Gallbladder Disease

The gallbladder operation is the most common operation in North America.  Every year, more than half a million people in the United States and more than 50,000 people in Canada undergo surgery to remove their gallbladders because of gallstones.  90% of people have gallstones; 80% of people do not know that they have gallstones.  50% of children have gallstones.  Approximately 80% of all gallstones show no symptoms and may remain "silent" for years. Gallstones are "pebbles" within the gallbladder.  The gallbladder is a pear-shaped sac located under the liver which stores the bile secreted by the liver.  During a meal (especially one containing fat or protein), the gallbladder contracts, delivering the bile through the bile ducts into the intestines to help with digestion.  Abnormal composition of bile leads to formation of gallstones.  Gallstone disease is a common cause of abdominal pain, inflammation, and infection of the gallbladder and the pancreas.

Incidence; Causes and Development; Contributing Risk Factors

Gallstones affect about 10% of adults over 40.  They occur in nearly 25% of women in the U.S.  by age 60 and in up to 50% by age 75.  About 20% of men have gallstones by the time they reach 75 years of age.  Because most cases are asymptomatic, however, these rates may underestimate the disease in elderly men.  Gallstone disease is relatively rare in children.  Women are probably at increased risk because the female hormone estrogen stimulates the liver to remove more cholesterol from blood and divert it into the bile.  Women of childbearing age may want to select an oral contraceptive with a low estrogen level to reduce their risk.

Native Americans are especially prone to developing gallstones; women in this population have an 80% chance of developing gallstones during their lives.

Pigment gallstones are more likely to affect the elderly, people with cirrhosis, and those with chronic hemolytic anemia, including sickle cell anemia.  People of Asian descent who develop gallstones are most likely to have the pigment type.

Bile is a fluid composed mostly of water, bile salts, lecithin, and cholesterol.  Bile is first produced by the liver and then secreted through tiny channels within the liver into a duct.  From here, bile passes through a larger tube called the common duct, which leads to the small intestines.  Then, except for a small amount that drains directly into the small intestine, bile flows into the gallbladder through the cystic duct.  The gallbladder is a four-inch sac with a muscular wall that is located under the liver.  Here, most of the fluid (about two to five cups a day) is removed, leaving a few tablespoons of concentrated bile.  The gallbladder serves as a reservoir until bile is needed in the small intestine for digestion of fat.  When food enters the small intestine, a hormone called cholecystokinin is released, signaling the gallbladder to contract.  The force of the contraction propels the bile back through the common bile duct and then into the small intestine, where it emulsifies fatty molecules so that fat and the fat-absorbable vitamins A, D, E, and K can enter the blood stream through the intestinal lining.

About three-quarters of the gallstones found in the U.S.  population are formed from cholesterol.  Cholesterol makes up only 5% of bile; it is not very soluble, however, so in order to remain suspended in fluid, it must be properly balanced with bile salts.  If the liver secretes too much cholesterol into the bile, if the bile becomes stagnant because of a defect in the mechanisms that cause the gallbladder to empty, or if other factors are present, supersaturation can occur.  Cholesterol may then precipitate out of the bile solution to form gallstones - a condition known as cholelithiasis.  The process is very slow and most often painless.  Gallstones can range from a few millimeters to several centimeters in diameter.

The other 25% of gallstones are known as pigment gallstones.  They are composed of calcium bilirubinate, or calcified bilirubin, the substance formed by the breakdown of hemoglobin in the blood.  These black stones often form in the gallbladders of people with hemolytic anemia or cirrhosis.

At any point, stones may obstruct the cystic duct, which leads from the gallbladder to the common bile duct, and cause pain (biliary colic), infection and inflammation (cholecystitis), or all of these.  About 15% of people with stones in the gallbladder also have stones in the common bile duct (choledocholithiasis), which sometimes pass into the small intestine but also may lodge in the duct and cause distention, infection, or pancreatitis.

Conditions that decrease the flow of bile and therefore increase the risk of gallstone formation include skipping meals, fasting, pregnancy, and intravenous feeding.

