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Cholelithiasis (Gall stones) 2 types = cholesterol monohydrate (80% -> yellow), pigmented (bilirubin calcium salts -> Radio-opaque, gritty) Risk factors for cholesterol stones western world, age (40+), females, Oral contraceptives, pregnancy, obesity, rapid weight reduction (protein/calorie malnutrition -> high fat metabolism), gall bladder stasis, inborn error of bile salt metabolism, hyperlipidemia syndromes Risk factors for pigment stones Asian, rural, chronic hemolytic syndromes, ineffective erythropoiesis, biliary infection, GI disorders (Crohn's disease, ileal resection or bypass, CF of pancreas) Clinical Cholelithiasis 70-80% asymptomatic, may present with pain (constant or colicky), Complications: empyema (inflammation can cross diaphragmatic boundaries), perforation, fistulas (crosses hepatic flexure), cholangitis (infection/inflammation), pancreatitis (one of the common causes of acute pancreatitis), gall stone ileus, increased risk of carcinoma Pathogenesis of gallstones bile is supersaturated with cholesterol -> GB hypomotility promotes nucleation (precipitation of cholesterol from bile into vesicles) -> cholesterol nucleation in bile is accelerated -> mucus hypersecretion traps the crystals permitting aggregation into stones (acts as a glue) Acute cholecystitis chemical irritation and inflammation in setting of obstruction to flow -> mucosal phospholipase converts lecithin to lysolecithin -> damage to glycoprotein layer of mucosa -> damage glycoprotein layer of mucosa -> further release of PGs from mucosa -> cumulatively leads to mucosal and mural inflammation -> gall bladder dysmotility and increased intraluminal pressure -> superimposed bacterial contamination (typhoid likes alkaline environment) Acute cholecystitis morphology Gall bladder enlarged -> capillary congestion (red), edematous (fluid is recruited to area) -> inflamed wall and large stone impacted in cystic duct Acute cholecystitis pain in right hypochondrium or epigastrium -> may appear like surgical emergency -> associated fever, nausea, vomiting -> rarely jaundice if obstruction of common bile duct (associated sludge) -> most patients recover Chronic cholecystitis most commonly no antecedent attacks of acute cholecystitis -> role of gall-stones not clear -> microorganisms can be cultured from bile in 1/3 of patients -> rarely extensive dystrophic calcification (Porcelain gall bladder -> increase in association with cancer) Carcinoma of the gall bladder 70 year old females (more frequently in southeast Asia) -> stones in 60-90% of patients, pyogenic and parasitic infections of the biliary tract are also risk factors -> carcinogenic derivatives of bile may play a role -> mostly adenocarcinomas, most invade liver by the time they are discovered