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==Overview==
==Overview==
Gallstone disease is the presence of gallstones ([[cholelithiasis]]) within the gallbladder —''chole-'' means "bile", ''lithia'' means "stone", and ''-sis'' means "process". Gallstones are [[crystalline]] bodies formed within the body by 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 called ''[[choledocholithiasis]],'' obstruction of the biliary tree can cause [[jaundice]] and obstruction of the outlet of the pancreatic exocrine system can cause [[pancreatitis]].  
[[Gallstone disease|Gallstone]] disease is the presence of gallstones ([[cholelithiasis]]) within the gallbladder —''chole-'' means "bile", ''lithia'' means "stone", and ''-sis'' means "process". Gallstones are [[crystalline]] bodies formed within the body by 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 called ''[[choledocholithiasis]],'' obstruction of the biliary tree can cause [[jaundice]] and obstruction of the outlet of the pancreatic exocrine system can cause [[pancreatitis]].  


==Historical Perspective==
==Historical Perspective==
Gallstone disease has been noted as far back as when Egyptian pharaohs ruled. Autopsies performed on mummies found gallstones present within the body cavities.
Humans have a long history with [[gallstones]] with the earliest recording being noted at least 7000 years ago. [[Autopsy|Autopsies]] performed on the earliest mummies in Egypt were discovered to have gallstones. Gallstones became easier to visualize in 1895 with the introduction of the plain [[X-rays|x-ray]] film. In 1924 and 1970, IV cholecystography and percutaneous transhepatic cholangiography were developed respectively.


==Classification==
==Classification==
Gallstone disease may be classified according to the chemical analysis of the stone found into 3 subtypes/groups: pure [[cholesterol]], pure [[bilirubin]] stones and mixed.
Gallstone disease may be classified according to the chemical analysis of gallstone. In this way, there are 3 subtypes: pure [[cholesterol]], pure [[bilirubin]] stones and mixed.


==Pathophysiology==
==Pathophysiology==
It has long been noted that gallbladder stone formation, and in particular [[cholesterol]] stones, are associated with [[bile]] [[supersaturation]], and this still remains the most common cause for gallstone formation.
Studies have shown that gallstone formation is mostly due to bile supersaturation. In the United States, patients that present with gallbladder stones mostly have [[cholesterol]] stones. [[Cholesterol]] stones form when the concentration of [[cholesterol]] in the bile is much higher than the concentration of [[cholesterol]] that can be dissolved in the bile. Normally [[cholesterol]] is metabolized in the body and excess [[cholesterol]] is disposed of in the bile. There is a balance between pronucleating (crystallization-promoting) and antinucleating (crystallization-inhibiting) forces, so that gallstones don't form. When pronucleating forces take the upper hand, gallstones will form. On the other hand, moderate intake of wine and the consumption of whole grain bread may decrease the risk of developing gallstones.


==Causes==
==Causes==
Common causes of [[gallstone]] disease include increasing [[Ageing|age]], [[Oral contraceptive|oral contraceptive pills]], [[pregnancy]], [[Diabetes mellitus|diabetes]], and [[obesity]]. Life threatening causes include conditions causing hepatic and biliary [[cirrhosis]].


Common causes of gallstone disease include increasing [[Ageing|age]], [[pregnancy]], [[Oral contraceptive|oral contraceptive pills]] and [[obesity]].
==Differentiating Gallstone disease from Other Diseases==
 
