Gallstones

Medical Author: Jay W. Marks, M.D.

Medical Editor: Dennis Lee, M.D.
What are gallstones?
Gallstones are stones that form in the gall (bile).
 Bile is a watery liquid made by the cells of the liver that is important for digesting food in the intestine,
particularly fat.
 Liver cells secrete the bile they make into small canals within the liver.
 The bile flows through the canals and into larger collecting ducts within the liver (the intrahepatic bile
ducts).
 The bile then flows within the intrahepatic bile ducts out of the liver and into the extrahepatic bile
ducts-first into the hepatic bile ducts, then into the common hepatic duct, and finally into the common
bile duct.
From the common bile duct, there are two different directions that bile can flow.
 The first direction is on down the common bile duct and into the intestine where the bile mixes with
food and promotes digestion of food.
 The second direction is into the cystic duct, and from there into the gallbladder (often misspelled as
gall bladder).
Once in the gallbladder, bile is concentrated by the removal (absorption) of water. During a meal, the muscle
that makes up the wall of the gallbladder contracts and squeezes the concentrated bile in the gallbladder back
through the cystic duct into the common duct and then into the intestine. (Concentrated bile is much more
effective for digestion than the un-concentrated bile that goes from the liver straight into the intestine.) The
timing of gallbladder contraction-during a meal-allows the concentrated bile from the gallbladder to mix with
food.
Gallstones usually form in the gallbladder; however, they also may form anywhere there is bile; in the
intrahepatic, hepatic, common bile, and cystic ducts.
Gallstones also may move about within bile, for example, from the gallbladder into the cystic or common duct.
What causes gallstones?
Gallstones are common; they occur in approximately 20% of women in the US, Canada and Europe, but there is
a large variation in prevalence among ethnic groups. For example, gallstones occur 1 ½ to 2 times more
commonly among Scandinavians and Mexican-Americans. Among American Indians, gallstone prevalence
reaches more than 80%. These differences probably are accounted for by genetic (hereditary) factors. First-
degree relatives (parents, siblings, and children) of individuals with gallstones are 1 ½ times more likely to have
gallstones than if they did not have a first-degree relative with gallstones. Further support comes from twin
studies that genetic factors are important in determining who gets gallstones. Among non-identical pairs of
twins (who share 50% of their genes with each other), both individuals in a pair have gallstones 8% of the time.
Among identical pairs of twins (who share 100% of their genes with each other), both individuals in a pair have
gallstones 23% of the time.
There are several types of gallstones and each type has a different cause.
Cholesterol gallstones
Cholesterol gallstones are made primarily of cholesterol. They are the most common type of gallstone,
comprising 80% of gallstones in individuals from Europe and the Americas. Cholesterol is one of the substances
that liver cells secrete into bile. (Secretion of cholesterol into bile is an important way in which the liver
eliminates excess cholesterol from the body.)
In order for bile to carry cholesterol, the cholesterol must be dissolved in the bile. Cholesterol is a fat, however,
and bile is an aqueous or watery solution; fats do not dissolve in watery solutions. In order to make the
cholesterol dissolve in bile, the liver also secretes two detergents-bile acids and lecithin-into the bile. These
detergents, just like dish-washing detergents, dissolve the fatty cholesterol so that it can be carried by bile
through the ducts. If the liver secretes too much cholesterol for the amount of bile acids and lecithin it secretes,
some of the cholesterol does not dissolve. Similarly, if the liver does not secrete enough bile acids and lecithin,
some of the cholesterol also does not dissolve. In either case, the undissolved cholesterol sticks together and
forms particles of cholesterol that grow in size and eventually form larger gallstones.
There are two other processes that promote the formation of cholesterol gallstones though neither process is able
to cause cholesterol gallstones by itself. The first is abnormally rapid formation and growth of cholesterol
particles into gallstones. Thus, with the same concentrations of cholesterol, bile acids and lecithin in their bile,
patients with gallstones form particles of cholesterol more rapidly than individuals without gallstones. The
second process that promotes the formation and growth of gallstones is reduced contraction and emptying of the
gallbladder that allows bile to sit in the gallbladder longer so that there is more time for cholesterol particles to
form and grow.
Pigment gallstones
Pigment gallstones are the second most common type of gallstone. Although pigment gallstones comprise only
15% of gallstones in individuals from Europe and the Americas, they are more common than cholesterol
gallstones in Southeast Asia. There are two types of pigment gallstones 1) black pigment gallstones, and 2)
brown pigment gallstones.
Pigment is a waste product formed from hemoglobin, the oxygen-carrying chemical in red blood cells. The
hemoglobin from old red blood cells that are being destroyed is changed into a chemical called bilirubin and
released into the blood. Bilirubin is removed from the blood by the liver. The liver modifies the bilirubin and
secretes the modified bilirubin or into bile.
Black pigment gallstones: If there is too much bilirubin in bile, the bilirubin combines with other constituents
in bile, for example, calcium, to form pigment (so-called because it is dark brown in color). Pigment dissolves
poorly in bile and, like cholesterol, it sticks together and forms particles that grow in size and eventually form
gallstones. The pigment gallstones that form in this manner are called black pigment gallstones because they are
black and hard.
Brown pigment gallstones: If there is reduced contraction of the gallbladder or obstruction to the flow of bile
through the ducts, bacteria may ascend from the duodenum into the bile ducts and gallbladder. The bacteria alter
the bilirubin in the ducts and gallbladder, and the altered bilirubin then combines with calcium to form pigment.
The pigment then combines with fats in bile (cholesterol and fatty acids from lecithin) to form particles that
grow into gallstones. This type of gallstone is called a brown pigment gallstone because it is more brown than
black. It also is softer than black pigment gallstones.
Other types of gallstones. Other types of gallstones are rare. Perhaps the most interesting type of gallstone is
the gallstone that forms in patients taking the antibiotic, ceftriaxone (Rocephin). Ceftriaxone is unusual in that it
is eliminated from the body in bile in high concentrations. It combines with calcium in bile and becomes
insoluble. Like cholesterol and pigment, the insoluble ceftriaxone and calcium form particles that grow into
gallstones. Fortunately, most of these gallstones disappear once the antibiotic is discontinued; however, they still
may cause problems until they disappear. Another rare type of gallstone is formed from calcium carbonate.

