The Gallbladder--An Organ You Can Live Without 
by Ricki Lewis, Ph.D. 

Even though she was about 15 pounds overweight, the woman indulged in her 
favorite fatty foods with gusto, consuming fried chicken, french fries, and 
topping it off with a hot fudge sundae. By 3 a.m., she regretted her
actions, awakening with indigestion and a sharp, stabbing pain in the upper 
right quarter of her abdomen. The pain continued for hours, spreading to her
shoulders, slowly ebbing away by the next afternoon.

Since the symptoms had abated and no one else in the family became ill, the 
woman forgot her experience--until a few weeks later. This time the seeming 
culprit was a pizza binge, another fatty meal. The unrelenting, severe
abdominal pain returned. Finally, the woman went to her doctor, who 
immediately suspected a gallbladder problem.

Although this woman is a composite of several gallstone patients, her 
experiences are fairly typical. She was not one of the 10 percent of
patients whose gallstones contain calcium, which makes them visible on a
standard x-ray. So she was given a tablet containing a radiopaque dye the 
night before undergoing a special x-ray called an oral cholecystogram. The
dye outlined her gallbladder and individual stones within it. Had the dye 
not shown up at all, it would have meant that her gallbladder was packed
full with stones. An ultrasound scan confirmed the presence of stones.

The diagnosis: acute cholecystitis. The tube leading from her gallbladder to
her small intestine was blocked by a cholesterol stone. Pressure was
building in her gallbladder, alerting the immune system to send in the white
blood cells and biochemicals of an inflammatory response. 

Although she was in intense pain, the woman would soon be helped by recent
developments that make treating a diseased gallbladder easier than ever.

The Gallbladder 

The gallbladder is a small, muscular, pear-shaped sac nestled in a
depression on the right underside of the liver. It holds about a quarter of 
a cup of a yellowish-green, pasty material called bile. Bile contains water,
bile salts and acids, pigments, cholesterol, phospholipids (a type of fat 
molecule), and electrolytes (electrically charged fluids). Bile tastes
bitter, and this is why the word "bile" has come to denote bitterness. Bile 
breaks up, or emulsifies, large globs of fat into smaller globs in the small
intestine, a first step in fat digestion. 

The gallbladder is a storage stop between the liver and the small intestine.
It fills with viscous bile, thickening it, until a hormone released after 
eating signals the gallbladder to squirt out its colorful contents. 

A healthy gallbladder keeps bile moving in several ways. The inner lining,
called the mucosa, secretes hydrogen ions into the gallbladder contents.
This maintains an acidic environment, necessary to keep calcium from
precipitating (coming out of solution as solid particles). As food is 
digested, water and electrolytes pour into the area, continually diluting 
and washing out the bile. Finally, bile salts latch onto cholesterol
molecules, keeping them in solution.

Stone Formation 

Should any of these biological balances backfire, the sludge-like 
gallbladder contents can crystallize. A stone forms when a speck of calcium 
becomes coated with either cholesterol or the pigment bilirubin. Bilirubin
comes from the blood's oxygen-carrying molecule, hemoglobin. The
brownish-black color of pigment stones is due to bilirubin, much as a 
vibrantly-hued bruise appears as blood spreads beneath the skin.

While pigment stones are small, dark, and relatively rare, cholesterol
stones are crystalline and waxy, can grow quite large, and may accumulate in
the hundreds. Many stones are mixed, with pigment on the inside, wrapped in 
a cholesterol coat. 

About half of people with gallbladder stones do not even know that they have
them. Painless stones probably float freely in the gallbladder. Pain results
when a stone is small enough to pass through and lodge in either the cystic 
duct leading from the gallbladder, or farther along in the common bile duct,
which is shared by the gallbladder and the liver and leads to the small 
intestine. In fact, one large stone trapped in the gallbladder is not as
likely to cause pain as are several small stones that can escape. 

The type and severity of symptoms depend upon where stones lodge. A stone 
stuck in the lower common bile duct results in jaundice (yellowing of the 
skin and whites of the eyes, due to bilirubin accumulation) and may cause 
pancreatitis, because a conduit from the pancreas joins the common bile 
duct. The pancreas' digestive enzymes, which normally go to the small 
intestine, become trapped in this essential gland, destroying it. 

A stone trapped in the neck of the gallbladder causes acute cholecystitis. A
milder condition is chronic recurrent acute cholecystitis, characterized by 
intermittent pain of shorter duration and less intensity. 

In the most severe scenario, pressure builds so much that the gallbladder 
bursts, sending bile into the abdominal cavity. Pus accumulates, bacteria 
move in, and the infected bile may lead to peritonitis, a severe infection
of the abdominal cavity. But this is very rare because a gallbladder is 
usually removed before disease can progress this far. 

Who Gets Gallstones?

Although gallstones are a very common medical problem, we know very little
about why some people develop them and some do not. We do know that women 
are twice as likely to have gallbladder problems as men.

