Progress in the study on the composition and formation mechanism of gallstone

Our serial studies from 1970s on chemical composition, structure determination and formation mechanism of gallstones were reviewed. The chemical component investigation of brown-pigment gallstone demonstrated that it consists of macromolecules such as proteins, glyco-proteins, polysaccharides, bilirubin polymers and pigment polymers, and biomolecules such as cholesterol, bile salts, calcium salts of carbonate, phosphate, fatty acids and bilirubinate as well as various metal ions. The binding of metal ions with bile salts and bilirubin plays important roles in gallstone formation, i.e., calcium bilirubinate complex is the major constitute of brown-pigment gallstones, and copper bilirubinate complex is critical in the black color appearance of black-pigment gallstone. The cross section of many gallstones exhibits a concentric ring structure composed of various small particles with a fractal character. This is nonlinear phenomenon in gallstone formation. A typical model system of metal ions-deoxycholate (or cholate)-gel was chosen to mimic an in vitro pattern formation system. The experimental results suggested that a nonlinear scientific concept should be considered in understanding gallstone formation. Minor changes in the chemical composition and/or the microenvironment may lead to very different precipitate patterns with a variety of shapes, colors, appearances, and structures. A new model was suggested that periodical templets of periodical and fractal patterns were formed in the initial stage, then the spatio-temporal patterns grew gradually on it. Furthermore, the interaction between divalent metal ions and bile salts in vitro was investigated, and the results indicated that non-stoichiometric M(DC)2-NaDC mixed complexes with mixed micelles structure can be formed in physiological condition.