Introduction:

Gallstones are small, hard deposits that can form in the gallbladder, a sac-like organ that lies under the liver on the right side of the abdomen. Most people with gallstones don't even know they have them. But in some cases a stone may cause the gallbladder to become inflamed, resulting in pain, infection, or other serious complications.

Bile and the Gallbladder

The formation of gallstones is a complex process that starts with bile, a fluid composed mostly of water, bile salts, lecithin (a fat known as a phospholipid), and cholesterol. Most gallstones are formed from cholesterol.

• Bile is important for the digestion of fat. It is first produced by the liver and then secreted through tiny channels that eventually lead into a larger tube called the common bile duct, which leads to the small intestine.

• Only a small amount of bile drains directly into the small intestine, however. Most flows into the gallbladder through the cystic duct, which is a side extension off the common bile duct. This system of ducts through which bile flows is called the biliary tree.

• The gallbladder is a 4-inch sac with a muscular wall that is located under the liver. Here, most of the bile fluid (about 2 - 5 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 to digest fats. This need is signaled by a hormone called cholecystokinin, which is released when food enters the small intestine.
• Cholecystokinin causes the gallbladder to contract and deliver bile into the intestine. The force of the contraction propels the bile down the common bile duct and into the small intestine, where it emulsifies (breaks down) fatty molecules.
• This part of the digestive process enables the emulsified fat, along with important fat-absorbable nutrients (such as vitamins A, D, E, and K), to pass through the intestinal lining and enter the bloodstream.

Formation of Gallstones (Cholelithiasis)

The process of gallstone formation is referred to as cholelithiasis. It is generally a slow process, and usually causes no pain or other symptoms. The majority of gallstones are either the cholesterol or mixed type. Gallstones can range in size from a few millimeters to several centimeters in diameter.

Most gallstones are formed from cholesterol. Pigment stones are also very common; they are formed from a brown-colored substance called calcium bilirubinate. Patients can have a mixture of the two gallstone types.

Cholesterol Stones. Although cholesterol makes up only 5% of bile, about three-fourths of the gallstones found in the US population are formed from cholesterol. Cholesterol gallstones typically form in the following way:

• Cholesterol is not very soluble, so in order to remain suspended in fluid it must be transported within clusters of bile salts called micelles. If there is an imbalance between these bile salts and cholesterol, then the bile fluid turns to sludge. This thickened fluid consists of a mucus gel containing cholesterol and calcium bilirubinate.
• If the imbalance worsens, cholesterol crystals form (a condition called supersaturation), which can eventually form gallstones.

Supersaturation and cholelithiasis can occur as a result of various abnormalities, although the cause is not entirely clear. There are many events that may promote cholelithiasis:

• The liver secretes too much cholesterol into the bile.
• The gallbladder may not be able to empty normally, so bile becomes stagnant.
• The cells lining the gallbladder may not be able to efficiently absorb cholesterol and fat from bile.
• There are high levels of bilirubin. Bilirubin is a substance normally formed by the breakdown of hemoglobin in the blood. It is removed from the body in bile. Some experts believe bilirubin may play an important role in the formation of cholesterol gallstones.

Pigment Stones. Pigment stones are composed of calcium bilirubinate, or calcified bilirubin. Pigment stones can be black or brown.

• Black stones form in the gallbladder and are the more common type. They represent 20% of all gallstones in the U.S. They are more likely to develop in people with hemolytic anemia (a relatively rare anemia in which red blood cells are destroyed) or cirrhosis (scarred liver).
• Brown pigment stones are more common in Asian populations. They contain more cholesterol and calcium than black pigment stones and are more likely to occur in the bile ducts. Infection plays a role in the development of these stones.

Mixed stones. Mixed stones are a mixture of cholesterol and pigment stones.

Choledocholithiasis (Common Bile Duct Stones)

Gallstones can also be present in the common bile duct, rather than the gallbladder. This condition is called choledocholithiasis.

Secondary Common Bile Duct Stones. In most cases, common bile duct stones originally form in the gallbladder and pass into the common duct. They are then called secondary stones. Secondary choledocholithiasis occurs in about 10% of patients with gallstones.

Primary Common Bile Duct Stones. Less often, the stones form in the common duct itself (called primary stones). Primary common duct stones are usually of the brown pigment type and are more likely to cause infection than secondary common duct stones.

Gallbladder Diseases without Stones (Acalculous Gallbladder Disease)

Gallbladder disease can occur without stones, a condition called acalculous gallbladder disease. This refers to a condition in which a person has symptoms of gallbladder stones, yet there is no evidence of stones in the gallbladder or biliary tract. It can be acute (arising suddenly) or chronic (persistent).

• Acute acalculous gallbladder disease usually occurs in patients who are very ill from other disorders. In these cases, inflammation occurs in the gallbladder. Such inflammation usually results from reduced blood supply or an inability of the gallbladder to properly contract and empty its bile.
• Chronic acalculous gallbladder disease (also called biliary dyskinesia) appears to be caused by muscle defects or other problems in the gallbladder, which interfere with the natural movements required to empty the sac.