Gallstone disease must be differentiated from other diseases that cause [[RUQ|right upper quadrant]] pain including [[Gastroesophageal reflux disease|gastroesophageal reflux disorder]], [[Peptic ulcer|peptic ulcer disease]], [[hepatitis]], [[sphincter of Oddi dysfunction]],[[appendicitis]], bile duct stricture, chronic [[pancreatitis]], [[irritable bowel syndrome]], [[Coronary heart disease|ischemic heart disease]], [[pyelonephritis]], ureteral calculi and complications of gallstone disease include: acute [[cholecystitis]], [[choledocholithiasis]], acute [[pancreatitis]], and acute [[cholangitis]].
==Differentiating {{PAGENAME}} from Other Diseases==
Gallstone disease must be differentiated from other diseases that cause right upper quadrant pain such as: [[Gastroesophageal reflux disease|gastroesophageal reflux disorder]], [[Peptic ulcer|peptic ulcer disease]], [[hepatitis]], [[sphincter of Oddi dysfunction]], [[appendicitis]], bile duct [[Stenosis|stricture]], [[chronic pancreatitis]], [[irritable bowel syndrome]], [[Coronary heart disease|ischemic heart disease]], [[pyelonephritis]], ureteral [[calculi]] and complications of gallstone disease include: acute [[cholecystitis]], [[choledocholithiasis]], [[acute pancreatitis]], and [[Cholangitis|acute cholangitis]].


==Epidemiology and Demographics==
==Epidemiology and Demographics==
Gallstone disease has an overall higher [[incidence]] in females than males of the Caucasian, Hispanic and Native American races. Whilst a lower incidence was found in Eastern European, African American, and Japanese populations. Approximately 6200 people will have gallstones per 100,000 worldwide.
The third National Health and Nutrition Examination Survey found that 630 per 100,000 and 1420 per 100,000 men and women aged 20 to 74 respectively in the United States had gallstone disease. In the United States, every year about 1-3% (3 to 9 million people/year) of the population develop gallstones. Gallstone disease has an overall higher incidence in females than males of the Caucasian, Hispanic and Native American nations. Whilst a lower incidence was found in Eastern European, African American, and Japanese populations.


==Risk Factors==
==Risk Factors==
Common risk factors in the development of gallstone disease include [[Ageing|age]], sex, [[pregnancy]], and [[Oral contraceptive|oral contraceptives]] and estrogen replacement therapy. Less common risk factors include rapid [[weight loss]], prolonged [[total parenteral nutrition]] and hepatic and biliary [[cirrhosis]].
Common risk factors in the development of gallstone disease include [[Ageing|age]], sex, [[pregnancy]], and [[Oral contraceptive|oral contraceptives]] and [[Hormone replacement therapy|estrogen replacement therapy]]. Less common risk factors include rapid [[weight loss]], prolonged [[total parenteral nutrition]] and hepatic and biliary [[cirrhosis]].


==Screening==
==Screening==
Periodic screening for gallstones is not currently indicated. However, it has been suggested that screening diabetic patients for gallstones and treating them earlier is good practice for avoiding a future cholecystectomy or possible complications.
Periodic screening for gallstones is not currently indicated. However, it has been suggested that screening [[Diabetes mellitus|diabetic]] patients for gallstones and treating them earlier is good practice for avoiding a future [[cholecystectomy]] or possible complications.


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
Gallstone disease patients should not undergo an elective [[cholecystectomy]] until symptoms develop, since almost 55% of patients will remain [[asymptomatic]]. Also, the [[Complication (medicine)|complications]] of [[asymptomatic]] gallstones are almost negligible unless symptoms develop. The complications of gallstone disease include [[acute cholecystitis]], [[Jaundice|obstructive jaundice]], acute [[cholangitis]] and acute [[pancreatitis]]. The prognosis after [[Cholecystectomy|laparoscopic cholecystectomy]] is excellent with [[morbidity]] and [[Mortality rate|mortality]] rates being as low as 0.5 and 10% respectively.
Gallstone disease patients should not undergo an elective [[cholecystectomy]] until symptoms develop, since almost 55% of patients will remain asymptomatic. Also, the complications of asymptomatic gallstones are almost negligible unless symptoms develop. The complications of gallstone disease include [[acute cholecystitis]], obstructive jaundice, [[Cholangitis|acute cholangitis]] and acute [[Acute pancreatitis|pancreatitis]]. The prognosis after [[Cholecystectomy|laparoscopic cholecystectomy]] is excellent with [[Morbidity & Mortality|morbidity]] and [[mortality]] rates being as low as 0.5 and 10% respectively.
===Diagnosis===
 
