Cholelithiasis is the pathologic state of stones or calculi within the gallbladder lumen. A common digestive disorder worldwide, the annual overall cost of cholelithiasis is approximately $5 billion in the United States, where 75-80% of gallstones are of the cholesterol type, and approximately 10-25% of gallstones are bilirubinate of either black or brown pigment. In Asia, pigmented stones predominate, although studies have shown an increase in cholesterol stones in the Far East. (See the images below.)

Cholelithiasis. Ultrasound image obtained with a 4-MHz transducer demonstrates a stone in the gallbladder neck with typical acoustic shadow.

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Cholelithiasis. Ultrasound image obtained with a 4-MHz transducer demonstrates a stone in the gallbladder neck with typical acoustic shadow.

Cholelithiasis. A noncalcified filling defect is present in the gallbladder on this contrast-enhanced CT. Ultrasound examination confirmed a mobile stone and excluded the other possible diagnoses of polyp or tumor.

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Cholelithiasis. A noncalcified filling defect is present in the gallbladder on this contrast-enhanced CT. Ultrasound examination confirmed a mobile stone and excluded the other possible diagnoses of polyp or tumor.

Cholelithiasis. Multiple tiny gallstones appear as signal void-filling defects in the gallbladder on this T1-weighted spoiled gradient-echo sequence.

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Cholelithiasis. Multiple tiny gallstones appear as signal void-filling defects in the gallbladder on this T1-weighted spoiled gradient-echo sequence.

Each type of stone has a particular pathophysiology and specific set of risk factors that alter the equilibrium and solubility of the components of bile. Biliary microlithiasis refers to the presence of gallbladder calculi smaller than 2 mm, which is too small to be detected by current imaging techniques.

Although it originally referred to ultrasonographic findings of echogenic, nonshadowing, microscopic material within the gallbladder, the term biliary sludge currently indicates a precipitate of microcrystals occurring in bile with high mucous content. Sludge may contain microliths. Milk of calcium bile, a calcium carbonate precipitate opaque on plain radiographs, may coexist with cholelithiasis.

Preferred examination

Ultrasonography (US) is the procedure of choice for identifying gallstones. Current high-resolution, real-time US can identify gallstones as small as 2 mm, with a sensitivity greater than 95%. The technique is rapid, noninvasive, can be performed at the bedside, and does not involve ionizing radiation.1

Limitations of techniques

Only 15-20% of stones are visible on plain radiographs.

On oral cholecystograms, nonvisualization of the gallbladder may occur in malabsorption, gastric outlet obstruction, inflammatory bowel disease, ileal disease, and liver disease, and in some patients with chronic cholecystitis. Calcified stones may be missed in an opacified gallbladder. Side effects to contrast may occur.

False negatives may occur on ultrasonograms when small stones are in the presence of biliary sludge. US is operator-dependent. Inadequate visualization of the gallbladder may occur in obese or contracted patients or in patients with abdominal wounds.

Only 74-79% of gallstones are identified in patients with computed tomography (CT) scanning. CT is not a screening tool for uncomplicated cholelithiasis.

Magnetic resonance imaging (MRI) is not a screening tool. Stones may be incidental findings on abdominal MRI.

For excellent patient education resources, see eMedicine's Liver, Gallbladder, and Pancreas Center and Cholesterol Center. Also, visit eMedicine's patient education article Gallstones.

GallstoneFrom Wikipedia, the free encyclopedia

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Gallstone

Classification and external resources

gallstones

ICD-10 K 80.

ICD-9 574

OMIM 600803

DiseasesDB 2533

MedlinePlus 000273

eMedicine emerg/97

MeSH D042882

Gall bladder opened to show numerous gallstones. Their brownish to greenish color suggest they are cholesterol calculi.

In medicine, gallstones (choleliths) are crystalline bodies formed within the body by accretion or concretion of normal or abnormal bile components.

Gallstones can occur anywhere within the biliary tree, including the gallbladder and the common bile duct. Obstruction of the common bile duct is choledocholithiasis; obstruction of the biliary tree can cause jaundice; obstruction of the outlet of the pancreatic exocrine system can cause pancreatitis. Cholelithiasis is the presence of stones in the gallbladder or bile ducts: chole- means "bile", lithia means "stone", and -sis means "process".

Contents[hide]

1 Characteristics o 1.1 Size

o 1.2 Content

1.2.1 Mixed stones

1.2.2 Pseudoliths

2 Causes

o 2.1 Pigment gallstones

o 2.2 Cholesterol gallstones

3 Symptoms

4 Treatment

o 4.1 Medical options

o 4.2 Surgical options

5 Temporary Relief

6 Value of animal gallstones

7 References

8 External links

[edit] Characteristics

[edit] Size

A gallstone's size can vary and may be as small as a sand grain or as large as a golf ball. The gallbladder may develop a single, often large stone or many smaller ones. They may occur in any part of the biliary system.

[edit] Content

Gallstones

Gallstones have different appearance, depending on their contents. On the basis of their contents, gallstones can be subdivided into the two following types:

Cholesterol stones are usually green, but are sometimes white or yellow in color. They are made primarily of cholesterol, the proportion required for classification as a cholesterol stone being either 70% (Japanese classification system) or 80% (US system).[1]

Pigment stones are small, dark stones made of bilirubin and calcium salts that are found in bile. They contain less than 20% of cholesterol. Risk factors for pigment stones include hemolytic anemia (such as sickle cell anemia and hereditary spherocytosis), cirrhosis, and biliary tract infections.

The proportions of these different types of stone found varies between samples, and is thought to be affected by the age and ethnic or regional origin of the patients.[2]

[edit] Mixed stones

All stones are of mixed content to some extent. Those classified as mixed, however, contain between 30% and 70% of cholesterol. In most cases the other majority constituent is calcium salts such as calcium carbonate, palmitate phosphate, and/or bilirubinate. Because of their calcium content, they can often be visualized radiographically.

[edit] Pseudoliths

Also known as "Fake stones," they are sludge-like gallbladder secretions that act like a stone.

[edit] Causes

Researchers believe that gallstones may be caused by a combination of factors, including inherited body chemistry, body weight, gallbladder motility (movement), and perhaps diet.

[edit] Pigment gallstones

Most commonly seen in the developing world. People with erythropoietic protoporphyria (EPP) are at increased risk to develop gallstones.[3]

Conditions causing hemolytic anemia can cause pigment gallstones.[4]

Risk factors for pigmented stones:

1. Chronic hemolytic syndromes2. Biliary infection

o Microbial beta-glucuronidases deconjugate the bilirubin in the biliary tract

3. Gastrointestinal disorders

[edit] Cholesterol gallstones

Cholesterol gallstones develop when bile contains too much cholesterol and not enough bile salts. Besides a high concentration of cholesterol, two other factors seem to be important in causing gallstones. The first is how often and how well the gallbladder contracts; incomplete and infrequent emptying of the gallbladder may cause the bile to become overconcentrated and contribute to gallstone formation. The second factor is the presence of proteins in the liver and bile that either promote or inhibit cholesterol crystallization into gallstones.

In addition, increased levels of the hormone estrogen as a result of pregnancy, hormone therapy, or the use of combined (estrogen-containing) forms of hormonal contraception, may increase cholesterol levels in bile and also decrease gallbladder movement, resulting in gallstone formation.