Who is at risk for gallstones?

Risk for cholesterol gallstones.
There is no relationship between cholesterol in the blood and cholesterol gallstones. Individuals with elevated
blood cholesterol do not have an increased prevalence of cholesterol gallstones. A common misconception is
that diet is responsible for the development of cholesterol gallstones, however, it isn't. The risk factors for
developing cholesterol gallstones include:
1. Gender. Gallstones form more commonly in women than men.
2. Age. Gallstone prevalence increases with age.
3. Obesity. Obese individuals are more likely to form gallstones than thin individuals.
4. Pregnancy. Women who have been pregnant are more likely to form gallstones than women who have
not been pregnant. Pregnancy increases the risk for cholesterol gallstones because during pregnancy,
bile contains more cholesterol, and the gallbladder does not contract normally.
5. Birth control pills and hormone therapy The increased levels of hormones caused by either
treatment mimics pregnancy.
6. Rapid weight loss. Rapid weight loss by whatever means, very low calorie diets or obesity surgery,
causes cholesterol gallstones in up to 50% of individuals. Many of the gallstones will disappear after
the weight is lost, but many do not. Moreover, until they are gone, they may cause problems.
7. Crohn's disease. Individuals with Crohn's disease of the terminal ileum are more likely to develop
gallstones. Gallstones form because patients with Crohn's disease lack enough bile acids to solubilize
the cholesterol in bile. Normally, bile acids that enter the small intestine from the liver and gallbladder
 are absorbed back into the body in the terminal ileum and are secreted again by the liver into bile. In
other words, the bile acids recycle. In Crohn's disease, the terminal ileum is diseased. Bile acids are not
absorbed normally, the body becomes depleted of bile acids, and less bile acids are secreted in bile.
There are not enough bile acids to keep cholesterol dissolved in bile, and gallstones form.
8. Increased blood triglycerides. Gallstones occur more frequently in individuals with elevated blood
triglyceride levels.
Risk for pigment gallstones
Black pigment gallstones form whenever there is an increased load of bilirubin that reaches the liver. This
occurs whenever there is increased destruction of red blood cells, as there is in sickle cell disease and
thalassemia. Black pigment gallstones also are more common among patients with cirrhosis of the liver. Brown
pigment gallstones form when there is stasis of bile (decreased flow), for example, when there are narrow,
obstructed bile ducts.
What are the symptoms of gallstones?
The majority of people with gallstones have no signs or symptoms and are unaware of their gallstones. (The
gallstones are "silent.") Their gallstones often are found as a result of tests (for example, ultrasound or X-ray
examination of the abdomen) performed while evaluating medical conditions other than gallstones. Symptoms
can appear later in life, however, after many years without symptoms. Thus, over a period of five years,
approximately 10% of people with silent gallstones will develop symptoms. Once symptoms develop, they are
likely to continue and often will worsen.
Gallstones are blamed for many symptoms they do not cause. Among the symptoms gallstones do not cause
are:
 dyspepsia (including abdominal bloating and discomfort after eating),
 intolerance to fatty foods,
 belching, and
 flatulence (passing gas or farting).
When signs and symptoms of gallstones occur, they virtually always occur because the gallstones obstruct the
bile ducts.
The most common symptom of gallstones is biliary colic. Biliary colic is a very specific type of pain,
occurring as the primary or only symptom in 80% of people with gallstones who develop symptoms. Biliary
colic occurs when the extrahepatic ducts-cystic, hepatic or common bile-are suddenly blocked by a gallstone.
(Slowly-progressing obstruction, as from a tumor, does not cause biliary colic.) Behind the obstruction, fluid
accumulates and distends the ducts and gallbladder. In the case of hepatic or common bile duct obstruction, this
is due to continued secretion of bile by the liver. In the case of cystic duct obstruction, the wall of the
gallbladder secretes fluid into the gallbladder. It is the distention of the ducts or gallbladder that causes biliary
colic.
Characteristically, biliary colic comes on suddenly or builds rapidly to a peak over a few minutes.
 It is a constant pain, it does not come and go, though it may vary in intensity while it is present.
 It lasts for 15 minutes to 4-5 hours. If the pain lasts more than 4-5 hours, it means that a complication -
usually cholecystitis - has developed.
 The pain usually is severe, but movement does not make the pain worse. In fact, patients experiencing
biliary colic often walk about or writhe (twist the body in different positions) in bed trying to find a
comfortable position.
 Biliary colic often is accompanied by nausea.
 Most commonly, biliary colic is felt in the middle of the upper abdomen just below the sternum.
 The second most common location for pain is the right upper abdomen just below the margin of the
ribs.
 Occasionally, the pain also may be felt in the back at the lower tip of the scapula on the right side.
 On rare occasions, the pain may be felt beneath the sternum and be mistaken for angina or a heart
attack.
 An episode of biliary colic subsides gradually once the gallstone shifts within the duct so that it is no
longer obstructing.
Biliary colic is a recurring symptom. Once the first episode occurs, there are likely to be other episodes. Also,
there is a pattern of recurrence for each individual, that is, for some individuals the episodes tend to remain
frequent while for others they tend to remain infrequent. The majority of people who develop biliary colic do
not go on to develop cholecystitis or other complications.
What are the complications of gallstones?
Biliary colic is the most common symptom of gallstones, but, fortunately, it is usually a self-limiting symptom.
There are, however, more serious complications of gallstones.
Cholecystitis
Cholecystitis means inflammation of the gallbladder. Like biliary colic, it too is caused by sudden obstruction of
the ducts by a gallstone, usually the cystic duct. In fact, cholecystitis may begin with an episode of biliary colic.
Obstruction of the cystic duct causes the wall of the gallbladder to begin secreting fluid just as with biliary colic,
however, for unclear reasons, inflammation sets in. At first the inflammation is sterile, that is, there is no
infection with bacteria; however, over time the bile and gallbladder become infected with bacteria that travel
through the ducts from the intestine.
With cholecystitis, there is constant pain in the right upper abdomen. Inflammation extends through the wall of
the gallbladder, and the right upper abdomen becomes particularly tender when it is pushed or even tapped.
Unlike with biliary colic, however, it is painful to move. Individuals with cholecystitis usually lie still. There is
fever, and the white blood cell count is elevated, both signs of inflammation. Cholecystitis usually is treated
with antibiotics, and most episodes will resolve over several days. Even without antibiotics, cholecystitis often
resolves. As with biliary colic, movement of the gallstone out of the cystic duct and back into the gallbladder
relieves the obstruction and allows the inflammation to resolve.
Cholangitis
Cholangitis is a condition in which bile in the common, hepatic, and intrahepatic ducts becomes infected. Like
cholecystitis, the infection spreads through the ducts from the intestine after the ducts become obstructed by a
gallstone. Patients with cholangitis are very sick with a high fever and elevated white blood cell counts.
Cholangitis may result in an abscess within the liver or sepsis. (See discussion of sepsis that follows.)
Gangrene
Gangrene of the gallbladder is a condition in which the inflammation of cholecystitis cuts off the supply of
blood to the gallbladder. Without blood, the tissues forming the wall of the gallbladder die, and this makes the
wall very weak. The weakness combined with infection often leads to rupture of the gallbladder. The infection
then may spread throughout the abdomen, though often the rupture is confined to a small area around the
gallbladder (a confined perforation).
Jaundice
Jaundice is a condition in which bilirubin accumulates in the body. Bilirubin is brownish-black but yellow when
it is not too concentrated. A build-up of bilirubin in the body turns the skin and whites of the eye (sclera) yellow.
Jaundice occurs when there is prolonged obstruction of the bile ducts. The obstruction may be due to gallstones,
but it also may be due to many other causes of obstruction, for example, tumors of the bile ducts or surrounding
tissues. (Other causes of jaundice are a rapid destruction of red blood cells that overwhelms the ability of the