Signs and Symptoms

Irritable bowel syndrome (IBS) has some of the same symptoms as gallbladder disease, including difficulty digesting fatty foods.  In IBS, however, pain usually occurs in the lower abdomen.  Acute appendicitis, pneumonia, stomach ulcers, hiatal hernia, pancreatitis, hepatitis, kidney infections, and even a heart attack may mimic a gallbladder attack, so it is important to see a physician immediately if symptoms occur.

In patients with abdominal pain, causes other than gallstones are often responsible if the pain lasts less than 15 minutes, is present most of the time, frequently comes and goes, or is not severe enough to limit activities.

Once diagnosed with gallstones, within the first five years 10% of patients develop symptoms, and within 20 years, 20% have symptoms.  This means someone with stones has an 80% chance of living without symptoms - that is, about 80% of people with gallstones never experience any symptoms.  They may be discovered by a routine chest X-ray or other diagnostic tests looking for problems unrelated to the gallbladder.

The risk of people with gallstones developing mild symptoms is 1% to 3% annually.  Most other people remain asymptomatic (without symptoms) for at least two years after stone formation begins.  If symptoms do occur, the chance of developing pain is about 2% per year for the first ten years after stone formation, after which the chance for developing symptoms decrease.  On average, symptoms take about eight years to develop.  The reason for the decline in incidence after ten years is not known, although some physicians suggest that "younger" stones may cause more symptoms.

Biliary Pain
Most people who develop symptomatic gallbladder disease have pain in the mid-upper or right-upper section of the abdomen and it often radiates to the right shoulder blade.  This pain is caused by obstruction of the bile-carrying duct, called the cystic duct, which leads from the gallbladder to the small intestine.  Large or fatty meals can precipitate the pain, but it usually occurs several hours after eating, often at night.

The pain is sometimes referred to as "colic," which would indicate mild, transient pain.  However, this is a misnomer because the pain is usually severe, steady, and lasts from 15 minutes to 6 hours.  The pain is often at night and not related to meals.  Once the first pain has occurred, the probability of a second attack is between 50% and 70% within 2 years (if no change in diet is made).  Nausea and vomiting are also common.  Between attacks everything is usually normal.

Changes in position, over-the-counter pain relievers, and passage of gas do not relieve the symptoms.  Biliary pain usually disappears after several hours.  Attacks of pain tend to be intermittent and infrequent; the chance of pain recurring within a year is less than 50%.  In one study, 30% of people who had had one or two attacks experienced no further biliary pain over the next ten years.

Acute Cholecystitis
Acute gallbladder inflammation (acute cholecystitis) is a more serious problem than biliary colic.  It begins abruptly and subsides gradually.  Nausea, vomiting, and severe pain and tenderness in the upper right abdomen are the most common complaints; fever is usual but may be absent.  The discomfort is intense and steady and lasts until the condition is treated with medicine or surgery.  Patients with acute cholecystitis frequently complain of pain when drawing a breath.  The pain can radiate from the abdomen to the back.  Acute cholecystitis is usually caused by gallstones, but, in some cases, can occur without stones.  Anyone who experiences an attack of acute cholecystitis should seek medical attention; it can progress to gangrene or perforation of the gallbladder if left untreated.

Chronic Cholecystitis
Chronic gallbladder disease (chronic cholecystitis) occurs because of the prolonged presence of gallstones and low-grade inflammation.  Scarring causes the gallbladder to become stiff and thick.  Symptoms of this condition tend to be vague.  Complaints of gas, nausea, and abdominal discomfort after meals are common, just as they often are in people without gallbladder disease.

Common Bile Duct Stones (Choledocholithiasis)
Stones lodged in the common bile duct (choledocholithiasis) can block the flow of bile and cause jaundice.  Serious infection of the bile duct (cholangitis) may develop that causes fever, chills, nausea and vomiting, and severe pain in the upper-right quadrant of the abdomen.  If there is evidence for common bile duct stones, such as dark urine, jaundice, pancreatitis, or elevated liver function tests, then more extensive tests may be used.

Most gallstones provoke no symptoms at all.  One study reported that the risk of developing symptoms was 10% at five years, 15% at ten years, and only 18% at fifteen years, with no deaths reported.  Asymptomatic gallstones seldom lead to problems.  Death from gallstones is very rare, accounting for only 0.2% of annual deaths in the United States.  Serious effects from gallstones are usually from stones in the bile duct or surgical complications.

