PATHOGENESIS OF CHOLELITHIASIS. MODERN CONCEPTION

ABSTRACT

The gallbladder plays an important role in metabolic regulation. Cholelithiasis is a common hepatobiliary disorder affecting 10–20% of the adult population. Laparoscopic cholecystectomy is the gold standard of treatment, but this surgical intervention is associated with severe pain in the postoperative period and a potential decrease in the quality of life of patients. Numerous clinical studies demonstrate a statistically significant correlation of cholelithiasis with age and gender characteristics, anthropometric parameters (in particular, body mass index) and comorbid metabolic disorders, including abdominal obesity, diabetes mellitus and non-alcoholic fatty liver disease. [1] This article discusses the factors, causes and mechanisms development cholelithiasis, and also her relationship with pathogenesis, accompanying diseases.

Keywords: cholelithiasis, bile acids, obesity, diabetes, non-alcoholic fatty liver disease, cardiovascular diseases.

Introduction. Cholelithiasis - common pathology digestive systems. Almost 75 % patients housing and communal services on initial stages proceeds asymptomatically. As it develops gallstones they can call such symptoms like nausea, epigastric colic, diarrhea, anorexia, etc. Critical complications requiring immediate intervention are life-threatening conditions: acute cholangitis, acute cholecystitis, biliary pancreatitis [1]. In this review described and summarized pathogenesis, reasons, process education and factors influencing the formation of gallstones, and are also discussed potential mechanisms.

Pathogenesis of cholelithiasis. Gallstones can develop when the gallbladder or other biliary tract components malfunction. Numerous factors, such as hormonal impacts, reduced gallbladder motility, genetic predisposition, and microbiota makeup, are to blame for this. The Lith1 and Lith2 genes, which control bile flow and the liver's release of cholesterol, have been discovered through mouse studies. Their functional analogs in humans are the ABCG5 and ABCG8 transporters, which have an impact on the excretion of cholesterol. The risk of developing cholesterol stones may be raised by mutations in these genes or by their overexpression. [2].

The metabolism of fats, cholesterol, and bile acids is significantly influenced by microorganisms found in the intestinal and biliary tract. Both pigment and cholesterol stones can form as a result of bacteria acting as foci for crystallization. The risk of cholelithiasis is linked to the microflora's makeup, the existence of biofilms, and the metabolic activities of bacteria, including the creation of enzymes and their effects on mucin. Patients with gallstones have altered intestinal microbiota composition, with a rise in potentially harmful microbes and a decline in helpful bacteria. Through the FXR and FGF15/19 receptors, which control bile acid production, the microbiota also affects bile acid metabolism. Certain probiotics might aid with cholesterol reduction. [2].

Although cholelithiasis is quite uncommon in infancy, it becomes much more common as people age, peaking at 70. This is because older people's bile is more lithogenic (secretes more cholesterol and produces fewer bile acids). Cholelithiasis affects women three to four times more frequently than it does males. It is more prevalent in women who have given birth frequently as a result of gallbladder malfunction during pregnancy. Women, especially during pregnancy and when using hormonal contraception, have an increased risk of developing gallstones. Estrogens, in particular 17β-estradiol (E2), increase the secretion of cholesterol by the liver, which leads to bile supersaturation. Estrogens act through the ESR1 and ESR2 receptors, as well as through GPR30, stimulating cholesterol synthesis and the activity of ABCG5/G8 transporters. [3].

A major risk factor is non-alcoholic fatty liver disease (NAFLD). In NAFLD, liver hypoxia triggers the HIF-1α factor, which lowers the production of aquaporin 8 (AQP8), the protein that secretes water into bile. This causes the bile to thicken and speeds up the development of stones. Energy balance and the metabolism of fat and glucose are regulated by the gallbladder. Cholecystectomy and gallstone disease can reduce insulin sensitivity. Biliary dyslipidemia may be exacerbated by liver insulin resistance, which raises the likelihood of stone development.

Gallstones, cardiovascular and cerebrovascular diseases. Gallstones are closely associated with an increased risk of cardiovascular and cerebrovascular diseases. This association is due to common risk factors (especially components of the metabolic syndrome, such as obesity and lipid/carbohydrate metabolism disorders), the key role of cholesterol in the development of both gallstones and atherosclerosis, and the involvement of inflammatory processes in both conditions. Disturbances in cholesterol transport (e.g., those associated with ABCG5/G8 and NPC1L1 proteins) can simultaneously affect its accumulation in vessels and concentration in bile. Patients with gallstones are more likely to suffer from hypertension, diabetes, coronary heart disease, atrial fibrillation, and hyperlipidemia [4].

Conclusions. The gallbladder plays an important role in metabolic regulation. Laparoscopic cholecystectomy is the gold standard of treatment, but this surgical intervention is associated with severe pain in the postoperative period and a potential decrease in the quality of life of patients. Numerous clinical studies demonstrate a statistically significant correlation of cholelithiasis with age and gender characteristics, anthropometric parameters (in particular, body mass index) and comorbid metabolic disorders, including abdominal obesity, diabetes mellitus and non-alcoholic fatty liver disease. Understanding these mechanisms may help develop more effective treatments for gallbladder disease.

References:

1. Tanaka H., Imasato M., Yamazaki Y., Matsumoto K., Kunimoto K., Delpierre J., Meyer K., Ceriale M., Kitamura N., Watanabe M., et al. Claudin-3 regulates the bile canalicular paracellular barrier and cholesterol gallstone core formation in mice // J. Hepatol. 2018. Vol. 69. P. 1308–1316.
2. Wang H.H., Lu M., Portincasa P., Wang D.K. Latest achievements in studying the most important roles carriers sterols ABCG5/G8 in maintaining health and fight against diseases. Medical specialist. Biol. 2020. -№1276. -P.105-136
3. I.P. Parfenov Modern concepts of etiopathogenesis cholelithiasis // Scientific Bulletin of Belgorod State University. Series: Medicine. Pharmacy. – 2011. - No. 16.- P. 27-32.