View source for Medicine:Gallstone

{{short description|Disease where stones form in the gallbladder}}
{{Infobox medical condition (new)
| name            = Gallstone
| image           = Gallstones.png
| caption         = Gallstones typically form in the [[Biology:Gallbladder|gallbladder]] and may result in symptoms if they block the biliary system.
| field           = [[Medicine:Gastroenterology|Gastroenterology]]<br/>General surgery
| pronounce       = Cholelith {{IPAc-en|ˈ|k|oʊ|l|ə|l|ɪ|θ}}, cholelithiasis {{IPAc-en|ˌ|k|oʊ|l|ə|l|ɪ|ˈ|θ|aɪ|ə|s|ᵻ|s}}
| synonyms        = Gallstone disease, cholelith, cholecystolithiasis (gallstone in the gallbladder), choledocholithiasis (gallstone in a bile duct)<ref name=Qui2013/>
| symptoms        = None, crampy pain in the right upper [[Biology:Abdomen|abdomen]]<ref name=NIH2013/><ref name=Lee2015/><ref name=WS2016/>
| complications   = [[Medicine:Cholecystitis|Inflammation of the gallbladder]], [[Medicine:Pancreatitis|inflammation of the pancreas]], [[Medicine:Hepatitis|liver inflammation]]<ref name=NIH2013/><ref name=WS2016/>
| onset           = After 40 years old<ref name=NIH2013/>
| duration        =
| types           =
| causes          =
| risks           = Birth control pills, [[Medicine:Pregnancy|pregnancy]], family history, obesity, [[Medicine:Diabetes|diabetes]], [[Medicine:Cirrhosis|liver disease]], rapid weight loss<ref name=NIH2013/>
| diagnosis       = Based on symptoms, confirmed by [[Physics:Ultrasound|ultrasound]]<ref name=NIH2013/><ref name=WS2016/>
| differential    =
| prevention      = Healthy weight, diet high in fiber, diet low in simple carbohydrates<ref name=NIH2013/>
| treatment       = '''Asymptomatic''': none,<ref name=NIH2013/>  ursodeoxycholic acid (UDCA) and Chenodeoxycholic acid <br>'''Pain''': surgery ERCP, [[Medicine:Cholecystectomy|Cholecystectomy]]<ref name=NIH2013/>
| medication      =
| prognosis       = Good after surgery<ref name=NIH2013/>
| frequency       = 10–15% of adults (developed world)<ref name=WS2016/>
| deaths          =
}}
<!-- Definition and symptoms -->
A '''gallstone''' is a [[Medicine:Calculus|stone]] formed within the [[Biology:Gallbladder|gallbladder]] from precipitated [[Biology:Bile|bile]] components.<ref name=NIH2013/> The term '''cholelithiasis''' may refer to the presence of gallstones or to any disease caused by gallstones,<ref name=NICE2014>{{cite journal | title = Gallstone Disease: Diagnosis and Management of Cholelithiasis, Cholecystitis and Choledocholithiasis. Clinical Guideline 188 | page = 101 | date = October 2014 | pmid = 25473723 | author1 = Internal Clinical Guidelines Team (UK) }}</ref> and choledocholithiasis refers to the presence of migrated gallstones within [[Biology:Bile duct|bile duct]]s.

Most people with gallstones (about 80%) are asymptomatic.<ref name=NIH2013/><ref name=Lee2015>{{cite journal | vauthors = Lee JY, Keane MG, Pereira S | title = Diagnosis and treatment of gallstone disease | journal = The Practitioner | volume = 259 | issue = 1783 | pages = 15–9, 2 | date = June 2015 | pmid = 26455113 }}</ref> However, when a gallstone obstructs the bile duct and causes acute [[Medicine:Cholestasis|cholestasis]], a [[Biology:Reflex|reflex]]ive [[Biology:Smooth muscle|smooth muscle]] spasm often occurs, resulting in an intense cramp-like [[Biology:Visceral pain|visceral pain]] in the right upper part of the [[Biology:Abdomen|abdomen]] known as a biliary colic (or "gallbladder attack").<ref name=WS2016/> This happens in 1–4% of those with gallstones each year.<ref name=WS2016/><!-- Quote = Biliary colic occurs in 1 to 4 % annually --> Complications from gallstones may include inflammation of the gallbladder ([[Medicine:Cholecystitis|cholecystitis]]), inflammation of the pancreas ([[Medicine:Pancreatitis|pancreatitis]]), [[Medicine:Jaundice#Post-hepatic|obstructive jaundice]], and infection in bile ducts ([[Medicine:Ascending cholangitis|cholangitis]]).<ref name=WS2016/><ref name=NHS2018>{{cite web|title=Complications|url=https://www.nhs.uk/conditions/gallstones/complications/|website=nhs.uk|access-date=13 May 2018}}</ref> Symptoms of these complications may include pain that lasts longer than five hours, [[Medicine:Fever|fever]], yellowish skin, vomiting, dark [[Biology:Urine|urine]], and pale [[Biology:Feces|stools]].<ref name=NIH2013/>

<!-- Cause and diagnosis -->
Risk factors for gallstones include birth control pills, [[Medicine:Pregnancy|pregnancy]], a [[Medicine:Family history|family history]] of gallstones, obesity, [[Medicine:Diabetes|diabetes]], [[Medicine:Cirrhosis|liver disease]], or rapid weight loss.<ref name=NIH2013/> The bile components that form gallstones include [[Chemistry:Cholesterol|cholesterol]], bile salts, and [[Chemistry:Bilirubin|bilirubin]].<ref name=NIH2013/> Gallstones formed mainly from cholesterol are termed ''cholesterol stones'', and those formed mainly from bilirubin are termed ''pigment stones''.<ref name=NIH2013>{{cite web|title=Gallstones|url=https://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/gallstones/Pages/facts.aspx|website=NIDDK|access-date=27 July 2016|date=November 2013|url-status=live|archive-url=https://web.archive.org/web/20160728005016/https://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/gallstones/Pages/facts.aspx|archive-date=28 July 2016}}</ref><ref name=Lee2015/> Gallstones may be suspected based on symptoms.<ref name=WS2016/> Diagnosis is then typically confirmed by [[Physics:Ultrasound|ultrasound]].<ref name=NIH2013/> Complications may be detected using blood tests.<ref name=NIH2013/>

