Cholelithiasis is the word used to describe
the presence of gallstones within the gallbladder or bile ducts,
whereas choledocholithiasis is the presence of
gallstones in the common bile duct. Cholelithiasis, or gallstones,
is increasingly recognized in children. This most likely can be
attributed to the pediatric obesity epidemic or to the increased
use of imaging techniques, especially abdominal ultrasound.
The incidence currently is reported to be 0.1% to 0.2% in
children. In comparison, gallstones are found in approximately 10% of
adults. Associated conditions leading to gallstone formation in
children differ by age group (Table 427-1).36 In infants, the most common causes are
prematurity, parenteral nutrition, infection, and a history of intestinal surgery
(including short bowel syndrome); in children ages 1 to 5 years, hepatobiliary
disease, a history of abdominal surgery, and congenital heart disease;
and in children ages 6 to 21 years, pregnancy, hemolytic disease,
and obesity.37 Other conditions associated with gallstone
formation include malabsorptive diseases (ie, Crohn disease), a
history of heart transplantation, prior abdominal trauma, and bronchopulmonary
dysplasia. Patients with cystic fibrosis have an increased incidence
of gallstones along with other hepatobiliary findings. Gallstones
are relatively uncommon in African Americans (except in sickle cell disease),
exceptionally common in select groups of Native Americans and Hispanics,
and a frequent occurrence in Caucasians.
Table 427-1. Associated
Conditions in Cholelithiasis by Age ||Download (.pdf)
Table 427-1. Associated
Conditions in Cholelithiasis by Age
|0–12 months||1–5 years||6–21 years|
|Parenteral nutrition||Hepatobiliary disease||Pregnancy|
|Abdominal surgery||Abdominal surgery||Hemolytic disease|
|Sepsis||Prosthetic heart valve||Obesity|
|Bronchopulmonary disease||Malabsorption||Abdominal surgery|
|Hemolytic disease||Hepatobiliary disease|
The three most common types of stones include cholesterol stones, black
pigmented stones, and brown pigmented stones. Cholesterol stones
are composed of cholesterol crystals and mucin (Fig.
427-3). Black pigmented stones are composed of calcium salts
and bilirubin, and brown pigmented stones are made of calcium bilirubinate,
calcium phosphate, calcium palmitate, cholesterol, and other residues
(eFig. 427.1). Stones
may form as a result of abnormalities in cholesterol and lecithin
concentrations, mucin secretion, gallbladder motility, enterohepatic
circulation of bile salts, or hydrolysis of bilirubin by bacteria.38,39
Endoscopic image of a cholesterol gallstone retrieved
during endoscopic retrograde cholangiopancreatography and endoscopic image
of a pigmented gallstone.
Endoscopic image of a pigmented stone from a 15-year-old
female with sickle cell anemia.
The differential diagnosis of gallbladder disease includes: acute
and chronic hepatitis, malignancy, pneumonia, pelvic inflammatory disease (including
Fitz-Hugh-Curtis perihepatitis), pancreatitis, esophagitis, gastritis,
duodenitis, nephrolithiasis, and urinary tract infection.
In children with cholelithiasis the most common symptoms include vomiting
and abdominal pain, typically in the right upper quadrant or epigastric
region. Biliary colic usually lasts between 15 to 30 minutes and
6 hours. These symptoms can be caused by a stone that is obstructing
the neck of the gallbladder or is within the cystic duct. In large
series, 40% to 60% of children under the age of
5 years with cholelithiasis
presented with jaundice, even in the absence of common duct stones.
This is less common in older children. Physical examination may
demonstrate a child with right upper quadrant tenderness, or guarding.
Rarely, a mass is palpable in the right upper quadrant or epigastrium.
Laboratory abnormalities may include mild elevation in serum aminotransferases,
GGT, or 5'-nucleotidase. Both conjugated and unconjugated bilirubin
may be elevated.40,41 Abdominal radiographs may
reveal calcium stones; gallstones are most commonly visualized by
abdominal ultrasound (Fig. 427-4). Computerized
tomography (CT) scan, magnetic resonance cholangiography (MRCP),
endoscopic ultrasound (EUS), or endoscopic retrograde cholangiopancreatography
(ERCP) may also demonstrate stones (eFig. 427.2).
