FAQ

hydrogen breath test

What is the hydrogen breath test?

The hydrogen breath test is a test that uses the measurement of hydrogen in the breath to diagnose several conditions that cause gastrointestinal symptoms. In humans, only bacteria – specifically, anaerobic bacteria in the colon – are capable of producing hydrogen. The bacteria produce hydrogen when they are exposed to unabsorbed food, particularly sugars and carbohydrates, not proteins or fats. Although limited hydrogen is produced from the small amounts of unabsorbed food that normally reach the colon, large amounts of hydrogen may be produced when there is a problem with the digestion or absorption of food in the small intestine, that allows more unabsorbed food to reach the colon.

Large amounts of hydrogen also may be produced when the colon bacteria move back into the small intestine, a condition called bacterial overgrowth of the small bowel. In this latter instance, the bacteria are exposed to unabsorbed food that has not had a chance to completely traverse the small intestine to be fully digested and absorbed. Some of the hydrogen produced by the bacteria, whether in the small intestine or the colon, is absorbed into the blood flowing through the wall of the small intestine and colon. The hydrogen-containing blood travels to the lungs where the hydrogen is released and exhaled in the breath where it can be measured.

 

When is hydrogen breath testing used?

Hydrogen breath testing is used in the diagnosis of three conditions.

  • The first is a condition in which dietary sugars are not digested normally. The most common sugar that is poorly digested is lactose, the sugar in milk. Individuals who are unable to properly digest lactose are referred to as lactose intolerant. Testing also may be used to diagnose problems with the digestion of other sugars such as sucrose, fructose and sorbitol.
  • The second condition for which hydrogen breath testing is used is for diagnosing bacterial overgrowth of the small bowel, a condition in which larger-than-normal numbers of colonic bacteria are present in the small intestine.
  • The third condition for which hydrogen breath testing is used is for diagnosing rapid passage of food through the small intestine. All three of these conditions may cause abdominal pain, abdominal bloating and distention, flatulence (passing gas in large amounts), and diarrhea.
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Sphincter of Oddi (SOD)

The sphincter of Oddi is a muscular valve that controls the flow of digestive juices (bile and pancreatic juice) through ducts from the liver and pancreas into the first part of the small intestine (duodenum). Sphincter of Oddi dysfunction (SOD) describes the situation when the sphincter does not relax at the appropriate time (due to scarring or spasm). The back-up of juices causes episodes of severe abdominal pain.

The sphincter of Oddi is a muscular valve that controls the flow of digestive juices (bile and pancreatic juice) through ducts from the liver and pancreas into the first part of the small intestine (duodenum). Sphincter of Oddi dysfunction (SOD) describes the situation when the sphincter does not relax at the appropriate time (due to scarring or spasm). The back-up of juices causes episodes of severe abdominal pain.

Doctors often consider SOD in patients who experience recurrent attacks of pain after surgical removal of the gallbladder (cholecystectomy). More than half a million of these surgeries are performed annually in the United States, and 10–20% of these patients present afterwards with continuing or recurrent pains. SOD is also considered in some patients who suffer from recurrent attacks of unexplained inflammation of the pancreas (pancreatitis).

About half of these patients will have findings on laboratory studies or imaging (blood test, ultrasound, CT scan, or MRCP) to suggest a definite abnormality, such as a stone in the bile duct. MRCP (magnetic resonance cholangiopancreatography) is nowadays a good non-invasive test for checking on the biliary and pancreatic drainage systems.

Based on patients histories, physical examinations, and other clinical data, doctors can categorize these patients as having SOD Types I and II. The categories help guide treatment of the disease. They are based on a system called the Milwaukee criteria.

When symptoms are severe, standard treatment is to perform an endoscopic procedure called ERCP (endoscopic retrograde cholangiopancreatography). ERCP is a procedure for the examination or treatment of the bile duct and pancreatic duct. The procedure carries a risk of serious complications and is done under sedation by experts trained in the technique. It combines the use of x-rays and an endoscope that is passed down to the duodenum, where the bile duct and pancreatic ducts drain, and a dye that is injected into the ducts.