Patients who present with [[Right upper quadrant (abdomen)|right upper quadrant]] pain are suspected of having gallstone disease. The patients symptoms are usually accompanied by a normal physical examination and normal laboratory results including those for [[leukocytosis]] and pancreatic enzyme levels. Typically, an evaluation will begin with a transabdominal [[ultrasound]](TAUS) since it is a [[Sensitivity (tests)|sensitive]] modality for detecting gallstones. In [[Obesity|obese]] patients, or patients where imaging is practically difficult an esophageal [[ultrasound]] (EUS) with high [[Sensitivity (tests)|sensitivity]] may be used.
===Diagnostic Study of Choice===
The best modality for detecting gallstones is a transabdominal [[ultrasound]] (TAUS). Patients who present with [[RUQ|right upper quadrant]] pain are suspected of having gallstone disease. The patients symptoms are usually accompanied by a normal physical examination and normal laboratory results including those for [[leukocytosis]] and pancreatic enzyme levels. In [[Obesity|obese]] patients, or patients where imaging is practically difficult an esophageal [[ultrasound]] (EUS) with high [[Sensitivity (tests)|sensitivity]] may be used.


===History and Symptoms===
===History and Symptoms===
Gallstone disease can manifest in a number of ways. Most patients have a history of [[obesity]], [[Pregnancy|multiple pregnancies]], use of [[Oral contraceptive|oral contraceptive pills]], [[Ageing|age]] of 40 years old and over, female and of Caucasian or Native American race.Some patients may be in a physical state that favors the development of gallstones but don't develop them, some patients may have gallstones, but are [[asymptomatic]]. These gallstones are detected incidentally. Some may have gallstones and experience biliary colic, [[Nausea and vomiting|nausea]], [[Nausea and vomiting|vomiting]] and [[diarrhea]], whilst others will have complications due to gallstones, such as [[acute cholecystitis]] and [[acute pancreatitis]]. 
Gallstone disease can manifest in a number of ways. Most patients have a history of [[obesity]], multiple pregnancies, use of [[Oral contraceptive|oral contraceptive pills]], age of 40 years old and over, female and of Caucasian or Native American race. Some patients may be in a physical state that favors the development of gallstones but don't develop them, some patients may have gallstones, but are [[asymptomatic]]. These gallstones are detected incidentally. Some may have gallstones and experience [[Gallstone disease history and symptoms|biliary colic]], [[Nausea and vomiting|nausea]], [[Nausea and vomiting|vomiting]] and [[diarrhea]], whilst others will have complications due to gallstones, such as acute [[cholecystitis]] and acute [[pancreatitis]].


===Physical Examination===
===Physical Examination===
Patients with gallstones are usually not ill-appearing and don't have [[fever]] or [[tachycardia]]. Physical examination of patients with gallstones is sometimes remarkable for [[Abdominal pain|right upper quadrant pain]], epigastric tenderness, [[Abdominal guarding|guarding]] and [[jaundice]]. Symptomization occurs when stones reach more than 8mm in size. Courvoisier's sign (a palpable gallbladder on physical examination) may be palpated when the common bile duct becomes obstructed and the gallbladder becomes dilated. This mostly occurs with malignant common bile duct obstruction, but has been reported with gallstone disease.
Patients with gallstones are usually not ill-appearing and don't have [[fever]] or [[tachycardia]]. Physical examination of patients with gallstones is sometimes remarkable for [[RUQ|right upper quadrant]] pain, epigastric tenderness, [[Abdominal guarding|guarding]] and [[jaundice]]. Symptoms occurs when stones reach more than 8 mm in size. Courvoisier's sign (a palpable gallbladder on physical examination) may be palpated when the [[common bile duct]] becomes obstructed and the gallbladder becomes dilated. This mostly occurs with malignant [[Common bile duct|common bile duct obstruction]], but has been reported with gallstone disease.


