What causes gallstone disease?

Factors predisposing to the formation of gallstones (primarily cholesterol):

The role of infection

Although infection is not thought to play a significant role in cholesterol stone formation, polymerase chain reaction has detected bacterial DNA in stones containing less than 90% cholesterol. It is possible that bacteria are able to deconjugate bile salts, resulting in bile acids being absorbed and cholesterol becoming less soluble.

The formation of brown pigment stones, most of which contain bacteria when examined with electron microscopy, is associated with bile duct infection.

Female gender

In women, especially those under 50 years of age, gallstones occur twice as often as in men.

Women who have given birth to many children are more likely to get the disease than women who have not. Incomplete emptying of the gallbladder in late pregnancy leads to an increase in its residual volume, accumulation of cholesterol crystals and, as a result, to the formation of gallstones. During pregnancy, gallstones are often detected, which usually do not manifest clinically and spontaneously resolve after childbirth in two thirds of women. In the postpartum period, gallstones were found in 8-12% of cases (9 times more often than in the corresponding control group). A third of women in whom gallstones were detected against the background of a functioning gallbladder had characteristic symptoms of the disease. Small stones disappeared on their own in 30% of cases.

Oral contraceptives lead to an increase in the lithogenic properties of bile. With long-term use of oral contraceptives, gallbladder diseases develop 2 times more often than in the control group. Taking estrogen-containing drugs in postmenopause significantly (2.5 times) increases the incidence of gallstone disease. An increase in bile saturation with cholesterol and the occurrence of gallstones were noted in men who received estrogens for prostate cancer. Estrogen and progesterone receptors were found in the wall of the human gallbladder.

Age

Aging is associated with an increased incidence of gallstones, possibly due to increased cholesterol levels in bile. By age 75, 20% of men and 35% of women have gallstones, which usually become clinically apparent after age 50–60.

Pigment and cholesterol stones have been reported in children.

Genetic and ethnic characteristics

Regardless of age, body weight and diet, gallstones are more common in relatives of patients with cholelithiasis than in the general population. This indicator is 2-4 times higher than expected values.

Dietary habits - excessive consumption of fatty foods with high cholesterol content, animal fats, sugar, sweets;

In Western countries, gallstone formation is associated with low fiber diets and longer gastrointestinal transit. This leads to increased concentrations of secondary bile acids in bile, such as deoxycholic acid, making bile more lithogenic. Refined carbohydrates increase bile cholesterol saturation, while small doses of alcohol have the opposite effect. Gallstones are less common in vegetarians, regardless of body weight.

Increasing dietary cholesterol intake increases cholesterol content in bile, but there is no epidemiological or dietary evidence linking cholesterol intake to gallstone formation. Endogenous cholesterol is probably the major source of bile cholesterol.

Pregnancy (history of multiple births)

Obesity

Obesity appears to be more common among patients with gallstone disease than in the general population, being an important risk factor in women under 50 years of age. Obesity is associated with increased synthesis and excretion of cholesterol, but is not associated with characteristic changes in residual gallbladder volume after meals. Gallstones are found in 50% of patients with severe obesity during abdominal surgery.

Low-calorie diets (2100 kJ per day) in obese patients can lead to the formation of gallstones with characteristic symptoms, as well as bile slurry. It has been noted that weight loss is associated with an increase in the content of mucin and calcium in the gallbladder. Ursodeoxycholic acid is used to prevent the formation of gallstones during rapid weight loss after gastric bypass surgery.

Serum factors

The most important risk factors for developing gallstones, both cholesterol and pigment, perhaps even more important than body weight, are low levels of high-density lipoproteins and high levels of triglycerides. High serum cholesterol does not affect the risk of developing gallstones.

Other factors

Resection of the ileum disrupts the enterohepatic circulation of bile salts, reduces their pool and leads to the formation of gallstones. Similar changes occur with subtotal and total colectomy.

Gallstones form more frequently after gastrectomy.

Long-term use of cholestyramine increases the loss of bile salts, leading to a decrease in the total pool of bile acids and cholelithiasis.

Low-cholesterol diets, rich in unsaturated fats and plant sterols but low in saturated fats and cholesterol, cause cholelithiasis.

Treatment with clofibrate increases cholesterol excretion and enhances bile lithogenicity.

With parenteral nutrition, expansion and hypokinesia of the gallbladder containing stones are observed.

Long-term treatment with octreotide causes cholelithiasis in 13-60% of patients with acromegaly. This is characterized by cholesterol oversaturation of bile, an unusually short sedimentation time, and high cholesterol content in stones. In addition, gallbladder emptying is impaired.