Gallstones: types and their composition

Gallstones can have different compositions and structures. The main types of gallstones are:

1. Cholesterol stones: Cholesterol stones are the most common type of gallstone. They form when cholesterol in the bile becomes too much and crystallizes. Cholesterol stones can be yellow or green.

2. Pigment stones: Pigment stones are formed from bilirubin, a pigment that forms when red blood cells break down. They can be black or brown in color. There are two types of pigment stones:

   • Bilirubin stones: Formed from direct bilirubin and more common in patients with biliary diseases.
   • Calcium bilirubin stones: Contain calcium deposits and are usually less dense.

3. Mixed stones: Mixed stones, as the name suggests, are made up of a mixture of cholesterol and pigment. They can have a variety of colors and textures.

4. Biliary mud stones: This type of stone consists of a stone formation trapped in the biliary mud. They can be hard or soft and come in various sizes.

Gallstones can vary in composition and structure, which can affect their clinical presentation and possible treatment options. Gallstones can be single or multiple, and their sizes can range from tiny crystals to large stones. Tests such as ultrasound of the gallbladder and bile ducts, computed tomography (CT) or magnetic resonance imaging (MRI) are often used to determine the type and characteristics of the stones.

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Pathogenesis of gallstone formation

The pathogenesis is complex and includes several key points. The main stages of the pathogenesis of gallstones include:

1. Imbalance of Bile Components: Healthy bile contains water, bile acids, phospholipids, and cholesterol. When there is an imbalance between these components, especially when cholesterol or bile acids are too high, it can contribute to the formation of bile crystals.
2. Crystal formation: When there is an imbalance between cholesterol and bile acids, crystals may begin to form in the bile. These crystals may be tiny and unnoticeable, but if the imbalance persists for a long time, they may join together and become larger.
3. Growth and increase in stone size: Crystals in bile can grow and join together to form stones of varying sizes. Stone growth can be gradual and take many years.
4. Inflammation and Symptoms: When stones reach a certain size or block the bile ducts, it can lead to inflammation of the gallbladder or bile ducts. Inflammation can cause symptoms such as pain in the right upper quadrant of the abdomen and other dyspeptic symptoms.
5. Complications: In some cases, gallstones can cause complications such as jaundice, pancreatitis (inflammation of the pancreas), choledocholithiasis (the presence of stones in the common bile duct), infections, and others.

The pathogenesis of gallstone formation can be multifactorial and depends on various factors including genetic predisposition, lifestyle, dietary habits and health conditions. Understanding this process helps in developing preventive and therapeutic measures for those who are at risk of developing gallstones or have already encountered this condition.

Cholesterol Gallstones

Cholesterol stones, the most common type of gallstone, are either composed of cholesterol alone or cholesterol is the main component of the stones. Cholesterol-only gallstones are usually large, white or yellowish in color, soft, crumble fairly easily, and often have a layered structure. Microscopically, pure cholesterol stones are represented by numerous thin, long, monohydrate crystals of cholesterol, which are connected to each other by mucin-glycoproteins with dark fibers consisting of calcium salts of unconjugated bilirubin.

Mixed cholesterol stones contain more than 50% cholesterol and are somewhat more common than pure cholesterol stones. They are usually smaller in size and are more often multiple.

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Pigment gallstones

Pigment stones account for 10-25% of all gallstones in patients in Europe and the United States, but their incidence is significantly higher in Asian populations. As with cholesterol stones, pigment stones are more common in women, and are usually small, fragile, black or dark brown in color, and their incidence increases with age.

Black pigment stones

Black pigment stones consist of either a black polymer - calcium bilirubinate, or polymer-like compounds of calcium, copper, and a large amount of mucin glycoproteins. They do not contain cholesterol. No clear crystalline structure can be detected in the stones. They are more common in patients with liver cirrhosis, chronic hemolytic conditions (hereditary spherocytic or sickle cell anemia, vascular prostheses, artificial heart valves, etc.). They make up approximately 20-25% of gallstones and can migrate into the bile ducts.

In the mechanism of formation of black pigment stones, a known role is attributed to the supersaturation of bile with unconjugated bilirubin and changes in its pH.

