Cholelithiasis (Gallstones)

DESCRIPTION

Cholelithiasis is the presence of stones, either cholesterol or pigmented, in the gallbladder.
Gallstone disease can affect the pancreaticobiliary system, liver, and small bowel. However, cholelithiasis is frequently asymptomatic.

Cholelithiasis is relatively uncommon in childhood and adolescence; however, the incidence is increasing secondary to improved diagnostic modalities and the rise in pediatric obesity.
Gallstones have been described both in utero and in infancy as well.
Native Africans and Asians have a lower risk of cholelithiasis. Native Americans (Pima, Hopi, Araucanian Indians), Hispanics, and Northern Europeans have the highest risk.
In prepubertal children, pigment stones are most common. In adolescence and adulthood, cholesterol stones become more predominant.
The incidence of cholecystectomy for gallstones in children appears to be rising, especially in association with nonhemolytic or cholesterol gallstones.
The prevalence of cholelithiasis in children and adolescents reported in the literature is ~0.13–0.2% but in children with sickle cell disease (SCD) is between 8.7% and 36%.

Cholesterol stones are the most common and are associated with the following:
- A decrease in bile salt pool
- Decreased bile acid synthesis
- Gallbladder stasis (weight loss, pregnancy, long-term total parenteral nutrition [TPN])
- Hypersecretion of cholesterol into bile
- Increased biliary mucus secretion
- Medications: furosemide, ceftriaxone, cyclosporine, oral contraceptives
- Obesity
Black pigment stones are associated with the following:
- Increased unconjugated bilirubin from congenital or acquired hemolytic anemias, abnormal erythropoiesis, and increased enterohepatic circulation of unconjugated bilirubin
- TPN
- Cirrhosis
Brown pigment stones are associated with common bile duct infection. Parasitic etiologies are public health concerns in developing countries.
Cholesterol or pigment stones have been associated with ileal resection, ileal Crohn disease, and cystic fibrosis (CF).

Age
Female gender
Pregnancy/parity
Obesity/metabolic syndrome: Pediatric obesity is estimated to increase the risk of gallstones by up to 8-fold.
Family history
Prolonged fasting/low-calorie diets/rapid weight loss
Lack of physical activity
Chronic hemolysis (SCD, thalassemia, hereditary spherocytosis, pyruvate kinase deficiency, malaria)
Dyslipidemia
CF
Hepatobiliary disease/cirrhosis
Medications (estrogens, octreotide, clofibrate, furosemide, cyclosporine, ceftriaxone, oral contraceptives)
Genetic predilection
- Mutations in genes encoding the ABC transporters for phosphatidylcholine (adenosine triphosphate-binding cassette, subfamily B), bile salts (ABCB11), and cholesterol 7α-hydroxylase (CYP7A1)
- CCK-A receptor (CCKAR) and CF gene (CFTR) mutations have been reported as well.
- Gilbert syndrome is a variant of UGT1A1 and is another risk factor for cholelithiasis.
Diabetes mellitus
TPN
Trauma, surgery (i.e., abdominal, bariatric, cardiac)
Severe Crohn disease of ileum and/or ileal resection
Acute renal failure
Anatomic abnormalities (biliary stricture, duodenal diverticulum)
Dehydration
Down syndrome
Ineffective erythropoiesis (vitamin B₁₂ and folate deficiencies)
Necrotizing enterocolitis

Gallstone formation can be decreased with moderate exercise and dietary modifications. Dietary changes can include increasing fiber intake and decreasing saturated fatty acid and refined carbohydrate intake.
If there are underlying risk factors present, then prevention of gallstone formation involves treating these risk factors.
- For example, for patients on long-term TPN, initiation of small amounts of enteral feeds may help prevent gallstone formation.
- For patients with CF, pancreatic enzyme supplementation should be started early.
- For obese patients, weight control is important.

Bile is an aqueous solution of bile salts, bilirubin, phospholipids, and cholesterol. Changes in the proportion of bile constituents (e.g. cholesterol supersaturation), nucleation (aggregation of cholesterol crystals), gallbladder hypomotility, or infection can lead to stone formation.
Biliary sludge may progress to stone formation.
Stone types are classified depending on constituents: pigment (black and brown), cholesterol, and mixed.