liver to remove bilirubin from the blood or a damaged liver that cannot remove bilirubin from the blood
normally.) Jaundice, by itself, generally does not cause problems.
Pancreatitis
Pancreatitis means inflammation of the pancreas. The two most common causes of pancreatitis are alcoholism
and gallstones. The pancreas surrounds the common bile duct as the duct enters the intestine. The pancreatic
duct that drains the digestive juices from the pancreas joins the common bile duct just before it empties into the
intestine. If a gallstone obstructs the common bile duct just after the pancreatic duct joins it, flow of pancreatic
juice from the pancreas is blocked. This results in inflammation within the pancreas. Pancreatitis due to
gallstones usually is mild, but it may cause serious illness and even death. Fortunately, severe pancreatitis due to
gallstones is rare.
Sepsis
Sepsis is a condition in which bacteria from any source within the body, including the gallbladder or bile ducts,
get into the blood stream and spread throughout the body. Although the bacteria usually remain within the blood,
they also may spread to distant tissues and lead to the formation of abscesses (localized areas of infection with
formation of pus). Sepsis is a feared complication of any infection. The signs of sepsis include high fever, high
white blood cell count, and, less frequently, rigors (shaking chills) or a drop in blood pressure.
Fistula. A fistula is an abnormal tract through which fluid can flow between two hollow organs or between an
abscess and a hollow organ or skin. Gallstones cause fistulas when the hard gallstone erodes through the soft
wall of the gallbladder or bile ducts. Most commonly, the gallstone erodes into the small intestine, stomach, or
common bile duct. This can leave a tract that allows bile to flow from the gallbladder to the small intestine,
stomach, or common duct. If the fistula enters the distal part of the small intestine, the concentrated bile can lead
to problems such as diarrhea. Rarely, the gallstone erodes into the abdominal cavity surrounding the abdominal
organs. The bile then leaks from the gallbladder or bile duct throughout the abdominal cavity and causes
inflammation of the lining of the abdomen (peritoneum), a condition called bile peritonitis.
Ileus. Ileus is a condition in which there is an obstruction of flow of digesting food, gas, and liquid within the
intestine. It may be due to a mechanical obstruction, for example, a tumor within the intestine, or a functional
obstruction, for example, inflammation of the intestine or surrounding tissues that prevents the muscle of the
intestine from working normally and propelling its contents. If a large gallstone erodes through the wall of the
gallbladder and into the stomach or small intestine, it will be propelled through the small intestine. The
narrowest part of the small intestine is the ileo-cecal valve, which is located where the small intestine joins the
colon. If the gallstone is too large to pass through the valve, it can obstruct the small intestine and cause an ileus.
Cancer. Cancer of the gallbladder almost always is associated with gallstones, but it is not clear which comes
first, that is, whether the gallstones precede the cancer and, therefore, could potentially be the cause of the
cancer. Moreover, cancer of the gallbladder arises in less than 1% of individuals with gallstones. Therefore,
concern about future development of cancer alone is not a good reason for removing the gallbladder when
gallstones are present.
What is the relationship of sludge to gallstones?
Sludge is a common term that is applied to an abnormality of bile that is seen with ultrasonography of the
gallbladder. Specifically, the bile within the gallbladder is seen to be of two different densities with the denser
bile on the bottom. The bile is denser because it contains microscopic particles, usually cholesterol or pigment,
embedded in mucus. (The mucus is secreted by the gallbladder.) Over time, sludge may remain in the
gallbladder, it may disappear and not return, or it may come and go. As discussed previously, these particles
may be precursors of gallstones, and they occur often in some situations in which gallstones frequently appear,
for example, rapid weight loss, pregnancy, and with prolonged fasting.
Nevertheless, it appears that sludge goes on to become gallstones in only a minority of individuals. Just to make
matters more difficult, it is not clear how often - if at all - sludge alone causes problems. Sludge has been
blamed for many of the same symptoms as gallstones-biliary colic, cholecystitis, and pancreatitis, but often
these symptoms and complications are caused by very small gallstones that are missed by ultrasonography.
Moreover, it is possible that these gallstone-like symptoms and complications are actually caused by small
gallstones that have passed through the ducts and into the intestine rather than the sludge itself. Thus, there is
uncertainty about the meaning of sludge.
It is clear, however, that sludge is not the equivalent of gallstones. The practical implication of this uncertainty
is that unless an individual's symptoms are typical of gallstones, sludge should not be considered the cause of
the symptoms.
How are gallstones diagnosed?
Gallstones are diagnosed in one of two situations.
 The first is when there are symptoms or signs that suggest gallstones, and the diagnosis of gallstones is
being pursued.
 The second is coincidentally while a non-gallstone-related medical problem is being evaluated.
Ultrasonography is the most important means of diagnosing gallstones. Standard computerized tomography (CT
or CAT scan) and magnetic resonance imaging (MRI) may occasionally demonstrate gallstones; however, they
are poor for doing so compared with ultrasonography.
Ultrasonography
Ultrasonography is a radiological technique that uses high-frequency sound waves to produce images of the
organs and structures of the body. The sound waves are emitted from a device called a transducer and are sent
through the body's tissues. The sound waves are reflected by the surfaces and interiors of internal organs and
structures as "echoes." These echoes return to the transducer and are transmitted electrically onto a viewing
monitor. From the monitor, the outline of organs and structures can be determined as well as their consistency,
for example, liquid or solid.
There are two types of ultrasonography that can be used for diagnosing gallstones, 1) transabdominal
ultrasonography and 2) endoscopic ultrasonography.
Transabdominal ultrasonography
For transabdominal ultrasonography the transducer is placed directly on the skin of the abdomen which has had
a gel applied to it. The sound waves travel through the skin and then into the abdominal organs. Transabdominal
ultrasonography is painless, inexpensive, and without risk to the patient. In addition to identifying 97% of
gallstones in the gallbladder, abdominal ultrasonography can identify many other abnormalities related to
gallstones. It can identify:
 the thickened wall of the gallbladder when there is cholecystitis,
 enlarged gallbladders and ducts due to obstruction of the ducts by gallstones,
 pancreatitis, and
 sludge.
Transabdominal ultrasonography also may identify diseases not related to gallstones that may be the cause of
the patient's problem, for example, appendicitis. The limitations of transabdominal ultrasonography are that it
can only identify gallstones larger than 4-5 millimeters in size, and it is poor at identifying gallstones in ducts.
Endoscopic ultrasonography
For endoscopic ultrasonography, a long flexible tube - the endoscope - is swallowed by the patient after he or
she has been sedated with intravenous medication. The tip of the endoscope is fitted with an ultrasound
transducer. The transducer is advanced into the duodenum where ultrasonographic images are obtained.
Endoscopic ultrasonography can identify gallstones and the same abnormalities as transabdominal
ultrasonography; however, since the transducer is much closer to the structures of interest - the gallbladder, bile
ducts, and pancreas - better images are obtained than with transabdominal ultrasonography. Thus, it is possible
to visualize smaller gallstones with endoscopic than transabdominal ultrasonography. It also is better for
identifying gallstones in the common bile duct.
Although endoscopic ultrasonography is in many ways better than transabdominal ultrasonography, it is
expensive, not available everywhere, and carries the small risks of intravenous sedation and intestinal
perforation by the endoscope. Fortunately, transabdominal ultrasonography usually gives all of the information
that is necessary, and endoscopic ultrasonography is infrequently needed. Endoscopic ultrasonography also is a
better way than transabdominal ultrasound to evaluate the pancreas.
Magnetic resonance cholangio-pancreatography (MRCP)

