Gallstone disease 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.

# 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.