<!-- Prevention and treatment -->
The risk of gallstones may be decreased by maintaining a healthy weight with exercise and a healthy diet.<ref name=NIH2013/> If there are no symptoms, treatment is usually not needed.<ref name=NIH2013/> In those who are having gallbladder attacks, [[Medicine:Cholecystectomy|surgery to remove the gallbladder]] is typically recommended.<ref name=NIH2013/> This can be carried out either through several small incisions or through a single larger incision, usually under general anesthesia.<ref name=NIH2013/> In rare cases when surgery is not possible, medication can be used to dissolve the stones or lithotripsy can be used to break them down.<ref name=NIH2017Tx>{{cite web |title=Treatment for Gallstones |url=https://www.niddk.nih.gov/health-information/digestive-diseases/gallstones/treatment |website=National Institute of Diabetes and Digestive and Kidney Diseases|date=November 2017}}</ref>

<!-- Epidemiology and prognosis -->
In [[Finance:Developed country|developed countries]], 10–15% of adults experience gallstones.<ref name=WS2016>{{cite journal | vauthors = Ansaloni L, Pisano M, Coccolini F, Peitzmann AB, Fingerhut A, Catena F, Agresta F, Allegri A, Bailey I, Balogh ZJ, Bendinelli C, Biffl W, Bonavina L, Borzellino G, Brunetti F, Burlew CC, Camapanelli G, Campanile FC, Ceresoli M, Chiara O, Civil I, Coimbra R, De Moya M, Di Saverio S, Fraga GP, Gupta S, Kashuk J, Kelly MD, Koka V, Jeekel H, Latifi R, Leppaniemi A, Maier RV, Marzi I, Moore F, Piazzalunga D, Sakakushev B, Sartelli M, Scalea T, Stahel PF, Taviloglu K, Tugnoli G, Uraneus S, Velmahos GC, Wani I, Weber DG, Viale P, Sugrue M, Ivatury R, Kluger Y, Gurusamy KS, Moore EE | display-authors = 6 | title = 2016 WSES guidelines on acute calculous cholecystitis | journal = World Journal of Emergency Surgery | volume = 11 | pages = 25 | date = 2016 | pmid = 27307785 | pmc = 4908702 | doi = 10.1186/s13017-016-0082-5 | doi-access = free }}</ref> Gallbladder and biliary-related diseases occurred in about 104 million people (1.6% of people) in 2013 and resulted in 106,000 deaths.<ref>{{cite journal | title = Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 | journal = Lancet | volume = 386 | issue = 9995 | pages = 743–800 | date = August 2015 | pmid = 26063472 | pmc = 4561509 | doi = 10.1016/s0140-6736(15)60692-4 | last1 = Vos | first1 = Theo | last2 = Barber | first2 = Ryan M. | last3 = Bell | first3 = Brad | last4 = Bertozzi-Villa | first4 = Amelia | last5 = Biryukov | first5 = Stan | last6 = Bolliger | first6 = Ian | last7 = Charlson | first7 = Fiona | last8 = Davis | first8 = Adrian | last9 = Degenhardt | first9 = Louisa | last10 = Dicker | first10 = Daniel | last11 = Duan | first11 = Leilei | last12 = Erskine | first12 = Holly | last13 = Feigin | first13 = Valery L. | last14 = Ferrari | first14 = Alize J. | last15 = Fitzmaurice | first15 = Christina | last16 = Fleming | first16 = Thomas | last17 = Graetz | first17 = Nicholas | last18 = Guinovart | first18 = Caterina | last19 = Haagsma | first19 = Juanita | last20 = Hansen | first20 = Gillian M. | last21 = Hanson | first21 = Sarah Wulf | last22 = Heuton | first22 = Kyle R. | last23 = Higashi | first23 = Hideki | last24 = Kassebaum | first24 = Nicholas | last25 = Kyu | first25 = Hmwe | last26 = Laurie | first26 = Evan | last27 = Liang | first27 = Xiofeng | last28 = Lofgren | first28 = Katherine | last29 = Lozano | first29 = Rafael | last30 = MacIntyre | first30 = Michael F. | display-authors = 1 }}</ref><ref>{{cite journal | title = Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 | journal = Lancet | volume = 385 | issue = 9963 | pages = 117–71 | date = January 2015 | pmid = 25530442 | pmc = 4340604 | doi = 10.1016/s0140-6736(14)61682-2 | author1 = GBD 2013 Mortality Causes of Death Collaborators }}</ref> Gallstones are more common among women than men and occur more commonly after the age of 40.<ref name=NIH2013/> Gallstones occur more frequently among [[Biology:Race and health|certain ethnic group]]s than others.<ref name=NIH2013/> For example, 48% of Native Americans experience gallstones, whereas gallstone rates in many parts of Africa are as low as 3%.<ref>{{cite book|url=https://books.google.com/books?id=VcgmpMZE6a8C&pg=PA944|title=Principles and practice of geriatric surgery|date=2011|publisher=Springer|isbn=9781441969996|veditors=Rosenthal RA, Zenilman ME, Katlic MR|edition=2nd|location=Berlin|page=944|archive-url=https://web.archive.org/web/20160815224542/https://books.google.ca/books?id=VcgmpMZE6a8C&pg=PA944|archive-date=2016-08-15|url-status=live}}</ref><ref name="NIH2013" /> Once the gallbladder is removed, outcomes are generally positive.<ref name="NIH2013" />

