A 45-year-old woman diagnosed with Crohn disease 3 years ago comes to the office due to recurrent right upper quadrant abdominal pain. The pain is graded 5/10 in intensity, is characterized as dull, and occasionally radiates to the right shoulder. It typically occurs after eating fatty meals and is associated with nausea. The patient has no fever, vomiting, melena, or hematochezia. She currently takes infliximab for Crohn disease and atorvastatin for hyperlipidemia. Vital signs and abdominal examination are normal. Abdominal ultrasonography reveals multiple mobile calculi within the gallbladder. Which of the following processes is most likely responsible for the development of gallstones in this patient?

Question

A 45-year-old woman diagnosed with Crohn disease 3 years ago comes to the office due to recurrent right upper quadrant abdominal pain.  The pain is graded 5/10 in intensity, is characterized as dull, and occasionally radiates to the right shoulder.  It typically occurs after eating fatty meals and is associated with nausea.  The patient has no fever, vomiting, melena, or hematochezia.  She currently takes infliximab for Crohn disease and atorvastatin for hyperlipidemia.  Vital signs and abdominal examination are normal.  Abdominal ultrasonography reveals multiple mobile calculi within the gallbladder.  Which of the following processes is most likely responsible for the development of gallstones in this patient?

Quizplus · Accepted Answer

11ec160b_3adc_4c40_9249_a3e6ff5386e5_MD0001_00 This patient with Crohn disease most likely developed gallstones due to inflammation of the terminal ileum causing decreased bile acid reabsorption. Bile acids are produced in the liver and excreted with bile into the duodenum. There, they emulsify fat droplets to form water-soluble micelles that allow pancreatic lipase to efficiently hydrolyze triglycerides into fatty acids and monoglycerides. In the jejunum, these micelles come in close contact with the gut epithelium, which facilitates the passive absorption of fatty acids, monoglycerides, and cholesterol across the brush border into enterocytes. However, bile acids are ionized molecules that cannot passively cross the intestinal wall. The bile acids eventually reach the terminal ileum, where specialized transport proteins allow them to be reabsorbed. The terminal ileum is a typical location of activity in Crohn disease. When the mucosa of the terminal ileum is inflamed, bile acids are lost in the feces. As a result, a lesser amount of bile acid is present in the bile, so the ratio of cholesterol/bile acids increases. Supersaturation of the bile with cholesterol then leads to formation of gallstones. (Choice A) Gallbladder hypomobility may contribute to cholesterol gallstone formation in patients with spinal cord injury or those receiving total parenteral nutrition; however, this is not observed with Crohn disease. (Choice C) Increased intestinal oxalate absorption can contribute to calcium oxalate kidney stone formation in patients with Crohn disease (enteric oxaluria). However, this process is not responsible for the development of gallstones. (Choice D) Statins inhibit the rate-limiting step of cholesterol synthesis (HMG-CoA reductase), which reduces the risk of gallstone formation. Infliximab is a tumor necrosis factor-alpha inhibitor used to treat severe or refractory Crohn disease; it is associated with an increased risk of serious infections. (Choice E) Chronic hemolytic anemias are associated with the development of pigment gallstones due to the increased secretion of bilirubin into bile. Crohn disease can cause anemia due to nutrient deficiency (eg, vitamin B₁₂, iron) and chronic inflammation (eg, anemia of chronic disease), but it does not typically cause hemolysis. Educational objective: Patients with Crohn disease affecting the terminal ileum (most common site of involvement) are prone to developing gallstones. Decreased bile acid reabsorption by the inflamed terminal ileum promotes cholesterol supersaturation of the bile, resulting in gallstone formation. __________ References: Pathogenesis of gall stones in Crohn's disease: an alternative explanation. (http://www.ncbi.nlm.nih.gov/pubmed/8307459) Gallbladder bile composition in patients with Crohn's disease. (http://www.ncbi.nlm.nih.gov/pubmed/16440420) Enterohepatic cycling of bilirubin: a putative mechanism for pigment gallstone formation in ileal Crohn's disease. (http://www.ncbi.nlm.nih.gov/pubmed/10348826)

A 45-Year-Old Woman Diagnosed with Crohn Disease 3 Years Ago