No clear relationship has been proven between diet and gallstone formation; however, low-fiber, high-cholesterol diets and diets high in starchy foods have been suggested as contributing to gallstone formation. Other nutritional factors that may increase risk of gallstones include rapid weight loss, constipation, eating fewer meals per day, eating less fish, and low intakes of the nutrients folate, magnesium, calcium, and vitamin C.[5] On the other hand, wine and whole grain bread may decrease the risk of gallstones.[6]

The common mnemonic for gallstone risk factors refer to the "four Fs": fat (i.e., overweight), forty (an age near or above 40), female, and fertile (pre-menopausal);[7] a fifth F, fair is sometimes added to indicate that the condition is more prevalent in Caucasians. The absence of these risk factors does not, however, preclude the formation of gallstones.

[edit] Symptoms

Gallstones usually remain asymptomatic initially. [9] They start developing symptoms once the stones reach a certain size (>8 mm).[10] A main symptom of gallstones is commonly referred to as a gallstone "attack", also known as biliary colic, in which a person will experience intense pain in the upper abdominal region that steadily increases for approximately 30 minutes to several hours. A patient may also experience pain in the back, ordinarily between the shoulder blades, or pain under the right shoulder. In some cases, the pain develops in the lower region of the abdomen, nearer to the pelvis, but this is less common.[citation needed] Nausea and vomiting may occur. Patients characteristically exhibit a positive Murphy's sign, (the patient is instructed to breathe in while the gallbladder is deeply palpated). If the gallbladder is inflamed, the patient will abruptly stop inhaling due to the pain, resulting in a positive Murphy's sign.

These attacks are sharp and intensely painful, similar to that of a kidney stone attack. Often, attacks occur after a particularly fatty meal and almost always happen at night. Other symptoms include abdominal bloating, intolerance of fatty foods, belching, gas and indigestion. If the above symptoms coincide with chills, low-grade fever, yellowing of the skin or eyes and/or clay-colored stool, a doctor should be consulted immediately.[11]

Some people who have gallstones are asymptomatic and do not feel any pain or discomfort. These gallstones are called "silent stones" and do not affect the gallbladder or other internal organs. They do not need treatment.[11]

[edit] Treatment

[edit] Medical options

Cholesterol gallstones can sometimes be dissolved by oral ursodeoxycholic acid, but it may be required that the patient takes this medication for up to two years.[12] Gallstones may recur however, once the drug is stopped. Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy (ERS) following endoscopic retrograde cholangiopancreatography (ERCP). Gallstones can be broken up using a procedure called lithotripsy (extracorporeal shock wave lithotripsy).[12] which is a method of concentrating ultrasonic shock waves onto the stones to break them into tiny pieces. They are then passed

safely in the feces. However, this form of treatment is only suitable when there are a small number of gallstones.

[edit] Surgical options

Cholecystectomy (gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. Only symptomatic patients must be indicated to surgery. The lack of a gall bladder may have no negative consequences in many people. However, there is a significant portion of the population — between 5 and 40% — who develop a condition called postcholecystectomy syndrome [13] which may cause gastrointestinal distress and persistent pain in the upper right abdomen. In addition, as many as 20% of patients develop chronic diarrhea.[14]

There are two surgical options for cholecystectomy:

Open cholecystectomy: This procedure is performed via an incision into the abdomen (laparotomy) below the right lower ribs. Recovery typically consists of 3–5 days of hospitalization, with a return to normal diet a week after release and normal activity several weeks after release.[15]

Laparoscopic cholecystectomy: This procedure, introduced in the 1980s,[16] is performed via three to four small puncture holes for a camera and instruments. Post-operative care typically includes a same-day release or a one night hospital stay, followed by a few days of home rest and pain medication.[15] Laparoscopic cholecystectomy patients can generally resume normal diet and light activity a week after release, with some decreased energy level and minor residual pain continuing for a month or two. Studies have shown that this procedure is as effective as the more invasive open cholecystectomy, provided the stones are accurately located by cholangiogram prior to the procedure so that they can all be removed.[citation needed]

[edit] Temporary Relief

Some patients have anecdotally reported that symptoms can be temporarily reduced by drinking several glasses of water when experiencing gallstone pain. This approach will not eliminate the gallstones or improve the patient's condition in the long term.

[edit] Value of animal gallstones

Gallstones are a valuable by-product of meat processing, fetching up to US$32–per–gram in their use as a purported antipyretic and antidote in the folk remedies of some cultures, particularly in China. The finest gallstones tend to be sourced from old dairy cows, which are called Niu-Huang (牛黄，yellow thing of oxen) in Chinese. Those obtained from dogs, called Gou-Bao (狗宝，treasure of dogs) in Chinese, are also used today. Much as in the manner of diamond mines, slaughterhouses carefully scrutinize offal department workers for gallstone theft.[17]

Background

Gallstones are concretions that form in the biliary tract, usually in the gallbladder (see image below).

Cholelithiasis. A gallbladder filled with gallstones (examined extracorporally after laparoscopic cholecystectomy [LC]).

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Cholelithiasis. A gallbladder filled with gallstones (examined extracorporally after laparoscopic cholecystectomy [LC]).

Their development is insidious, and they may remain asymptomatic for decades. Migration of gallstones may lead to occlusion of the biliary and pancreatic ducts, causing pain (biliary colic) and producing acute complications, such as acute cholecystitis, ascending cholangitis, or acute pancreatitis.1,2 Chronic gallstone disease may lead to fibrosis and loss of function of the gallbladder and predisposes to

gallbladder cancer. Excision of the gallbladder (cholecystectomy) to cure gallstone disease is among the most frequently performed abdominal surgical procedures.

Pathophysiology

Gallstone formation occurs because certain substances in bile are present in concentrations that approach the limits of their solubility. When bile is concentrated in the gallbladder, it can become supersaturated with these substances, which then precipitate from solution as microscopic crystals. The crystals are trapped in gallbladder mucus, producing gallbladder sludge. Over time, the crystals grow, aggregate, and fuse to form macroscopic stones. Occlusion of the ducts by sludge and stones produces the complications of gallstone disease.

The 2 main substances involved in gallstone formation are cholesterol and calcium bilirubinate.

Cholesterol gallstones

More than 80% of gallstones in the United States contain cholesterol as their major component. Liver cells secrete cholesterol into bile along with phospholipid (lecithin) in the form of small spherical membranous bubbles, termed unilamellar vesicles. Liver cells also secrete bile salts, which are powerful detergents required for digestion and absorption of dietary fats. Bile salts in bile dissolve the unilamellar vesicles to form soluble aggregates called mixed micelles. This happens mainly in the gallbladder, where bile is concentrated by reabsorption of electrolytes and water.

Compared with vesicles (which can hold up to 1 molecule of cholesterol for every molecule of lecithin), mixed micelles have a lower carrying capacity for cholesterol (about 1 molecule of cholesterol for every 3 molecules of lecithin). If bile contains a relatively high proportion of cholesterol to begin with, then as bile is concentrated, progressive dissolution of vesicles may lead to a state in which the cholesterol carrying capacity of the micelles and residual vesicles is exceeded. At this point, bile is supersaturated with cholesterol, and cholesterol monohydrate crystals may form. Thus, the main factors that determine whether cholesterol gallstones will form are: (1) the amount of cholesterol secreted by liver cells, relative to lecithin and bile salts, and (2) the degree of concentration and extent of stasis of bile in the gallbladder.