==Definition==
Gallstone disease refers to the condition where gallstones are either in the gallbladder or common bile duct.<ref name=NICE2014/> The presence of stones in the gallbladder is referred to as ''cholelithiasis'', from the Greek {{wikt-lang|en|chole-}} ({{lang|grc|χολή}}, 'bile') + {{wikt-lang|en|lith-}} ({{lang|grc|λίθος}}, 'stone') + {{wikt-lang|en|-iasis}} ({{lang|grc|ἴασις}}, 'process').<ref name=Qui2013>{{cite book | vauthors = Quick CR, Reed JB, Harper SJ, Saeb-Parsy K, Deakin PJ |title=Essential Surgery E-Book: Problems, Diagnosis and Management: With STUDENT CONSULT Online Access |date=2013 |publisher=Elsevier Health Sciences |isbn=9780702054839 |page=281 |url=https://books.google.com/books?id=RYhRAAAAQBAJ&pg=PA281 |language=en}}</ref> The presence of gallstones in the [[Biology:Common bile duct|common bile duct]] is called ''choledocholithiasis'', from the Greek {{wikt-lang|en|choledocho-}} ({{lang|grc|χοληδόχος}}, 'bile-containing', from {{lang|grc-Latn|chol-}} + {{lang|grc-Latn|docho-}}, 'duct') + {{lang|grc-Latn|lith-}} + {{lang|en|-iasis|italic=yes}}.<ref name=Qui2013/> Choledocholithiasis is frequently associated with obstruction of the bile ducts, which can lead to ''[[Medicine:Ascending cholangitis|cholangitis]]'', from the Greek: {{lang|grc-Latn|chol-}} + {{wikt-lang|en|angio-|ang-}} ({{lang|grc|ἄγγος}}, 'vessel') + {{wikt-lang|en|-itis}} ({{wikt-lang|grc|-ῖτις}}, 'inflammation'), a serious infection of the bile ducts. Gallstones within the ampulla of Vater can obstruct the exocrine system of the pancreas and can result in [[Medicine:Pancreatitis|pancreatitis]].{{cn|date=March 2022}}

==Signs and symptoms==
Gallstones, regardless of size or number, are often asymptomatic.<ref name=Acalovschi2003/> These "silent stones" do not require treatment and can remain asymptomatic even years after they form.<ref name=NDDIC/><ref name=Heuman2010/>

A characteristic symptom of a gallstone attack is the presence of [[Medicine:Colic|colic-like]] pain in the upper-right side of the abdomen, often accompanied by nausea and vomiting. Pain from symptomatic gallstones may range from mild to severe and can steadily increase over a period lasting from 30 minutes to several hours. Other symptoms may include fever, as well as referred pain between the [[Biology:Scapula|shoulder blades]] or below the right shoulder. If one or more gallstones block the bile ducts and cause bilirubin to leak into the bloodstream and surrounding tissue, jaundice and itching may also occur. In this case, liver enzyme levels are likely to be raised.<ref name=":1">{{Cite web|url=http://emedicine.medscape.com/article/175667-clinical#b3|title=Gallstones (Cholelithiasis) Clinical Presentation: History, Physical Examination|website=emedicine.medscape.com|access-date=2016-11-14|url-status=live|archive-url=https://web.archive.org/web/20161114232506/http://emedicine.medscape.com/article/175667-clinical#b3|archive-date=2016-11-14}}</ref>

Often, gallbladder attacks occur after eating a heavy meal. Attacks are most common in the evening or at night.<ref>{{Cite web |title=Symptoms & Causes of Gallstones {{!}} NIDDK |url=https://www.niddk.nih.gov/health-information/digestive-diseases/gallstones/symptoms-causes |access-date=2022-06-28 |website=National Institute of Diabetes and Digestive and Kidney Diseases |language=en-US}}</ref>

===Other complications===
In rare cases, gallstones that cause severe inflammation can erode through the gallbladder into adherent bowel, potentially causing an obstruction termed gallstone ileus.<ref>{{cite journal | vauthors = Fitzgerald JE, Fitzgerald LA, Maxwell-Armstrong CA, Brooks AJ | title = Recurrent gallstone ileus: time to change our surgery? | journal = Journal of Digestive Diseases | volume = 10 | issue = 2 | pages = 149–51 | date = May 2009 | pmid = 19426399 | doi = 10.1111/j.1751-2980.2009.00378.x | s2cid = 43696188 | doi-access = free }}</ref>

Other complications can include [[Medicine:Ascending cholangitis|ascending cholangitis]], which occurs when a bacterial infection causes purulent inflammation in the biliary tree and liver, and [[Medicine:Acute pancreatitis|acute pancreatitis]] caused by blockage of the bile ducts that prevents active enzymes from being secreted into the bowel, instead damaging the pancreas.<ref name=":1" /> Rarely, [[Medicine:Gallbladder cancer|gallbladder cancer]] may occur as a complication.<ref name=NHS2018/>