Magnetic resonance cholangio-pancreatography or MRCP is a relatively new modification of magnetic

resonance imaging (MRI) that allows the bile and pancreatic ducts to be examined.
 For MRCP, the patient is placed in a strong magnetic field that aligns (magnetizes) the protons in the
molecules of water in the tissues. (Protons are parts of the atoms that make up water molecules. All
tissues of the body contain water though they contain different amounts of water.)
 Energy-carrying radio waves then are passed through the tissues, and the energy is absorbed by the
water's protons.
 The radio waves then are turned off, and the protons release the energy they absorbed.
 The released energy is used to form an image of the tissues and organs of the body.
 The MRI separates tissues and organs based on their concentration of water. Since different tissues
contain different amounts of water, the MRCP is very good at providing images of organs and tissues.
 Since bile is mostly water, MRCP gives an excellent image of bile within the gallbladder and bile ducts.
The pancreatic duct, which, like the bile ducts, is filled with a watery fluid, also is well-seen.
Thus, the procedure is called cholangio- (referring to the bile ducts) pancreatography (referring to the pancreatic
duct).
MRCP has in many instances replaced other procedures such as cholescintigraphy (HIDA scan) and endoscopic
retrograde cholangiopancreatography (ERCP). It can identify gallstones in the bile ducts, obstruction of the
ducts, and bile leaks. There are no risks to the patient with MRCP.
Cholescintigraphy (HIDA scan)