A: Ultrasound image showing gallstones
within the gallbladder. B: Ultrasound image
of gallbladder layered with sludge.
Cholangiogram from endoscopic retrograde cholangiopancreatography
demonstrating dilated bile duct with multiple filling defects and
presence of clips from prior cholecystectomy.
With choledocholithiasis, stones may be found within either the
intra- or extrahepatic bile ducts. The majority of stones come from
the gallbladder, because primary bile duct stones occur rarely in
childhood, most often in hemolytic disease or associated with abnormal
ducts due to genetic or inflammatory disorders. The clinical presentation of
bile duct stones is similar to that of cholelithiasis; however,
abdominal pain, nausea, and jaundice are more prominent symptoms.
Physical exam findings include jaundice and right upper quadrant
tenderness. Common bile duct stones are most commonly visualized
by abdominal ultrasound, but more specific imaging modalities include
MRCP, EUS, ERCP, or intraoperative cholangiogram. In a subset of
patients, stones are not visualized, but the common bile duct is
dilated (normal adult size is 5 mm), suggesting a distally obstructing
Asymptomatic patients found to have stones may be followed with
conservative management. However, in certain conditions such as
sickle cell anemia, elective cholecystemy is recommended. Similarly,
in patients with hereditary spherocytosis, cholecystectomy is recommended
at the time of splenectomy if gallstones are present. The use of
ursodiol and lithotripsy are not well studied in children and are
not beneficial for pigmented stones. In symptomatic patients with
gallstones, laparascopic cholecystectomy, with or without intraoperative
cholangiogram (IOC), is the procedure of choice. The timing of surgery
is dependent on clinical status, comorbidities, and presence of
complications.42 Endoscopic retrograde cholangiopancreatography
(ERCP) may also be done pre- or postoperatively for retained stones
or if IOC does not demonstrate stone clearance. Percutaneous cholecystostomy
can be performed in patients that are not surgical candidates. ERCP
is performed for patients with gallstone disease when they have
persistent jaundice or pain from an obstructing common bile duct
stone, imaging abnormality, cholangitis, or gallstone pancreatitis.
Complications of cholelithiasis and choledocholithiasis include
cholecystitis, cholangitis, and bile duct perforation. Pancreatitis
is common secondary to obstruction of the nearby pancreatic duct.
Stones passing through the sphincter of Oddi may cause scarring
and stenosis of the distal common bile duct. More than 80% of
older children with gallstones may have evidence of chronic cholecystitis.41 Acute
histologic evidence of cholecystitis in patients with gallstones
occurs in less than 10% of cases.
Inflammation of the gallbladder may manifest as either acute
or chronic cholecystitis. Cholecystitis is frequently caused by
obstruction of the neck of the gallbladder or cystic duct by a stone, referred
to as calculous cholecystitis. Acalculous cholecystitis occurs in
the absence of stones and is frequently related to systemic illness.
Cholangitis is inflammation of the biliary tree.
The acute form of calculous cholecystitis presents in children
with right upper quadrant pain (biliary colic in older children),
nausea, vomiting, jaundice (in up to 50%), and fever. Exam findings
are notable for tenderness over the affected area. A Murphy sign,
which is pain on inspiration, may be elicited.
Laboratory evaluation is notable for an elevated white blood count,
as well as moderate elevations in aminotransferases and GGT.40 Ultrasound
findings include a thickened, anechoic gallbladder wall, with sludge,
or gallstones. Ten to twenty percent of patients may also have common
bile duct stones.
Thickened gallbladder walls may also be seen in patients with
hypoalbuminemia and ascites, and in those who have recently eaten
a meal.43 A hepatobiliary iminodiacetic acid (HIDA)
scan may show lack of uptake in the gallbladder. The majority of
patients can be managed conservatively by administering intravenous
fluids, maintaining no oral intake, and providing opioid analgesics.