==Risk factors==
Gallstone risk increases for females (especially before menopause) and for people near or above 40 years;<ref name=Roizen2005/> the condition is more prevalent among people of European or American Indigenous descent than among other ethnicities.<ref name=":0">{{Cite web |last1=Afdhal |first1=Nezam |last2=Zakko |first2=Salam |date=Sep 2022 |title=Gallstones: Epidemiology, risk factors and prevention |url=https://www.uptodate.com/contents/gallstones-epidemiology-risk-factors-and-prevention |access-date=2023-05-26 |website=UpToDate}}</ref> A lack of [[Chemistry:Melatonin|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.<ref name=Koppisetti2008/> [[Medicine:Gilbert's syndrome|Gilbert syndrome]] has been linked to an increased risk of gallstones.<ref>{{Cite journal |last1=del Giudice |first1=Emanuele Miraglia |last2=Perrotta |first2=Silverio |last3=Nobili |first3=Bruno |last4=Specchia |first4=Claudia |last5=d’Urzo |first5=Giovanna |last6=Iolascon |first6=Achille |date=1999-10-01 |title=Coinheritance of Gilbert Syndrome Increases the Risk for Developing Gallstones in Patients With Hereditary Spherocytosis |url=https://ashpublications.org/blood/article/94/7/2259/125485/Coinheritance-of-Gilbert-Syndrome-Increases-the |journal=Blood |language=en |volume=94 |issue=7 |pages=2259–2262 |doi=10.1182/blood.V94.7.2259.419k42_2259_2262 |pmid=10498597 |s2cid=40558696 |issn=1528-0020|url-access=subscription }}</ref> Researchers believe that gallstones may be caused by a combination of factors, including inherited body chemistry, body weight, gallbladder [[Biology:Motility|motility]] (movement), and low-calorie diet.<ref name=":0" /> The absence of such risk factors does not, however, preclude the formation of gallstones.

Nutritional factors that may increase risk of gallstones include [[Medicine:Constipation|constipation]]; eating fewer meals per day; low intake of the nutrients folate, [[Chemistry:Magnesium|magnesium]], [[Chemistry:Calcium|calcium]], and [[Biology:Vitamin C|vitamin C]];<ref name=Ortega1997/> low fluid consumption;<ref>{{Cite book|url=https://www.nap.edu/read/10925/chapter/6#124|title=4 Water {{!}} Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate | publisher = The National Academies Press|year=2005|isbn=978-0-309-09169-5 |pages=124|doi=10.17226/10925 | author1 = Institute of Medicine | author2 = Food Nutrition Board |author3 = Standing Committee on the Scientific Evaluation of Dietary Reference Intakes | author4 = Panel on Dietary Reference Intakes for Electrolytes and Water}}</ref> and, at least for men, a high intake of [[Chemistry:Carbohydrate|carbohydrate]], a high glycemic load, and high [[Medicine:Glycemic index|glycemic index]] diet.<ref>{{cite journal | vauthors = Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL | title = Dietary carbohydrates and glycaemic load and the incidence of symptomatic gall stone disease in men | journal = Gut | volume = 54 | issue = 6 | pages = 823–8 | date = June 2005 | pmid = 15888792 | pmc = 1774557 | doi = 10.1136/gut.2003.031435 }}</ref> Wine and whole-grained bread may decrease the risk of gallstones.<ref name=Misciagna1996/>

Rapid weight loss increases risk of gallstones.<ref>{{Cite web|url=http://www.nhs.uk/Livewell/loseweight/Pages/should-you-lose-weight-fast.aspx|title=Should you lose weight fast? - Live Well—NHS Choices | author = NHS Choices |website=www.nhs.uk|access-date=2016-02-16|url-status=live|archive-url=https://web.archive.org/web/20160216025459/http://www.nhs.uk/livewell/loseweight/Pages/should-you-lose-weight-fast.aspx|archive-date=2016-02-16}}</ref> The weight loss drug [[Biology:Orlistat|orlistat]] is known to increase the risk of gallstones.<ref>{{Cite web|url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm215504.htm|title=Safety Information—Xenical (orlistat) capsules | author = Office of the Commissioner |website=www.fda.gov|language=en|access-date=2016-06-18|url-status=live|archive-url=https://web.archive.org/web/20160611084534/https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm215504.htm|archive-date=2016-06-11}}</ref>

Cholecystokinin deficiency caused by celiac disease increases risk of gallstone formation, especially when diagnosis of celiac disease is delayed.<ref name=WangLiu2017>{{cite journal | vauthors = Wang HH, Liu M, Li X, Portincasa P, Wang DQ | title = Impaired intestinal cholecystokinin secretion, a fascinating but overlooked link between coeliac disease and cholesterol gallstone disease | journal = European Journal of Clinical Investigation | volume = 47 | issue = 4 | pages = 328–333 | date = April 2017 | pmid = 28186337 | pmc = 8135131 | doi = 10.1111/eci.12734 | type = Review | doi-access = free }}</ref>

Pigment gallstones are most commonly seen in the developing world. Risk factors for pigment stones include hemolytic anemias (such as from sickle-cell disease and hereditary spherocytosis), [[Medicine:Cirrhosis|cirrhosis]], and biliary tract infections.<ref name="pmid7410545" /> People with [[Medicine:Erythropoietic protoporphyria|erythropoietic protoporphyria]] (EPP) are at increased risk to develop gallstones.<ref name="Merck2006" /><ref name="Thunell2008" /> Additionally, prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to gallstone formation.<ref>{{cite journal | vauthors = Cahan MA, Balduf L, Colton K, Palacioz B, McCartney W, Farrell TM | title = Proton pump inhibitors reduce gallbladder function | journal = Surgical Endoscopy | volume = 20 | issue = 9 | pages = 1364–7 | date = September 2006 | pmid = 16858534 | doi = 10.1007/s00464-005-0247-x | s2cid = 20833380 }}</ref>

