eMedicine Specialties > Emergency Medicine > Gastrointestinal

Cholelithiasis

Author: William K Chiang, MD, Associate Professor, Department of Emergency Medicine, New York University School of Medicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center
Coauthor(s): Faye Maryann Lee, MD, Staff Physician, Department of Emergency Medicine, New York University/Bellevue Hospital Center; Sally Santen, MD, Program Director, Assistant Professor, Department of Emergency Medicine, Vanderbilt University
Contributor Information and Disclosures

Updated: Nov 3, 2009

Introduction

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.

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 the ratio of cholesterol to biles acids or phospholipids is increased, 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.

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.¹
• 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

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 may radiate to the right shoulder or back (Collins's sign).² 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. Any prolonged pain episode lasting more than 5-6 hours should dictate a search for obstructed stone(s) or complications from cholelithiasis.
  • 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. Diosgenin-rich beans, particularly associated with a South American diet, increase cholesterol secretion and gallstone formation.
• 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.
  • Crohn disease, ileal resection, or other diseases of the ileum decrease bile salt reabsorption and increase the risk of gallstone formation.
  • Hemolytic diseases, including sickle cell disease and spherocytosis, promote the formation of pigmented stones.
  • Bacterial or parasitic infections from organisms that contain B -glucuronidase, an enzyme that deconjugates bilirubin glucuronide, increase the risk for 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.

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