Calcium, bilirubin, and pigment gallstones

Bilirubin, a yellow pigment derived from the breakdown of heme, is actively secreted into bile by liver cells. Most of the bilirubin in bile is in the form of glucuronide conjugates, which are quite water soluble and stable, but a small proportion consists of unconjugated bilirubin. Unconjugated bilirubin, like fatty acids, phosphate, carbonate, and other anions, tends to form insoluble precipitates with calcium. Calcium enters bile passively along with other electrolytes.

In situations of high heme turnover, such as chronic hemolysis or cirrhosis, unconjugated bilirubin may be present in bile at higher than normal concentrations. Calcium bilirubinate may then crystallize from solution and eventually form stones. Over time, various oxidations cause

the bilirubin precipitates to take on a jet black color, and stones formed in this manner are termed black pigment stones. Black pigment stones represent 10-20% of gallstones in the United States.

Bile is normally sterile, but, in some unusual circumstances (eg, above a biliary stricture), it may become colonized with bacteria. The bacteria hydrolyze conjugated bilirubin, and the resulting increase in unconjugated bilirubin may lead to precipitation of calcium bilirubinate crystals. Bacterial hydrolysis of lecithin leads to the release of fatty acids, which complex with calcium and precipitate from solution. The resulting concretions have a claylike consistency and are termed brown pigment stones. Unlike cholesterol or black pigment stones, which form almost exclusively in the gallbladder, brown pigment stones often form de novo in the bile ducts. Brown pigment stones are unusual in the United States but are fairly common in some parts of Southeast Asia, possibly related to liver flukes.

Mixed gallstones

Cholesterol gallstones may become colonized with bacteria and can elicit gallbladder mucosal inflammation. Lytic enzymes from bacteria and leukocytes hydrolyze bilirubin conjugates and fatty acids. As a result, over time, cholesterol stones may accumulate a substantial proportion of calcium bilirubinate and other calcium salts, producing mixed gallstones. Large stones may develop a surface rim of calcium resembling an eggshell that may be visible on plain x-ray films.

Frequency

United States

Gallstones are uncommon in children. Beginning at puberty, the concentration of cholesterol in bile increases. After age 15 years, the prevalence of gallstones in US women increases by about 1% per year; in men, the rate is less, about 0.5% per year. The incidence in women falls with menopause, but new stone formation in men and women continues at a rate of about 0.4% per year until late in life.

The lifetime risk of developing gallstones in white individuals is 50% for women and 30% for men. Prevalence in Mexican Americans and Native Americans is similar, whereas black individuals have a somewhat lower risk.

International

The prevalence of cholesterol cholelithiasis in other Western cultures is similar to that in the United States, but it appears to be somewhat lower in Asia and Africa.

A Swedish epidemiologic study found that the incidence of gallstones was 1.39 per 100 person-years.3 In a study of randomly selected individuals aged 35-85 years in a general population who had been screened previously with ultrasonography and found to have no gallbladder stones, Halldestam et al reexamined 503 study subjects after a minimum interval of 5 years. On reexamination, 8.3% (42/503) had developed gallstones. Gallstone development was related to

length of follow-up and low-density lipoprotein (LDL) cholesterol levels, and inversely related to alcohol consumption.3

Mortality/Morbidity

Each year, in the United States, approximately 500,000 people develop symptoms or complications of gallstones requiring cholecystectomy. Gallstone disease is responsible for about 10,000 deaths per year in the United States. About 7000 deaths are attributable to acute gallstone complications, such as acute pancreatitis. About 2000-3000 deaths are caused by gallbladder cancers (80% of which occur in the setting of gallstone disease with chronic cholecystitis). Although gallstone surgery is relatively safe, cholecystectomy is a very common procedure, and its rare complications result in several hundred deaths each year.

Race

White individuals, Mexican Americans, and Native Americans have a relatively high prevalence of gallstones. Gallstone disease is less common in Asians and Africans and their descendants.

Sex

Women are more likely to develop cholesterol gallstones than men, especially during their reproductive years, when the incidence of gallstones in women is 2 to 3 times that in men. The difference appears to be attributable mainly to estrogen, which increases biliary cholesterol secretion.4 Pigment gallstones affect men and women equally.

Age

Gallstones continue to form throughout adult life, and the prevalence is greatest at advanced age.

Clinical

History

Gallstone disease may be thought of as having the following 4 stages: (1) the lithogenic state, in which conditions favor gallstone formation; (2) asymptomatic gallstones; (3) symptomatic gallstones, characterized by episodes of biliary colic; and (4) complicated cholelithiasis. Symptoms and complications of gallstone disease result from effects occurring within the gallbladder or from stones that escape the gallbladder to lodge in the common bile duct.

Asymptomatic gallstoneso Gallstones may be present in the gallbladder for decades without causing symptoms or

complications. In patients with asymptomatic gallstones discovered incidentally, the likelihood of developing symptoms or complications is 1-2% per year. In most cases, asymptomatic gallstones do not require any treatment.

o Because they are common, gallstones often coexist with other gastrointestinal conditions. There is little evidence to support a causal association between gallstones

and chronic abdominal pain, heartburn, postprandial distress, bloating, flatulence, constipation, or diarrhea. Dyspepsia that occurs reproducibly following ingestion of fatty foods is often wrongly attributed to gallstones, when irritable bowel syndrome or gastroesophageal reflux is the true culprit. Gallstones discovered during an evaluation for nonspecific symptoms are usually innocent bystanders, and treatment directed at the gallstones is unlikely to relieve these symptoms.

Biliary colic

o Pain termed biliary colic occurs when gallstones fortuitously impact in the cystic duct during a gallbladder contraction, increasing gallbladder wall tension. In most cases, the pain resolves over 30 to 90 minutes as the gallbladder relaxes and the obstruction is relieved.

o Episodes of biliary colic are sporadic and unpredictable. The patient localizes the pain to the epigastrium or right upper quadrant and may describe radiation to the right scapular tip. From onset, the pain increases steadily over about 10 to 20 minutes and then gradually wanes. The pain is constant in nature and is not relieved by emesis, antacids, defecation, or positional changes. It may be accompanied by nausea and vomiting.

Complications of gallbladder stones

o Acute cholecystitis occurs when persistent stone impaction in the cystic duct causes the gallbladder to become distended and progressively inflamed. Patients experience the pain of biliary colic, but, instead of resolving spontaneously, the pain persists and worsens. Overgrowth of colonizing bacteria in the gallbladder often occurs, and, in severe cases, accumulation of pus in the gallbladder, termed gallbladder empyema, occurs. The gallbladder wall may become necrotic, resulting in perforation and pericholecystic abscess. Acute cholecystitis is considered a surgical emergency, although pain and inflammation may subside with conservative measures, such as hydration and antibiotics.

o Chronically, gallstones may cause progressive fibrosis of the gallbladder wall and loss of gallbladder function, termed chronic cholecystitis. The pathogenesis of this complication is not completely understood. Repeated attacks of acute cholecystitis may play a role, as may localized ischemia produced by pressure of stones against the gallbladder wall. The chronically fibrotic gallbladder may become shrunken and adherent to adjacent viscera.

o Gallbladder adenocarcinoma is an uncommon cancer that usually develops in the setting of gallstones and chronic cholecystitis. Gallbladder cancers commonly invade the adjacent liver and common bile duct, producing jaundice. The prognosis is poor unless the cancer is localized to the gallbladder, in which case cholecystectomy may be curative.

o Occasionally, a large stone may erode through the wall of the gallbladder into an adjacent viscus (typically the duodenum), producing a cholecystoenteric fistula. The stone, if sufficiently large, may obstruct the small intestine, usually at the level of the ileum, a phenomenon termed gallstone ileus.