Cholesterol modifying medications can affect gallstone formation. [[Biology:Statin|Statin]]s inhibit cholesterol synthesis and there is evidence that their use may decrease the risk of getting gallstones.<ref>{{cite journal | vauthors = Kan HP, Guo WB, Tan YF, Zhou J, Liu CD, Huang YQ | title = Statin use and risk of gallstone disease: A meta-analysis | journal = Hepatology Research | volume = 45 | issue = 9 | pages = 942–948 | date = September 2015 | pmid = 25297889 | doi = 10.1111/hepr.12433 | s2cid = 25636425 }}</ref><ref name=":2">{{cite journal | vauthors = Preiss D, Tikkanen MJ, Welsh P, Ford I, Lovato LC, Elam MB, LaRosa JC, DeMicco DA, Colhoun HM, Goldenberg I, Murphy MJ, MacDonald TM, Pedersen TR, Keech AC, Ridker PM, Kjekshus J, Sattar N, McMurray JJ | display-authors = 6 | title = Lipid-modifying therapies and risk of pancreatitis: a meta-analysis | journal = JAMA | volume = 308 | issue = 8 | pages = 804–11 | date = August 2012 | pmid = 22910758 | doi = 10.1001/jama.2012.8439 | doi-access = free }}</ref> [[Chemistry:Fibrate|Fibrate]]s increase cholesterol concentration in bile and their use has been associated with an increased risk of gallstones.<ref name=":2" /> [[Medicine:Bile acid malabsorption|Bile acid malabsorption]] may also be a risk.

==Pathophysiology==
Cholesterol gallstones develop when bile contains too much cholesterol and not enough [[Chemistry:Bile acid|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.<ref>Experimental investigation of the flow of bile in patient specific cystic duct models M Al-Atabi, SB Chin…, Journal of biomechanical engineering, 2010</ref> 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 [[Biology:Estrogen|estrogen]], as a result of [[Medicine:Pregnancy|pregnancy]] or [[Medicine:Hormone therapy|hormone therapy]], or the use of combined (estrogen-containing) forms of [[Chemistry:Hormonal contraception|hormonal contraception]], may increase cholesterol levels in bile and also decrease gallbladder motility, resulting in gallstone formation.{{cn|date=March 2022}}

===Composition===
[[File:Types of Gallstones.jpg|thumb|upright=1.3|From left to right: cholesterol stone, mixed stone, pigment stone.]]
The composition of gallstones is affected by age, diet and [[Social:Ethnic group|ethnicity]].<ref name=Channa2007/> On the basis of their composition, gallstones can be divided into the following types: cholesterol stones, pigment stones, and mixed stones.<ref name=Lee2015/> An ideal classification system is yet to be defined.<ref name=Kim2003/>

====Cholesterol stones====
[[Chemistry:Cholesterol|Cholesterol]] stones vary from light yellow to dark green or brown or chalk white and are oval, usually solitary, between 2 and 3&nbsp;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).<ref name=Kim2003/> Between 35% and 90% of stones are cholesterol stones.<ref name=Lee2015/>

====Pigment stones====
[[Chemistry:Bilirubin|Bilirubin]] ("pigment", "black pigment") stones are small, dark (often appearing black), and usually numerous. They are composed primarily of bilirubin (insoluble bilirubin pigment polymer) and [[Chemistry:Calcium|calcium]] (calcium phosphate) [[Chemistry:Salt|salts]] that are found in bile. They contain less than 20% of cholesterol (or 30%, according to the Japanese classification system).<ref name=Kim2003/> Between 2% and 30% of stones are bilirubin stones.<ref name=Lee2015/>

====Mixed stones====
Mixed ([[Chemistry:Stercobilin#Brown pigment stone|brown pigment]] stones) typically contain 20–80% cholesterol (or 30–70%, according to the Japanese classification system).<ref name=Kim2003/> Other common constituents are [[Chemistry:Calcium carbonate|calcium carbonate]], palmitate phosphate, bilirubin and other [[Chemistry:Bilin (biochemistry)|bile pigments]] (calcium bilirubinate, calcium palmitate and [[Chemistry:Calcium stearate|calcium stearate]]). Because of their calcium content, they are often radiographically visible. They typically arise secondary to infection of the biliary tract which results in the release of β-glucuronidase (by injured [[Biology:Hepatocyte|hepatocyte]]s and bacteria) which hydrolyzes bilirubin [[Chemistry:Glucuronide|glucuronide]]s and increases the amount of unconjugated bilirubin in bile. Between 4% and 20% of stones are mixed.<ref name=Lee2015/>

Gallstones can vary in size and shape from as small as a grain of sand to as large as a golf ball.<ref>[https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001318 Gallstones—Cholelithiasis; Gallbladder attack; Biliary colic; Gallstone attack; Bile calculus; Biliary calculus] {{webarchive|url=https://web.archive.org/web/20110207050708/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001318 |date=2011-02-07 }} Last reviewed: July 6, 2009. Reviewed by: George F. Longstreth. Also reviewed by David Zieve</ref> The gallbladder may contain a single large stone or many smaller ones. Pseudoliths, sometimes referred to as sludge, are thick [[Biology:Secretion|secretion]]s that may be present within the gallbladder, either alone or in conjunction with fully formed gallstones.