Cholescintigraphy is a procedure done by nuclear medicine physicians. It sometimes is referred to as a HIDA

scan or a gallbladder scan.
 For a HIDA scan, a radioactive chemical is injected intravenously into the patient.
 The radioactive chemical is removed from the blood by the liver and secreted into the bile.
 The chemical then disperses everywhere that the bile goes-into the bile ducts, the gallbladder, the
intestine, and any place else that bile goes.
 A camera that senses radioactivity (like a Geiger counter) is then placed over the patient's abdomen and
a "picture" of the liver, bile ducts, and gallbladder is obtained which corresponds to where the
radioactive chemical has traveled within, or outside of the bile-filled bile ducts, and gallbladder.
HIDA scans are used to identify obstruction of the bile ducts, for example, by a gallstone. They also may
identify bile leaks and fistulas. There are no risks to the patient with HIDA scans.
Cholescintigraphy is also used to study emptying of the gallbladder. Some patients with gallstones have had
inflammation of their gallbladders due to recognized or unrecognized episodes of cholecystitis. (There also are
uncommon, non-gallstone-related causes of inflammation of the gallbladder.) The inflammation can result in
scarring of the gallbladder's wall and muscle, which reduces the ability of the gallbladder to contract. As a result,
the gallbladder does not empty normally. During cholescintigraphy, a synthetic hormone related to
cholecystokinin (the hormone the body produces and releases during a meal to cause the gallbladder to contract)
can be injected intravenously to cause the gallbladder to contract and squeeze out its bile and radioactivity into
the intestine. If the gallbladder does not empty the bile and radioactivity normally, it is assumed that the
gallbladder is diseased as a result of gallstones or non-gallstone related inflammation.
The problem with interpreting a gallbladder emptying study is that many people with normal gallbladders have
abnormal emptying of the gallbladder. Therefore, it is hazardous to base a diagnosis of a diseased gallbladder on
abnormal gallbladder emptying alone.
Endoscopic retrograde cholangio-pancreatography (ERCP)

ERCP is an x-ray procedure to examine the duodenum (the first portion of the small intestine), the papilla of
Vater (a small nipple-like structure where the common bile and pancreatic ducts enter the duodenum), the bile
ducts, the gallbladder and the pancreatic duct.
The procedure is performed by using a long, flexible, viewing instrument (a duodenoscope, a type of endoscope)
about the diameter of a fountain pen. The duodenoscope is flexible and can be directed and moved around the
many bends of the stomach and intestine. The video-endoscope, the most common type of duodenoscope, uses a
thin wire with a chip at the tip of the instrument to transmit video images to a TV screen.
 First the patient is sedated with intravenous drugs.
 The duodenoscope then is inserted through the mouth, to the back of the throat, down the food pipe
(esophagus), through the stomach and into the first portion of the small intestine (duodenum).
 Once the papilla of Vater is identified, a small plastic catheter (cannula) is passed through a channel in
the duodenoscope into the papilla of Vater, and into the bile ducts and the pancreatic duct.
 Contrast material (dye) then is injected, and x-rays are taken of the bile ducts, gallbladder and/or the
pancreatic duct.
ERCP can identify 1) gallstones in the gallbladder (though it is not particularly good at this) and 2) blockage of
the bile ducts, for example, by gallstones, and 3) bile leaks. ERCP also may identify diseases not related to
gallstones that may be the cause of the patient's problem, for example, pancreatitis or pancreatic cancer.
An advantage of ERCP is that instruments can be passed through the same channel as the cannula used to inject
the dye to extract gallstones stuck in the common and hepatic ducts. This can save the patient from having an
operation. ERCP has several important risks associated with it, including the drugs used for sedation,
perforation of the duodenum by the duodenoscope, and pancreatitis (due to damage to the pancreas). If
gallstones are extracted, bleeding also may occur.
Liver and pancreatic blood tests

When the liver or pancreas becomes inflamed or their ducts become obstructed, the cells of the liver and
pancreas release some of their enzymes into the blood. The most commonly-measured liver enzymes in blood
are aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The most commonly-measured
pancreatic enzymes in blood are amylase and lipase. Many medical conditions that affect the liver or pancreas
cause these blood tests to become abnormal, so abnormalities cannot be used to diagnose gallstones.
Nevertheless, abnormalities in these tests suggest there is a problem with the liver, bile ducts, or pancreas, and
gallstones are a common cause of such abnormal tests, particularly during sudden obstruction of the bile or
pancreatic ducts. Thus, abnormal liver and pancreatic blood tests direct attention to the possibility that gallstones
may be present and causing the acute problem.
Duodenal biliary drainage

Duodenal biliary drainage is a procedure that occasionally can be useful in diagnosing gallstones, however, it is
not often used. As previously discussed, gallstones begin as microscopic particles of cholesterol or pigment that
grow in size. It is clear that some people who develop biliary colic, cholecystitis, or pancreatitis have only these
particles in their gallbladders, yet the particles are too small to obstruct the ducts. There are two potential
explanations for how obstruction might occur in this situation. The first is that a small gallstone has obstructed
and then finally passed through the bile ducts into the intestine. The second is that particles passing through the
bile ducts can "irritate" the ducts, causing spasm of the muscle within the walls of the ducts (which obstructs the
flow of bile) or inflammation of the duct that causes the wall of the duct to swell (and also obstructs the duct).
 For duodenal drainage, a thin plastic or rubber tube with several holes at its tip is passed through a
patient's anesthetized nostril, down the back of the throat, through the esophagus and stomach, and into
the duodenum where the bile and pancreatic ducts enter the small intestine. This is done with the help
of x-ray (fluoroscopy).
 Once the tube is in place, a synthetic hormone related to cholecystokinin is injected intravenously. The
hormone causes the gallbladder to contract and squeeze out its concentrated bile into the duodenum.
 The bile then is sucked up through the tube in the duodenum and examined for the presence of
cholesterol and pigment particles under a microscope.
The risks to the patient of duodenal drainage are minimal. (There have been no reports of reactions to the
synthetic hormone.) Nevertheless, duodenal drainage is uncomfortable.
A modification of duodenal drainage involves collection of bile through an endoscope at the time of an upper
gastrointestinal endoscopy-either esophago-gastro-duodenoscopy (EGD) or ERCP.
Oral cholecystogram (OCG)