Complications of stones in the common bile duct

o Gallstones are initially retained in the gallbladder by the spiral valves of the cystic duct. Following episodes of gallstone impaction in the cystic duct, these valves may become obliterated and stones may pass into the common bile duct. Patients who have passed one stone tend to pass more stones over the subsequent months.

o Stones in the common bile duct may be asymptomatic, but, more commonly, they impact distally in the ampulla of Vater. This may produce biliary colic indistinguishable from that caused by cystic duct stones. Because impaction of common bile duct stones occludes the flow of bile from the liver to the intestine, pressure rises in the intrahepatic bile ducts, leading to increased liver enzymes and jaundice.

o Bacterial overgrowth in stagnant bile above an obstructing common duct stone produces purulent inflammation of the liver and biliary tree, termed ascending cholangitis. Characteristic features include the Charcot triad of fever, jaundice, and right upper quadrant pain. Patients may rapidly develop septic shock unless ductal obstruction is relieved.

o A stone impacted in the ampulla of Vater may transiently obstruct the pancreatic duct, leading to in situ activation of pancreatic proteases and triggering an attack of acute pancreatitis.

o Stone impaction in the distal common bile duct is often relieved spontaneously within hours to days by passage of the stone into the intestine.

Physical

Patients with the lithogenic state or asymptomatic gallstones have no abnormal findings on physical examination.

During attacks of biliary colic, and especially in acute cholecystitis, patients may experience tenderness to palpation over the gallbladder. This can be elicited by having the patient inhale while the examiner maintains steady pressure below the right costal margin (Murphy sign). Localized rebound tenderness, guarding, or rigidity may occur with pericholecystic inflammation.

Patients with acute cholecystitis, ascending cholangitis, or acute pancreatitis, in addition to abdominal pain, may exhibit fever and may be tachycardic and hypotensive. In severe cases, bowel sounds are often absent or hypoactive.

Choledocholithiasis with obstruction of the common bile duct produces cutaneous and scleral icterus that evolves over hours to days as bilirubin accumulates.

The Charcot triad of severe right upper quadrant tenderness with jaundice and fever is characteristic of ascending cholangitis.

Acute gallstone pancreatitis is often characterized by epigastric tenderness. In severe cases, retroperitoneal hemorrhage may produce ecchymoses of the flanks and periumbilical ecchymoses (Cullen sign and Grey-Turner sign).

Causes

Cholesterol gallstones, black pigment gallstones, and brown pigment gallstones have different pathogenesis and different risk factors, which will be discussed separately.

Cholesterol gallstones are associated with female gender, European or Native American ancestry, and increasing age, as discussed above. Other risk factors include the following:

o Obesity: The metabolic syndrome of truncal obesity, insulin resistance, type II diabetes mellitus, hypertension, and hyperlipidemia is associated with increased hepatic cholesterol secretion and is a major risk factor for the development of cholesterol gallstones.

o Pregnancy: Cholesterol gallstones are more common in women who have experienced multiple pregnancies. A major contributing factor is thought to be the high progesterone levels of pregnancy. Progesterone reduces gallbladder contractility, leading to prolonged retention and greater concentration of bile in the gallbladder.

o Gallbladder stasis: Other causes of gallbladder stasis associated with increased risk of gallstones include high spinal cord injuries, prolonged fasting with total parenteral nutrition, and rapid weight loss associated with severe caloric and fat restriction (eg, diet, gastric bypass surgery).

o Drugs: Estrogens administered for contraception or for treatment of prostate cancer increase the risk of cholesterol gallstones. Clofibrate and other fibrate hypolipidemic drugs increase hepatic elimination of cholesterol via biliary secretion and appear to increase the risk of cholesterol gallstones. Somatostatin analogues appear to predispose to gallstones by decreasing gallbladder emptying.

o Heredity: About 25% of the predisposition to cholesterol gallstones appears to be hereditary, as judged from studies of identical and fraternal twins. At least a dozen genes may contribute to the risk. A rare syndrome of low phospholipid-associated cholelithiasis occurs in individuals with a hereditary deficiency of the biliary transport protein required for lecithin secretion.

Black pigment gallstones occur disproportionately in individuals with high heme turnover. In most cases, however, no risk factor can be identified.

o Disorders of hemolysis associated with pigment gallstones include sickle cell anemia, hereditary spherocytosis, and beta-thalassemia.

o In cirrhosis, portal hypertension leads to splenomegaly. This, in turn, causes red cell sequestration, leading to a modest increase in hemoglobin turnover. About half of all cirrhotic patients have pigment gallstones.

Prerequisites for formation of brown pigment gallstones include colonization of bile with bacteria and intraductal stasis. In the United States, this combination is most often encountered in patients with postsurgical biliary strictures or choledochal cysts. In hepatolithiasis, a condition encountered mainly in rice-growing regions of East Asia, intraductal formation of brown pigment stones accompanies multiple strictures throughout intrahepatic and extrahepatic bile

ducts. This condition causes recurrent cholangitis and predisposes to biliary cirrhosis and cholangiocarcinoma. The etiology is unknown, but liver flukes have been implicated.

Background

Gallbladder disease is one of the most common gastrointestinal disorders in the United States. The spectrum of gallbladder disease ranges from asymptomatic cholelithiasis to gallbladder (or biliary) colic, cholecystitis, choledocholithiasis, and cholangitis. Further complications of gallbladder disease include gallstone pancreatitis, gallstone ileus, biliary cirrhosis, and gallbladder cancer.

Cholelithiasis is the presence of gallstones in the gallbladder. Biliary colic is pain caused by a stone temporarily obstructing the cystic duct. Cholecystitis is inflammation of the gallbladder from obstruction of the cystic duct. Choledocholithiasis is the presence of a stone in the common bile duct.

Common bile duct stone (choledocholithiasis). The sensitivity of transabdominal ultrasonography for choledocholithiasis is approximately 75% in the presence of dilated ducts and 50% for nondilated ducts. Image courtesy of DT Schwartz.

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Common bile duct stone (choledocholithiasis). The sensitivity of transabdominal ultrasonography for choledocholithiasis is approximately 75% in the presence of dilated ducts and 50% for nondilated ducts. Image courtesy of DT Schwartz.

Cholangitis occurs when a gallstone obstructs the biliary or hepatic ducts, causing inflammation and infection.

This article focuses on the pathophysiology and epidemiology of gallstones and biliary colic. Cholecystitis, cholangitis, and gallstone pancreatitis are covered in other articles.

Pathophysiology

Gallstones are rocklike collections of material that form inside the gallbladder. Different types exist, and they are categorized by their primary composition; cholesterol stones are most common (75-80% in the United States) followed by pigment, then mixed stones. The stones form when there is an imbalance or change in the composition of bile.

