AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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Background

Gallbladder disease is one of the most common gastrointestinal disorders in the United States. The spectrum of gallbladder disease ranges from asymptomatic cholelithiasis to gallbladder (or biliary) colic, cholecystitis, choledocholithiasis, and cholangitis. Further complications of gallbladder disease include gallstone pancreatitis, gallstone ileus, biliary cirrhosis, and gallbladder cancer.

Cholelithiasis is the presence of gallstones in the gallbladder. Biliary colic is pain caused by a stone temporarily obstructing the cystic duct. Cholecystitis is inflammation of the gallbladder from obstruction of the cystic duct. Choledocholithiasis is the presence of a stone in the common bile duct. Cholangitis occurs when a gallstone obstructs the biliary or hepatic ducts, causing inflammation and infection.

This article focuses on the pathophysiology and epidemiology of gallstones and biliary colic. Cholecystitis, cholangitis, and gallstone pancreatitis are covered in other articles.

Pathophysiology

Gallstones are rocklike collections of material that form inside the gallbladder. Different types exist, and they are categorized by their primary composition; cholesterol stones are most common (75-80% in the United States) followed by pigment, then mixed stones. The stones form when there is an imbalance or change in the composition of bile.

Normally, bile acids, lecithin, and phospholipids help to maintain cholesterol solubility in bile. When bile becomes supersaturated with cholesterol, it crystallizes and forms a nidus for stone formation. Calcium and pigment also may be incorporated in the stone. Impaired gallbladder motility, biliary stasis, and bile content predispose people to the formation of gallstones.

Gallbladder sludge is crystallization within bile without stone formation. Sludge may be a step in the formation of stones, or it may occur independently. Five to fifteen percent of patients with acute cholecystitis present without stones (acalculous cholecystitis). This typically occurs in patients with prolonged illness, such as those with major trauma or with prolonged ICU stays.

Pigment stones, which comprise 15% of gallstones, are formed by the crystallization of calcium bilirubinate. Diseases that lead to increased destruction of red blood cells (hemolysis), abnormal metabolism of hemoglobin (cirrhosis), or infections (including parasitic) predispose people to pigment stones. Black stones and brown stones exist. Black stones are found in people with hemolytic disorders. Brown stones are found in the intrahepatic or extrahepatic duct. They are associated with infection in the gallbladder and commonly are found in people of Asian descent.

Gallstone differentiation is an important consideration in management; cholesterol stones are more likely to respond to nonsurgical management than are pigment or mixed stones.

Frequency

United States

Prevalence of cholelithiasis is affected by many factors including ethnicity, gender, comorbidities, and genetics. In the United States, about 20 million people (10-20% of adults) have gallstones. Every year 1-3% of people develop gallstones and about 1-3% of people become symptomatic.

International

In an Italian study, 20% of women had stones, and 14% of men had stones. In a Danish study, gallstone prevalence in persons aged 30 years was 1.8% for men and 4.8% for women; gallstone prevalence in persons aged 60 years was 12.9% for men and 22.4% for women.

Mortality/Morbidity

• Every year, 1-3% of people develop gallstones and about the same number develop symptoms of gallstones. Asymptomatic gallstones are not associated with fatalities. Morbidity and fatalities are associated with symptomatic cholelithiasis, cholecystitis, or cholangitis.

Race

• Prevalence of gallstones is highest in fair-skinned people of northern European descent and in Hispanic populations and Native American populations
• Prevalence of gallstones is low in Asians and African Americans; however, African Americans with sickle cell disease have gallstones early in life secondary to associated hemolysis.

Sex

• Gallstones are more common in women than in men. It is postulated that estrogens cause increased cholesterol secretion and progesterone promotes biliary stasis.
• Women who are pregnant are more likely to experience symptomatic gallstones due to the hormonal influences and decreased gut motility. Whether women who are pregnant are more likely to form stones is uncertain; however, women with multiple pregnancies are more likely to have stones.

Age

• Risk of developing gallstones increases with age. Incidence of gallstones increases by 1-3% per year.
• It is uncommon for children to form gallstones. Children with gallstones are more likely to have congenital anomalies, biliary malformation and disease, or hemolytic pigment stones.
• Other risk factors for gallstones include exogenous estrogen intake, obesity, frequent fasting, rapid weight loss, lack of physical activity, diabetes mellitus, diseases associated with increased hemolysis (eg, sickle cell disease), cirrhosis, and certain medications (eg, octreotide, estrogens, fibrates).

