Causes of gallstone disease

There is no single cause for the formation of gallstones. Gallstone disease, regardless of age, is a multifactorial disease. The leading role in stone formation in children is given to hereditary factors, a congenital disorder of phospholipid metabolism is assumed. A decrease in the activity of lecithin-cholesterol-acyltransferases, as well as a lipoprotein defect. The leading role is given to genes and transport proteins involved in the intrahepatic excretion of bile into the tubules, as well as genes determining the lipid composition of the blood and bile. According to the HLA system, the determinant genes of gallstone disease are the histocompatibility antigens of class I - B12 and B18.

There is no doubt about the role of developmental abnormalities of the biliary system, leading to stagnation of bile both in the bladder and in the intrahepatic bile ducts. Nutritional features (consumption of fats, easily digestible proteins and carbohydrates, deficiency of vitamins, fresh vegetables and fruits) have an effect. Lifelong prevention of hyperlipidemia, hyperinsulinemia, hypercholesterolemia, obesity is ensured by breastfeeding. Breast milk contains a lot of taurine, which improves lipid absorption, increases the secretion of bile acids and reduces the rate of cholesterol secretion. Taurine has a protective effect on the formation of cholesterol stones.

The adverse effects of xenobiotics, drugs, biologically active substances, etc. cannot be underestimated. The gastrointestinal microflora carries out hydrolytic, restorative, and anaerobic processes. When the detoxifying function of the gastrointestinal microflora decreases, metabolic (endotoxemia) and structural damage to cellular organelles, hepatocytes, and the liver as a whole occurs, and bile acquires lithogenic properties. In this regard, both congenital and acquired stone formation are considered possible.

Of exceptional importance is hypodynamia, accompanied by a violation of the exocrine function of the liver, passage of bile and hypotension of the gallbladder. The influence of neurotic factors is great (overload of the school curriculum, excessive use of audiovisual equipment, early involvement in industrial activities, etc.). The consequences of alcoholism, active and passive smoking, and substance abuse are extremely negative.

Pathogenesis of cholelithiasis

In the pathogenesis of cholelithiasis, a significant role is played by changes in the ratio of bile acids and other components of bile. In the mechanism of formation of cholesterol gallstones, the leading role is played by the disruption of the synthesis and enterohepatic circulation of cholesterol, bile acids, hypersecretion of mucoid substances, and a decrease in the evacuation function of the gallbladder.

The formation of lithogenic bile is a complex biochemical process, the primary link of lithogenesis being the disruption of liver enzyme synthesis (increased activity of 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase and decreased activity of cholesterol-7b-hydrolase). As a result, the liver synthesizes an excess amount of cholesterol and an insufficient amount of bile acids.

Increased secretion of mucoid substances (mucin, glycoproteins) by the mucous membrane and decreased evacuation function of the gallbladder contribute to the formation of the core of the future calculus. Activation of anaerobic intestinal microflora leads to disruption of bile acid deconjugation, increased formation of secondary bile acids (deoxycholic and lithocholic), and a decrease in the content of tertiary bile acid (ursodeoxycholic). All of the above stages increase the lithogenicity of bile.

In pigment lithogenesis, the main significance is given to the high concentration of unconjugated free fraction of bilirubin in bile and cholestatic processes in the liver and bile ducts. It has been established that the formation of pigment gallstones in childhood is facilitated by the gradual accumulation of copper and iron in bile. Both trace elements form strong compounds with high-molecular proteins and free bilirubin of bile, leading to the formation of gallstones. Black pigment stones occur in combination with gallstone disease and liver cirrhosis, with hemolytic jaundice, congenital heart defects, and thyrotoxicosis. Brown stones occur as a result of secondary infection of the bile ducts, more often primarily forming in the bile ducts. It is believed that under the influence of Escherichia coli or Clostridium spp. Bilirubin released from diglucuronide inside the bile ducts binds with calcium, forming water-insoluble calcium bilirubinate, and under the influence of the organic matrix it precipitates as a brown pigment.

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