The oral cholecystogram or OCG is a radiologic (x-ray) procedure for diagnosing gallstones.
 For an OCG, the patient takes iodine-containing tablets for one or two nights in a row and then has an
x-ray of his or her abdomen.
 The iodine is absorbed from the intestine, removed from the blood by the liver, and excreted into bile.
 In the gallbladder, the iodine becomes concentrated along with the bile.
  On the x-ray, the iodine, which is dense and stops x-rays, fills the gallbladder and outlines the
gallstones which are not dense, and allow x-rays to pass through them. The ducts cannot be seen on the
x-ray because the iodine is not concentrated in the ducts.
The OCG is an excellent procedure for diagnosing gallstones; it finds 95% of them. The OCG has been replaced,
however, by ultrasonography because ultrasonography is slightly better at diagnosing gallstones and can be done
immediately without waiting one or two days for the OCG's iodine to be absorbed, excreted, and concentrated.
The OCG also cannot give information about the presence of non-gallstone related diseases like ultrasonography.
As would be expected, ultrasonography sometimes finds gallstones that are missed by the OCG. Less frequently,
the OCG finds gallstones that are missed by ultrasonography. For this reason, if there is a strong suspicion that
gallstones are present but ultrasonography does not show them, it is reasonable to consider doing an OCG. An
OCG should not be done in individuals who are allergic to iodine.
Intravenous cholangiogram (IVC)

The intravenous cholangiogram or IVC is a radiologic (x-ray) procedure that is used primarily for looking at the
larger intrahepatic and the extrahepatic bile ducts. It can be used to locate gallstones within these ducts.
For an IVC, an iodine-containing dye is injected intravenously into the blood. The dye is removed from blood
by the liver and excreted into bile. Unlike the iodine used in the OCG, the iodine in the IVC is concentrated
enough in the bile ducts to outline the ducts and gallstones within them. The IVC is rarely used because it has
been replaced by MRI cholangiography and endoscopic ultrasound . Moreover, occasional serious reactions to
the iodine-containing dye can occur, which rarely may result in the death of the patient.
What are the potential pitfalls of diagnosing gallstones?
Usually, it is not difficult to diagnose gallstones. Problems arise, however, because of the high prevalence of
silent gallstones and the occasional gallstone that is difficult to diagnose.
If a patient has symptoms that are typical for gallstones, for example, biliary colic, cholecystitis, or pancreatitis,
and has gallstones on ultrasonography, little else usually can or needs to be done to demonstrate that the
gallstones are causing the episode unless the patient has complicating medical issues.
If episodes are not typical for gallstones, however, any gallstones found may be silent. These silent gallstones
may be innocent bystanders, and most importantly, removing the gallbladder surgically will not treat the acute
problem or prevent further episodes. In addition, the real cause of the problem will not be pursued. In such a
situation, there is a need to have further evidence, other than their mere presence, that the gallstones are causing
the episode. Such evidence can be obtained during an episode or shortly thereafter.
If ultrasonography can be done during an episode of pain or inflammation caused by gallstones, it may be
possible to demonstrate an enlarged gallbladder or bile duct caused by obstruction of the ducts by the gallstone.
This is likely to require ultrasonography again after the episode has resolved in order to demonstrate that the
gallbladder indeed was larger during the episode than before or after the episode. It is easier to obtain the
necessary ultrasonography if the episode lasts several hours, but it is much more difficult to obtain
ultrasonography rapidly enough if the episode lasts only 15 minutes.
Another approach is to test the blood for abnormal liver and pancreatic enzymes. The advantage here is that the
enzymes, though not always elevated, can be elevated during and for several hours after an episode of gallstone-
related pain or inflammation, so they might be abnormal even after the episode has subsided. It is important to
remember, however, that the enzymes are not specific for gallstones, and it is necessary to exclude other liver
and pancreatic causes for abnormal enzymes.
Sometimes, episodes of pain or inflammation may be more or less typical of gallstones, but transabdominal
ultrasonography may not demonstrate either gallstones or another cause of the episodes. In this case, it is
necessary to decide whether suspicion is high or low for gallstones as a cause of the episodes. If suspicion is low
because of less typical symptoms, it may be reasonable only to repeat the ultrasonography, obtain an OCG,
and/or test for abnormalities of liver or pancreatic enzymes. If suspicion is high because of more typical
symptoms, it is reasonable to go even further with endoscopic ultrasonography, ERCP, and duodenal drainage.
Prior to these "invasive" procedures, some physicians recommend MRCP; however, the exact role of MRCP is
not yet clear.
What are the potential pitfalls of diagnosing gallstones?
Usually, it is not difficult to diagnose gallstones. Problems arise, however, because of the high prevalence of
silent gallstones and the occasional gallstone that is difficult to diagnose.
If a patient has symptoms that are typical for gallstones, for example, biliary colic, cholecystitis, or pancreatitis,
and has gallstones on ultrasonography, little else usually can or needs to be done to demonstrate that the
gallstones are causing the episode unless the patient has complicating medical issues.
If episodes are not typical for gallstones, however, any gallstones found may be silent. These silent gallstones
may be innocent bystanders, and most importantly, removing the gallbladder surgically will not treat the acute
problem or prevent further episodes. In addition, the real cause of the problem will not be pursued. In such a
situation, there is a need to have further evidence, other than their mere presence, that the gallstones are causing
the episode. Such evidence can be obtained during an episode or shortly thereafter.
If ultrasonography can be done during an episode of pain or inflammation caused by gallstones, it may be
possible to demonstrate an enlarged gallbladder or bile duct caused by obstruction of the ducts by the gallstone.
This is likely to require ultrasonography again after the episode has resolved in order to demonstrate that the
gallbladder indeed was larger during the episode than before or after the episode. It is easier to obtain the
necessary ultrasonography if the episode lasts several hours, but it is much more difficult to obtain
ultrasonography rapidly enough if the episode lasts only 15 minutes.
Another approach is to test the blood for abnormal liver and pancreatic enzymes. The advantage here is that the
enzymes, though not always elevated, can be elevated during and for several hours after an episode of gallstone-
related pain or inflammation, so they might be abnormal even after the episode has subsided. It is important to
remember, however, that the enzymes are not specific for gallstones, and it is necessary to exclude other liver
and pancreatic causes for abnormal enzymes.
Sometimes, episodes of pain or inflammation may be more or less typical of gallstones, but transabdominal
ultrasonography may not demonstrate either gallstones or another cause of the episodes. In this case, it is
necessary to decide whether suspicion is high or low for gallstones as a cause of the episodes. If suspicion is low
because of less typical symptoms, it may be reasonable only to repeat the ultrasonography, obtain an OCG,
and/or test for abnormalities of liver or pancreatic enzymes. If suspicion is high because of more typical
symptoms, it is reasonable to go even further with endoscopic ultrasonography, ERCP, and duodenal drainage.
Prior to these "invasive" procedures, some physicians recommend MRCP; however, the exact role of MRCP is
not yet clear.
How are gallstones treated?
Observation
Most gallstones are silent.
 If silent gallstones are discovered in an individual at age 65 (or older), the chance of developing
symptoms from the gallstones is only 20% (or less) assuming a life span of 75 years. In this instance, it
is reasonable not to treat the individual.
 Among younger individuals, no treatment also might be appropriate if the individuals have serious,
life-threatening diseases, for example, serious heart disease, that are likely to shorten their life span.
 On the other hand, in healthy young individuals, treatment should be considered even for silent
gallstones because the individuals' chances of developing symptoms from the gallstones over a lifetime
will be higher. Once symptoms begin, treatment should be recommended since further symptoms are
likely and more serious complications can be prevented.
Cholecystectomy