An additional procedure, sphincter of Oddi manometry (SOM), involves passing a catheter into the bile and/or pancreatic duct during ERCP to measure the pressure of the biliary and/or pancreatic sphincter. It is considered the gold standard diagnostic modality for SOD.

Treatment depends on what is found. It may often involve cutting the muscular sphincter (sphincterotomy) to remove any stones or to relieve any scarring or spasm of the sphincter.

As noted above, a very important problem in this context is that these ERCP procedures carry a significant risk of complications. In particular, ERCP (with or without sphincter of Oddi manometry) can cause an attack of pancreatitis in 5–10% of cases. While most of these result in a few days in the hospital, about 1% of patients suffer a major attack, with weeks or months in the hospital. Sphincterotomy also carries a small risk of other severe complications such as bleeding and perforation, and the possibility of delayed narrowing of a duct (stenosis) due to scarring.

Functional SOD

Patients with a similar pain problem, but who have little or no abnormalities on blood tests and standard scans (including MRCP), are categorized as having SOD Type III. The episodes of pain are assumed due to intermittent spasm of the sphincter. It is very difficult to effectively evaluate and manage patients with Type III SOD. Some physicians are skeptical of its existence, or assume that it is a part of a broader problem of a functional digestive disturbance such as irritable bowel syndrome.

Because of the risks of ERCP, patients with suspected SOD III are usually advised to try medical treatments first. Some respond to the use of antispasmodic drugs and/or antidepressants that may help decrease pain.  There have been studies of other medical therapies, such as calcium channel blocking drugs. Despite a few encouraging reports, these methods have not proven to be effective generally, and are not widely used.

Patients who fail these approaches (at least those with severe symptoms) are usually advised to see specialists at referral centers. Further evaluation may involve additional or more specialized tests to help guide treatment options.

Clinical Research Study

The uncertainties in how best to diagnose and to treat “suspected” sphincter of Oddi dysfunction (and the risks involved) mandate further scientific investigation. The National Institutes of Health has recently funded an important study called “EPISOD” in 6 major Gastroenterology centers in USA.

The studies are being conducted at centers located in:

  • Johns Hopkins Hospital, Baltimore, MD
  • University of Alabama at Birmingham, Birmingham, AL
  • Medical University of South Carolina Digestive Disease Center, Charleston, SC
  • Indiana University, Indianapolis, IN
  • Hennepin County Medical Center, Minneapolis, MN
  • Virginia Mason Medical Center, Seattle, WA

Additional details are available at the NIH website at http://clinicaltrials.gov/ by searching: sphincter of Oddi dysfunction III.

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IBD versus IBS

Is inflammatory bowel disease (IBD) the same thing as Irritable Bowel Syndrome (IBS)?

No. Inflammatory bowel disease, including UC and CD, is different from irritable bowel syndrome (IBS). Unlike IBD, IBS does not cause inflammation, ulcers or other damage to the bowel. Instead, IBS is a much less serious problem called a functional disorder. This means that the digestive system looks normal but doesn’t work as it should. Symptoms of IBS may include crampy pain, bloating, gas, mucus in the stool, diarrhea and constipation. IBS has also been called spastic colon or spastic bowel

Source: http://www.webmd.com/ibd-crohns-disease/crohns-disease/ibd-versus-ibs

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Bloating

For further information see related separate article Irritable Bowel Syndrome.

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Ursodeoxycholic acid
Aust Prescr 1999;22:95-8

Ursofalk (Orphan Australia)
250 mg capsules
Approved indication: chronic cholestasis
Australian Medicines Handbook Section 12

In primary biliary cirrhosis, there is chronic inflammation which destroys the intrahepatic bile ductules. At first, patients may be asymptomatic, but the reduced excretion of bile can cause steatorrhoea. The disease slowly progresses and death can result from hepatic failure or the complications of cirrhosis. Primary biliary cirrhosis is now a common indication for a liver transplant. Although there is no effective drug treatment, some patients will benefit from ursodeoxycholic acid.