CLINICAL

Section 3 of 11  

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History

The clinical stages of cholelithiasis are asymptomatic (the presence of gallstones without symptoms), symptomatic (biliary colic), and complicated (eg, cholecystitis, choledocholithiasis, cholangitis). Most gallstones (60-80%) are asymptomatic. Classically, biliary colic is described as episodic pain in the right upper quadrant that radiates to the right shoulder or back. It begins postprandially (usually within an hour) and may last from 1-5 hours. It is caused by contraction of the gallbladder (in response to a fatty meal) against an obstructing gallstone (or sludge) in the cystic duct. This leads to increased pressure within the gallbladder and pain. The pain is often described as intense and dull and typically subsides after several hours, when the gallbladder stops contracting and the stone falls back into the gallbladder. Associated symptoms may include diaphoresis, nausea, and vomiting.

• These symptoms can be nonspecific and insensitive. The pain may be more prominent in the midepigastrium, wake the patient from sleep, and be unrelated to meals.
• The pain of biliary colic is not characteristically positional, pleuritic, or relieved by bowel movement or flatus.
• Other symptoms, often associated with cholelithiasis, include indigestion, dyspepsia, belching, bloating, and fat intolerance. However, these are very nonspecific and occur in similar frequencies in individuals with and without gallstones; cholecystectomy has not been shown to improve these symptoms.
• Most patients develop symptoms prior to complications. Once symptoms of biliary colic occur, severe symptoms develop in 3-9% of patients, with complications in 1-3% per year and a cholecystectomy rate of 3-8% per year. Therefore, in people with mild symptoms, 50% have complications after 20 years.
• Zollinger performed studies in the 1930s in which the gallbladder wall or common bile duct was distended with a balloon; pain was elicited in the epigastric region. Only if the distended gallbladder touched the peritoneum did the patient experience right upper quadrant pain. Associated symptoms of nausea, vomiting, or referred pain were present in distention of the common bile duct (CBD) but not of the gallbladder.
• • In classic cases, pain is in the right upper quadrant; however, visceral pain and gallbladder wall distention may be only in the epigastric area.
  • Once the peritoneum is irritated, pain localizes into the right upper quadrant. Small stones are more likely to be symptomatic than large stones.

Physical

Physical findings vary along the spectrum of gallbladder disease.

• Vital signs and physical examination findings in asymptomatic cholelithiasis are normal. These are generally patients with an incidental finding of gallstones.
• Findings in between acute biliary colic attacks are generally also normal, though some mild residual upper abdominal pain with little or no tenderness may persist shortly after an attack.
• During an acute attack of biliary colic, the patient may complain of severe, poorly localized upper abdominal pain, but is non-toxic and has a benign abdominal exam with little or no tenderness.
• • Although voluntary guarding may be present, no peritoneal signs are present.
  • Tachycardia and diaphoresis may be present as a consequence of pain. These should resolve with appropriate pain management.
• Nausea and vomiting are commonly present as well, although rarely to the extent of electrolyte imbalance. Intravenous fluids may be necessary to restore intravascular volume.
• Distinguishing uncomplicated biliary colic from acute cholecystitis or other complications is important. Both often present with the same constellation of symptoms, and physical examination may help to differentiate the two.
• • Since the gallbladder is not inflamed in uncomplicated biliary colic, the pain is poorly localized and visceral in origin; the patient has an essentially benign abdominal examination without rebound or guarding. Fever is absent.
  • In acute cholecystitis, inflammation of the gallbladder with resultant peritoneal irritation leads to well-localized pain in the right upper quadrant, usually with rebound and guarding. Although nonspecific, a positive Murphy sign (inspiratory arrest on deep palpation of the right upper quadrant during deep inspiration) is highly suggestive of cholecystitis. Fever is often present, but it may lag behind other signs or symptoms.
• The presence of fever, persistent tachycardia, hypotension, or jaundice necessitate a search for complications of cholelithiasis, including cholecystitis, cholangitis, pancreatitis, or other systemic causes.
• Consider that both intra-abdominal and extra-abdominal pathology can present with upper abdominal pain, and often coexist with cholelithiasis. Among the different entities to consider are peptic ulcer disease, pancreatitis (acute or chronic), hepatitis, dyspepsia, gastroesophageal reflux disease (GERD), irritable bowel syndrome, esophageal spasm, pneumonia, cardiac chest pain, and diabetic ketoacidosis. A careful history and physical examination should guide further workup.

Causes

Ethnicity, gender, age, genetics, dietary considerations, and presence of certain comorbidities are major risk factors in the development of cholelithiasis and associated complications.

