The formation and symptomatology of gallstones is well understood but the exact reason for many cases of gallstones, particularly cholesterol stones, is still unclear. There are known risks for the development of gallstones but despite the presence of these contributing factors, not every person will develop gallstones.
The classic clinical presentation is a patient who is fat, forty, female and fertile, which is also known as the 4 F’s for gallstone presentation. Another factor to consider is the fifth F which stands for fair in reference to Caucasians, particularly those of north European descent (“fair skin, fair hair”). However, this does not encompass all the risk factors associated with the development of gallstones.
There are two types of gallstones – cholesterol stones and pigment stones – although most stones are of mixed composition.
Causes of Cholesterol Stones
Cholesterol stones form when the amount of cholesterol in the bile exceeds its solubilizing capacity. Cholesterol is a normal product of fat metabolism in the liver and is excreted in the bile. Since it is insoluble in water, it is held in suspension by the water-soluble bile salts and water-insoluble lecithin as micelles or vesicles. When the quantity of bile salts is insufficient to hold cholesterol in suspension, cholesterol sediments start aggregating together with the help of mucus from the gallbladder to form cholesterol stones.
Risk Factors for Cholesterol Stones
- Age – older age groups.
- Ethnicity – northern Europeans, north and south Americans, including Caucasians, Hispanics and Native Americans.
- High triglyceride and low HDL levels in the blood – hyperlipidemia.
- Female. Apart from gender, the use of female hormone medication like oral contraceptives, and pregnancy increases the risk of gallstone formation.
- Metabolic syndrome
- Rapid weight loss
- Fasting or dieting and other factors that slows gallbladder emptying like neurological defects as a result of injuries to the spinal cord.
- Other factors such as a family history, diet high in fats and sugars (refer to Gallstones Diet), drugs like cholesterol-lowering agents and certain chronic conditions like diabetes may also increase the risk for cholesterol stones.
- Inborn errors in bile acid metabolism, like cerebrotendinous xanthomatosis
Causes of Pigment Stones
Pigment stones are a result of large amounts of unconjugated bilirubin in the blood. Most bilirubin in the bile is conjugated with only a small amount being unconjugated. Any factor that increases the amount of unconjugated bilirubin may result in pigment gallstones. Bacterial enzymes, rapid and excessive breakdown of red blood cells and impaired bile flow or static bile are the main contributing factors.
Risk Factors of Pigment Stones
- Advancing age and ethnicity is also a risk factor – pigment stones are more commonly seen in Asians, particularly those living in a rural setting.
- Chronic hemolytic syndromes – this is the breakdown of red blood cells that is above the norm (black stones)
- Hepatic cirrhosis (black stones)
- Gastrointestinal diseases or surgery that impairs the resorption of bile salts (black stones)
- Impaired emptying of the gallbladder or static bile (brown stones)
- Infection, particularly bacterial or parasitic infections of the biliary tree (brown stones)