Fat, female, and over forty. That alliterative and condescending phrase is often used to describe the typical patient with gallstones. Yet, while it bears some truth, it doesn't begin to tell the entire story of gallbladder disease.

It's true that gallstones become more commonplace as we get older; they cause problems for 10% of adults over 40. Women are about twice as likely to develop gallstones as men are, and cholecystectomy -- the surgical removal of the gallbladder -- is one of the most frequently performed operations on women. However, obesity is only one of the many factors that increase the risk of developing gall-stones.

Gallstone formation
The gallstone story actually begins in the liver, with the manufacture of bile. The components of bile -- water, bile salts, cholesterol, lecithin, and bilirubin (a pigment from red blood cells that have been broken down) -- are secreted by liver cells into a network of microscopic channels. Bile drains into the larger hepatic duct and flows out of the liver into the common bile duct.

Some of the bile empties directly into the duodenum -- or upper intestine; most is diverted through the cystic duct to the gall-bladder. There, cells lining the wall of the gallbladder absorb water and electroLytes, concentrating the two to five cups of bile produced daily into a few tablespoons.

The bile is stored in the gallbladder until it is required by the small intestine. When food, especially fat, enters the duodenum, it triggers the release of the hormone cholecystokinin, which stimulates the gallbladder to contract, forcing bile down the duct toward the duodenum. At the same time, the sphincter of Oddi, a muscular "valve" in the common bile duct, relaxes, allowing bile to flow into the duodenum. There bile salts pick up fat molecules and ferry them to cells on the surface of the duodenum for absorption into the bloodstream.

Without bile salts in the intestinal tract, up to 40% of dietary lipids would be lost into the feces. When fats are not absorbed adequately, neither are the fat-soluble vitamins A, D, E, and K.

About 80% of gallstones develop when the amount of cholesterol is disproportionately greater than the other components of bile -- a condition that has nothing to do with blood cholesterol levels. In such cases cholesterol precipitates out of the bile, forming many small crystals on the interior surface of the gallbladder. These develop into stones over a number of years. A mature gallstone may range in size from that of a pea to that of a marble.

The remaining 20% of gallstones are usually associated with specific medical conditions. Black pigment stones are composed primarily of bilirubin and occur principally in people who have hemolytic anemia -- a condition in which excessive numbers of red blood cells are destroyed --or cirrhosis. Brown pigment stones, found almost exclusively in bile ducts, are usually the result of ductal infections and are formed of substances produced when bacteria act on bile.

Most gallstones aren't harmful and cause no symptoms. However, if a stone is squeezed from the gall- bladder into the cystic or common bile duct, it can become the source of problems that range from recurrent abdominal pain to severe infection. When a stone obstructs a duct intermittently, pain typically begins rather suddenly, builds to a maximum within an hour, and persists for 2 to 4 hours. It usually originates in the middle of the upper abdomen and spreads to the right, near the bottom of the rib cage. It often radiates to the back be- tween the shoulder blades. Some patients describe the pain as knife- like, while others portray it as a deep ache or cramp.

A stone lodged in a duct may set the stage for infection. Most commonly the blockage will occur in the cystic duct, producing an infection in the gallbladder (cholecystitis). When a stone obstructs the upper common duct, the pancreas may be infected (pancreatitis); when the site is the lower common duct or hepatic duct, cholangitis may result. Symptoms include nausea, vomiting, fever, severe abdominal pain, and tenderness in the upper right abdomen. These infections often require several days of hospital treatment with pain medicine and intravenous antibiotics.

People who have recurrent obstructions may have new episodes of abdominal pain and chronic inflammation, resulting in a scarred or thickened gallbladder that does not expand or contract normally. As gallbladder emptying slows, bile accumulates, setting the stage for additional cholesterol precipitation and further stone formation.