<gallery mode="packed" widths="360px" heights="220">
File:Gallstones.JPG|Gallbladder opened to show small cholesterol gallstones
File:Gallstone µCT.jpg|[[Astronomy:X-ray microtomography|X-ray microtomograph]] of a gallstone
File:Gallstones.jpg|The large, yellow stone is largely cholesterol, while the green-to-brown stones are mostly composed of [[Chemistry:Bilin (biochemistry)|bile pigments]]
File:Gallenstein FRONT.OGG|[[CT scan|CT]] images of gallstones
File:Big Gallstone.JPG|Large gallstone
File:Human gallstones 2015 G1.jpg|Numerous small gallstones made up largely of [[Chemistry:Cholesterol|cholesterol]]
</gallery>

==Diagnosis==
Diagnosis is typically confirmed by abdominal ultrasound.<!-- <ref name=NIH2013/> --> Other imaging techniques used are ERCP and [[Physics:Magnetic resonance cholangiopancreatography|MRCP]]. Gallstone complications may be detected on blood tests.<ref name=NIH2013/>

On abdominal ultrasound, sinking gallstones usually have posterior acoustic shadowing. In floating gallstones, reverberation echoes (or comet-tail artifact) is seen instead in a clinical condition called [[Medicine:Adenomyomatosis|adenomyomatosis]]. Another sign is wall-echo-shadow (WES) triad (or double-arc shadow) which is also characteristic of gallstones.<ref>{{cite journal | vauthors = Fitzgerald EJ, Toi A | title = Pitfalls in the ultrasonographic diagnosis of gallbladder diseases | journal = Postgraduate Medical Journal | volume = 63 | issue = 741 | pages = 525–32 | date = July 1987 | pmid = 3309915 | pmc = 2428351 | doi = 10.1136/pgmj.63.741.525 }}</ref>

A positive [[Medicine:Murphy's sign|Murphy's sign]] is a common finding on physical examination during a gallbladder attack.
<gallery mode="packed" widths="360px" heights="220">
File:Gallstones.PNG|A 1.9&nbsp;cm gallstone impacted in the neck of the gallbladder and leading to cholecystitis as seen on ultrasound. There is 4&nbsp;mm gall bladder wall thickening.
File:Ultrasonography of sludge and gallstones, annotated.jpg|[[Medicine:Biliary sludge|Biliary sludge]] and gallstones. There is borderline thickening of the gallbladder wall.
File:StonesXray.PNG|Gallstones as seen on plain X-ray
File:LargeGstoneMark.png|Large gallstone as seen on CT
File:UOTW 8 - Ultrasound of the Week 1.webm|A normal gallbladder on ultrasound with bowel peristalsis creating the false appearance of stones
</gallery>

==Prevention==
Maintaining a healthy weight by getting sufficient exercise and eating a healthy diet that is high in fiber may help prevent gallstone formation.<ref name=NIH2013/>

[[Chemistry:Ursodeoxycholic acid|Ursodeoxycholic acid]] (UDCA) appears to prevent formation of gallstones during weight loss. A high fat diet during weight loss also appears to prevent gallstones.<ref name=stokes>{{cite journal | vauthors = Stokes CS, Gluud LL, Casper M, Lammert F | title = Ursodeoxycholic acid and diets higher in fat prevent gallbladder stones during weight loss: a meta-analysis of randomized controlled trials | journal = Clinical Gastroenterology and Hepatology | volume = 12 | issue = 7 | pages = 1090–1100.e2; quiz e61 | date = July 2014 | pmid = 24321208 | doi = 10.1016/j.cgh.2013.11.031 | doi-access = free }}</ref>

==Treatment==
===Lithotripsy===
[[Medicine:Extracorporeal shockwave therapy|Extracorporeal shock wave lithotripsy]] is a non-invasive method to manage gallstones that uses high-energy sound waves to disintegrate them first applied in January 1985.<ref name="Johns Hopkins Medicine">{{cite web | title=Gallstone Disease Treatment | website=Johns Hopkins Medicine | url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/gallstone-disease-treatment | access-date=2021-09-25}}</ref><ref name="LWW 2021">{{cite journal | title=European Journal of Gastroenterology & Hepatology | website=LWW | date=2021-09-25 | volume=17 | issue=5 | pages=525–527 | url=https://journals.lww.com/eurojgh/Fulltext/2005/05000/Extracorporeal_shock_wave_lithotripsy_of.9.aspx | access-date=2021-09-25| last1=Paumgartner | first1=Gustav }}</ref>
Side effects of extracorporeal shock wave lithotripsy include biliary pancreatitis and liver haematoma.<ref name="Paumgartner Sauter 2005 pp. 525–527">{{cite journal | last1=Paumgartner | first1=Gustav | last2=Sauter | first2=Gerd H. | title=Extracorporeal shock wave lithotripsy of gallstones: 20th anniversary of the first treatment | journal=European Journal of Gastroenterology & Hepatology | publisher=Ovid Technologies (Wolters Kluwer Health) | volume=17 | issue=5 | year=2005 | issn=0954-691X | doi=10.1097/00042737-200505000-00009 | pages=525–527| pmid=15827443 | s2cid=9803771 | doi-access=free }}</ref>
The term is derived from the Greek words meaning 'breaking (or pulverizing) stones': {{wikt-lang|en|litho-}} + {{wikt-lang|grc|τρίβω|τρίψω}}, {{lang|grc-Latn|tripso}}).

===Surgical===
[[Medicine:Cholecystectomy|Cholecystectomy]] (gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. The lack of a gallbladder has no negative consequences in most people, however 10 to 15% of people develop [[Medicine:Postcholecystectomy syndrome|postcholecystectomy syndrome]],<ref name=eMedicine/> which may cause nausea, indigestion, diarrhea, and episodes of abdominal pain.<ref>{{cite journal | title = Postcholecystectomy Syndrome | journal = StatPearls | date = January 2019 | pmid = 30969724 | last1 = Zackria | first1 = R. | last2 = Lopez | first2 = R. A. }}</ref>

There are two surgical options for cholecystectomy:
* Open cholecystectomy is performed via an abdominal 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.<ref name=NDDIC/>
* [[Medicine:Laparoscopy|Laparoscopic]] cholecystectomy, introduced in the 1980s, 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.<ref name=NDDIC/> Perforation of the gall bladder is not uncommon—it has been reported in the range of 10% to 40%. Unretrieved gallstone spillage has been reported as 6% to 30%, but gallstones that are not retrieved rarely cause complications (0.08%–0.3%).<ref>{{cite journal | last=Sathesh-Kumar | first=T | title=Spilled gall stones during laparoscopic cholecystectomy: a review of the literature | journal=Postgraduate Medical Journal | publisher=BMJ | volume=80 | issue=940 | date=1 February 2004 | issn=0032-5473 | doi=10.1136/pmj.2003.006023|doi-access=free | pages=77–79| pmid=14970293 | pmc=1742934 }}</ref>

Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy (ERS) following endoscopic retrograde cholangiopancreatography (ERCP).<ref name=NHS/>

===Medical===
The medications [[Chemistry:Ursodeoxycholic acid|ursodeoxycholic acid]] (UDCA) and [[Chemistry:Chenodeoxycholic acid|chenodeoxycholic acid]] (CDCA) have been used in treatment to dissolve gallstones.<ref name="pmid4580472">{{cite journal | vauthors = Thistle JL, Hofmann AF | title = Efficacy and specificity of chenodeoxycholic acid therapy for dissolving gallstones | journal = The New England Journal of Medicine | volume = 289 | issue = 13 | pages = 655–9 | date = September 1973 | pmid = 4580472 | doi = 10.1056/NEJM197309272891303 }}</ref><ref name="PMID2672842">{{cite journal | vauthors = Hofmann AF | title = Medical dissolution of gallstones by oral bile acid therapy | journal = American Journal of Surgery | volume = 158 | issue = 3 | pages = 198–204 | date = September 1989 | pmid = 2672842 | doi = 10.1016/0002-9610(89)90252-3 }}</ref> A 2013 meta-analysis concluded that UDCA or higher dietary fat content appeared to prevent formation of gallstones during weight loss.<ref name=stokes/> Medical therapy with oral bile acids has been used to treat small cholesterol stones, and for larger cholesterol gallstones when surgery is either not possible or unwanted. CDCA treatment can cause diarrhea, mild reversible hepatic injury, and a small increase in the plasma cholesterol level.<ref name="PMID2672842"/> UDCA may need to be taken for years.<ref name=NHS/>

==Use in traditional medicine==
Gallstones can be a valued by-product of animals butchered for meat because of their use as an [[Chemistry:Antipyretic|antipyretic]] and antidote in the [[Medicine:Traditional medicine|traditional medicine]] of some cultures, particularly [[Medicine:Traditional Chinese medicine|traditional Chinese medicine]]. The most highly prized gallstones tend to be sourced from old dairy cows, termed calculus bovis or ''niu-huang'' (yellow thing of cattle) in Chinese. Some slaughterhouses carefully scrutinize workers for gallstone theft.<ref name=Wise/>

== See also ==
* Mirizzi's syndrome
* Porcelain gallbladder

== References ==
{{reflist|30em|refs=

<ref name=Acalovschi2003>{{cite journal | vauthors = Acalovschi M, Blendea D, Feier C, Letia AI, Ratiu N, Dumitrascu DL, Veres A | title = Risk factors for symptomatic gallstones in patients with liver cirrhosis: a case-control study | journal = The American Journal of Gastroenterology | volume = 98 | issue = 8 | pages = 1856–60 | date = August 2003 | doi = 10.1111/j.1572-0241.2003.07618.x | pmid = 12907344 | s2cid = 26695806 }}</ref>

<ref name=Channa2007>{{cite journal | vauthors = Channa NA, Khand FD, Khand TU, Leghari MH, Memon AN |title=Analysis of human gallstones by Fourier Transform Infrared (FTIR) |journal=Pakistan Journal of Medical Sciences |volume=23 |issue=4 |pages=546–50 |year=2007 |issn=1682-024X |url=http://pjms.com.pk/issues/julsep07/article/article15.html |access-date=2010-11-06 |url-status=live |archive-url=https://web.archive.org/web/20110824133936/http://pjms.com.pk/issues/julsep07/article/article15.html |archive-date=2011-08-24 }}</ref>

<ref name=Heuman2010>{{cite web|vauthors=Heuman DM, Mihas AA, Allen J|title=Cholelithiasis|year=2010|publisher=[[Medicine:Medscape|Medscape]] ([[Company:WebMD|WebMD]])|location=Omaha, Nebraska|url=http://emedicine.medscape.com/article/175667-overview|access-date=2010-11-06|url-status=live|archive-url=https://web.archive.org/web/20101120182736/http://emedicine.medscape.com/article/175667-overview|archive-date=2010-11-20}}</ref>

<ref name=Kim2003>{{cite journal | vauthors = Kim IS, Myung SJ, Lee SS, Lee SK, Kim MH | title = Classification and nomenclature of gallstones revisited | journal = Yonsei Medical Journal | volume = 44 | issue = 4 | pages = 561–70 | date = August 2003 | pmid = 12950109 | doi = 10.3349/ymj.2003.44.4.561 | doi-access = free }}</ref>

<ref name=Koppisetti2008>{{cite journal | vauthors = Koppisetti S, Jenigiri B, Terron MP, Tengattini S, Tamura H, Flores LJ, Tan DX, Reiter RJ | display-authors = 6 | title = Reactive oxygen species and the hypomotility of the gall bladder as targets for the treatment of gallstones with melatonin: a review | journal = Digestive Diseases and Sciences | volume = 53 | issue = 10 | pages = 2592–603 | date = October 2008 | pmid = 18338264 | doi = 10.1007/s10620-007-0195-5 | s2cid = 22785223 }}</ref>

<ref name=Merck2006>''Endocrine and Metabolic Disorders: Cutaneous Porphyrias'', pp. 63–220 in Beers, Porter and Jones (2006)</ref>