Normally, bile acids, lecithin, and phospholipids help to maintain cholesterol solubility in bile. When the ratio of cholesterol to biles acids or phospholipids is increased, bile becomes supersaturated with cholesterol; it crystallizes and forms a nidus for stone formation. Calcium and pigment also may be incorporated in the stone. Impaired gallbladder motility, biliary stasis, and bile content predispose people to the formation of gallstones.

Gallbladder sludge is crystallization within bile without stone formation. Sludge may be a step in the formation of stones, or it may occur independently. Five to fifteen percent of patients with acute cholecystitis present without stones (acalculous cholecystitis). This typically occurs in patients with prolonged illness, such as those with major trauma or with prolonged ICU stays.

Sludge in the gallbladder. Note the lack of shadowing. Image courtesy of DT Schwartz.

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Sludge in the gallbladder. Note the lack of shadowing. Image courtesy of DT Schwartz.

Pigment stones, which comprise 15% of gallstones, are formed by the crystallization of calcium bilirubinate. Diseases that lead to increased destruction of red blood cells (hemolysis), abnormal metabolism of hemoglobin (cirrhosis), or infections (including parasitic) predispose people to pigment stones. Black stones and brown stones exist. Black stones are found in people with hemolytic disorders. Brown stones are found in the intrahepatic or extrahepatic duct. They are associated with infection in the gallbladder and commonly are found in people of Asian descent.

Gallstone differentiation is an important consideration in management; cholesterol stones are more likely to respond to nonsurgical management than are pigment or mixed stones.

Frequency

United States

Prevalence of cholelithiasis is affected by many factors including ethnicity, gender, comorbidities, and genetics. In the United States, about 20 million people (10-20% of adults) have gallstones. Every year 1-3% of people develop gallstones and about 1-3% of people become symptomatic.

International

In an Italian study, 20% of women had stones, and 14% of men had stones. In a Danish study, gallstone prevalence in persons aged 30 years was 1.8% for men and 4.8% for women; gallstone prevalence in persons aged 60 years was 12.9% for men and 22.4% for women.

Mortality/Morbidity

Every year, 1-3% of people develop gallstones and about the same number develop symptoms of gallstones. Asymptomatic gallstones are not associated with fatalities. Morbidity and fatalities are associated with symptomatic cholelithiasis, cholecystitis, or cholangitis.

Race Prevalence of gallstones is highest in fair-skinned people of northern European descent and in

Hispanic populations and Native American populations. Prevalence of gallstones is low in Asians and African Americans; however, African Americans

with sickle cell disease have gallstones early in life secondary to associated hemolysis.

Sex Gallstones are more common in women than in men. It is postulated that estrogens cause

increased cholesterol secretion and progesterone promotes biliary stasis.1

Women who are pregnant are more likely to experience symptomatic gallstones due to the hormonal influences and decreased gut motility. Whether women who are pregnant are more likely to form stones is uncertain; however, women with multiple pregnancies are more likely to have stones.

Age Risk of developing gallstones increases with age. Incidence of gallstones increases by 1-3% per

year. It is uncommon for children to form gallstones. Children with gallstones are more likely to have

congenital anomalies, biliary malformation and disease, or hemolytic pigment stones.

Other risk factors for gallstones include exogenous estrogen intake, obesity, frequent fasting, rapid weight loss, lack of physical activity, diabetes mellitus, diseases associated with increased hemolysis (eg, sickle cell disease), cirrhosis, and certain medications (eg, octreotide, estrogens, fibrates).

Clinical

History

The clinical stages of cholelithiasis are asymptomatic (the presence of gallstones without symptoms), symptomatic (biliary colic), and complicated (eg, cholecystitis, choledocholithiasis, cholangitis). Most gallstones (60-80%) are asymptomatic. Classically, biliary colic is described as episodic pain in the right upper quadrant, that may radiate to the right shoulder or back (Collins's sign).2 It begins postprandially (usually within an hour) and may last from 1-5 hours. It is caused by contraction of the gallbladder (in response to a fatty meal) against an obstructing

gallstone (or sludge) in the cystic duct. This leads to increased pressure within the gallbladder and pain. The pain is often described as intense and dull and typically subsides after several hours, when the gallbladder stops contracting and the stone falls back into the gallbladder. Associated symptoms may include diaphoresis, nausea, and vomiting.

These symptoms can be nonspecific and insensitive. The pain may be more prominent in the midepigastrium, wake the patient from sleep, and be unrelated to meals.

The pain of biliary colic is not characteristically positional, pleuritic, or relieved by bowel movement or flatus.

Other symptoms, often associated with cholelithiasis, include indigestion, dyspepsia, belching, bloating, and fat intolerance. However, these are very nonspecific and occur in similar frequencies in individuals with and without gallstones; cholecystectomy has not been shown to improve these symptoms.

Most patients develop symptoms prior to complications. Once symptoms of biliary colic occur, severe symptoms develop in 3-9% of patients, with complications in 1-3% per year and a cholecystectomy rate of 3-8% per year. Therefore, in people with mild symptoms, 50% have complications after 20 years.

Zollinger performed studies in the 1930s in which the gallbladder wall or common bile duct was distended with a balloon; pain was elicited in the epigastric region. Only if the distended gallbladder touched the peritoneum did the patient experience right upper quadrant pain. Associated symptoms of nausea, vomiting, or referred pain were present in distention of the common bile duct (CBD) but not of the gallbladder.

o In classic cases, pain is in the right upper quadrant; however, visceral pain and gallbladder wall distention may be only in the epigastric area.

o Once the peritoneum is irritated, pain localizes into the right upper quadrant. Small stones are more likely to be symptomatic than large stones.

Physical

Physical findings vary along the spectrum of gallbladder disease.

Vital signs and physical examination findings in asymptomatic cholelithiasis are normal. These are generally patients with an incidental finding of gallstones.

Findings in between acute biliary colic attacks are generally also normal, though some mild residual upper abdominal pain with little or no tenderness may persist shortly after an attack.

During an acute attack of biliary colic, the patient may complain of severe, poorly localized upper abdominal pain, but is non-toxic and has a benign abdominal exam with little or no tenderness. Any prolonged pain episode lasting more than 5-6 hours should dictate a search for obstructed stone(s) or complications from cholelithiasis.

o Although voluntary guarding may be present, no peritoneal signs are present.

o Tachycardia and diaphoresis may be present as a consequence of pain. These should resolve with appropriate pain management.

Nausea and vomiting are commonly present as well, although rarely to the extent of electrolyte imbalance. Intravenous fluids may be necessary to restore intravascular volume.

Distinguishing uncomplicated biliary colic from acute cholecystitis or other complications is important. Both often present with the same constellation of symptoms, and physical examination may help to differentiate the two.

o Since the gallbladder is not inflamed in uncomplicated biliary colic, the pain is poorly localized and visceral in origin; the patient has an essentially benign abdominal examination without rebound or guarding. Fever is absent.

o In acute cholecystitis, inflammation of the gallbladder with resultant peritoneal irritation leads to well-localized pain in the right upper quadrant, usually with rebound and guarding. Although nonspecific, a positive Murphy sign (inspiratory arrest on deep palpation of the right upper quadrant during deep inspiration) is highly suggestive of cholecystitis. Fever is often present, but it may lag behind other signs or symptoms.