Surgical consultation should be obtained early in the course of
the illness. Antibiotics are not necessary unless there is persistent
fever, signs of sepsis, or other biliary complications. Selection
of antimicrobials should include coverage for gram-negative bacteria
and enteric anaerobes.
Unless there are emergent indications, cholecystectomy is the
definitive treatment once the initial infection and complications
have resolved. Open or percutaneous cholecystostomy can be performed
in high-risk patients if necessary. Intraoperative cholangiogram
and common bile duct exploration can evaluate whether there are
retained common bile duct stones.37 The most common
complications of acute cholecystitis include perforation, empyema,
and pericholecystic abscess.
Chronic calculous cholecystitis is more common in children than
the acute form. It presents with a series of acute episodes. Pain
is often associated with eating, specifically eating fatty meals.
Laboratory findings may be normal or have mild perturbations in
aminotransferases and GGT. Ultrasound may show thickened gallbladder
wall and stones.43 The treatment is also cholecystectomy.
Acalculous cholecystitis is an inflammatory condition seen in
the absence of gallstones. There are two forms: acute, which is
less than 1 month’s duration and chronic, which is greater
than 3 months’ duration.44 Acalculous
cholecystitis most commonly occurs in association with infection
or systemic illness. The most common infections include group A
beta-hemolytic streptococcus and gram-negative enterics (ie, salmonella,
shigella, and E coli). Parasitic infections have
been described in patients with cryptosporidiosis, giardiasis, and ascariasis.
Leptospirosis is a spirochetal infection described in a large US
midwestern outbreak in patients who developed acalculous cholecystitis.45 Hemolytic
uremic syndrome, cystic fibrosis, and systemic vasculitides (systemic
lupus erythematosus, polyarteritis nososum, Kawasaki disease) may
also cause acalculous cholecystitis. Risk factors for acute acalculous cholecystitis
include prolonged fasting, total parenteral nutrition (TPN), shock,
intravenous opiate use, history of transfusion, and sepsis.
Most patients with the acute form will have fever, right upper
quadrant pain, and vomiting. Jaundice and palpable mass may be present.46 Laboratory
evaluation is notable for an elevated white blood count, abnormal
aminotransferases, abnormal GGT, and elevated bilirubin. Children
with chronic acalculous cholecystitis have right upper quadrant
pain with nausea or vomiting, but typically have a normal complete
blood count (CBC) and liver panel. Abdominal ultrasound in acute
and chronic acalculous cholecystitis will show a thickened gallbladder
wall without stones, but some patients will have sludge. A hepatobiliary
iminodiacetic acid (HIDA) scan will not demonstrate gallbladder
filling. Treatment of the underlying illness should be initiated,
and cholecystectomy is performed in most patients.
Infection of the biliary tree is rare, but most frequently seen
in the setting of obstruction. Cholecystitis, choledocholithiasis,
sclerosing cholangitis, and biliary cystic disorders (Caroli’s)
may be complicated by cholangitis. Patients at greatest risk are
those patients with biliary atresia or choledochal cyst who have
had hepatoportoenterostomy. Most patients have fever and jaundice
or may have acholic stools. Charcot triad, which includes fever,
right upper quadrant pain, and jaundice, is commonly described in
adults. Laboratory abnormalities include an elevated conjugated
bilirubin, elevated GGT, and serum aminotransferases. Blood cultures
are frequently positive and the most commonly isolated organisms
are E coli, enterococci, and Klebsiella. Ultrasound,
magnetic resonance imaging (MRI), or hepatobiliary iminodiacetic
acid (HIDA) scan may show evidence of obstruction. Acute therapy
includes fluid management, treatment of the underlying condition,
and broad-spectrum antibiotics. Antimicrobial selection should incorporate
therapy to achieve appropriate biliary and serum coverage. Combination
therapy is necessary and may include piperacillin/tazobactam
and gentamicin. Biliary decompression with percutaneous drainage
or endoscopic retrograde cholangiopancreatography (ERCP) may be necessary
to restore flow. In patients with negative blood cultures, liver
biopsy may help identify an organism. Complications of cholangitis
include liver abscess, biliary stricture, biloma, and acute perforation.
