What are gallstones?
Gallstones (often misspelled as gall stones, or gall stone) are stones that form in the gall (bile) within the gallbladder. (The gallbladder is a pear-shaped organ just below the liver that stores the bile secreted by the liver.) 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 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 through 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 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 in the 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 in 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 show that genetic factors are important in determining who develops gallstones. Among non-identical pair of twins (who share 50% of their genes with each other), both individuals in a pair have gallstones 8% of the time. Among identical pair 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 are primarily of made up of cholesterol. They are the most common type of gallstone, comprising 80% of gallstones in individuals in Europe and the Americas. Cholesterol is one of the substances that liver cells secrete into bile. (Secretion of cholesterol into bile is an important mechanism by 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 detergent-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 gallstones.
There are two other processes that promote the formation of cholesterol gallstones though neither process is able to form cholesterol gallstones by itself. The first is an 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 stay in the gallbladder longer than normal so that there is more time for cholesterol particles to form and grow.
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 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 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.
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:
Gender: Gallstones occur more commonly in women than men.
Age: Gallstone prevalence increases with age.
Obesity: Obese individuals are more likely to form gallstones than thin individuals.
Pregnancy: Pregnancy increases the risk for cholesterol gallstones because during pregnancy, bile contains more cholesterol, and the gallbladder does not contract normally. Birth control pills and hormone therapy The increased levels of hormones caused by either treatment mimics pregnancy.
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.
Crohn’s disease: Individuals with Crohn’s disease of the terminalileum 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. As a result there is not enough bile acids to keep cholesterol dissolved in bile, resulting in gallstone formation.
Increased blood triglycerides. Gallstones occur more frequently in individuals with elevated blood triglyceride levels.
Risk for pigment gallstones. Black pigment gallstones form whenever an increased load of bilirubin reaches the liver. This occurs when there is increased destruction of red blood cells, as in diseases such as sickle cell disease and thalassemia. Black pigment gallstones also are more common in patients with cirrhosis of the liver. Brown pigment gallstones form when there is stasis of bile (decreased flow), for example, when there are narrow or 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.”) The gallstones often are found as a result of tests (for example, ultrasound orX-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 duct or common bile duct) 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 duct 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 is 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 causing obstruction.
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, in some individuals the episodes tend to remain frequent while in others they are 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 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 bile 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 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 high fever and elevated white blood cell counts. Cholangitis may result in anabscess within the liver or sepsis. (See discussion of sepsis that follows.)
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 is a condition in which bilirubin accumulates in the body. Bilirubin is brownish-black in color but is 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, 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 means inflammation of the pancreas. The two most common causes of pancreatitis are alcoholism and gallstones. The pancreas surrounds the common bile duct as it 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 is a condition in which bacteria from any source within the body, including the gallbladder or bile ducts, enter 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 adrop in blood pressure.
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 the common bile 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. 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 is a condition in which there is an obstruction to the flow of 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 muscles 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 at the site 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 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.
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