Gallstone
Classification and external resources
Numerous small gallstones made up largely of cholesterol.
ICD-10	K80
ICD-9	574
OMIM	600803
DiseasesDB	2533
MedlinePlus	000273
eMedicine	emerg/97
MeSH	D042882

A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder but may distally pass into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of Vater. Rarely, in cases of severe inflammation, gallstones may erode through the gallbladder into adherent bowel potentially causing an obstruction termed gallstone ileus.^[1]

Presence of gallstones in the gallbladder may lead to acute cholecystitis,^[2] an inflammatory condition characterized by retention of bile in the gallbladder and often secondary infection by intestinal microorganisms, predominantly Escherichia coli, Klebsiella, Enterobacter, and Bacteroides species^[3]. Presence of gallstones in other parts of the biliary tract can cause obstruction of the bile ducts, which can lead to serious conditions such as ascending cholangitis or pancreatitis. Either of these two conditions can be life-threatening and are therefore considered to be medical emergencies.

Definitions [edit]

Presence of stones in the gallbladder is referred to as cholelithiasis (from the Greek chol- (bile) + lith- (stone) + iasis- (process). If gallstones migrate into the ducts of the biliary tract, the condition is referred to as choledocholithiasis, from the Greek chol- (bile) + docho- (duct) + lith- (stone) + iasis- (process). Choledocholithiasis is frequently associated with obstruction of the biliary tree, which in turn can lead to acute ascending cholangitis, from the Greek: chol- (bile) + ang- (vessel) + itis- (inflammation), a serious infection of the bile ducts. Gallstones within the ampulla of Vater can obstruct the exocrine system of the pancreas, which in turn can result in pancreatitis.

Characteristics and composition [edit]

Gallbladder opened to show numerous gallstones. The large, yellow calculus probably comprises cholesterol, while the green-to-brown stones suggest bile pigments, such as biliverdin and stercobilin.

Images of a CT of gallstones

Big Gallstone

Gallstones can vary in size and shape from as small as a grain of sand to as large as a golf ball.^[4] The gallbladder may contain a single large stone or many smaller ones. Pseudoliths, sometimes referred to as sludge, are thick secretions that may be present within the gallbladder, either alone or in conjunction with fully formed gallstones. The clinical presentation is similar to that of cholelithiasis.^{[citation needed]} The composition of gallstones is affected by age, diet, and ethnicity.^[5] On the basis of their composition, gallstones can be divided into the following types:

Cholesterol stones

Cholesterol stones vary from light yellow to dark green or brown and are oval, between 2 and 3 cm long, each often having a tiny, dark, central spot. To be classified as such, they must be at least 80% cholesterol by weight (or 70%, according to the Japanese- classification system).^[6]

Pigment stones

Pigment stones are small and dark and comprise bilirubin and calcium salts that are found in bile. They contain less than 20% of cholesterol (or 30%, according to the Japanese-classification system).^[6]

Mixed stones

Mixed gallstones typically contain 20–80% cholesterol (or 30–70%, according to the Japanese- classification system).^[6] Other common constituents are calcium carbonate, palmitate phosphate, bilirubin, and other bile pigments. Because of their calcium content, they are often radiographically visible.

• 

  Gallbladder opened to show numerous small cholesterol gallstones

• 

  µCT of a gallstone. Image acquisition done using "CT Alpha" by "Procon X-Ray GmbH", Garbsen, Germany. Visualization done with "VG Studio Max 2.0" by "Volume Graphics", Heidelberg, Germany

Cholelithiasis [edit]

Symptoms [edit]

Gallstones may be asymptomatic, even for years. These gallstones are called "silent stones" and do not require treatment.^[7][8] Symptoms commonly begin to appear once the stones reach a certain size (>8 mm).^[9] A characteristic symptom of gallstones is a "gallstone attack", in which a person may experience intense pain in the upper-right side of the abdomen, often accompanied by nausea and vomiting, that steadily increases for approximately 30 minutes to several hours. A patient may also experience referred pain between the shoulder blades or below the right shoulder. These symptoms may resemble those of a "kidney stone attack". Often, attacks occur after a particularly fatty meal and almost always happen at night, and after drink.

A positive Murphy's sign is a common finding on physical examination.

Causes [edit]

Gallstone risk increases for females (especially before menopause) and for people near or above 40 years;^[10] the condition is more prevalent among both North and South Amerindians and among those of European descent than among other ethnicities. A lack of melatonin could significantly contribute to gallbladder stones, as melatonin inhibits cholesterol secretion from the gallbladder, enhances the conversion of cholesterol to bile, and is an antioxidant, which is able to reduce oxidative stress to the gallbladder.^[11] Researchers believe that gallstones may be caused by a combination of factors, including inherited body chemistry, body weight, gallbladder motility (movement), and perhaps diet^{[citation needed]}. The absence of such risk factors does not, however, preclude the formation of gallstones.