Diagnosis and Tests

Diagnosis is by physical exam and by diagnostic testing.  A physical exam often reveals tenderness in the right upper area of the abdomen in acute cholecystitis and sometimes in biliary colic.  There is usually no tenderness in chronic cholecystitis.

Blood tests are usually normal in people with simple biliary pain or chronic cholecystitis.  In acute cholecystitis, and especially choledocholithiasis (stones in the bile duct), however, blood tests of the liver show elevations of the enzyme alkaline phosphatase and bilirubin.  Bilirubin is the orange-yellow pigment found in bile; high levels cause jaundice, which gives the skin a yellowish tone.  A high white blood cell count (leukocytosis) is another common finding but should not be relied on to establish a diagnosis of acute cholecystitis.

The diagnostic challenge posed by gallstones is to be sure that abdominal pain is caused by stones and not by some other condition.  Ultrasound or other imaging techniques easily find gallstones.  Nevertheless, because gallstones are common and most cause no symptoms, simply finding stones does not necessarily explain a patient's pain, which may be caused by numerous other conditions.

Treatment and Prevention

Gallstones almost never spontaneously disappear, except sometimes when they are formed under special circumstances, such as pregnancy or sudden weight loss.  Many natural doctors claim that some stones can be encouraged to pass, and that there are treatments to reduce or eliminate symptoms.  Apart from natural or other preventive treatments, the probability of eventually needing an operation for a 30-year-old is about 30%; for 50-year-olds it is 20%; and for 70-year-olds it is 15%.

Although removal of the gallbladder has not been known to cause any long-term effects aside from occasional diarrhea, some researchers have been concerned about its effects on the body's cholesterol levels.  One study found that within three days of the operation, levels of total cholesterol and LDL returned to their preoperative levels.  After three years, however, some types of cholesterol not ordinarily associated with coronary artery disease had risen significantly.  These results did not necessarily indicate any increased risk for coronary artery disease, but they did show that the metabolism of cholesterol by the liver had been altered.  People who have had their gallbladders removed should have their cholesterol levels checked periodically, as should every adult.

Extraporeal Shock Wave Lithotripsy (ESWL)
ESWL has been used for over 15 years to break up kidney stones.  During this treatment, shock waves generated outside the body are focused on gallstones in order to fracture them into smaller particles, the size of sand granules.  The success rate with small stones (under 20mm) is 77%, larger stones is 60%, and multiple stones is 41% - success means complete disappearance in 6 months.  The addition of bile acids to dissolve the small fragments may improve upon the success rate.  This approach is of particular value for those patients who are poor surgical candidates and for those wanting to keep their gallbladders.

Bile Acid Treatment
In the normal gallbladder, bile acids keep the cholesterol in solution, preventing stone formation.  Two bile acids, chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), when given as medications have been found to dissolve gallstones.  CDCA has significant side-effects, auch as diarrhea and abnormal liver tests.  UDCA has few side-effects.  Successful treatment is most commonly seen with noncalcified stones of less than 5mm.  The rate of dissolving is about 1mm per month.  A combination of CDCA with UDCA has about a 50% rate of complete dissolving of noncalcified stones with 6 months of therapy.

The addition of cholesterol-lowering medications, known as "statins", like lovastatin (Mevacor) and simvastatin (Zocor), improve the effectiveness of UDCA therapy.  These cholesterol-lowering agents reduce both serum and bile cholesterol in humans, and also inhibit cholesterol gallstone formation in animals.  With the same cholesterol-lowering benefits, a healthy diet helps dissolve gallstones when used in combination with ursodeoxycholic acid (UDCA), which is sold as Actigall.  A doctor's prescription is needed.

Prognosis; Complications

Simple pain, rather than serious complications, is the first symptom of gallbladder disease in over 90% of people with stones, therefore waiting has few serious consequences.  Most people with gallstones remain asymptomatic, and symptoms when they do occur are usually not life threatening, so some believe "you should be allowed to die with your gallstones."

When obstruction of the bile-carrying duct is prolonged (more than 6 hours), then distention and inflammation can develop with secondary bacterial infection in about 50% of cases.  This is a serious complication that usually requires immediate medical attention.  Stones can also block the ducts draining the pancreas and cause pancreatitis.