Drs. Simpson, Yen and Ahmed are from the Department of Medicine, Division of Gastroenterology, Stanford University School of Medicine, Stanford, California and *Division of General Internal Medicine and Geriatrics Veteran's Administration Medical Center, San Diego, California University of California, San Diego School of Medicine, San Diego, California.

We all have a gallbladder but most of us do not spend much time thinking about it. Those that do are probably among the 25 million or so Americans who suffer from gallstones.

The pear-shaped gallbladder sits below the liver in the upper right-hand corner of the abdomen. It is connected to the liver and to the small intestine by several tubes called bile ducts. Its purpose is to store bile, a liquid which is produced by the liver that helps us digest fat. After a meal, the gallbladder contracts and sends bile into the intestine. Once a meal has been digested, the gallbladder stops sending bile and returns to its old job of storing up bile for our next steak dinner.

What is a Gallstone?
Bile is a brown liquid made up of bile salts, cholesterol, bilirubin and lecithin. Bile salts and lecithin help break up fat so that it can be digested more easily. Bilirubin, which gives both bile and stool their characteristic color, is a waste product.

Problems begin when some of the components of bile form hard crystals (or stones). Most gallstones are made up of either cholesterol or bilirubin but not both. Because they range in size from as small as a grain of sand to as large as a golf ball, a gallbladder may contain anywhere from one stone to hundreds. These gallstones may cause problems in the gallbladder or in the bile duct, or they may cause no problems at all.

We are not sure why gallstones happen but we do know that people with high levels of cholesterol in their bile are more likely to develop cholesterol stones and those with high levels of bilirubin are more likely to develop bilirubin stones. Problems with the gallbladder muscle, causing incomplete emptying of the gallbladder, also seem to play a part in gallstone development. Exactly how diet affects gallstone formation is not well understood but it is suspected that a diet high in cholesterol and fat can increase a person's risk of developing gallstones

Really Bad Pain
The most typical first sign of gallstones is pain — sometimes excruciating pain — in the upper abdomen or right side. This is sometimes accompanied by fever, vomiting or sweating. The most common treatment is surgical removal of the gallbladder, although there are other treatments, depending on the type of gallstone, the severity of a person's attacks and the presence of complications such as infection.

Most treatments are much more successful if they are given early on. Anyone who thinks they might have gallstones should see a doctor as soon as possible.

Typical symptoms
  • steady pain in the upper abdomen that worsens rapidly and lasts as long as several hours
  • pain in the back between the shoulder blades
  • pain under the right shoulder
  • nausea or vomiting
  • abdominal bloating
  • recurring intolerance of fatty foods
  • colic
  • belching
  • gas
  • indigestion
  • sweating
  • chills
  • low-grade fever
  • yellowish color of the skin or whites of the eyes
  • clay-colored stools

Table 1.
Risk Factors for Cholesterol Gallstone Formation.
  1. Increasing age, female sex
  2. Ethnicity: Pima Indians, Scandinavians
  3. Family history of gallstones on the mother's side
  4. Pregnancy
  5. Obesity, rapid weight loss, fasting, tube feeding or total parenteral nutrition (TPN)
  6. Drugs: fibric acid derivatives, cholesterol-reducing drugs, contraceptive steroids (birth control pills) and postmenopausal estrogen, progesterone, octreotide, ceftriaxone (hormone replacement therapy)
  7. Crohn's disease, certain types of surgery involving the digestive system, hyperlipidemia (excess fat in the bloodstream) and diabetes.

A Gallstone Attack
As many as one-third of patients with gallstones have symptoms; the remaining two thirds either never know that they have the disease or find out accidentally, for instance by having an X-ray or CT scan for another purpose. The most common symptom is called biliary colic; this occurs in 70% to 80% of gallstone sufferers. The main feature of biliary colic is severe pain above the stomach area or less frequently in the upper right-hand section of the abdomen. The term biliary colic is a little misleading because the pain is steady, not colicky. A large meal may bring on an attack of biliary colic. More often than not, however, there is no warning or apparent cause.

Biliary colic occurs more commonly at night, often with a sudden onset and increasing intensity over a 15-20 minute period, ending in a steady plateau which can last for several hours. The pain may spread to the area around the right shoulder. Nausea, vomiting and sweating often follow. The pain may gradually go away or decrease, becoming a less severe but persistent abdominal pain. The time period between biliary colic attacks is extremely variable; it may be weeks, months or even years.

When the pain of an attack lasts longer than several hours, it may mean that the gallbladder has become inflamed. This condition, called cholecystitis, can lead to an infection of the gallbladder. Patients with cholecystitis are normally hospitalized for observation, treatment with antibiotics and pain medications, sometimes followed by surgery. Elderly people suffering from acute cholecystitis sometimes do not have any pain or fever, and soreness or tenderness in the abdomen may be their only symptom. Jaundice develops in 15% of those with acute cholecystitis.

