs the cystic duct, common bile duct or pancreatic duct, producing conditions such as biliary colic, cholecystitis, cholangitis or pancreatitis.

Aetiology and Pathogenesis

Gallstone formation generally involves three main processes:

1. Supersaturation of bile
   • Excess cholesterol or bilirubin becomes insoluble within bile.
   • Cholesterol supersaturation is the main mechanism for cholesterol stones.
2. Crystal nucleation
   • Cholesterol or calcium bilirubinate precipitates into microscopic crystals.
   • Gallbladder mucus may promote crystal aggregation.
3. Gallbladder hypomotility and bile stasis
   • Incomplete emptying allows crystals to remain within the gallbladder, grow and combine into stones.

Types of Gallstones

Feature	Cholesterol stones	Mixed stones	Pigment stones
Incidence	~10%	~80%	~10%
Main composition	Mainly cholesterol	Cholesterol, calcium salts and bile pigments	Mainly calcium bilirubinate
Morphology	Usually solitary and large	Usually multiple and faceted	Small, friable and irregular; black or brown
Causes and risk factors	Female sex, increasing age, obesity and Admirand’s triangle	Similar risk factors to cholesterol stones; bile stasis and inflammation	Black: haemolytic disease and cirrhosis. Brown: biliary infection, obstruction, stasis and parasites

Risk Factors

Cholesterol gallstones

• Female sex
• Increasing age
• Pregnancy and multiparity
• Oestrogen exposure, including oral contraceptives or hormone replacement therapy
• Obesity, particularly central obesity
• Rapid weight loss, very-low-calorie diets or bariatric surgery
• Family history and genetic predisposition
• Type 2 diabetes and insulin resistance
• Metabolic syndrome
• Hypertriglyceridaemia and low HDL cholesterol
• Sedentary lifestyle
• Crohn disease or terminal ileal resection, resulting in reduced bile-salt absorption
• Prolonged fasting or total parenteral nutrition, causing gallbladder stasis
• Certain medications, including ceftriaxone, fibrates and somatostatin analogues

Pigment gallstones

• Chronic haemolytic disorders:
  • Hereditary spherocytosis
  • Sickle cell disease
  • Thalassaemia
• Cirrhosis
• Increasing age
• Biliary infection
• Biliary obstruction or strictures
• Parasitic infection of the biliary tract
• Previous biliary surgery

Clinical Types of Gallstone Disease

Asymptomatic cholelithiasis

Gallstones are present but produce no symptoms. These are also called silent gallstones and are often found incidentally on imaging. Most do not require treatment.

Biliary colic

Temporary obstruction of the cystic duct by a gallstone causes:

• Episodic right upper quadrant or epigastric pain
• Often occurs after eating, particularly a fatty meal
• May radiate to the right shoulder or back
• Usually lasts from 30 minutes to several hours
• No persistent fever or marked systemic inflammation

Despite the name, the pain is usually constant rather than truly colicky.

Acute calculous cholecystitis

Persistent cystic duct obstruction causes inflammation of the gallbladder.

Typical features include:

• Persistent right upper quadrant pain
• Fever
• Nausea and vomiting
• Positive Murphy sign
• Raised inflammatory markers

Chronic cholecystitis

Repeated episodes of gallbladder inflammation cause fibrosis, thickening and reduced gallbladder function. It may present with recurrent biliary pain and food intolerance.

Choledocholithiasis

A gallstone is present within the common bile duct. It may cause:

• Obstructive jaundice
• Dark urine and pale stools
• Abnormal liver function tests
• Cholangitis
• Acute pancreatitis

Common bile duct stones may migrate from the gallbladder or, less commonly, form directly within the bile duct.

Acute ascending cholangitis

Infection of an obstructed biliary system, commonly due to choledocholithiasis.

Charcot triad: Right upper quadrant pain, Fever and Jaundice

Severe cholangitis may also cause hypotension and altered mental state, forming Reynolds pentad.

Gallstone pancreatitis

A stone obstructs the ampulla or pancreatic duct, causing acute pancreatic inflammation. It typically presents with severe epigastric pain radiating to the back and elevated pancreatic enzymes.

Mirizzi syndrome

A stone impacted in the gallbladder neck or cystic duct externally compresses the common hepatic duct, producing obstructive jaundice.

Gallstone ileus

A large gallstone erodes through the gallbladder into the gastrointestinal tract through a fistula and causes mechanical bowel obstruction, commonly near the terminal ileum.

Hepatolithiasis

Gallstones form within the intrahepatic bile ducts. This is more common in some Asian populations and is associated with biliary infection, strictures and recurrent cholangitis.

References

UpToDate
Best Practice
Oxford Handbook Clinical Surgery
Oxford Handbook Clinical Medicine