Ursodeoxycholic acid is a bile acid which is synthesised from its precursor by intestinal bacteria. Its mechanism of action in primary biliary cirrhosis is uncertain. Ursodeoxycholic acid may have an effect by increasing the flow and altering the composition of bile. It has also been used in the treatment of gallstones.

In clinical trials with at least two years of follow up, patients who took ursodeoxycholic acid had improved liver function tests. This may not always improve the patient’s symptoms or the histology of the liver.

Ursodeoxycholic acid has few known adverse effects. Diarrhoea is the main adverse reaction. Patients can complain of an increase in itching when they begin treatment. This may respond to a reduction in the dose. Ursodeoxycholic acid is contraindicated if there is acute inflammation of the gall bladder or obstruction of the common bile duct.

Ursodeoxycholic acid will probably have a role in delaying the need for liver transplantation. A placebo-controlled study of 145 patients with primary biliary cirrhosis found that the disease progressed more slowly in patients given ursodeoxycholic acid. This group also had a significantly lower probability of transplantation or death during the two-year study.1

Reference

. Poupon RE, Poupon R, Balkau B. Ursodiol for the long-term treatment of primary biliary cirrhosis. The UDCA-PBC Study Group. N Engl J Med 1994;330:1342-7.

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Celecoxib
Aust Prescr 1999;22:147-51

Celebrex (Searle)
100 mg and 200 mg capsules
Approved indication: arthritis
Australian Medicines Handbook Section 15.1

Non-steroidal anti-inflammatory drugs act by inhibiting the enzyme cyclo-oxygenase(COX).1 This enzyme is required for the synthesis of prostaglandins and its activity increases in inflammation. It has two isoforms, COX-1 andCOX-2, both of which are blocked to varying degrees by non-steroidal anti-inflammatory drugs. As COX-1 may produce protective prostaglandins in the stomach, its inhibition could be responsible for some of the adverse effects of the drugs. Celecoxib is much more selective for COX-2, so it may cause fewer adverse effects than the older drugs.

Patients with symptoms of rheumatoid arthritis take celecoxib in two divided doses. A single daily dose may be used in osteoarthritis. The drug is quickly absorbed. Although taking the capsules with food delays absorption, the bioavailability is increased. Celecoxib is metabolised in the liver by cytochrome P450 CYP2C9so there is a potential for interactions with drugs such as fluconazole.

In studies lasting up to 12 weeks, celecoxib has reduced the pain of osteoarthritis more effectively than placebo. Trials, of up to 24 weeks, in patients with rheumatoid arthritis have found the efficacy of celecoxib to be similar to that of naproxen 500 mg twice daily.

The effect of celecoxib on the gut has been assessed by endoscopy. Gastric ulcers were seen significantly less frequently during treatment with celecoxib, than they were in patients taking naproxen or diclofenac. Celecoxib, however, is not free of gastrointestinal adverse effects. Dyspepsia, abdominal pain and diarrhoea occur more frequently than with placebo. In animal studies, COX-2inhibitors retard ulcer healing.1

Most of the enzyme activity in platelets is COX-1, so celecoxib should have little effect on bleeding time. The potential of COX-2 inhibitors to cause fluid retention, renal impairment or hypertension is unknown. In clinical trials peripheral oedema occurred with equal frequency (2.1%) in patients taking celecoxib or naproxen. Celecoxib is not recommended for patients with aspirin-sensitive asthma.

The COX-2 inhibitors have the potential to replace non-steroidal anti-inflammatory drugs for the relief of arthritic symptoms. Whether or not they fulfill this potential will depend on their long-term safety. For example, will they cause fewer gastrointestinal haemorrhages than the non-steroidal anti-inflammatory drugs?

Reference

1. Hawkey CJ. COX-2 inhibitors. Lancet 1999;353:307-14.

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Postcholecystectomy Syndrome

The laparoscopic cholecystectomy is considered the “gold standard” in chronic calculous cholecystitis treatment. After the gallbladder removal the physiology of gallbladder bile formation is changed.

Absence of the gallbladder leads to development of functional biliary hypertension and dilatation of common bile duct and the common hepatic duct. The dilatation of right and left hepatic ducts may be formed within 3-5 years after cholecystectomy. Functional hypertension in the common bile duct leads to development of functional hypertension in Wirsung’s pancreatic duct accompanied by chronic pancreatitis symptoms.