Cholecystectomy (removal of the gallbladder surgically) is the standard treatment for gallstones in the
gallbladder. Surgery may be done through a large abdominal incision or laparoscopically through small
punctures of the abdominal wall. Laparoscopic surgery results in less pain and a faster recovery.
Cholecystectomy has a low rate of complications, but serious complications such as damage to the bile ducts
and leakage of bile occasionally occur. There also is risk associated with the general anesthesia that is necessary
for either type of surgery. Problems following removal of the gallbladder are few. Digestion is not affected, and
no change in diet is necessary. Chronic diarrhea occurs in approximately 10% of patients.
Sphincterotomy and extraction of gallstones

Sometimes a gallstone may be stuck in the hepatic or common bile ducts. In such situations, there usually are
gallstones in the gallbladder as well, and cholecystectomy is necessary. It may be possible to remove the
gallstone stuck in the duct at the time of surgery, but this may not always be possible. An alternative means for
removing gallstones in the duct before or after cholecystectomy is with sphincterotomy followed by extraction
of the gallstone.
Sphincterotomy involves cutting the muscle of the common bile duct (sphincter) at the junction of the common
bile duct and the duodenum in order to allow easier access to the common bile duct. The cutting is done with an
electrosurgical instrument passed through the same type of endoscope that is used for ERCP. After the sphincter
is cut, instruments may be passed through the endoscope and up into the hepatic and common bile ducts to grab
and pull out the gallstone or to crush the gallstone. It also is possible to pass a lithotripsy instrument that uses
high frequency sound waves to break up the gallstone. Complications of sphincterotomy and extraction of
gallstones include the general anesthesia, perforation of the bile ducts or duodenum, bleeding, and pancreatitis.
Oral dissolution therapy

It is possible to dissolve some cholesterol gallstones with medication taken orally. The medication is a naturally-
occurring bile acid called ursodeoxycholic acid or ursodiol (Actigall, Urso). Bile acids are one of the detergents
that the liver secretes into bile to dissolve cholesterol. Although one might expect therapy with ursodiol to work
by increasing the amount of bile acids in bile and thereby cause the cholesterol in gallstones to dissolve, the
mechanism of ursodiol's action actually is different. Ursodiol reduces the amount of cholesterol secreted in bile.
The bile then has less cholesterol and becomes capable of dissolving the cholesterol in the gallstones.
There are important limitations to the use of ursodiol:
 It is only effective for cholesterol gallstones and not pigment gallstones.
 It works only for small gallstones, less than 1-1.5 cm in diameter.
 It takes one to two years for the gallstones to dissolve, and many of the gallstones reform following
cessation of treatment.
Due to these limitations, ursodiol generally is used only in individuals with smaller gallstones that are likely to
have a very high cholesterol content and who are at high risk for surgery because of ill health. It also is
reasonable to use ursodiol in individuals whose gallstones were likely to have formed because of a transient
event, for example, rapid loss of weight, since the gallstones would not be expected to recur following
successful dissolution.
Extracorporeal shock-wave lithotripsy