The presence of fever, persistent tachycardia, hypotension, or jaundice necessitate a search for complications of cholelithiasis, including cholecystitis, cholangitis, pancreatitis, or other systemic causes.

Consider that both intra-abdominal and extra-abdominal pathology can present with upper abdominal pain, and often coexist with cholelithiasis. Among the different entities to consider are peptic ulcer disease, pancreatitis (acute or chronic), hepatitis, dyspepsia, gastroesophageal reflux disease (GERD), irritable bowel syndrome, esophageal spasm, pneumonia, cardiac chest pain, and diabetic ketoacidosis. A careful history and physical examination should guide further workup.

Causes

Ethnicity, gender, age, genetics, dietary considerations, and presence of certain comorbidities are major risk factors in the development of cholelithiasis and associated complications.

Ethnicity: Prevalence rates of cholelithiasis are highest among western Caucasian, Hispanic, and Native American populations. Eastern European, African American, and Asian populations are less afflicted.

Age: Advancing age is a major risk factor for gallbladder disease; gallstones are exceedingly rare in children.

Gender: The prevalence rate of cholelithiasis is higher in women of all age groups. The difference is attributed to increased levels of estrogens and progesterone, which ultimately promote the formation of gallstones. Estrogens increase cholesterol formation, which supersaturate the bile, leading to precipitation of cholesterol stones; progesterone inhibits gallbladder motility leading to biliary stasis and stone formation. Pregnancy contributes to the female preponderance in prevalence due to increases in circulating sex steroids in the gravid state.

High-fat diet: Historically, but not statistically, high-fat diet is associated with the formation of gallstones and symptoms associated with gallstones. Estrogen therapy, in similar fashion, is associated with higher risk of cholelithiasis.

Genetics: Studies in family history suggest that genetics have a significant role in development of gallstones.

Dietary considerations: Obesity, high-fat diet, and hypertriglyceridemia are strongly associated with the formation of gallstones and arising complications. Additional dietary risk factors include decreased oral intake, rapid weight loss, and use of parenteral nutrition. Diosgenin-rich beans, particularly associated with a South American diet, increase cholesterol secretion and gallstone formation.

Bariatric surgery: More than one third of the patients develop gallstones after bariatric surgery. Weight loss greater than 25% is the best predictor for the gallstone formation. Rapid weight loss mobilizes tissue cholesterol stores and increases the saturation of bile.3

Comorbidities

o Diabetes mellitus is associated with an increased risk of gallstone, though the mechanism is unclear; once symptomatic, patients with diabetes are prone to more severe complications.

o Crohn disease , ileal resection, or other diseases of the ileum decrease bile salt reabsorption and increase the risk of gallstone formation.

o Hemolytic diseases, including sickle cell disease and spherocytosis, promote the formation of pigmented stones.

o Bacterial or parasitic infections from organisms that contain B -glucuronidase, an enzyme that deconjugates bilirubin glucuronide, increase the risk for pigmented stones.

o Cirrhosis carries major multifactorial risks for gallstone formation and gallbladder disease. Reduced hepatic synthesis and transport of bile salts, hyperestrogenemia, impaired gallbladder contraction and increased biliary stasis, among other factors, contribute to the formation of gallstones (typically pigment stones) in cirrhosis.

o Other illnesses or states that predispose to gallstone formation include the following: burns, use of total parenteral nutrition, paralysis, ICU care, or major trauma.

o This is due, in general, to decreased enteral stimulation of the gallbladder with resultant biliary stasis and stone formation.

General Illness Information Medical Term: GALLSTONES (Cholelithiasis)

Common Name: Gallstones Description: Gallstones are a  collection of one or more stones in the gallbladder, which is the

hollow organ under the liver, that stores bile. When the gallstones are in the gallbladder, the condition is called cholelithiasis; when they are in the bile ducts the condition is called choledocolithiasis.

 Most gallstones in North America are composed primarily of cholesterol (75%). 25% of gallstones are composed of pigment (60% in Japan). 

Affects both sexes  but twice as common in females. It is also more common in certain groups of people, such as Native Americans and Hispanics.. It can occur at any age, but incidence increases with age and peaks at age 65.Rarely occurs in children under ten. 

Most gallstones form in the gallbladder. Most gallstones in the bile ducts travel there from the gallbladder. Stones may form in the bile duct when bile backs up because a duct has narrowed or after the gallbladder has been removed. 

    Causes:  Definite cause unknown. Possible causes are as follows: Alterations in bile composition, such as

increased concentration of cholesterol or decrease in concentration of phopholipids or bile acids;  Failure of gallbladder to empty adequately;  Infection; Hemolytic disorders such as sickle cell anemia.

  Prevention: Avoid risk factors where possible.  Use of ursodiol (drug that dissolves gallstones)  with rapid  weight loss prevents stone formation. Signs & Symptoms

Mostly asymptomatic. In the  United States, 20% of people over age 65  have gallstones but most have no symptoms. 5-10% become symptomatic each year. Over lifetime, less than half of the patients with gallstones develop symptoms.Episodic  pain in the upper right abdomen or between the shoulder blades.

Intolerance for fatty foods (indigestion, pain, bloating and belching).

Nausea and vomiting.

Bloating or belching.

Jaundice- sometimes.

Risk Factors Family history of gallstones.Genetic factors. Some ethnic groups are more susceptible, such as Native Americans and Hispanics.

Obesity.

Excess alcohol consumption

Oral contraceptives.

High fat, low fiber diet.

Rapid weight loss.

Women who have had many children.(multiparity)

Hemolytic disorders such as sickle cell anemia, hereditary spherocytosis. 

Liver cirrhosis.

Diabetes.

Female gender.

Inflammatory bowel disease such as crohns.

Diagnosis & Treatment Diagnostic tests may include laboratory studies such as blood count and blood chemistry, CT scan, ultrasound, cholecystography, and X-rays of the gallbladder. Ultrasound scanning is the best method for diagnosing gallstones in the gallbladder.

General Measures:

Treatment steps vary depending on severity of symptoms. Most people who have "silent" gallstones do not require any treatment.Gallstones that cause no symptoms can safely be left alone. They are unlikely to cause problems. They do no need surgery.

People with intermittent pain can try  a low fat diet. Doing so may help prevent or reduce the number of pain episodes.

 If you know you have gallstones and experience pain in the upper right abdomen, apply heat to the area. If pain worsens or continues more than 3 hours, seek medical help.    Hospitalization may be required for patients with pain lasting more than 6 hours. 

If gallstones in the gallbladder cause recurring bouts of pain  in spite of dietary changes than surgery to remove the gallbladder  (cholecystectomy)  is indicated. Surgery to remove the gallbladder and stones in the bile duct may be needed for patients with severe symptoms.  Laparoscopic cholecystectomy is usually the preferred procedure. Laproscopic surgery was first introduced in 1990. About 90% of cholecystectomies are performed laproscopically. In laproscopic surgery, the gallbladder is removed through tubes  that are inserted through small incisions in the abdominal wall. The whole procedure is performed with the help of a camera (laproscope) , also placed in the abdomen through the small incisions. Laproscopic surgery has markedly reduced post-operative discomfort, shortened hospital stay, and reduced time of work.