During this period in some patients this is accompanied by chronic pancreatitis progression, dysfunction of the sphincter of Oddi and duodeno-gastral reflux. Duodeno-gastral reflux causes the development of atrophic (bile-acid-depen­dent) antral gastritis . After cholecystectomy 40% to 60% of patients suffer from dyspeptic disorders, 5% to 40% from pains of different localizations. Up to 70% of patients show symptoms of chronic “bland” intrahepatic cholestasis, chronic cholestatic hepatitis and compensatory bile-acid-dependent apoptosis of hepatocytes. In some of cholecystectomized patients with high concentration of hydrophobic hepatotoxic co-cancerogenic deoxycholic bile acid in serum and/or feces high risk of the colon cancer is found.

Therefore, depending on dysfunction (hyper tonus) or relaxation (hypo tonus) of the sphincter of Oddi, pathology in hepato-biliary-pancreato-duodenal-gastral zone will form after cholecystectomy.

Postcholecystectomy syndrome is a dysfunction of the sphincter of Oddi, caused by noncalculous obstructive disorder, which decrease bile passage and pancreatic juice outflow into the duodenum.

More reading

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Gastroparesis

CDR0000428446_largeGastroparesis, also called delayed gastric emptying, is a disorder in which the stomach takes too long to empty its contents. Normally, the stomach contracts to move food down into the small intestine for digestion. The vagus nerve controls the movement of food from the stomach through the digestive tract. Gastroparesis occurs when the vagus nerve is damaged and the muscles of the stomach and intestines do not work normally. Food then moves slowly or stops moving through the digestive tract.

What causes gastroparesis?

The most common cause of gastroparesis is diabetes. People with diabetes have high blood glucose, also called blood sugar, which in turn causes chemical changes in nerves and damages the blood vessels that carry oxygen and nutrients to the nerves. Over time, high blood glucose can damage the vagus nerve.

Some other causes of gastroparesis are

  • surgery on the stomach or vagus nerve
  • viral infections
  • anorexia nervosa or bulimia
  • medications-anticholinergics and narcotics-that slow contractions in the intestine
  • gastroesophageal reflux disease
  • smooth muscle disorders, such as amyloidosis and scleroderma
  • nervous system diseases, including abdominal migraine and Parkinson’s disease
  • metabolic disorders, including hypothyroidism

Many people have what is called idiopathic gastroparesis, meaning the cause is unknown and cannot be found even after medical tests.

What are the symptoms of gastroparesis?

Signs and symptoms of gastroparesis are

  • heartburn
  • pain in the upper abdomen
  • nausea
  • vomiting of undigested food-sometimes several hours after a meal
  • early feeling of fullness after only a few bites of food
  • weight loss due to poor absorption of nutrients or low calorie intake
  • abdominal bloating
  • high and low blood glucose levels
  • lack of appetite
  • gastroesophageal reflux
  • spasms in the stomach area

Eating solid foods, high-fiber foods such as raw fruits and vegetables, fatty foods, or drinks high in fat or carbonation may contribute to these symptoms.

The symptoms of gastroparesis may be mild or severe, depending on the person. Symptoms can happen frequently in some people and less often in others. Many people with gastroparesis experience a wide range of symptoms, and sometimes the disorder is difficult for the physician to diagnose.

What are the complications of gastroparesis?

If food lingers too long in the stomach, it can cause bacterial overgrowth from the fermentation of food. Also, the food can harden into solid masses called bezoars that may cause nausea, vomiting, and obstruction in the stomach. Bezoars can be dangerous if they block the passage of food into the small intestine.

Gastroparesis can make diabetes worse by making blood glucose control more difficult. When food that has been delayed in the stomach finally enters the small intestine and is absorbed, blood glucose levels rise. Since gastroparesis makes stomach emptying unpredictable, a person’s blood glucose levels can be erratic and difficult to control.

How is gastroparesis diagnosed?