• Ethnicity: Prevalence rates of cholelithiasis are highest among western Caucasian, Hispanic, and Native American populations. Eastern European, African American, and Asian populations are less afflicted.
• Age: Advancing age is a major risk factor for gallbladder disease; gallstones are exceedingly rare in children.
• Gender: The prevalence rate of cholelithiasis is higher in women of all age groups. The difference is attributed to increased levels of estrogens and progesterone, which ultimately promote the formation of gallstones. Estrogens increase cholesterol formation, which supersaturate the bile, leading to precipitation of cholesterol stones; progesterone inhibits gallbladder motility leading to biliary stasis and stone formation. Pregnancy contributes to the female preponderance in prevalence due to increases in circulating sex steroids in the gravid state.
• High-fat diet: Historically, but not statistically, high-fat diet is associated with the formation of gallstones and symptoms associated with gallstones Estrogen therapy, in similar fashion, is associated with higher risk of cholelithiasis.
• Genetics: Studies in family history suggest that genetics have a significant role in development of gallstones.
• Dietary considerations: Obesity, high-fat diet, and hypertriglyceridemia are strongly associated with the formation of gallstones and arising complications. Additional dietary risk factors include decreased oral intake, rapid weight loss, and use of parenteral nutrition.
• Comorbidities
• • Diabetes mellitus is associated with an increased risk of gallstone, though the mechanism is unclear; once symptomatic, patients with diabetes are prone to more severe complications.
  • Hemolytic diseases, including sickle cell disease and spherocytosis, promote the formation of pigmented stones.
  • Cirrhosis carries major multifactorial risks for gallstone formation and gallbladder disease. Reduced hepatic synthesis and transport of bile salts, hyperestrogenemia, impaired gallbladder contraction and increased biliary stasis, among other factors, contribute to the formation of gallstones (typically pigment stones) in cirrhosis.
  • Other illnesses or states that predispose to gallstone formation include the following:
    • Burns
    • Use of total parenteral nutrition
    • Paralysis
    • ICU care
    • Major trauma
  • This is due, in general, to decreased enteral stimulation of the gallbladder with resultant biliary stasis and stone formation.

DIFFERENTIALS

Section 4 of 11  

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WORKUP

Section 5 of 11  

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Lab Studies

• Laboratory study results are normal in the asymptomatic patient and patients with uncomplicated biliary colic. They are generally not necessary unless cholecystitis is a concern.
• • An elevated white count should raise the suspicion for cholecystitis or other infectious process. However, up to one third of the patients with cholecystitis may not manifest leukocytosis.
  • Elevated transaminases levels indicate a hepatic process, while hyperbilirubinemia and an elevated alkaline phosphatase level are evidence for common bile duct obstruction.
• An elevated lipase is indicative of pancreatitis, the most common causes of which are alcohol and gallstones.

Imaging Studies

• Asymptomatic gallstones are often found incidentally on plain radiographs, abdominal sonograms, or CT scan for workup of other processes.
• Radiography: Cholesterol and pigment stones are radiopaque and visible on radiographs in only 10-30% of instances, depending on their extent of calcification, and have little role in the diagnosis of gallstones or gallbladder disease.
• Ultrasonography: The procedure of choice in suspected gallbladder or biliary disease, it is a simple, rapid test that is safe in pregnancy and does not expose the patient to harmful radiation or intravenous contrast. An added advantage is that it can be performed by skilled practitioners at the bedside.
• • Sensitivity is variable and dependent upon operator proficiency, but in general, it is highly sensitive and specific for gallstones greater than 2 mm. It is less so for microlithiasis or biliary sludge.
  • Ultrasonography is very useful for diagnosing uncomplicated acute cholecystitis. The sonographic features of acute cholecystitis include gallbladder wall thickening (>5 mm), pericholecystic fluid, gallbladder distention (>5 cm), and a sonographic Murphy sign. The presence of multiple criteria increases its diagnostic accuracy.
• Computerized tomography: Gallstones are often found incidentally on CT. Findings on CT for acute cholecystitis are similar to those found on sonograms. Although not the initial study of choice in biliary colic, CT can be used in diagnostic challenges or to further characterize complications of gallbladder disease. CT is particularly useful for the detection of intrahepatic stones or recurrent pyogenic cholangitis.
• Biliary scintigraphy (HIDA scan): Scintigraphy gives little information about nonobstructing cholelithiasis and cannot detect other pathologic states, although it is highly accurate for the diagnosis of cystic duct obstruction.

TREATMENT

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Emergency Department Care

Gallstones found incidentally may be followed until they become symptomatic.

• Surgical treatment of asymptomatic gallstones without medically complicating diseases is discouraged. The risk of complications arising from interventions is higher than the risk of symptomatic disease. Approximately 25% of patients with asymptomatic gallstones develop symptoms within 10 years.
• In patients with symptomatic gallstones, discuss the options for surgical and nonsurgical intervention and refer the patient to their primary care provider and surgical consultant for outpatient follow-up.
• Persons with diabetes and women who are pregnant should have close follow-up to determine if they become symptomatic or develop complications.
• Patients with risk factors for complications of gallstones may be offered elective cholecystectomy, even with asymptomatic gallstones. These groups include persons with the following conditions and demographics:
• • Cirrhosis
  • Portal hypertension
  • Sickle cell disease
  • Children
  • Transplant candidates
  • Diabetes with minor symptoms
• Patients with a calcified or porcelain gallbladder should consider elective cholecystectomy due to the increased risk of carcinoma (25%). Refer to a surgeon for removal as an outpatient procedure.
• If cholecystitis or other infectious complication is suspected, emergent consultation with a general surgeon should be obtained.

