Cholelithiasis (gallstones)

In developed countries, 90% of gallstones are composed of cholesterol and form in the gallbladder.[2]

Some risk factors for the development of cholesterol gallstones are modifiable, such as obesity, total parenteral nutrition, rapid weight loss after weight loss surgery, and medications (e.g., oestrogen, octreotide, ceftriaxone).[19][20][21][22][23][24] Non-modifiable risk factors include age, genetic factors, and female sex.[3][4][5][6] Factors that may protect against cholelithiasis are; a diet high in protein and fibre, calcium, vitamin C, and physical activity.[2][7][25][26]

Cholesterol stones form in the gallbladder but can then migrate into the common bile duct, as occurs in 10% to 15% of patients presenting for cholecystectomy.[27]

Approximately 15% of all gallstones are black pigment stones.[7][2][28] The pigment material consists of polymerised calcium bilirubinate. Patients with chronic haemolytic anaemia, cirrhosis, cystic fibrosis, and ileal diseases are at highest risk of developing black pigment stones.[1][2]

Brown pigment gallstones form de novo in bile ducts as a result of stasis and infection.[1] They consist of calcium bilirubinate, calcium salts of long-chain fatty acids, cholesterol, and mucin (glycoproteins primarily from bacterial biofilms). In Western countries, brown pigment stones usually develop following bacterial infection, or from partial biliary obstruction such as inflammatory strictures (e.g., primary biliary cirrhosis) or malignancy (e.g., cholangiocarcinoma).[1][2][7] In South East Asia, the major risk factor is chronic infectious cholangitis associated with biliary parasites such as Clonorchis sinensis, Opisthorchis species, and Fasciola hepatica.[1][7]

Cholesterol cholelithiasis occurs as a result of three principal defects: bile supersaturated with cholesterol, accelerated nucleation, and gallbladder hypomotility such that this abnormal bile stagnates.

Cholesterol supersaturation of gallbladder bile occurs primarily when the liver secretes excessive amounts of cholesterol compared with its solubilising agents (bile salts and lecithin). Precipitation of cholesterol microcrystals in the gallbladder then follows, initiated by the presence of nucleating agents (primarily biliary glycoproteins such as mucin). Impaired gallbladder contractility causes the cholesterol-rich bile to stagnate and be retained in the gallbladder; these microcrystals collect in a mucin scaffold and grow into overt gallstones.[29]

Symptoms and complications of cholelithiasis result when stones obstruct the cystic and/or bile ducts. Biliary pain occurs when a stone transiently obstructs the cystic duct. More persistent obstruction leads to acute cholecystitis.

If gallstones pass into and obstruct the bile ducts, the result can be biliary pain and, importantly, acute cholangitis.

If the stones pass distally through the bile duct they can cause obstruction at the ampulla, leading to an increase in pancreatic ductal pressure and reflux of pancreaticobiliary secretions into the pancreatic duct, which can cause acute biliary pancreatitis. Risk factors for acute biliary pancreatitis are multiple small stones (<5 mm), a dilated cystic duct, and normal gallbladder motility.[30][31][32]

Mirizzi syndrome is an uncommon condition where a large gallstone becomes impacted in the cystic duct or the neck of the gallbladder, compressing on or causing inflammation of the common bile duct, resulting in biliary obstruction and jaundice.[33]

If a gallstone erodes through the gallbladder wall, a cholecystoenteric fistula can develop and lead to duodenal obstruction (Bouveret syndrome) or obstruction in the narrowest segment of an otherwise healthy bowel causing gallstone ileus.[34]

Types of stones in the biliary tract

Cholesterol gallstones

Approximately 90% of gallstones in developed countries are composed of cholesterol.[2] These form in the gallbladder. Risk factors for their development include age, female sex, diet, obesity, metabolic syndrome, sudden weight reduction (e.g., after weight loss surgery), genetics, and family history.[3][4][5][6]

Black pigment gallstones

Around 15% of all gallstones are black pigment stones, which consist of polymerised calcium bilirubinate.[1][2][7] Risk factors for these include age, chronic haemolytic anaemia, cirrhosis, cystic fibrosis, and ileal disease.[1][2]

Brown pigment stones (ductal stones)

These stones form in the bile ducts as a result of stasis and infection.[1] They consist of unconjugated bilirubin and calcium salts of long-chain fatty acids. Bile duct strictures or parasitic infestation represent the major risk factors. In Western countries, brown pigment stones usually develop following bacterial infection, or from partial biliary obstruction such as inflammatory strictures (e.g., primary biliary cirrhosis) or malignancy (e.g., cholangiocarcinoma).[1][2][7] In South East Asia, the major risk factor is chronic infectious cholangitis associated with biliary parasites such as Clonorchis sinensis, Opisthorchis species, and Fasciola hepatica.[1][7]

Pathophysiology

Classification

Types of stones in the biliary tract