Gallstone

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Gallstone
Classification and external resources
Gallensteine 2006 03 28.JPG
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 (also called cholelithiasis) 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
Large 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.

Cholelithiasis[edit]

Symptoms[edit]

Gallstones may be asymptomatic, even for years. These gallstones are called "silent stones" and do not require treatment.[7][8] The size and number of gallstones present does not appear to influence whether or not patients are symptomatic or asymptomatic.[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 Americans 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 low calorie diet.[12] 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.[13] On the other hand, wine and whole-grained bread may decrease the risk of gallstones.[14] 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.[15] People with erythropoietic protoporphyria (EPP) are at increased risk to develop gallstones.[16][17] Additionally, prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to gallstone formation.[18]

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.[19] 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.

Diagnosis can be made using ultrasound

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.[20] 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"),[20] 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[21] which may cause gastrointestinal distress and persistent pain in the upper-right abdomen, as well as a 10% risk of developing chronic diarrhea.[22]

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,[23] 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]

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.

Greater than 70% of people with gallstones are asymptomatic and are found incidentally on ultrasound. Studies have shown that 10% of those people will develop symptoms within five years of diagnosis and 20% within 20 years.[24]

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 an operation called a choledocholithotomy, which is the removal of the gallstone from the bile duct using ERCP, although surgeons are now increasingly using laparoscopy with cholangiography. In this procedure, tiny incisions are made in the abdomen and then in the cystic duct that connects the gallbladder to the bile duct, and a thin tube is introduced to perform a cholangiography. If stones are identified, the surgeon inserts a tube with an inflatable balloon to widen the duct and the stones are usually removed using either a balloon or tiny basket.

If laparoscopy is unsuccessful, an open choledocholithotomy is performed. This procedure may be used in the case of large stones, when the duct anatomy is complex, during or after some gallbladder operations when stones are detected, or when ERCP or laparoscopic procedures are not available.[25]

Typically, the gallbladder is then removed, an operation called cholecystectomy, to prevent a future occurrence of common bile duct obstruction or other complications.[26]

Other animals[edit]

Gallstones are a valuable by-product of animals butchered for meat because 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 workers for gallstone theft.[27]

See also[edit]

References[edit]

