What Are Risk Factors for Cholelithiasis?

Patient Presentation
An 18-year-old female came to clinic for weight management after having a cholecystectomy 5 months previously. She was now walking 3-4 days a week and had improved some of her eating habits. The past medical history showed that she had always been at the high end of the body mass index (BMI), but after puberty had dramatically put on weight and was up to a BMI of 44. Over the previous year she had intermittent abdominal pain that 5 months ago had become acute and she was evaluated in the emergency room where she was diagnosed with acute cholecystitis. She was admitted and several days later had a cholecystectomy. The pathology reported cholesterol stones.

The pertinent physical exam showed an obese female with a BMI of 40.1. Blood pressure was 132/84. She had a well healed scar in the upper right quadrant and abdominal striae. She had no acanthosis nigracans. The diagnosis of an obese female with improving BMI, status-post cholecystectomy was made. The physician applauded her efforts and they discussed ways that she could continue to slowly lose weight including a referral to a dietician that she had previously rejected seeing.

Bile is produced by the liver to aid absorption of fat soluble vitamins and lipids from the gastrointestinal tract and to transport bilirubin, cholesterol and other substances to the gastrointestinal tract. Bile is the main form of cholesterol excretion. Gallstones or cholelithiasis form when the balance of substances within the hepatobiliary tract favors supersaturation with crystal formation and gallstone formation. It is a dynamic state of affairs as gallstones can form and also have a high rate of resorption of up to 50%. Gallstones 3 mm are called gallstones.

Gallstones, while not as common as adult population (15-20%), do occur in the pediatric population. A prevalence rate of 0.13-0.22% is often quoted. The prevalence increases up to 1.9% in a study from the Netherlands that used ultrasound screening. Infants and adolescents have the highest risk creating a bimodal distribution.

Patients can be asymptomatic (~33% for pediatrics vs 80% for adults) or symptomatic. Those that are symptomatic may not have the classic presentation of emesis, abdominal pain, fever and leukocytosis. Children can present with different problems including nausea and vomiting, jaundice, fatty food intolerance, acholic stools and fever. The abdominal pain may be generalized or more specifically attributable to biliary colic. Murphy’s sign or pain causing inspiration cessation when the gallbladder is palpated is helpful if present but can be difficult to illicit or determine in the pediatric age group.

There are 4 types of gallstones:

  • Cholesterol stones
    • An increased cholesterol relative to bile salts creates supersaturated cholesterol stones
    • Constituent – 70% cholesterol and 30% other constituents including also bilirubin, protein, calcium carbonate
    • Increased incidence and prevalence because of increasing obesity
  • Black pigment stones
    • Increased unconjugated bilirubin and calcium forms the stones
    • Constituent – calcium bilirubinate
    • Usually due to increased hemolysis
    • Occurs in 20-40% of children with gallstones
  • Brown pigment stones
    • Increased fatty acid and calcium forms the stones
    • Constituent – calcium bilirubinate and fatty acids
    • Associated with infection, either bacterial or helminthic, in the biliary tract
    • Rare in children
  • Calcium carbonate stones
    • Possibly due to cystic duct narrowing which allows calcium salts to precipitate
    • Constituent – calcium salts
    • Only seen in children

Laboratory evaluation includes liver enzymes (AST, ALT, GGT), bilirubin and alkaline phosphatase, amylase, and a complete blood count. These tests can be normal even in acute cholecystitis. Transabdominal ultrasound is usually the initial imaging test. Gallstones may be detected as echogenic shadows in the gallbladder and potentially the common bile duct (although that can be difficult to detect). Evaluation of the size of the bile duct and also the pancreas can also be done by ultrasound. Endoscopic retrograde cholangiopancreatography (ERCP) is helpful both diagnostically and therapeutically.

Treatment includes monitoring (especially because of high rate of resolution for many patients), medications to help dissolve the stones including ursodeoxycholic acid which can be very helpful for cholesterol stones, extracorporeal shock-wave lithotripsy, cholcystolithotomy (removal of stones but gallbladder is left in-situ) or cholecystectomy. Cholecystectomy is often used for patients with black pigment stones particulary caused by sickle cell anemia. Patients with sickle cell disease are more likely to have acute cholecystitis and to have complications related to cholecystectomy at the time of acute cholecystitis. Therefore once gallstones are detected in patients with sickle cell disease, prophylactic cholecystectomy should be discussed.

Learning Point
Risk factors for gallstones include:

  • Hemolytic disease – sickle cell anemia, thalassemia, glucose-6-phosphate deficiency, hereditary spherocytosis, Gilbert syndrome
  • Parenteral nutrition
  • Systemic infection
  • Necrotizing enterocolitis
  • Antibiotic use – particularly ceftriaxone
  • Anatomic abnormalities of the hepatic/pancreatic system and also terminal ileum (i.e. Crohn’s disease)
  • Obesity
  • Genetic – Cystic fibrosis, Native American, Mexican American
  • Increased estrogen state – pregnancy, oral contraceptives, post-pubertal female
  • Prematurity
  • Congenital heart disease and heart transplant
  • Surgery – Bowel resection and cardiac bypass

Questions for Further Discussion
1. What is a sonographic Murphy sign?
2. What should be included in the differential diagnosis of right upper quadrant pain?
3. What are complications of cholelithiasis?
4. What is the differential diagnosis of abdominal pain? See here for abdominal pain or recurrent abdominal pain

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Gallstones and Obesity.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Poddar U. Gallstone disease in children. Indian Pediatr. 2010 Nov;47(11):945-53.

Poffenberger CM, Gausche-Hill M, Ngai S, Myers A, Renslo R. Cholelithiasis and its complications in children and adolescents: update and case discussion. Pediatr Emerg Care. 2012 Jan;28(1):68-76.

Svensson J, Makin E. Gallstone disease in children. Semin Pediatr Surg. 2012 Aug;21(3):255-65.

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital