16. Cholelithiasis (aetiology and complications) and pathology of the extrahepatic biliary tract

Page created on March 2, 2019. Last updated on March 14, 2024 at 21:01

Gallstone disease

Introduction and epidemiology

Cholelithiasis refers to the presence of gallstones in the gallbladder, while choledocholithiasis refers to gallstones in the common bile duct. Gallstone disease refers to various clinical manifestations involving gallstones, including:

  • Asymptomatic gallstones
  • Uncomplicated gallstone disease
    • Biliary colic
  • Complicated gallstone disease
    • Acute calculous cholecystitis
    • Cholangitis
    • Gallstone pancreatitis
    • Gallstone ileus

Complicated gallstone disease refers to the presence of gallstone-related complications, like the ones mentioned above. Complicated gallstone disease may present with biliary colic. If biliary colic is present without gallstone-related complications, the condition is called uncomplicated gallstone disease.

The majority of gallstones are asymptomatic and are discovered incidentally on imaging. Gallstones exist in 10 – 15% of the Western population, but only 1 – 4% become symptomatic.

Types and pathogenesis

Two types of stones exist. The most common type is the cholesterol stone, which accounts for 80% of all stones in the west. Bile formation is the only significant pathway for the body to eliminate excess cholesterol, either as free cholesterol or as bile salts. Cholesterol is dissolved in bile. The solution gets supersaturated if the cholesterol concentration exceeds the solubilization capacity of the bile.

Cholesterol won’t crystallize out of the solution until there is a nucleus, a “starting point” that it can precipitate onto. This nucleation process is then followed by growth, as more and more cholesterol precipitate into the nucleus, causing the stone to grow in size. Biliary stasis is also essential for the development of a stone.

It should be noted that most cholesterol stones aren’t comprised of only cholesterol. They most commonly also contain some bilirubin-calcium salts. Pure cholesterol stones are rare.

The second type of stone is the pigment stone, which is comprised of bilirubin-calcium salts. These usually occur in association with chronic haemolysis, which increases the production of bilirubin.

Cholesterol stones arise exclusively in the gallbladder and are yellowish. Pigment stones may arise anywhere in the biliary tree and are black or brownish.

Risk factors

The risk factors for the two different stones are different.

For cholesterol stones:

  • 6 Fs
    • Fat (obesity)
    • Female
    • Fertile (multiparity or pregnancy)
    • Forty (above 40 years of age)
    • Fair-skinned (Caucasian)
    • Family history
  • Gallbladder stasis

For pigment stones:

  • Chronic haemolytic anaemias
  • Billiary infection
  • Gastrointestinal disorders
    • Crohn disease
    • Ileal resection
    • Cystic fibrosis with pancreatic insuficciency.


Gallstones can be removed from the biliary tree by a procedure called ERCP, where a tube is led through the upper GI tract into the biliary tree through the ampulla of Vater. This tube can visualize and remove stones if necessary. Gallstones in the gallbladder cannot be removed by ERCP; cholecystectomy is required.


Only a minority of people with gallstones are symptomatic. Colicky biliary pain in the right upper quadrant is common.

There are many possible complications of gallstones:

  • Biliary colic
  • Cholecystitis
  • Empyema
  • Cholangitis
  • Gallstone pancreatitis
  • Gallstone ileus
  • Fistula formation
  • Perforation

Biliary colic

Biliary colic refers to the characteristic pain which occurs when the gallbladder tries to contract against an outlet which is obstructed by gallstones, causing increased intraluminal pressure. The pain is typically intense and dull, and located in the right upper quadrant. Sweating and  nausea or vomiting are common. As explained by the pathomechanism, pain is usually worsened by meals, especially fatty meals.


Cholecystitis is almost always associated with gallstones, in which case it’s called calculous cholecystitis. It is most often acute but may be chronic as well. Gallstones cause cholecystitis by obstructs the neck of the gallbladder or the cystic duct, causing biliary stasis. However, obstruction alone is insufficient to cause inflammation. Some as of yet unknown irritant must also contribute.

The inflammation of the gallbladder in response to gallstone blockage can be chronic as well. These cases have no striking symptoms. Chronic cholecystitis causes the gallbladder to become fibrotic, and the risk for gallbladder carcinoma increases.

In some cases of compliacted acute cholecystitis, the gallbladder may perforate.

The treatment for cholecystitis is cholecystectomy.

Gallbladder empyema

Bacterial superinfection may occur in case of bile stasis, causing the gallbladder to fill with pus and causing empyema.


Cholangitis, sometimes called ascending cholangitis, refers to inflammation of the biliary tract due to bile stasis due to choledocholithiasis, which causes superinfection. It classically presents with Charcot’s triad of:

  • Fever
  • Abdominal pain
  • Jaundice

Cholangitis is managed with antibiotics and biliary drainage.

Gallstone pancreatitis

Gallstones which obstruct the flow of bile distally to the confluence of the pancreatic duct and the common bile duct may cause reflux of bile into the pancreas, causing gallstone pancreatitis. The offending stone is often in the ampulla of Vater. This is managed with ERCP.

Cholangiocellular carcinoma

Introduction and epidemiology

Cholangiocellular carcinoma (CCC), also called cholangiocarcinoma, is a malignancy of the cholangiocytes that line the bile ducts. It can occur in the extrahepatic or intrahepatic bile ducts, with the former being more common.

Extrahepatic CCCs cause obstruction of the bile ducts rather quickly, so posthepatic jaundice occurs. This allows diagnosis to be made early. The same can not be said for intrahepatic types, which are discovered late, giving it a worse prognosis.

If a CCC occurs at the confluence of the right and left hepatic bile ducts, it’s known as a Klatskin tumor.

Cholangiocarcinoma is a rare cancer. It mostly affects elderly men.

The treatment is surgical, but at the time of diagnosis, >90% are unresectable and therefore incurable.


Risk factors include:

  • Cirrhosis
  • Choledocholithiasis
  • Primary sclerosing cholangitis

Gallbladder cancer

Cancer of the gallbladder arises from the gallbladder mucosa. It may develop from gallbladder polyps. It’s asymptomatic in the early stages, and is often diagnosed incidentally after a cholecystectomy for gallstones.

It’s a rare cancer. The most common cause is chronic cholecystitis due to cholelithiasis.

5 thoughts on “16. Cholelithiasis (aetiology and complications) and pathology of the extrahepatic biliary tract”

  1. It might be worth mentioning that ERCP can only remove gallstones in the common bile duct, and not in the gallbladder itself. Gallstones in the gallbladder can only be removed by cholecystectomy or lithotripsy. 🙂

  2. I’d previously written in this topic that “It’s important to keep in mind that up to 80% of people with gallstones don’t have any identifiable risk factors.”

    I don’t know if this is true (a quick search through the Internet and lectures doesn’t yield anything), and it doesn’t sound correct to me. I don’t know where I got it from. If it is true, it probably refers to all gallstones, asymptomatic ones included, in which case it’s not clinically relevant.

    I’ve removed it for now, but if anyone has any clues as to where I found that number, please leave a comment.

  3. hey,
    in seminar we actually learned about 3 different kinds of stones : billiary, pigmentous and mixed stones- mixed stones are the most common, and pure cholesterole stones are pretty rare

    1. You’re right in that most cholesterol stones aren’t pure, but most sources divide the types of bile stones into cholesterol (pure and not pure), black pigment stones and brown pigment stones, so I’ll keep the current composition of the topic. But I’ll add that most cholesterol stones aren’t pure.

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