===Laboratory Findings===
===Laboratory Findings===
There are no diagnostic laboratory findings associated with an uncomplicated case of gallstone disease. Laboratory findings are usually normal among patients with uncomplicated gallstone disease, both during asymptomatic periods and during attacks of biliary colic. Abnormal blood tests including ([[leukocytosis]], [[Liver function tests|elevated liver]] or [[Pancreatic lipase|pancreas tests]]) suggest the development of a complication of gallstone disease, such as acute [[cholecystitis]], acute [[cholangitis]], or acute [[pancreatitis]].
There are no diagnostic laboratory findings associated with an uncomplicated case of gallstone disease. Laboratory findings are usually normal among patients with uncomplicated gallstone disease, both during [[asymptomatic]] periods and during attacks of [[Gallstone disease history and symptoms|biliary colic]]. Abnormal blood tests including ([[leukocytosis]], elevated liver or pancreas tests) suggest the development of a complication of gallstone disease, such as acute [[cholecystitis]], acute [[cholangitis]], or acute [[pancreatitis]].


===Imaging findings===
===Imaging findings===
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==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
Patients with [[asymptomatic]] gallstones are usually not treated since the chances of [[Complication (medicine)|complications]] developing in the future are low, however, patients with symptomatic gallstones can be treated medically, for example, with [[Ursodiol|ursodeoxycholic acid]] and with lithotripsy. However, the mainstay of treatment for gallstone disease is surgically, especially since the introduction of [[Laparoscopic surgery|laparoscopic]] [[cholecystectomy]].
Patients with [[asymptomatic]] gallstones are usually not treated since the chances of complications developing in the future are low, however, patients with symptomatic gallstones can be treated medically, for example, with [[Ursodiol|ursodeoxycholic acid]]. However, the mainstay of treatment for gallstone disease is surgically, especially since the introduction of laparoscopic [[cholecystectomy]]. [[Fibrate|Fibrates]], including [[gemfibrozil]] and [[Fenofibrate|fenofibrates]] are an absolute contraindication in gallstone disease.
 
===Lithotripsy===
Occasionally, extracorporeal shock wave [[Lithotriptor|lithotripsy]] can be used to fracture gallstones into small pieces and sand to increase the surface area that is exposed to the bile acids, facilitating dissolution and clearance of the stones. Stone may also be manually extracted or a stent may be placed to relief symptoms of [[biliary colic]]. This may be an option in those who refuse or are unfit for surgery, or when medical dissolution therapy has been ineffective.


===Surgery===
===Surgery===
Surgery is the first line treatment option in patients with symptomatic gallstones and willing to undergo surgery or patients with gallstone-related complications or patients that are at risk of [[gallbladder cancer]] and having symptomatic recurrent attacks, and diabetic patients. [[Asymptomatic]] gallstones are not recommended for surgery.
Surgery is the first line treatment option in patients with symptomatic gallstones and willing to undergo surgery or patients with gallstone-related complications or patients that are at risk of [[gallbladder cancer]] and having symptomatic recurrent attacks, and [[Diabetes mellitus|diabetic]] patients. [[Asymptomatic]] gallstones are not recommended for surgery.


===Primary Prevention===
===Primary Prevention===
Effective measures for the [[Prevention (medical)|primary prevention]] of gallstone disease include diet with sufficient fat and [[protein]], maintaining [[Body mass index|low body weight]], and avoiding prolonged fasting.
Effective measures for the primary prevention of gallstone disease include [[Diet (nutrition)|diet]] with sufficient [[fat]] and [[protein]], maintaining a [[Body mass index|low body weight]], and avoiding prolonged fasting.


===Secondary Prevention===
===Secondary Prevention===
Effective measures for the [[Prevention (medical)|secondary prevention]] of symptoms developing in an asymptomatic case or for preventing complications with symptomatic gallstone disease includes [[Ursodiol|bile acid]] therapy. However, medical therapy of asymptomatic stones is not currently indicated.
Effective measures for the secondary prevention of symptoms developing in an [[asymptomatic]] case or for preventing complications with symptomatic gallstone disease includes [[Ursodiol|bile acid therapy]]. However, medical therapy of [[asymptomatic]] stones is not currently indicated.
 
