Causes of cholelithiasis
Last reviewed: 23.04.2024
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There is no common cause for the formation of gallstones. Gallstone disease, regardless of age, is a multifactorial disease. The leading role in stone formation in children is attributed to hereditary factors, suggesting an inborn violation of phospholipid metabolism. A decrease in the activity of lecithin-cholesteryl acyltransferases, as well as a defect in lipoprotein. The leading role is assigned to genes and protein transporters involved in intrahepatic excretion of bile in the tubules, as well as to genes that determine the lipid composition of the blood and bile. According to the HLA system, the histocompatibility antigens of the first class - B12 and B18 - are the gene-determinants of cholelithiasis.
There is no doubt about the role of anomalies in the development of the bile excretory system, leading to stagnation of bile both in the bladder and intrahepatic bile ducts. Influence of nutrition features (consumption of fats, digestible proteins and carbohydrates, deficiency of vitamins, fresh vegetables and fruits). Lifelong prophylaxis of hyperlipidemia, hyperinsulinemia, hypercholesterolemia, obesity provides natural feeding. In human milk, there is 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.
Do not underestimate the adverse effects of xenobiotics, drugs, biologically active substances, and the like. The microflora of the gastrointestinal tract produces hydrolytic, reducing anaerobic processes. With a decrease in the detoxification function of the gastrointestinal microflora, metabolic (endotoxemia) and structural damage to cellular organelles, hepatocytes and the liver as a whole, the bile acquires lithogenic properties. In this regard, it is considered possible both the congenital and acquired nature of stone formation.
Exceptional importance is hypodynamia, accompanied by a violation of the external secretory function of the liver, passage of bile and hypotension of the gallbladder. Great influence of neurotic factors (congestion of the school curriculum, excessive use of audiovisual equipment, early involvement in production activities, etc.). Exceptionally negative consequences of alcoholism, active and passive smoking, substance abuse.
Pathogenesis of cholelithiasis
In the pathogenesis of cholelithiasis, a significant role is played by a change in the ratio of bile acids and other components of bile. In the mechanism of formation of cholesteric gallstones, the synthesis and enterohepatic circulation of cholesterol, bile acids, hypersecretion of mucoid substances, and the decrease in the evacuation function of the gallbladder play a leading role.
The formation of lithogenic bile is a complex biochemical process, the primary link in lithogenesis is a disruption in the synthesis of hepatic enzymes (increased activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and a decrease in the activity of cholesterol-7b-hydrolase). As a result, excessive amounts of cholesterol and insufficient amounts of bile acids are synthesized in the liver.
Increased secretion of mucoid substances (mucin, glycoproteins) by the mucosa and a decrease in the evacuation function of the gallbladder contribute to the formation of the nucleus of the future calculus. Activation of anaerobic microflora of the intestine leads to a violation of deconjugation of bile acids. Increased formation of secondary bile acids (deoxycholic and lithocholic), a decrease in the content of tertiary bile acid (ursodeoxycholic). All these stages increase the lithogenicity of bile.
In pigmental lithogenesis, a high concentration of unconjugated free bilirubin fraction in bile and cholestatic processes in the liver and biliary tract is of primary importance. It is established that the formation of pigmentary gallstones in childhood contributes to the gradual accumulation of copper and iron in bile. Both microelements form strong compounds with high molecular proteins and free bilirubin bile, leading to the formation of gallstones. Black pigmented stones occur when a combination of cholelithiasis with cirrhosis of the liver, with hemolytic jaundice, congenital heart disease, thyrotoxicosis. Brown concrements arise as a result of secondary infection of the bile ducts, often primarily formed in the bile ducts. It is believed that under the influence of Escherichia coli or Clostridium spp. released from diglukuronida bilirubin inside the bile ducts binds with calcium, forming water insoluble calcium bilirubinate, under the influence of the organic matrix precipitates as a brown pigment.
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