Frequent episodes of cholangitis can lead to acute and chronic worsening
of underlying liver disease.
Hydrops of the Gallbladder
Acute distention of the gallbladder wall without stones or evidence
of local inflammation is the hallmark of gallbladder hydrops. The
pathogenesis is unknown and may affect children at any age. This
condition is most commonly associated with Kawasaki syndrome, but
has been described as the sequelae of group A beta-hemolytic streptococccal and
leptospiral infection. Hydrops has also been associated with Henoch-Schönlein
Common presenting symptoms of gallbladder hydrops include abdominal
pain, nausea, and vomiting. Some patients may have fever and jaundice,
and often have abdominal distention and right upper quadrant pain
on physical examination. A distended gallbladder may be palpable. Laboratory
investigations are often unrevealing and may be indistinguishable
from cholecystitis, but may include mild elevations in aminotransferases,
alkaline phosphatase, or GGT.40
Diagnosis is usually by ultrasound, which shows a thin-walled and
distended gallbladder without gallstones, radiographic evidence of
common bile duct enlargement, or inflammatory changes in the gallbladder
mucosa. Treatment is usually conservative and surgical intervention
is reserved for complicated illness or progression with ischemia
or gangrenous changes. Therapeutic intervention may include percutaneous
cholecystostomy, open cholecystostomy, or cholecystectomy.
and Sphincter Dysfunction
A spectrum of functional biliary disorders including functional
gallbladder disease (biliary dyskinesia) and sphincter of Oddi dysfunction have
been described. In adults, diagnostic criteria for this disorder
include (1) pain that is localized to the epigastric and/or
right upper quadrant region and lasts 30 minutes or longer; (2)
recurrent pain that occurs at different intervals, builds to a steady
level, and is severe enough to interrupt daily activities or lead
to an emergency room visit; and (3) pain that is not relieved by
bowel movements or postural change, and not relieved by antacids.
Associated symptoms include nausea, vomiting, radiation of pain
to the back, and pain that wakens patient from sleep. Laboratory
testing may show elevation of aminotransferases, alkaline phosphatase,
GGT, or bilirubin during pain episodes. Abdominal ultrasound and
magnetic resonance cholangiography (MRCP) studies are usually normal.
Biliary dyskinesia is likely a form of chronic
cholecystitis. Hepatobiliary scintigraphy using a hepatobiliary iminodiacetic
acid (HIDA) scan is often abnormal. A cholecystokinin (CCK) analog
(sincalide) is given by intravenous (IV) infusion, which may mimic
symptoms and cause nausea, pain, or vomiting and may be suggestive
of gallbladder dysfunction. A fatty meal or Lipomul can be given
to stimulate the gallbladder.47 Although an ejection
fraction of HIDA greater than 35% is considered normal,
values of less than 35% should be taken in the clinical context.
False-positive reading (poor emptying) may occur during acute illness,
pancreatitis, prolonged fasting, stress, or opiate use. Patients
with markedly abnormal studies may benefit from cholecystectomy;
however, more than 20% may still have pain, so conservative
management may be appropriate.
Patients with sphincter of Oddi dysfunction (SOD)
have biliary colic symptoms but may have elevated serum aminotransferases,
alkaline phosphatase, or bilirubin temporarily associated with pain
episodes. These patients may also have bile duct dilation. The physiology
of SOD is likely the result of stenosis of the papilla or dysmotility
of the biliary ducts and papilla. Endoscopic retrograde cholangiopancreatography
(ERCP) with biliary manometry has been used for diagnosis; however,
no pediatric normal values are available. For patients with normal
sphincter pressures, medications to treat hyperalgesia (ie, antidepressants
or antispasmodics) may be effective. In the presence of laboratory
and/or imaging abnormalities, ERCP with stenting or sphincterotomy
may be curative but patient selection for these treatment approaches
remains somewhat controversial.48