Consultations

• In patients with symptomatic gallstones, discuss the options of medical management or elective surgery with the patient and refer for follow-up to the primary care provider and general surgeon.
• Refer patients with a calcified or porcelain gallbladder to a surgeon for removal on an outpatient basis.
• Emergency consultation with a general surgeon should be sought if cholecystitis is strongly suspected or diagnosed.

MEDICATION

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For asymptomatic gallstones, medical therapies are rarely used because they require long-term therapy, may have adverse reactions or complications, and recurrence of gallstones is relatively common (25% within 5 years).

In patients who present with an acute attack of biliary colic, pain can be controlled with oral or parenteral opioids.

In uncomplicated cholelithiasis with biliary colic, medical management may be useful alternative to cholecystectomy in select patients. Medical treatment, beyond pain control however, is not initiated in the emergency department, and patients should be referred to their primary care giver for further medical management.

Medical management of gallstones, used alone or in combination, include the following: oral bile salt therapy (ursodeoxycholic acid, chenodeoxycholic acid), contact dissolution, and extracorporeal shockwave lithotripsy.

FOLLOW-UP

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Further Outpatient Care

• Refer patients with asymptomatic gallstones to their primary care physician.
• It may be difficult to determine if nonspecific presenting symptoms are due to cholelithiasis.
• Dyspepsia, bloating, and flatulence are nonspecific and usually are not due to gallstones; these symptoms are not likely to be cured by cholecystectomy.

Deterrence/Prevention

• Recommending dietary changes of decreased fat intake is prudent; this may decrease the incidence of biliary colic attacks; however, it has not been shown to cause dissolution of stones.

Complications

• Biliary colic
• Cholecystitis (acute or chronic)
• Choledocholithiasis
• Cholangitis
• Sepsis
• Gallstone pancreatitis
• Gallstone ileus

Prognosis

• Less than half of patients with gallstones become symptomatic.
• The mortality rate for an elective cholecystectomy is 0.5% with less than 10% morbidity.
• The mortality rate for an emergent cholecystectomy is 3-5% with 30-50% morbidity.
• Approximately 10-15% of patients have an associated choledocholithiasis.
• Following cholecystectomy, stones may recur in the bile duct.

Patient Education

• Instruct patients about symptoms of gallstones and the stress the importance of return for signs or symptoms of complications. Discuss the importance of follow-up care with their primary care giver for long-term management and treatment options.
• A low-fat diet is advisable though not proven to be preventative.
• For excellent patient education resources, see eMedicine's Liver, Gallbladder, and Pancreas Center and Cholesterol Center. Also, visit eMedicine's patient education article Gallstones.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Failure to recognize life-threatening complications of gallbladder disease (cholecystitis, cholangitis, others).
• Failure to consider other causes of upper abdominal pain, such as myocardial infarct, pneumonia, peptic ulcer disease, pancreatitis, diabetic ketoacidosis, and others.
• Failure to provide adequate instructions for the patients to return back to the emergency department.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  The pathology in the accompanying ultrasound image was found incidentally in a person without abdominal complaints. One to 3% of gallstones become symptomatic each year.
	View Full Size Image
Media type:  Ultrasound

REFERENCES

Section 11 of 11

• Authors and Editors
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• Sievert W, Vakil NB. Emergencies of the biliary tract. Gastroenterol Clin North Am. Jun 1988;17(2):245-64. [Medline].
• Swisher SG, Schmit PJ, Hunt KK, et al. Biliary disease during pregnancy. Am J Surg. Dec 1994;168(6):576-9; discussion 580-1. [Medline].
• Tait N, Little JM. The treatment of gall stones. BMJ. Jul 8 1995;311(6997):99-105. [Medline].
• Talley NJ. Gallstones and upper abdominal discomfort. Innocent bystander or a cause of dyspepsia?. J Clin Gastroenterol. Apr 1995;20(3):182-3. [Medline].
• Tsimoyiannis E, Antoniou NC, Tsaboulas T, Papanikolaou N. Cholelithiasis during pregnancy and lactation. Eur J Surg. 1994;160:627-631. [Medline].
• Weltman DI, Zeman RK. Acute diseases of the gallbladder and biliary ducts. Radiol Clin North Am. Sep 1994;32(5):933-50. [Medline].
• Yusoff IF, Barkun JS, Barkun AN. Diagnosis and management of cholecystitis and cholangitis. Gastroenterol Clin North Am. Dec 2003;32(4):1145-68. [Medline].

Article Last Updated: Jun 12, 2006