<ref name=Misciagna1996>{{cite journal | vauthors = Misciagna G, Leoci C, Guerra V, Chiloiro M, Elba S, Petruzzi J, Mossa A, Noviello MR, Coviello A, Minutolo MC, Mangini V, Messa C, Cavallini A, De Michele G, Giorgio I | display-authors = 6 | title = Epidemiology of cholelithiasis in southern Italy. Part II: Risk factors | journal = European Journal of Gastroenterology & Hepatology | volume = 8 | issue = 6 | pages = 585–93 | date = June 1996 | pmid = 8823575 | doi = 10.1097/00042737-199606000-00017 | s2cid = 11355563 }}</ref>

<ref name=NDDIC>{{cite web|author=National Institute of Diabetes and Digestive and Kidney Diseases|title=Gallstones|year=2007|publisher=[[Organization:National Digestive Diseases Information Clearinghouse|National Digestive Diseases Information Clearinghouse]], [[Organization:National Institutes of Health|National Institutes of Health]], United States Department of Health and Human Services|location=Bethesda, Maryland|url=http://digestive.niddk.nih.gov/ddiseases/pubs/gallstones/Gallstones.pdf|access-date=2010-11-06|url-status=dead|archive-url=https://web.archive.org/web/20101205101957/http://digestive.niddk.nih.gov/ddiseases/pubs/gallstones/Gallstones.pdf|archive-date=2010-12-05}}</ref>

<ref name=NHS>{{cite web|author=National Health Service|title=Gallstones — Treatment|year=2010|publisher=National Health Service|location=London|work=NHS Choices: Health A-Z—Conditions and treatments|url=http://www.nhs.uk/conditions/gallstones/pages/treatment.aspx|access-date=2010-11-06|url-status=live|archive-url=https://web.archive.org/web/20101114084152/http://www.nhs.uk/Conditions/Gallstones/Pages/Treatment.aspx|archive-date=2010-11-14}}</ref>

<ref name=Ortega1997>{{cite journal | vauthors = Ortega RM, Fernández-Azuela M, Encinas-Sotillos A, Andrés P, López-Sobaler AM | title = Differences in diet and food habits between patients with gallstones and controls | journal = Journal of the American College of Nutrition | volume = 16 | issue = 1 | pages = 88–95 | date = February 1997 | pmid = 9013440 | doi = 10.1080/07315724.1997.10718655 | url = http://www.jacn.org/cgi/content/abstract/16/1/88 | access-date = 2010-11-06 | url-status = dead | archive-url = https://web.archive.org/web/20080720125626/http://www.jacn.org/cgi/content/abstract/16/1/88 | archive-date = 2008-07-20 }}</ref>

<ref name=pmid7410545>{{cite journal | vauthors = Trotman BW, Bernstein SE, Bove KE, Wirt GD | title = Studies on the pathogenesis of pigment gallstones in hemolytic anemia: description and characteristics of a mouse model | journal = The Journal of Clinical Investigation | volume = 65 | issue = 6 | pages = 1301–8 | date = June 1980 | pmid = 7410545 | pmc = 371467 | doi = 10.1172/JCI109793 }}</ref>

<ref name=Roizen2005>{{cite book | vauthors = Roizen MF, Oz MC | title = Gut Feelings: Your Digestive System | pages = 175–206 | date = 2005 |publisher=HarperCollins e-books |location=Pymble, NSW |isbn=978-0-06-198079-4}}</ref>

<ref name=Thunell2008>{{cite web|vauthors=Thunell S|title=Endocrine and Metabolic Disorders: Cutaneous Porphyrias|year=2008|publisher=Merck Sharp & Dohme Corporation|location=Whitehouse Station, New Jersey|url=http://www.merck.com/mmpe/sec12/ch155/ch155c.html?qt=Erythropoietic%20Protoporphyria&alt=sh#sec12-ch155-ch155c-635|access-date=2010-11-07|archive-date=2020-03-12|archive-url=https://web.archive.org/web/20200312142747/http://www.merck.com/mmpe/sec12/ch155/ch155c.html?qt=Erythropoietic%20Protoporphyria&alt=sh#sec12-ch155-ch155c-635|url-status=dead}}</ref>

<ref name=eMedicine>{{cite web|author=Jensen|title=Postcholecystectomy syndrome|year=2010|publisher=Medscape (WebMD)|location=Omaha, Nebraska|url=http://emedicine.medscape.com/article/192761-overview|access-date=2011-01-20|url-status=live|archive-url=https://web.archive.org/web/20101223003851/http://emedicine.medscape.com/article/192761-overview|archive-date=2010-12-23}}</ref>

<ref name=Wise>{{cite web  |title=Interview with Darren Wise. Transcrip  |publisher=Medscape (WebMD)  |location=Omaha, Nebraska  |url=http://sgp1.paddington.ninemsn.com.au/sunday/cover_stories/transcript_785.asp  |access-date=2010-11-06  |url-status=dead  |archive-url=https://web.archive.org/web/20101121121630/http://sgp1.paddington.ninemsn.com.au/sunday/cover_stories/transcript_785.asp  |archive-date=2010-11-21  }}</ref>
}}

== External links ==
* {{cite web | url = https://medlineplus.gov/gallstones.html | publisher = U.S. National Library of Medicine | department = [[Social:MedlinePlus|MedlinePlus]] | title = Gallstones }}

{{Medical resources
| ICD10           = {{ICD10|K|80||k|80}}
| ICD9            = {{ICD9|574}}
| ICDO            =
| OMIM            = 600803
| MedlinePlus     = 000273
| eMedicineSubj   = emerg
| eMedicineTopic  = 97
| DiseasesDB      = 2533
| MeshID          = D042882
| SNOMED CT       = 235919008
}}
{{Gastroenterology}}

[[Category:Hepatology]]
[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|Gallstone}}