 
 
{{WH}}
{{WS}}
 
[[Category:Gastroenterology]]
[[Category:Hepatology]]
[[Category:Surgery]]
[[Category:Disease]]

Latest revision as of 21:46, 22 December 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Overview

Gallstone disease is the presence of gallstones (cholelithiasis) within the gallbladder —chole- means "bile", lithia means "stone", and -sis means "process". Gallstones are crystalline bodies formed within the body by 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 called choledocholithiasis, obstruction of the biliary tree can cause jaundice and obstruction of the outlet of the pancreatic exocrine system can cause pancreatitis.

Historical Perspective

Humans have a long history with gallstones with the earliest recording being noted at least 7000 years ago. Autopsies performed on the earliest mummies in Egypt were discovered to have gallstones. Gallstones became easier to visualize in 1895 with the introduction of the plain x-ray film. In 1924 and 1970, IV cholecystography and percutaneous transhepatic cholangiography were developed respectively.

Classification

Gallstone disease may be classified according to the chemical analysis of gallstone. In this way, there are 3 subtypes: pure cholesterol, pure bilirubin stones and mixed.

Pathophysiology

Studies have shown that gallstone formation is mostly due to bile supersaturation. In the United States, patients that present with gallbladder stones mostly have cholesterol stones. Cholesterol stones form when the concentration of cholesterol in the bile is much higher than the concentration of cholesterol that can be dissolved in the bile. Normally cholesterol is metabolized in the body and excess cholesterol is disposed of in the bile. There is a balance between pronucleating (crystallization-promoting) and antinucleating (crystallization-inhibiting) forces, so that gallstones don't form. When pronucleating forces take the upper hand, gallstones will form. On the other hand, moderate intake of wine and the consumption of whole grain bread may decrease the risk of developing gallstones.

Causes

Common causes of gallstone disease include increasing age, oral contraceptive pills, pregnancy, diabetes, and obesity. Life threatening causes include conditions causing hepatic and biliary cirrhosis.

Differentiating Gallstone disease from Other Diseases

Gallstone disease must be differentiated from other diseases that cause right upper quadrant pain including gastroesophageal reflux disorder, peptic ulcer disease, hepatitis, sphincter of Oddi dysfunction,appendicitis, bile duct stricture, chronic pancreatitis, irritable bowel syndrome, ischemic heart disease, pyelonephritis, ureteral calculi and complications of gallstone disease include: acute cholecystitis, choledocholithiasis, acute pancreatitis, and acute cholangitis.

Epidemiology and Demographics

The third National Health and Nutrition Examination Survey found that 630 per 100,000 and 1420 per 100,000 men and women aged 20 to 74 respectively in the United States had gallstone disease. In the United States, every year about 1-3% (3 to 9 million people/year) of the population develop gallstones. Gallstone disease has an overall higher incidence in females than males of the Caucasian, Hispanic and Native American nations. Whilst a lower incidence was found in Eastern European, African American, and Japanese populations.

Risk Factors

Common risk factors in the development of gallstone disease include age, sex, pregnancy, and oral contraceptives and estrogen replacement therapy. Less common risk factors include rapid weight loss, prolonged total parenteral nutrition and hepatic and biliary cirrhosis.

Screening

Periodic screening for gallstones is not currently indicated. However, it has been suggested that screening diabetic patients for gallstones and treating them earlier is good practice for avoiding a future cholecystectomy or possible complications.

Natural History, Complications, and Prognosis

Gallstone disease patients should not undergo an elective cholecystectomy until symptoms develop, since almost 55% of patients will remain asymptomatic. Also, the complications of asymptomatic gallstones are almost negligible unless symptoms develop. The complications of gallstone disease include acute cholecystitis, obstructive jaundice, acute cholangitis and acute pancreatitis. The prognosis after laparoscopic cholecystectomy is excellent with morbidity and mortality rates being as low as 0.5 and 10% respectively.