No clear relationship has been proved between diet and gallstone formation; however, low-fiber and high-cholesterol diets have been suggested as contributing to gallstone formation^{[citation needed]}. Other nutritional factors that may increase risk of gallstones include rapid weight loss; constipation; eating fewer meals per day; and low intake of the nutrients folate, magnesium, calcium, and vitamin C.^[12] On the other hand, wine and whole-grained bread may decrease the risk of gallstones.^[13] Pigment gallstones are most commonly seen in the developing world. Risk factors for pigment stones include hemolytic anemias (such as sickle-cell disease and hereditary spherocytosis), cirrhosis, and biliary tract infections.^[14] People with erythropoietic protoporphyria (EPP) are at increased risk to develop gallstones.^[15][16] Additionally, prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to gallstone formation.^[17]

Pathophysiology [edit]

Cholesterol gallstones develop when bile contains too much cholesterol and not enough bile salts. Besides a high concentration of cholesterol, two other factors are 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. This can be caused by high resistance to the flow of bile out of the gallbladder due to the complicated internal geometry of the cystic duct.^[18] 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 or 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.

Diagnosis [edit]

A 1.9 cm gallstone impacted in the neck of the gallbladder and leading to cholecystitis as seen on ultrasound. Note the 4 mm gall bladder wall thickening.

Gallstones as seen on plain Xray.

Treatment [edit]

Medical

Cholesterol gallstones can sometimes be dissolved by oral ursodeoxycholic acid, but it may be necessary for the patient to take this medication for up to two years.^[19] 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 extracorporeal shock wave lithotripsy (often simply called "lithotripsy"),^[19] 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 suitable only when there is a small number of gallstones.

Surgical

Cholecystectomy (gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. Surgery is only indicated in symptomatic patients. The lack of a gallbladder may have no negative consequences in many people. However, there is a portion of the population — between 10 and 15% — who develop a condition called postcholecystectomy syndrome^[20] which may cause gastrointestinal distress and persistent pain in the upper-right abdomen, as well as a 10% risk of developing chronic diarrhea.^[21]

There are two surgical options for cholecystectomy:

• Open cholecystectomy is performed via an abdomenal incision (laparotomy) below the lower right ribs. Recovery typically requires 3–5 days of hospitalization, with a return to normal diet a week after release and to normal activity several weeks after release.^[7]
• Laparoscopic cholecystectomy, introduced in the 1980s,^[22] 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.^[7] Laparoscopic cholecystectomy patients can, in general, 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]}

A New Alternative Surgical Technique 

A new surgical technique is available to remove Gallstones without excision of gallbladder. This technique is available in China.^[23]

Alternative medicine

A regimen called a "gallbladder flush" or "liver flush" is a popular remedy in alternative medicine.^[24] In this treatment, often self-administered, the patient drinks four glasses of pure apple juice (not cider) and eats five apples (or applesauce) per day for five days, then fasts briefly, takes magnesium, and then drinks large quantities of lemon juice mixed with olive oil before bed. The next morning, they painlessly pass a number of green and brown pebbles purported to be stones flushed from the biliary system. Apples are a source of pectin, which has been shown to sequester bile and facilitate its elimination in the stool.^[25]

A brief communication in The Lancet ^[26] presents a case report of such a treatment where the patient released many soft stones. According to the letter, "At the university hospital the stones were recognized as fatty stones". In another case report, a patient with ultrasonography-confirmed gallstones drank olive oil and lemon juice, suffered diarrhea and intense abdominal pain, and released several gallstones. After that treatment, the gallbladder was empty, as confirmed by ultrasonography.^[27]

On the other hand, a couple of case reports challenge whether the stones retrieved from the stool after the "gallbladder flush" really come from the gallbladder. A New Zealand hospital analyzed stones from a typical gallbladder flush and found them to be composed of fatty acids similar to those in olive oil, with no detectable cholesterol or bile salts,^[28] demonstrating that they are little more than hardened olive oil. Despite the gallbladder flush, the patient still required surgical removal of multiple true gallstones. A similar case report in The Lancet,^[29] accompanied by a simple chemical experiment, concludes that the observed stones from a typical gallbladder flush actually are a consequence of the flush: they form in the stomach under the action of digestive enzymes on the mix of olive oil and lemon.

Finally, drinking an infusion of "Chanca Piedra", or "Break Stones" (Phyllanthus niruri), a plant that is native to the Amazon, has long been used in South American traditional medicine to maintain kidney, liver, and gallbladder health and to treat gallstones and kidney stones and jaundice.