  1. ^ Fitzgerald JEF, Fitzgerald LA, Maxwell-Armstrong CA, Brooks AJ (2009). "Recurrent gallstone ileus: time to change our surgery?". Journal of Digestive Diseases 10 (2): 149–151. doi:10.1111/j.1751-2980.2009.00378.x. PMID 19426399. 
  2. ^ "Acute cholecystitis (MedilinePlus, A service of the U.S. National Library of Medicine)".  Available on: April 26, 2013.
  3. ^ Simultaneous bacteriologic assessment of bile from gallbladder and common bile duct in control subjects and patients with gallstones and common duct stones, Csendes A, Burdiles P, Maluenda F, Diaz JC, Csendes P, Mitru N, Arch Surg. 1996;131(4):389.
  4. ^ Gallstones - Cholelithiasis; Gallbladder attack; Biliary colic; Gallstone attack; Bile calculus; Biliary calculus Last reviewed: July 6, 2009. Reviewed by: George F. Longstreth. Also reviewed by David Zieve
  5. ^ Channa, Naseem A.; Khand, Fateh D.; Khand, Tayab U.; Leghari, Mhhammad H.; Memon, Allah N. (2007). "Analysis of human gallstones by Fourier Transform Infrared (FTIR)". Pakistan Journal of Medical Sciences 23 (4): 546–50. ISSN 1682-024X. Retrieved 2010-11-06. 
  6. ^ a b c Kim IS, Myung SJ, Lee SS, Lee SK, Kim MH (2003). "Classification and nomenclature of gallstones revisited". Yonsei Medical Journal 44 (4): 561–70. ISSN 0513-5796. PMID 12950109. Retrieved 2010-11-06. 
  7. ^ a b c d National Institute of Diabetes and Digestive and Kidney Diseases (2007). "Gallstones". Bethesda, Maryland: National Digestive Diseases Information Clearinghouse, National Institutes of Health, United States Department of Health and Human Services. Retrieved 2010-11-06. 
  8. ^ Heuman DM, Mihas AA, Allen J (2010). "Cholelithiasis". Omaha, Nebraska: Medscape (WebMD). Retrieved 2010-11-06. 
  9. ^ Acalovschi, Monica; Blendea, Dan; Feier, Cristina; Letia, Alfred I.; Raitu, Nadia; Dumitrascu, Dan L.; Veres, Adina (2003). "Risk factors for symptomatic gallstones in patients with liver cirrhosis: a case-control study". The American Journal of Gastroenterology 98 (8): 1856–1860. doi:10.1111/j.1572-0241.2003.07618.x. PMID 12907344. 
  10. ^ Roizen MF and Oz MC, Gut Feelings: Your Digestive System, pp. 175–206 in Roizen and Oz (2005)
  11. ^ Koppisetti, Sreedevi; Jenigiri, Bharat; Terron, M. Pilar; Tengattini, Sandra; Tamura, Hiroshi; Flores, Luis J.; Tan, Dun-Xian; Reiter, Russel J. (2008). "Reactive Oxygen Species and the Hypomotility of the Gall Bladder as Targets for the Treatment of Gallstones with Melatonin: A Review". Digestive Diseases and Sciences 53 (10): 2592–603. doi:10.1007/s10620-007-0195-5. PMID 18338264. 
  12. ^ http://www.nhs.uk/Livewell/loseweight/Pages/should-you-lose-weight-fast.aspx
  13. ^ Ortega RM, Fernández-Azuela M, Encinas-Sotillos A, Andrés P, López-Sobaler AM (1997). "Differences in diet and food habits between patients with gallstones and controls". Journal of the American College of Nutrition 16 (1): 88–95. doi:10.1080/07315724.1997.10718655. PMID 9013440. Retrieved 2010-11-06. 
  14. ^ Misciagna, Giovanni; Leoci, Claudio; Guerra, Vito; Chiloiro, Marisa; Elba, Silvana; Petruzzi, José; Mossa, Ascanio; Noviello, Maria R.; Coviello, Angelo; Minutolo, Marino Capece; Mangini, Vito; Messa, Caterina; Cavallini, Aldo; Michele, Giampiero De; Giorgio, Italo (1996). "Epidemiology of cholelithiasis in southern Italy. Part II". European Journal of Gastroenterology & Hepatology 8 (6): 585–93. doi:10.1097/00042737-199606000-00017. 
  15. ^ Trotman, Bruce W.; Bernstein, Seldon E.; Bove, Kevin E.; Wirt, Gary D. (1980). "Studies on the Pathogenesis of Pigment Gallstones in Hemolytic Anemia". Journal of Clinical Investigation 65 (6): 1301–8. doi:10.1172/JCI109793. PMC 371467. PMID 7410545. 
  16. ^ Endocrine and Metabolic Disorders: Cutaneous Porphyrias, pp. 63–220 in Beers, Porter and Jones (2006)
  17. ^ Thunell S (2008). "Endocrine and Metabolic Disorders: Cutaneous Porphyrias". Whitehouse Station, New Jersey: Merck Sharp & Dohme Corporation. Retrieved 2010-11-07. 
  18. ^ M. A. Cahan, M. A.; L. Balduf, K. Colton, B. Palacioz, W. McCartney and T. M. Farrell (2006). "Proton pump inhibitors reduce gallbladder function". Surgical Endoscopy 20 (9): 1364–1367. doi:10.1007/s00464-005-0247-x. PMID 16858534. 
  19. ^ Experimental investigation of the flow of bile in patient specific cystic duct models M Al-Atabi, SB Chin… - Journal of biomechanical engineering, 2010
  20. ^ a b National Health Service (2010). "Gallstones — Treatment". NHS Choices: Health A-Z - Conditions and treatments. London: National Health Service. Retrieved 2010-11-06. 
  21. ^ Jensen (2010). "Postcholecystectomy syndrome". Omaha, Nebraska: Medscape (WebMD). Retrieved 2011-01-20. 
  22. ^ Marks, Janet; Shuster, Sam; Watson, A. J. (1966). "Small-bowel changes in dermatitis herpetiformis". The Lancet 288 (7476): 1280–2. doi:10.1016/S0140-6736(66)91692-8. PMID 4163419. 
  23. ^ Keus, Frederik; de Jong, Jeroen; Gooszen, H G; Laarhoven, C JHM; Keus, Frederik (2006). "Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis". Cochrane Database of Systematic Reviews (4): CD006231. doi:10.1002/14651858.CD006231. PMID 17054285. 
  24. ^ Portincasa, P.; Moschetta, A.; Petruzzelli, M.; Palasciano, G.; Di Ciaula, A.; Pezzolla, A. (2006). "Gallstone disease: Symptoms and diagnosis of gallbladder stones.". Best Pract Res Clin Gastroenterol 20 (6): 1017–29. doi:10.1016/j.bpg.2006.05.005. PMID 17127185. 
  25. ^ "Open or Laparoscopic Common Bile Duct Exploration (Choledocholithotomy)". The New York Times Health Guide. The New York Times Company. 26 Aug 2013. Retrieved 17 April 2014. 
  26. ^ Vivian McAlister, Eric Davenport, and Elizabeth Renouf. "Cholecystectomy Deferral in Patients with Endoscopic Sphincterotomy. Cochrane Database of Systematic Reviews .4 (2007): CD006233. Available at: [1]
  27. ^ "Interview with Darren Wise. Transcrip". Omaha, Nebraska: Medscape (WebMD). Retrieved 2010-11-06. 

External links[edit]