After performing a full physical exam and taking your medical history, your doctor may order several blood tests to check blood counts and chemical and electrolyte levels. To rule out an obstruction or other conditions, the doctor may perform the following tests:

  • Upper endoscopy. After giving you a sedative to help you become drowsy, the doctor passes a long, thin tube called an endoscope through your mouth and gently guides it down the throat, also called the esophagus, into the stomach. Through the endoscope, the doctor can look at the lining of the stomach to check for any abnormalities.
  • Ultrasound. To rule out gallbladder disease and pancreatitis as sources of the problem, you may have an ultrasound test, which uses harmless sound waves to outline and define the shape of the gallbladder and pancreas.
  • Barium x ray. After fasting for 12 hours, you will drink a thick liquid called barium, which coats the stomach, making it show up on the x ray. If you have diabetes, your doctor may have special instructions about fasting. Normally, the stomach will be empty of all food after 12 hours of fasting. Gastroparesis is likely if the x ray shows food in the stomach. Because a person with gastroparesis can sometimes have normal emptying, the doctor may repeat the test another day if gastroparesis is suspected.

Once other causes have been ruled out, the doctor will perform one of the following gastric emptying tests to confirm a diagnosis of gastroparesis.

  • Gastric emptying scintigraphy. This test involves eating a bland meal, such as eggs or egg substitute, that contains a small amount of a radioactive substance, called radioisotope, that shows up on scans. The dose of radiation from the radioisotope is not dangerous. The scan measures the rate of gastric emptying at 1, 2, 3, and 4 hours. When more than 10 percent of the meal is still in the stomach at 4 hours, the diagnosis of gastroparesis is confirmed.
  • Breath test. After ingestion of a meal containing a small amount of isotope, breath samples are taken to measure the presence of the isotope in carbon dioxide, which is expelled when a person exhales. The results reveal how fast the stomach is emptying.
  • SmartPill. Approved by the U.S. Food and Drug Administration (FDA) in 2006, the SmartPill is a small device in capsule form that can be swallowed.The device then moves through the digestive tract and collects information about its progress that is sent to a cell phone-sized receiver worn around your waist or neck. When the capsule is passed from the body with the stool in a couple of days, you take the receiver back to the doctor, who enters the information into a computer.

How is gastroparesis treated?

Treatment of gastroparesis depends on the severity of the symptoms. In most cases, treatment does not cure gastroparesis-it is usually a chronic condition. Treatment helps you manage the condition so you can be as healthy and comfortable as possible.

Medication

Several medications are used to treat gastroparesis. Your doctor may try different medications or combinations to find the most effective treatment. Discussing the risk of side effects of any medication with your doctor is important.

  • Metoclopramide (Reglan). This drug stimulates stomach muscle contractions to help emptying. Metoclopramide also helps reduce nausea and vomiting. Metoclopramide is taken 20 to 30 minutes before meals and at bedtime. Side effects of this drug include fatigue, sleepiness, depression, anxiety, and problems with physical movement.
  • Erythromycin. This antibiotic also improves stomach emptying. It works by increasing the contractions that move food through the stomach. Side effects include nausea, vomiting, and abdominal cramps.
  • Domperidone. This drug works like metoclopramide to improve stomach emptying and decrease nausea and vomiting. The FDA is reviewing domperidone, which has been used elsewhere in the world to treat gastroparesis. Use of the drug is restricted in the United States.
  • Other medications. Other medications may be used to treat symptoms and problems related to gastroparesis. For example, an antiemetic can help with nausea and vomiting. Antibiotics will clear up a bacterial infection. If you have a bezoar in the stomach, the doctor may use an endoscope to inject medication into it to dissolve it.

Dietary Changes

Changing your eating habits can help control gastroparesis. Your doctor or dietitian may prescribe six small meals a day instead of three large ones. If less food enters the stomach each time you eat, it may not become overly full. In more severe cases, a liquid or pureed diet may be prescribed.

The doctor may recommend that you avoid high-fat and high-fiber foods. Fat naturally slows digestion-a problem you do not need if you have gastroparesis-and fiber is difficult to digest. Some high-fiber foods like oranges and broccoli contain material that cannot be digested. Avoid these foods because the indigestible part will remain in the stomach too long and possibly form bezoars.