Other patients have anecdotally reported that symptoms can be temporarily reduced by drinking several glasses of water when experiencing gallstone pain. There is no known evidence backing this claim, and this approach will not eliminate the gallstones or improve the patient's condition in the long term.

Choledocholithiasis [edit]

MRCP image of two stones in the distal common bile duct

Choledocholithiasis is the presence of gallstones in the common bile duct. This condition causes jaundice and liver cell damage, and requires treatment by cholecystectomy and/or ERCP.

Signs and symptoms [edit]

Murphy's sign is commonly negative on physical examination in choledocholithiasis, helping to distinguish it from cholecystitis. Jaundice of the skin or eyes is an important physical finding in biliary obstruction. Jaundice and/or clay-colored stool may raise suspicion of choledocholithiasis or even gallstone pancreatitis.^[7] If the above symptoms coincide with fever and chills, the diagnosis of ascending cholangitis may also be considered.

Causes [edit]

While stones can frequently pass through the common bile duct (CBD) into the duodenum, some stones may be too large to pass through the CBD and may cause an obstruction. One risk factor for this is duodenal diverticulum.

Pathophysiology [edit]

This obstruction may lead to jaundice, elevation in alkaline phosphatase, increase in conjugated bilirubin in the blood and increase in cholesterol in the blood. It can also cause acute pancreatitis and ascending cholangitis.

Diagnosis [edit]

Common bile duct stone impacted at ampulla of Vater seen at time of ERCP

Choledocholithiasis (stones in common bile duct) is one of the complications of cholelithiasis (gallstones), so the initial step is to confirm the diagnosis of cholelithiasis. Patients with cholelithiasis typically present with pain in the right-upper quadrant of the abdomen with the associated symptoms of nausea and vomiting, especially after a fatty meal. The physician can confirm the diagnosis of cholelithiasis with an abdominal ultrasound that shows the ultrasonic shadows of the stones in the gallbladder.

The diagnosis of choledocholithiasis is suggested when the liver function blood test shows an elevation in bilirubin and serum transaminases. Other indicators include raised indicators of ampulla of vater (pancreatic duct obstruction) such as lipases and amylases. In prolonged cases the INR may change due to a decrease in vitamin K absorption. (It is the decreased bile flow which reduces fat breakdown and therefore absorption of fat soluble vitamins). The diagnosis is confirmed with either an MRCP (magnetic resonance cholangiopancreatography), an ERCP, or an intraoperative cholangiogram. If the patient must have the gallbladder removed for gallstones, the surgeon may choose to proceed with the surgery, and obtain a cholangiogram during the surgery. If the cholangiogram shows a stone in the bile duct, the surgeon may attempt to treat the problem by flushing the stone into the intestine or retrieve the stone back through the cystic duct.

On a different pathway, the physician may choose to proceed with ERCP before surgery. The benefit of ERCP is that it can be utilized not just to diagnose, but also to treat the problem. During ERCP the endoscopist may surgically widen the opening into the bile duct and remove the stone through that opening. ERCP, however, is an invasive procedure and has its own potential complications. Thus, if the suspicion is low, the physician may choose to confirm the diagnosis with MRCP, a non-invasive imaging technique, before proceeding with ERCP or surgery.

Treatment [edit]

Fluoroscopic image taken during ERCP. Multiple gallstones are present in the gallbladder and cystic duct. The common bile duct and pancreatic duct appear to be patent.

Treatment involves removing the stone using ERCP. Typically, the gallbladder is then removed, an operation called cholecystectomy, to prevent a future occurrence of common bile duct obstruction or other complications.^[30]

In other animals [edit]

Gallstones are a valuable by-product of meat processing, fetching up to US$12–per–gram in their use as a purported antipyretic and antidote in the folk remedies of some cultures, in particular, in China. The finest gallstones tend to be sourced from old dairy cows, which are called Niu-Huang (yellow thing of cattle) in Chinese. Much as in the manner of diamond mines, slaughterhouses carefully scrutinize offal department workers for gallstone theft.^[31]

See also [edit]

• Porcelain gallbladder

References [edit]

• Beers, MH; Porter, RS; Jones, TV, eds. (2006). Merck Manual of Diagnosis and Therapy (18th ed.). Whitehouse Station, New Jersey: Merck Sharp & Dohme Corporation. ISBN 978-0-911910-18-6.  |accessdate= requires |url= (help)

External links [edit]

Wikimedia Commons has media related to: Gallstones

• Public domain NIH/NIDDK e-pub on gallstones
• MedlinePlus Encyclopedia Gallbladder removal
• Gallstones Information
• 5-Minute Clinical Consult Cholelithiasis
• cholelithiasis US Classic gallstone with shadow and cholecystitis