Shockwave (lithotripsy) treatment to break up (shatter) the stones may be recommended in some cases.

Medications:

For minor discomfort, you may use non-prescription drugs such as acetaminophen.

Oral medication to try to dissolve stones. This treatment is used for certain types of stones and can take up to two years.

Activity:

No restriction, except to rest during attacks of gallbladder colic.Diet:

During an attack, sip water occasionally, but don't eat.

At other times, eat low-fat diet. Fatty meals may bring on mild attacks.

If you are overweight, begin a weight reduction program.

Possible Complications :

Infection or rupture of the gallbladder.

Common bile duct stone with obstructive jaundice.

Gall bladder cancer.

Small bowel obstruction and paralysis due to gallstone causing obstruction.

Prognosis Most people with gallstones have no symptoms. For those who do, the disorder is curable with surgery.  About 10 to 15% of people with gall bladder stones will have associated choledocolithiasis  (stones in the bile duct). Also, after cholecystectomy, stones may recur in the bile duct.

Other

 'Nothing Specified'.

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Cholelithiasis is the presence of one or more calculi (gallstones) in the gallbladder. In developed countries, about 10% of adults and 20% of people > 65 yr have gallstones. Gallstones tend to be asymptomatic. The most common symptom is biliary colic; gallstones do not cause dyspepsia or fatty food intolerance. More serious complications include cholecystitis; biliary tract obstruction (from stones in the bile ducts or choledocholithiasis), sometimes with infection (cholangitis); and gallstone pancreatitis. Diagnosis is usually by ultrasonography. If cholelithiasis causes symptoms or complications, cholecystectomy is necessary.

Risk factors for gallstones include female sex, obesity, increased age, American Indian ethnicity, a Western diet, and a family history. Most disorders of the biliary tract result from gallstones.

Pathophysiology

Biliary sludge is often a precursor of gallstones. It consists of Ca bilirubinate (a

Cholelithiasis

polymer of bilirubin), cholesterol microcrystals, and mucin. Sludge develops during gallbladder stasis, as occurs during pregnancy or while receiving TPN. Most sludge is asymptomatic and disappears when the primary condition resolves. Alternatively, sludge can evolve into gallstones or migrate into the biliary tract, obstructing the ducts and leading to biliary colic, cholangitis, or pancreatitis.

There are several types of gallstones.

Cholesterol stones account for > 85% of gallstones in the Western world. For cholesterol gallstones to form, the following is required:

Bile must be supersaturated with cholesterol. Normally, water-insoluble cholesterol is made water-soluble by combining with bile salts and lecithin to form mixed micelles. Supersaturation of bile with cholesterol most commonly results from excessive cholesterol secretion (as occurs in obesity or diabetes) but may result from a decrease in bile salt secretion (eg, in cystic fibrosis because of bile salt malabsorption) or in lecithin secretion (eg, in a rare genetic disorder that causes a form of progressive intrahepatic familial cholestasis).

The excess cholesterol must precipitate from solution as solid microcrystals. Such precipitation in the gallbladder is accelerated by mucin, a glycoprotein, or other proteins in bile.

The microcrystals must aggregate and grow. This is facilitated by the binding effect of mucin forming a scaffold and retention in the gallbladder (impaired contractility from the excess cholesterol in bile).

Black pigment stones are small, hard gallstones composed of Ca bilirubinate and inorganic Ca salts (eg, Ca carbonate, Ca phosphate). Factors that accelerate their development include alcoholic liver disease, chronic hemolysis, and older age.

Brown pigment stones are soft and greasy, consisting of bilirubinate and fatty acids (Ca palmitate or stearate). They form during infection, inflammation, and parasitic infestation (eg, liver flukes in Asia).

Gallstones grow at about 1 to 2 mm/yr, taking 5 to 20 yr before becoming large enough to cause problems. Most gallstones form within the gallbladder, but brown pigment stones form in the ducts. Gallstones may migrate to the bile duct after cholecystectomy or, particularly in the case of brown pigment stones, develop behind strictures as a result of stasis and infection.

Symptoms and Signs

About 80% of people with gallstones are asymptomatic. The remainder have

symptoms ranging from biliary-type pain (biliary colic) to cholecystitis to life-threatening cholangitis. Biliary colic is the most common symptom.

Stones occasionally may traverse the cystic duct without causing symptoms. Most gallstone migration, however, leads to cystic duct obstruction, which, even if transient, causes biliary colic. Biliary colic characteristically begins in the right upper quadrant but may occur elsewhere in the abdomen. It is often poorly localized, particularly in diabetics and the elderly. The pain may radiate into the back or down the arm. Episodes begin suddenly, become intense within 15 min to 1 h, remain at a steady intensity (not colicky) for up to 12 h (usually < 6 h), and then gradually disappear over 30 to 90 min, leaving a dull ache. The pain is usually severe enough to send patients to the emergency department for relief. Nausea and some vomiting are common, but fever and chills do not occur unless cholecystitis has developed. Mild right upper quadrant or epigastric tenderness may be present; peritoneal findings are absent. Between episodes, patients feel well.

Although biliary-type pain can follow a heavy meal, fatty food is not a specific precipitating factor. Nonspecific GI symptoms, such as gas, bloating, and nausea, have been inaccurately ascribed to gallbladder disease. These symptoms are common, having about equal prevalence in cholelithiasis, peptic ulcer disease, and functional GI disorders.

Little correlation exists between the severity and frequency of biliary colic and pathologic changes in the gallbladder. Biliary colic can occur in the absence of cholecystitis. Should colic last > 12 h, particularly if accompanied by vomiting or fever, acute cholecystitis or pancreatitis is likely.

Diagnosis

Ultrasonography

Gallstones are suspected in patients with biliary colic. Abdominal ultrasonography is the method of choice for detecting gallbladder stones; sensitivity and specificity are 95%. Ultrasonography also accurately detects sludge. CT, MRI, and oral cholecystography (rarely available now, although quite accurate) are alternatives (see Testing for Hepatic and Biliary Disorders: Imaging Tests). Endoscopic ultrasonography accurately detects small gallstones (< 3 mm) and may be needed if other tests are equivocal. Laboratory tests usually are not helpful; typically, results are normal unless complications develop. Asymptomatic gallstones and biliary sludge are often detected incidentally when imaging, usually ultrasonography, is done for other reasons. About 10 to 15% of gallstones are calcified and visible on plain x-rays.

Prognosis

Those with asymptomatic gallstones become symptomatic at a rate of about 2%/yr. The symptom that develops most commonly is biliary colic rather than a major biliary complication. Once biliary symptoms begin, they are likely to recur; pain returns in 20 to 40% of patients/yr, while about 1 to 2% of patients/yr develop complications such as cholecystitis, choledocholithiasis, cholangitis, and gallstone pancreatitis.

Treatment

Laparoscopic cholecystectomy for symptomatic stones Expectant for asymptomatic stones; sometimes stone dissolution

Most asymptomatic patients decide that the discomfort, expense, and risk of elective surgery are not worth removing an organ that may never cause clinical illness. However, if symptoms occur, gallbladder removal (cholecystectomy) is indicated because pain is likely to recur and serious complications can develop.

