Cholesterol gall stones are due to -
Ans. is 'd' i.e., .AH of the above o Bile salts and phospholipids in bile keep cholesterol in solution by the formation of micelles,o An excess of cholesterol relative to bite salts and phospholipids allows cholesterol to form crystals and such bile is called Lithogenic or super-saturated bile.Pathogenesis of Cholesterol gall stoneso There are three elements necessary for the formation of cholesterol gall stonesLithogenic bileNucleation andStasis or gall bladder hypomotilityAll three are necessary! for cholesterol stone formation.Lithogenic {stone-forming) bileo Cholesterol is insoluble in water (water is major constituent of bile. 85-95%). It is made soluble by bile acids and phospholipid - lecithin which form micelles with cholesterolo So any mechanism which increases the cholesterol in bile or decreases the bile acids (salts) or lecithin makes the bile supersaturated or lithogenic. If to such a bile, the other two elements i.e. nucleation and stasis are provided, the cholesterol in solution precipitates to form cholesterol crystals which grow to form cholesterol stones,o Factors which increase biliary cholesterolObesityHigh calorie and cholesterol rich dietClofibrate therapyo Factors which decrease bile acidsPrimary biliary cirrhosisOral contraceptive pillsGenetic factorsA mutation in CYP7A1 gene which results in deficiency1 of enzyme cholesterol 7 -hydroxylase. It results in impaired hepatic conversion of cholesterol to bile acids, thus it increases the cholesterol/bile acid ratio.Decreased/impaired enterohepatic circulation of bile acids:Ileal diseaseIleal resectionCholestyramine, colestipol (bile acid sequestrants) therapy.Deoxycholateo Factors which decrease biliary lecithin- A mutation in MDR3 gene leads to defective phospholipid (lecithin) secretion into bile.Nucleationo Nucleation refers to the process by wrhich cholesterol monohydrate crystals form and agglomerate to become macroscopic crystals.o Formation of cholesterol stones requires either an excess of pronucleating factors or a deficiency of antinucleating factors.o Mucin and certain non-mucin glycoproteins (and infection according to Bailey & Love) appear to be pronucleating factors, while apolipoproteins AI and All and certain other glycoproteins appear to be antinucleating factor.C) Stasis or gall bladder hypomotilityo Stones would not be able to form if the gall bladder emptied all supersaturated or crystal containing bile completely.o Gall bladder hypomotility is caused byProlonged parenteral nutritionFastingPregnancyDrugs such as octreotideOral contraceptive pillsSurgery, bums
Decreased motility of Gall bladder
Hypo secretion of bile salts
Hyper cholesterolemia
All of the above
Gallstone Disease