Extracorporeal shock-wave lithotripsy (ESWL) is an infrequently used method for treating gallstones,
particularly those lodged in bile ducts. ESWL generators produces shock waves outside of the body that are then
focused on the gallstone. The shock waves shatter the gallstone, and the resulting pieces of the gallstone either
drain into the intestine on their own or are extracted endoscopically as in sphincterotomy.
Prevention of gallstones
It would be better if gallstones could be prevented rather than treated. Prevention of cholesterol gallstones is
feasible since ursodiol, the bile acid medication that dissolves some cholesterol gallstones, also prevents them
from forming. The difficulty is identifying a group of individuals who are at high risk for developing cholesterol
gallstones during a relatively short period of time so that the duration of preventive treatment can be limited.
One such group is obese individuals losing weight rapidly with very low calorie diets or with surgery. The risk
of gallstones in this group is as high as 40%-60%. In fact, ursodiol has been shown in several studies to be very
effective at preventing gallstones in these individuals.
Can symptoms continue after gallstones are removed?
Removal of the gallbladder (cholecystectomy) should eliminate all gallstone-related symptoms except in three
situations:
1. gallstones were left in the ducts,
2. there were problems with the bile ducts in addition to gallstones, and
3. the gallstones were and are not the cause of the symptoms.
The possibility of gallstones in the ducts can be pursued with MRCP, endoscopic ultrasound, and ERCP. There
is only one problem with the ducts that can cause gallstone-like symptoms, and that is a rare condition called
sphincter of Oddi dysfunction, discussed below.
The common bile duct has a muscular wall. The last several centimeters of the common bile duct's muscle
immediately before the duct joins the duodenum comprise the sphincter of Oddi. The sphincter of Oddi controls
the flow of bile. Since the pancreatic duct usually joins the common bile duct shortly before it enters the
duodenum, the sphincter also controls the flow of fluid from the pancreatic duct. When the muscle of the
sphincter tightens, it shuts off the flow of bile and pancreatic fluid. When it relaxes, bile and pancreatic fluid
flow into the duodenum, for example, after a meal. The sphincter may become scarred, and the duct is narrowed
by the scarring. (The cause of the scarring is unknown.) The sphincter also may go into spasm intermittently. In
either case, the flow of bile and pancreatic fluid may intermittently stop abruptly, mimicking the effects of a
gallstone, particularly causing biliary colic and pancreatitis.
The diagnosis of sphincter of Oddi dysfunction can be difficult to make. The best diagnostic test requires an
endoscopic procedure with the same type of endoscope as ERCP. Instead of filling the ducts with dye, however,
the pressure within the sphincter is measured. If the pressure is abnormally high, scarring or spasm of the
sphincter are likely. The treatment for sphincter of Oddi dysfunction is sphincterotomy. (described previously).
Measurement of liver and pancreatic enzymes in the blood also may be useful for diagnosing sphincter
dysfunction.
What's new with gallstones?
It is clear that genetic factors are important in determining who gets gallstones. Current scientific studies are
directed at uncovering the specific genes that are responsible for gallstones. To date, 8-10 genes have been
identified as being associated with cholesterol gallstones, at least in animals that develop cholesterol gallstones.
Not surprisingly, the products of many of these genes control the production and secretion (by the liver) of
cholesterol, bile acids, and lecithin. The long-term goal is to be able to identify individuals who are genetically
at very high risk for cholesterol gallstones and to offer them preventive treatment. An understanding of the exact
mechanism(s) of gallstone formation also may result in new therapies for treatment and prevention.
Surgery for gallstones has undergone a major transition from requiring large abdominal incisions to requiring
only tiny incisions for laparoscopic instruments (laparoscopic cholecystectomy). It is possible that there will be
another transition. Surgeons are experimenting with a technique called natural orifice transluminal endoscopic
surgery (NOTES). NOTES is a new technique for accomplishing standard intraabdominal surgery, but access to
the abdomen is through a natural orifice - the mouth, anus or vagina.
Flexible endoscopic instruments similar to the flexible endoscopes presently being used widely are introduced
through the chosen orifice, through an incision somewhere inside the orifice (for example, the stomach), and
into the abdominal cavity. Thus, the only incision is within the body and not visible on the body's surface. There
are potential advantages to this type of surgery, but it is in the earliest stages of development, and it is unclear
what a future role for NOTES will be in gallbladder surgery. Nevertheless, series of patients have already been
described who have had their gallbladders removed via NOTES primarily through the vagina.
Gallstones At A Glance
 Gallstones are "stones" that form in the gallbladder or bile ducts.
 The common types of gallstones are cholesterol, black pigment, and brown pigment.
 Cholesterol gallstones occur more frequently among several ethnic groups and are associated with
female gender, obesity, pregnancy, oral hormonal therapy, rapid loss of weight, elevated blood
triglyceride levels, and Crohn's disease.
 Black pigment gallstones occur when there is increased destruction of red blood cells, and brown
pigment gallstones occur when there is slow flow and infection of bile.
 The majority of gallstones do not cause symptoms.
 The most common symptoms of gallstones are biliary colic and cholecystitis. Gallstones do not cause
intolerance to fatty foods, belching, abdominal distention, or gas.
 Complications of gallstones include cholangitis, gangrene, jaundice, pancreatitis, sepsis, fistula, and
ileus.
 Gallbladder sludge is associated with symptoms and complications of gallstones; however, like
gallstones, sludge usually does not cause problems.
 The best single test for diagnosing gallstones is transabdominal ultrasonography. Other tests include
endoscopic ultrasonography, magnetic resonance cholangio-pancreatography (MRCP),
cholescintigraphy (HIDA scan), endoscopic retrograde cholangio-pancreatography (ERCP), liver and
pancreatic blood tests, duodenal drainage, oral cholecystogram (OCG), and intravenous cholangiogram
(IVC).
 Gallstones are managed primarily with observation (no treatment) or removal of the gallbladder
(cholecystectomy). Less commonly used treatments include sphincterotomy and extraction of
gallstones, dissolution with oral medications, and extra-corporeal shock-wave lithotripsy (ESWL).
Prevention of cholesterol gallstones also is possible with oral medications.
 Symptoms of gallstones should stop following cholecystectomy. If they do not, it is likely that
gallstones were left in the ducts, there is a second problem within the bile ducts, or there is sphincter of
Oddi dysfunction.
 Continuing research is directed at uncovering the genes that are responsible for the formation of
gallstones.
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