Women may owe their higher risk of gallbladder disease to hormones. The 
female hormone estrogen is known to increase the rate of lipid (fat)
synthesis, use and excretion, while at the same time calming gallbladder
movements that would mix up the contents. Pregnancy raises risk by altering 
the chemical composition of bile to favor stone formation and decreasing the
contractability of the gallbladder. Birth control pills containing estrogen 
increase the cholesterol content of bile, and seem to heighten the risk of
gallbladder disease in women under 29 who have taken them for less than 5 
years.

Studies indicate that gallstones are more prevalent in some populations than
others, but it is difficult to tell whether this is due to heredity or
environmental factors. For example, gallstones are common in the United 
States (with 20 million sufferers) and Great Britain (with 100,000 affected)
and have the highest incidence in Sweden, where 44 percent of the population
is affected. Yet gallstones are very rare in Africa and Asia. 

But does prevalent gallbladder disease reflect a particular diet, or genetic
similarity among the people? It's hard to say.

The fact that the rate of gallbladder disease is high in cultures with
high-fat, low-fiber diets and low in cultures with high-fiber, low-fat diets
suggests a nutritional influence. In addition, people who move from the 
high-fiber, low-fat areas to high-fat, low-fiber areas soon develop more
gallbladder disease. For example, East Asians moving to the United States 
and adopting our fattier diet show a sixfold increase in gallbladder
problems within a single generation.

On the other hand, certain population groups, most notably Native Americans,
have a high incidence of gallbladder disease, leading scientists to suspect 
a hereditary factor. About 80 percent of the Pima Indians of southern 
Arizona develop gallstones by age 35. Numbers are also high among the 
Navajos of the southwestern states, the Chippewas of northern Minnesota, the
Micmacs of Nova Scotia, Alaskan tribes, and especially the Araucanian 
Indians of Chile. Another genetic link is the association of pigment
gallstones with sickle cell disease, an inherited anemia most common in 
blacks. 

The Role of Diet

Since the gallbladder is part of the digestive system, it seems logical that
its health would depend, at least in part, on what one eats. Establishing a 
dietary cause of gallbladder disease is difficult.

Still, some clinical studies track interesting trends. A group of Boston
researchers led by K. Malcolm MacLure, Sc.D., of the Harvard School of
Public Health, and Walter C. Willett, M.D., of Harvard Medical School,
followed 88,837 women between the ages of 34 and 59 who had filled out a
detailed dietary questionnaire in 1980. By 1984, 433 had had their
gallbladders removed, and 179 had stones not yet treated. What, if anything,
did these women have or do that the others didn't? Weight.

"Overall, we observed a roughly linear relation between relative weight and 
the risk of gallstones," write the researchers in the Aug. 31, 1989, issue
of the New England Journal of Medicine. They warn that even moderate
overweight can raise the risk, estimating that the very obese face a sixfold
higher risk, and the slightly overweight a 1.7-fold increase in risk. 

A team led by Harris Pastides, Ph.D., of the University of Massachusetts
School of Public Health in Amherst, compared the diets of 84 female and 16
male gallbladder patients admitted consecutively to a hospital in Athens, 
Greece, to accident victims without gallbladder problems. They conclude in
the July 1990 Archives of Internal Medicine, "Our findings suggest that 
there is a rather strong association between frequent consumption of starchy
food items such as breads, pasta, rice, and potatoes with risk of 
gallbladder disease in women. Furthermore, a modest protective effect was 
observed among women reporting relatively high consumption of vegetables of 
all kinds." They recommend that overweight women with starchy diets try to
include more vegetables.

But the diet-gallbladder link, if indeed there is one, is far from clear. 
Consider a class action suit being filed against a popular dietary plan.
"Last spring, according to newspaper reports, 19 people filed suit against
NutriSystem for developing gallbladder disease after the diet," says Carol
Heppe, a consumer safety officer at the Food and Drug Administration. But 
would they have become ill anyway? There is no ready answer.

For women, common risk factors for developing the disease include age,
weight, and number of children. Among obese women between 20 and 30 years of
age, the risk is six times greater than that for women of normal weight. By 
age 60, almost one-third of obese women can expect to develop gallbladder 
disease.

Drug Treatment

Drug treatment to dissolve gallstones began about 20 years ago, when
researchers found that a deficiency of bile salts enabled cholesterol to
crystallize out of solution and form stones. Today, drugs are typically 
given for small stones or if a person cannot tolerate surgery.

The two approved cholesterol gallstone dissolution drugs are the natural
bile constituents chenodeoxycholic acid (Chenix) and its chemical 
non-identical twin ursodeoxycholic acid (Actigall). 

"These drugs can change the cholesterol saturation in the gallbladder and 
permit cholesterol in the stone to go into solution, so that it dissolves," 
says Stephen Fredd, M.D., director of FDA's division of gastrointestinal and
coagulation drug products at FDA. "Ursodeoxycholic acid is less likely to be
toxic to the liver, but is more expensive." 

But the drugs have major drawbacks. "In 50 percent of patients, stones recur
within 5 years of drug treatment," explains Fredd. "A common side effect of 
these drugs is diarrhea. The drugs work slowly and must be taken daily for a
long time and, even then, are not always effective. About 12 percent of 
patients improve after six months, and up to 50 percent show improvement by 
a year. The cost of drug treatment is about $1,200 a year.