Diagnostic Study of Choice

The best modality for detecting gallstones is a transabdominal ultrasound (TAUS). Patients who present with right upper quadrant pain are suspected of having gallstone disease. The patients symptoms are usually accompanied by a normal physical examination and normal laboratory results including those for leukocytosis and pancreatic enzyme levels. In obese patients, or patients where imaging is practically difficult an esophageal ultrasound (EUS) with high sensitivity may be used.

History and Symptoms

Gallstone disease can manifest in a number of ways. Most patients have a history of obesity, multiple pregnancies, use of oral contraceptive pills, age of 40 years old and over, female and of Caucasian or Native American race. Some patients may be in a physical state that favors the development of gallstones but don't develop them, some patients may have gallstones, but are asymptomatic. These gallstones are detected incidentally. Some may have gallstones and experience biliary colic, nausea, vomiting and diarrhea, whilst others will have complications due to gallstones, such as acute cholecystitis and acute pancreatitis.

Physical Examination

Patients with gallstones are usually not ill-appearing and don't have fever or tachycardia. Physical examination of patients with gallstones is sometimes remarkable for right upper quadrant pain, epigastric tenderness, guarding and jaundice. Symptoms occurs when stones reach more than 8 mm in size. Courvoisier's sign (a palpable gallbladder on physical examination) may be palpated when the common bile duct becomes obstructed and the gallbladder becomes dilated. This mostly occurs with malignant common bile duct obstruction, but has been reported with gallstone disease.

Laboratory Findings

There are no diagnostic laboratory findings associated with an uncomplicated case of gallstone disease. Laboratory findings are usually normal among patients with uncomplicated gallstone disease, both during asymptomatic periods and during attacks of biliary colic. Abnormal blood tests including (leukocytosis, elevated liver or pancreas tests) suggest the development of a complication of gallstone disease, such as acute cholecystitis, acute cholangitis, or acute pancreatitis.

Imaging findings

Stones are mainly visualised using transabdominal ultrasonography. Echogenic foci that cast acoustic shadows are usually seen. There are other imaging modalities, these include; x-ray, computed tomography, magnetic resonance cholangiopancreatography, esophageal ultrasound, endoscopic retrograde cholangiopancreatography (ERCP), bile microscopy and oral cholecystography.

Other diagnostic studies

Bile microscopy has been largely replaced by transabdominal ultrasound, however it may be helpful in evaluating obese patients. Other tests like upper GI endoscopy for peptic ulcer disease may be indicated depending upon the patient's symptoms and history to rule out other differential diagnoses.

Treatment

Medical Therapy

Patients with asymptomatic gallstones are usually not treated since the chances of complications developing in the future are low, however, patients with symptomatic gallstones can be treated medically, for example, with ursodeoxycholic acid. However, the mainstay of treatment for gallstone disease is surgically, especially since the introduction of laparoscopic cholecystectomy. Fibrates, including gemfibrozil and fenofibrates are an absolute contraindication in gallstone disease.

Lithotripsy

Occasionally, extracorporeal shock wave lithotripsy can be used to fracture gallstones into small pieces and sand to increase the surface area that is exposed to the bile acids, facilitating dissolution and clearance of the stones. Stone may also be manually extracted or a stent may be placed to relief symptoms of biliary colic. This may be an option in those who refuse or are unfit for surgery, or when medical dissolution therapy has been ineffective.

Surgery

Surgery is the first line treatment option in patients with symptomatic gallstones and willing to undergo surgery or patients with gallstone-related complications or patients that are at risk of gallbladder cancer and having symptomatic recurrent attacks, and diabetic patients. Asymptomatic gallstones are not recommended for surgery.

Primary Prevention

Effective measures for the primary prevention of gallstone disease include diet with sufficient fat and protein, maintaining a low body weight, and avoiding prolonged fasting.

Secondary Prevention

Effective measures for the secondary prevention of symptoms developing in an asymptomatic case or for preventing complications with symptomatic gallstone disease includes bile acid therapy. However, medical therapy of asymptomatic stones is not currently indicated.


Template:WH Template:WS