Fisiopatologia de la litiasis biliar

Cálculos de colesterol

Abstract

Biliary stones constitute an important issue in public health, until recently treated exclusively by surgical means. In the western world 80-90% of stones are composed of cholesterol, secondary to abnormalities in cholesterol and lipoprotein metabolism. In the last two decades significant advances in the treatment of this problem have been made, such as medical dissoluFisiopatologia dc la litiasis biliar tion and extracorporeal lithotripsy. The most significant risk factors are: obesity, rapid weight loss, female sex, pregnancy, diabetes, hypertriglyceridemia, estrogens, clofibrate and gastrectomy with vagotomy. Bile salts derived from cholesterol are hydrophylic sterols that are essential to micelle formation. The predominance of the hydrophylic domain makes them amphophylic. Primary bile salts: cholate and deoxycholate are synthetized in the liver; secondary bile salts: deoxycholate and lithocholate derived from primary ones by bacterial transformation in the gut; tertiary bile salts: ursodeoxycholate and sulpholithocholate derived from secondary salts by bacterial action. Lecithin is the main phospholipid in bile, its main function is to solubilize cholesterol associated to bile salts. Micelles arc complex structures made of cholesterol, lecithin and bile salts. Experimentally a triangular diagram has been designed representing molar concentrations of cholesterol, lecithin and bile salts. This diagram facilitates the understanding of biliary stones formation. Changing its components keeping constant total lipids, identifies several phases essential in stones formation, such as the micellar phase and the metastable phase. Supersaturated bile results from excess of cholesterol or deficiency of bile salts, and represents the initial abnormality that predispose to stone formation. However this important factor is not sufficient by itself and other factors such as nucleation defects and gallbladder dysfunction must be present. The most important factors associated to cholesterol hypersecretion in bile arc: increased liver lipoprotein receptors due to diet and estrogens; increased cholesterol synthesis by the liver through increased activity of 3-hydroxy-3-melhyl-glutaryl A reductase by obesity and hypertriglyceridemia; bile salts hyposecretion by disminution of the 7alpha-hydroxylase activity as seen in the elderly; decrease of cholesterol esters by inhibition of cholesterolacyl-transferase as seen with clofibrate and progesterone. Recently nucleating factors have been described such as glycoproteins, apoproteins Al and A2, which are synthetized in the liver and promotes or inhibits nucleation at the gallbladder, the function of the cholesterol carrying vesicles in bile is basic for nucleation, and are detectable between two to for hours after its appearance, simple vesicles aggregates into multilamelar ones with posterior cholesterol precipitation. Other factors of questionable importance are: mucus, prostaglandins and calcium. Finally the physiopathology of pigment gallstones made mainly of bilirubinate, calcium and fatty acids included: pigment overload (hemolysis), infected bile, ascaris, clonorchis sinensis, cirrhosis, parenteral hyperalimentation and biliary tree abnormalities