Because the pain associated with gallstones can be caused by peptic ulcer disease or other digestive problems, doctors usually try to confirm the existence of the stones and pinpoint their location by ultrasound. This procedure, which harnesses high-frequency sound waves to produce images, is non-invasive, painless, and detects stones in the gallbladder with an accuracy of 90-95%; however, it finds only 40-70% of stones trapped in bile ducts. If a doctor suspects acute cholecystitis and wants to confirm it, he or she may perform cholescintigraphy, a scanning procedure using a radioactive injection, which is almost 100% accurate in revealing cholecystitis.

Occasionally, when ultrasound does not provide a good gallbladder image or detect a stone in a patient suspected of having chronic cholecystitis, CT or MRI scans or endoscopic retrograde cholangiopancreatography (ERCP) -- which requires the passage of a scope into the stomach -- may be employed.

Most patients with recurrent pain and gallstones are advised to undergo cholecystectomy, because the risk of potential complications stemming from gall-stones is usually much greater than the risk of surgery. Introduced in 1988, laparoscopic cholecystectomy has rapidly replaced the conventional "open" operation, which requires a 5-inch abdominal incision. In the laparoscopic procedure, imaging and surgical instruments are introduced into the abdomen through several small incisions, and surgeons are guided by a video monitor as they remove the gallbladder. In about 5% of cases, difficulties in removing the gallbladder or complications such as bleeding will occur, and surgeons will "convert" the laparoscopic procedure into an open one by making an abdominal incision.

Patients report much less postoperative pain and recover more rapidly from laparoscopic surgery than from open cholecystectomy. In fact, most patients spend only a single night in the hospital and are back to work within a week or two.

Medical treatment is available for patients who are unwilling or too frail to undergo surgery. The most common approach involves taking ursodeoxycholic acid -- a natural component of bile -- to dissolve the gallstones. When given in large doses and under the right conditions, ursodeoxycholic acid, or ursodiol, will dissolve stones in about two-thirds of patients over about two years. It has no significant toxicity, although it may cause diarrhea. However, once treatment is discontinued, stones recur in about half of patients within about 5 years, with most reappearing about one year after therapy is stopped. Because it acts slowly, oral treatment isn't recommended for patients who have intense symptoms or urgent complications of gallstones.

Lithotripsy -- the use of shock waves to pulverize stones -- which has been very useful for treating kidney stones, can break gallstones into fragments small enough to pass through the ducts or to be dissolved with ursodiol. Ursodiol is usually continued for about three months after lithotripsy to dissolve remaining fragments. Even so, gallstones recur within five years in 50% of patients who have lithotripsy.

Risk and risk reduction
Contrary to earlier teachings, diet isn't a major cause of gallstones. The strongest risk factors are:

Ethnic origin. Native Americans have a genetic predisposition to secrete high levels of cholesterol into bile. Thus, these women have an 80% lifetime chance of developing gallstones.

Estrogen -- whether supplied by a hormonal surge at puberty and pregnancy or taken as oral contraceptives or hormone replacement therapy -acts on the liver to increase cholesterol concentration in bile. Excess risk may be reduced by using oral contraceptives with lower doses of estrogen and postmenopausal estrogen patches, which deliver the hormone through the skin and reduce its effect on the liver.

Hypertriglyceridemia. High levels of triglycerides -- molecules of fatty acids made from carbohydrates -- increase the risk for cholesterol stones. People with diabetes, who generally have high triglyceride levels, are at especially high risk not only for gall-stones but for complications of gallbladder disease.
Cholesterol-lowering drugs. Clofibrate and gemfibrozil, which lower blood cholesterol by increasing the amount secreted into the bile, also elevate risk, while drugs like lovastatin, which block cholesterol production, can reduce risk.
Obesity increases risk for women, but not for men.

Rapid weight loss. Women who lose a significant amount of weight through crash dieting have a 20% risk for developing gallstones during that period. Excess cholesterol is secreted into bile as body fat is metabolized during weight loss, and a drastic reduction in dietary fats reduces the effectiveness of gall-bladder contractions. Taking ursodiol if crash dieting can help reduce risk.

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