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Brown pigment stones

Brown pigment stones consist mainly of calcium salts of unconjugated bilirubin (calcium bilirubinate, polymerized less than in black pigment stones) with the inclusion of varying amounts of cholesterol and protein. The formation of brown pigment stones is associated with the presence of infection (cholecystitis, ascending cholangitis); microscopic examination reveals bacterial cytoskeletons in them. Stones can form both in the gallbladder and in the ducts, and in the latter they form more often than stones of other composition. In recent decades, a decrease in the frequency of pigment gallstones has been noted, which many researchers associate with a decrease in the level of infectious diseases of the biliary tract.

In the mechanism of stone formation, great importance is attached to the hydrolysis of bilirubin glucuronide already in the bile ducts under the action of bacterial beta-glucuronidase with subsequent precipitation of bilirubin.

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Formation of pigment stones

Black pigment stones, as a rule, are formed in the gallbladder of patients with liver cirrhosis (up to 30% of observations), chronic hemolysis, chronic pancreatitis. The composition of stones primarily includes calcium bilirubinate, as well as calcium carbonate, calcium phosphate, mucin-glycoprotein (up to 20% of the mass), etc.

As is known, bilirubin is a hydrophobic (insoluble in water) and potentially toxic substance that circulates in plasma in a tightly bound compound with albumin and cannot be excreted in urine. The body's ability to excrete bilirubin is associated with its removal from blood plasma by the liver cell by conjugation with glucuronic acid and subsequent excretion of a water-soluble compound into bile - bound or direct bilirubin (bilirubin diglucuronide, bilirubin monoglucuronide). The unifying factor predisposing to the formation of the first pigment stones is increased secretion of bilirubin compounds (especially bilirubin monoglucuronide) into bile. For example, during hemolysis, the excretion of bilirubin compounds into bile can increase 10-fold.

As a result of the disruption of acidification in the gallbladder (for example, during its inflammation), bile becomes oversaturated with calcium carbonate and phosphate, which does not occur in an acidic environment and which in turn facilitates the process of precipitation of bilirubin compounds and subsequent stone formation. It is important to note that patients with black gallstones have not been found to have any disruption of the motor function of the gallbladder.

The formation of brown pigment stones is believed to be the result of anaerobic infection, with bacterial cytoskeletons found in the stones. The presence of bile stasis may facilitate bacterial infection, accumulation of mucus and bacterial cytoskeletons in the ducts. Under the action of enzymes produced by enterobacteria, unconjugated bile acids (acid hydrolase) are produced, and palmitic and stearic acids (phosphatase A) are produced from phospholipids.

The anionic products of the described enzymatic process can bind with calcium, forming insoluble calcium salts and leading to the formation of gallstones.

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Complications

Gallstones can cause a variety of complications that can be serious and require medical intervention. Some of the most common complications include:

1. Jaundice: A stone that blocks the bile ducts (bile ducts) can cause jaundice. Jaundice is characterized by a yellow discoloration of the skin and sclera (whites of the eyes) due to a disruption in the normal flow of bile and increased levels of bilirubin in the blood.
2. Pancreatitis: Inflammation of the pancreas (pancreatitis) can be caused by gallstones blocking the common bile duct and interfering with the normal flow of digestive enzymes. Pancreatitis can cause severe upper abdominal pain, vomiting, and other symptoms.
3. Choledocholithiasis: Stones can move from the gallbladder into the common bile duct, which is called choledocholithiasis. This can cause blockage of the duct, which in turn leads to complications such as jaundice and pancreatitis.
4. Cholecystitis: Inflammation of the gallbladder (cholecystitis) can develop if a gallstone blocks or irritates the gallbladder. This can cause acute or chronic pain in the right upper quadrant of the abdomen.
5. Liver abscess: Sometimes, an infection can enter the liver through the bile ducts, causing a liver abscess to form. This is a serious complication that requires immediate medical attention.
6. Gallbladder perforation: Rarely, gallstones can cause a perforation (rupture) of the gallbladder wall, resulting in acute abdominal pain syndrome requiring surgery.
7. Pyoesthetic stones: Some stones can move from the gallbladder into the bile ducts and cause repeated attacks of gallstone pain.
8. Sepsis: If an infection occurs or the infection spreads due to blockage of the bile ducts, sepsis (a severe infectious condition) may develop.

Gallstone complications can be dangerous, so it’s important to see a doctor if you have symptoms or are at risk of developing these complications. Treatment may include removing the gallstones and managing related conditions.