A new investigational drug is methyl-tert-butyl-ether. It works fast on 
cholesterol stones, dissolving them in 24 to 48 hours, but administering the
drug is an invasive procedure.

"It is not taken orally," explains Fredd. "It is put in the gallbladder by a
catheter through the liver to the gallbladder. This is not minor stuff, but 
in expert hands, it can be done safely. But it has dangerous propensities.
It is an ether, and can put you to sleep. It can irritate the intestines."

Another new drug is mono-octanoin (Moctanin), which is approved only to 
treat stones lodged in the common bile duct. This sometimes happens after 
the gallbladder is removed and small stones migrate into the duct.

Shock Wave Lithotripsy

Shock wave lithotripsy, a noninvasive procedure that FDA approved for 
treating kidney stones in 1985, seemed to hold great promise for treating 
gallstones as well. (To treat kidney stones, the torso of the anesthetized
but conscious patient is immobilized and lowered into a large tub of water, 
where x-rays are used to locate the stone and position the patient properly.
In a procedure lasting one to two hours, the kidney stones are then crushed,
without harming bone or soft tissue, by repeated shock waves from a 
generator at the bottom of the tub.)

"At the outset we thought, gee, it'll be great for gallstones, too. But 
gallstones turned out to be a whole different animal," says FDA's Mark
Kramer, chief of the office of device evaluation's gastroenterology/urology 
branch I. 

Not only are gallbladder stones chemically different from kidney stones, but
kidney stones are easier to pass once shattered because urine forms in the
kidney and collects in the bladder all the time. In contrast, the 
gallbladder squirts only intermittently, and may not contract and expand
enough in patients who form stones for the stones to be passed. As a result,
gallstone dissolution drugs usually must be taken along with the lithotripsy
treatment. Based on the clinical data available, lithotripsy for gallstones 
may only work for 10 to 15 percent of sufferers, Kramer says, and it is not 
yet known which types of patients would benefit more from it than from drugs
or surgery. 

Surgery 

Cholecystectomy--gallbladder removal--is the most common elective abdominal 
operation in western nations. Before the procedure was perfected a century
ago, the cholecystostomies performed only removed the stones--which came
back. Researchers then realized they had to remove the stones plus their
pouch, the gallbladder. In a classical cholecystectomy, the surgeon removes 
the gallbladder through a 5- to 8-inch incision. The duct from the liver is 
then attached directly to the small intestine. Afterwards, a steady trickle 
of less concentrated bile is sent to the small intestine. In most cases,
life returns to normal. 

Cholecystectomy costs from $6,000 to $10,000, and requires a five- to 
seven-day hospital stay. The patient needs about a month to fully recover.
Considering the invasiveness of the procedure, and that symptoms are often
intermittent or even nonexistent, it is not surprising that the operation is
declining in popularity. In 1975, 600,000 cholecystectomies were performed
in the United States; by 1989, the number had dropped to 475,000. 

A new surgical procedure, laparoscopic laser cholecystectomy (LLC, popularly
known as "keyhole laser surgery"), is an alternative to conventional
cholecystectomy. It is fast, effective, and far less invasive. A typical
hospital stay is 36 hours or less, with return to normal activities within a
week. 

LLC requires four incisions: two half-inch-long cuts and two
quarter-inch-long cuts. The laser energy is delivered along a tiny flexible 
quartz fiber through one of the larger openings, and is focused on a
sapphire scalpel, which directly contacts the tissue. The scalpel channels
the energy, minimizing damage to nearby tissue. A miniature TV camera is
threaded through a tube called a laparoscope inserted in the second large 
hole. The two smaller holes permit entry of surgical instruments. The 
procedure can be performed by one or two surgeons.

Postoperative pain, if any, can be controlled with over-the-counter 
painkillers rather than the narcotics often needed following traditional
cholecystectomy. This latest "band aid" surgery (so-called because it 
requires tiny incisions) promises to be particularly beneficial for the 
elderly.

"Older people often cough more frequently than others, and in the past, they
have suffered badly with a large abdominal incision," says Phillip Rosett,
M.D., who performs LLC at Thorek Hospital in Chicago. 

"With the bigger incisions [of traditional gallbladder removal], older
patients have a greater risk of developing pneumonia. They also have greater
difficulty getting out of bed. It usually takes 24 hours before they can
move from the bed to a chair and close to another 24 hours to start walking 
again. However, with LLC, my patients are up and walking the same afternoon,
and they walk out of the hospital the following morning," he adds.

It's nice to know that gallbladder disease is one problem for which 
treatment is becoming both simpler and more successful. Although the answers
aren't all in on what causes gallbladder disease, it couldn't hurt to follow
the advice of the American Heart Association and the National Cancer
Institute and add more fiber to our diets and cut back on fat. n

Ricki Lewis teaches biology at the State University of New York at Albany 
and is the author of Beginnings of Life.