Surgery: Surgery can be done with an open or laparoscopic technique.

Open cholecystectomy, which involves a large abdominal incision and direct exploration, is safe and effective. Its overall mortality rate is about 0.1% when done electively during a period free of complications.

Laparoscopic cholecystectomy is the treatment of choice. Using video endoscopy and instrumentation through small abdominal incisions, the procedure is less invasive than open cholecystectomy. The result is a much shorter convalescence, decreased postoperative discomfort, improved cosmetic results, yet no increase in morbidity or mortality. Laparoscopic cholecystectomy is converted to an open procedure in 2 to 5% of patients, usually because biliary anatomy cannot be identified or a complication cannot be managed. Older age typically increases the risks of any type of surgery.

Cholecystectomy effectively prevents future biliary colic but is less effective for preventing atypical symptoms such as dyspepsia. Cholecystectomy does not result in nutritional problems or a need for dietary limitations. Some patients develop diarrhea, often because bile salt malabsorption in the ileum is unmasked. Prophylactic cholecystectomy in asymptomatic patients with cholelithiasis is not warranted except in those with quite large gallstones (> 3 cm) or those with a calcified gallbladder (porcelain gallbladder) because of an increased risk of gallbladder carcinoma.

Stone dissolution: For patients who decline surgery or who are at high surgical risk (eg, because of concomitant medical disorders or advanced age), gallbladder

stones can sometimes be dissolved by ingesting bile acids orally for many months. The best candidates for this treatment are those with small, radiolucent stones (more likely to be composed of cholesterol) in a functioning nonobstructed gallbladder—normal filling on cholescintigraphy or oral cholecystography or absence of stones in the neck.

Ursodeoxycholic acid 8 to 10 mg/kg/day po dissolves 80% of tiny stones < 0.5 cm in diameter within 6 mo. For larger stones (the majority), the success rate is much lower, even with higher doses of ursodeoxycholic acid. Further, after successful dissolution, stones recur in 50% within 5 yr. Most patients are thus not candidates and prefer laparoscopic cholecystectomy. Stone fragmentation (extracorporeal shock wave lithotripsy) to assist stone dissolution and clearance is now unavailable. Ursodeoxycholic acid, however, has value in preventing stone formation in morbidly obese patients who are losing weight rapidly after bariatric surgery or while on a very low calorie diet.

Cholelithiasis also known is Gallbladder. Gallstones are concretions that form in the biliary tract, usually in the gallbladder. Gallstones are formed within the gallbladder, an organ that stores bile excreted from the liver. Further complications of gallbladder disease include gallstone pancreatitis, gallstone ileus, biliary cirrhosis, and gallbladder cancer. Gallstones may be as small as a grain of sand, or they may become as large as an inch in diameter, depending on how long they have been forming. A stone blocking the opening from the gallbladder or cystic duct usually produces symptoms of biliary colic, which is right upper abdominal pain that feels like cramping.

If the stone does not pass into the duodenum, but continues to block the cystic duct, acute cholecystitis results. Gallbladder calculi are relatively uncommon in children. However, the incidence of cholelithiasis has been increasing recently. Children may harbor cholesterol gallstones, black- or brown-pigmented stones, or mixed-type gallstones. Complications that occur in adults with this condition may also occur in children. Gallstones may cause irritation and inflammation of the gallbladder mucosa, resulting in chronic calculous cholecystitis and symptoms of biliary colic. Chronic gallstone disease may lead to fibrosis and loss of function of the gallbladder and predisposes to gallbladder cancer. Excision of the gallbladder (cholecystectomy) to cure gallstone disease is among the most frequently performed abdominal surgical procedures.

Gallstones are a common health problem worldwide. Gallstones can occur anywhere within the biliary tree, including the gallbladder and the common bile duct. Obstruction of the common bile duct is choledocholithiasis; obstruction of the biliary tree can cause jaundice; obstruction of the outlet of the pancreatic exocrine system can cause pancreatitis. Gallstones are rocklike collections of material that form inside the gallbladder. Different types exist, and they are categorized by their primary composition; cholesterol stones are most common (75-80% in the United States) followed by pigment, then mixed stones. The stones form when there is an imbalance or change in the composition of bile. The first is how often and how well the

gallbladder contracts; incomplete and infrequent emptying of the gallbladder may cause the bile to become overconcentrated and contribute to gallstone formation.

The second factor is the presence of proteins in the liver and bile that either promote or inhibit cholesterol crystallization into gallstones. Increased levels of the hormone estrogen as a result of pregnancy, hormone therapy, or the use of birth control pills, may increase cholesterol levels in bile and also decrease gallbladder movement, resulting in gallstone formation. The pain of biliary colic is not characteristically positional, pleuritic, or relieved by bowel movement or flatus.Other symptoms, often associated with cholelithiasis, include indigestion, dyspepsia, belching, bloating, and fat intolerance. However, these are very nonspecific and occur in similar frequencies in individuals with and without gallstones; cholecystectomy has not been shown to improve these symptoms.

Gallbladder sludge is crystallization within bile without stone formation. Cholesterol gallstones may become colonized with bacteria and can elicit gallbladder mucosal inflammation. Lytic enzymes from bacteria and leukocytes hydrolyze bilirubin conjugates and fatty acids. Gallstones are present in about 80% of people with gallbladder cancer. Symptoms of gallbladder cancer are usually not present until the disease has reached an advanced stage and may include weight loss, anemia, recurrent vomiting, and a lump in the abdomen. When the cancer is caught at an early stage and has not spread deeper than the mucosa (the inner lining), removal of the gallbladder results in five-year survival rates of 68%. If cancer has spread to deeper layers, more extensive surgery or other treatments may be required. Sickle cell disease has been identified as an independent risk factor associated with an increase in the frequency of cholelithiasis. Cholesterol gallstones develop when bile contains too much cholesterol and not enough bile salts. Besides a high concentration of cholesterol, two other factors seem to be important in causing gallstones. Acute gallstone pancreatitis is often characterized by epigastric tenderness. In severe cases, retroperitoneal hemorrhage may produce ecchymoses of the flanks and periumbilical ecchymoses.

There are several available treatments for Cholelithiasis. Electrohydraulic shock wave lithotripsy (ESWL) has also been employed to treat cholelithiasis. Urodeoxycholic acid (UDCA, ursodiol), a more contemporary medical therapy, is successful in only 40% of cases. Both CDCA and UDCA therapies are useful only for gallstones formed from cholesterol. Surgery-Removal of the gallbladder, or cholecystectomy , is usually needed to treat symptoms associated with gallstones. It is a relatively safe procedure that does not cause any nutritional problems. Oral Bile Salts-If surgery is not desirable, bile salts to dissolve gallstones can be taken by mouth. However, it may take a long time to dissolve the gallstones, and because the gallbladder is still present, gallstones may recur. Laparoscopic techniques, which have been used for years in the field of gynecology, have recently been adapted to cholecystectomy, in an effort to decrease complications, recovery time and cost. Laparoscopic cholecystectomy is associated with a lower incidence of intra-abdominal adhesions, wound site hernia and scar formation. Postoperative pain is also reduced, and recovery time is shorter. Lithotripsy has been investigated as adjunctive therapy for failed endoscopic stone retrieval and for retained ductal stones after laparoscopic cholecystectomy.