In some rare cases, acute cholecystitis is caused not by gallstones but by infections such as salmonella food poisoning. Cytomegalovirus and cryptosporidia infections have also been found to cause cholecystitis in severely immunocompromised patients, such as those with AIDS or those who have recently undergone bone marrow transplantation.

How Doctors Diagnose Gallstones
Two tests help doctors find gallstones within the gallbladder. The first, ultrasound, uses sound waves to detect hard objects. In the second, oral cholecystogram (or OCG), an X-ray is taken of the gallbladder after the patient swallows pills containing dye. These tests are extremely accurate. Ultrasound is more common because it is non-invasive and does not involve exposure to X-rays.

It is more difficult to detect gallstones that have entered the bile duct because ultrasound is much less sensitive in the bile duct and OCG cannot be used at all. The best tests involve putting X-ray dye directly into the bile ducts. A flexible swallowed tube can be used (endoscopic retrograde cholangiopancreatography or ERCP), or a needle can be passed through the liver and into the bile ducts (percutaneous transhepatic cholangiography or PTC). These tests both carry a small amount of risk, require the use of an X-ray and may be uncomfortable or require patients to be sedated. But thanks to recent technological advances, there is now a non-invasive alternative — CAT scan and MRI data can be processed into a three dimensional image that offers diagnostic accuracy comparable to ERCP.

Gallstone-induced Complications
Gallbladder disease often leads to complications that can become a greater health problem than the gallstones themselves:

According to the studies, 60% to 80% of all gallstones are asymptomatic; that is, they cause no pain or other symptoms. In most cases, this means that little or no treatment is needed. One exception, however, is when asymptomatic gallstones occur in people who are at high risk for developing cancer of the gallbladder. This includes those with a generally calcified ("porcelain") gallbladder, those with gallstones greater than 2.5 cm in size, those with gallbladder polyps greater than 10 mm in diameter and Pima Indians. People in these categories may want to consider seeking treatment even if they have no pain or other symptoms.

Biliary Colic
Studies of gallstone sufferers have revealed that 38% to 50% of those with biliary colic will have another attack within a year. We also know that as much as 90% of gallstone complications, including acute cholecystitis, are preceded by attacks of biliary colic. There is a 1 to 2% per year risk of developing biliary complications after an initial attack of biliary colic. On the other hand, a third of those who suffer an attack of biliary colic will never have a recurrence.

Acute Cholecystitis
In most cases, acute cholecystitis is treated with emergency surgery to remove the entire gallbladder (cholecystectomy). The sooner this is done, the better — usually within 24 to 48 hours after diagnosis. Laparoscopic cholecystectomy, also called "belly-button surgery," is a new technique that is taking the place of traditional open surgery. In the open technique, the gallbladder is removed through an incision in the abdomen several inches long. Four or five days of hospitalization, followed by weeks of recuperation at home, are usually needed.

In the laparoscopic method, the surgeon makes several much smaller incisions in the abdomen through which a tiny video camera and surgical instruments are inserted. Using the video picture as a guide, the surgeon is able to remove the gallbladder through the tiny incisions without making big cuts in the abdominal muscles. After surgery, because the abdominal muscles are intact, there is less pain, faster healing and a much smaller scar. Patients usually leave the hospital in a day and return to their normal routine within a few days. Laparoscopic cholecystectomy is now used for most cholecystectomies in the United States.

A test called hepatobiliary scintigraphy helps doctors determine whether someone is suffering from acute cholecystitis. A liquid called an IDA agent is injected into the gallbladder and computer imaging then tracks the agent as it is passes through the bile duct. If an obstruction is not seen, then the patient's abdominal pain or other symptoms must be caused by something else.

This is the medical term for the presence of gallstones in the bile duct. In general, patients with jaundice and inflammation of the bile duct should be promptly scheduled for a ERCP examination, and, if necessary, a laparoscopic cholecystectomy within 1 or 2 days.

Alternatives to Surgery
There are alternatives to surgery for both stones in the gallbladder and stones in the bile duct. ERCP can be used not only to find stones in the bile duct but also to remove them. For elderly patients or those too frail for surgery, removal of bile duct stones can relieve symptoms. Stones can also be dissolved by certain chemicals taken in pill form. Unfortunately, this works only on small cholesterol stones.

A big drawback of all non-surgical approaches is that gallstones eventually recur in about half of all patients treated.

Life without the Gallbladder
We do not know a lot about what causes gallbladder disease or why some people have associated pain and other symptoms while others do not. Fortunately, the gallbladder is one of those rare organs that are fairly easy to live without. Once the gallbladder is removed, bile travels from the liver directly into the small intestine instead of being stored in the gallbladder. Sometimes, as a consequence, people without a gallbladder experience diarrhea but this occurs in no more than about 1 percent of those who undergo the surgery.