Feeding Tube

If a liquid or pureed diet does not work, you may need surgery to insert a feeding tube. The tube, called a jejunostomy, is inserted through the skin on your abdomen into the small intestine. The feeding tube bypasses the stomach and places nutrients and medication directly into the small intestine. These products are then digested and delivered to your bloodstream quickly. You will receive special liquid food to use with the tube. The jejunostomy is used only when gastroparesis is severe or the tube is necessary to stabilize blood glucose levels in people with diabetes.

Parenteral Nutrition

Parenteral nutrition refers to delivering nutrients directly into the bloodstream, bypassing the digestive system. The doctor places a thin tube called a catheter in a chest vein, leaving an opening to it outside the skin. For feeding, you attach a bag containing liquid nutrients or medication to the catheter. The fluid enters your bloodstream through the vein. Your doctor will tell you what type of liquid nutrition to use.

This approach is an alternative to the jejunostomy tube and is usually a temporary method to get you through a difficult period with gastroparesis. Parenteral nutrition is used only when gastroparesis is severe and is not helped by other methods.

Refractory Gastroparesis

Gastric Electrical Stimulation

Neurostimulator Device

When gastroparesis does not respond to standard medical management including drugs and dietary changes, the condition is said to “refactory”. For patients who have documented delayed gastric emptying with no evidence of abnormal obstruction, a gastric neurostimulator may be implanted to reduce or eliminate nausea and other symptoms.

A gastric neurostimulator is a surgically implanted battery-operated device that releases mild electrical pulses to help control nausea and vomiting associated with gastroparesis. This option is available to people whose nausea and vomiting do not improve with medications. Further studies will help determine who will benefit most from this procedure, which is available in a few centers across the United States.

Implanted neurostimulator device

Gastric electrical stimulation uses a device, surgically implanted in the abdomen, to deliver mild electrical pulses to the nerves and smooth muscle of the lower part of the stomach. This stimulation may reduce chronic nausea and vomiting in patients with gastroparesis resulting from diabetes (diabetic gastropathy) or ideopathic gastroparesis (unknown cause).

 

Pyloroplasty

If gastroparesis is related to an injury of the vagus nerve, patients may benefit from a procedure called pyloroplasty. This procedure widens and relaxes the valve separating the stomach from the upper part of the small intestine, called the pyloric valve. This permits the stomach to empty more quickly.

In some cases,before deciding to perform the procedure, botulinum toxin (Botox) will be injected at the pyloric valve to temporarily paralyze and relax it. The purpose is to determine if the patient would benefit from a pyloroplasty. While use of botulinum toxin has been associated with improvement in symptoms of gastroparesis in some patients, further research is required to validate its efficacy.

Treatment Goals

The primary treatment goals for gastroparesis related to diabetes are to improve stomach emptying and regain control of blood glucose levels. Treatment includes dietary changes, insulin, oral medications, and, in severe cases, a feeding tube and parenteral nutrition.

Dietary Changes

The doctor will suggest dietary changes such as six smaller meals to help restore your blood glucose to more normal levels before testing you for gastroparesis. In some cases, the doctor or dietitian may suggest you try eating several liquid or pureed meals a day until your blood glucose levels are stable and the symptoms improve. Liquid meals provide all the nutrients found in solid foods, but can pass through the stomach more easily and quickly.

Insulin for Blood Glucose Control

If you have gastroparesis, food is being absorbed more slowly and at unpredictable times. To control blood glucose, you may need to

  • take insulin more often or change the type of insulin you take
  • take your insulin after you eat instead of before
  • check your blood glucose levels frequently after you eat and administer insulin whenever necessary

Your doctor will give you specific instructions for taking insulin based on your particular needs.


 

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Small Intestine Bacterial Overgrowt

Simply put, Small Intestine Bacterial Overgrowth is a chronic bacterial infection of the small intestine.  The infection is of bacteria that normally live in the gastrointestinal tract but have abnormally overgrown in a location not meant for so many bacteria.  

The Problem
The bacteria interfere with our normal digestion and absorption of food and are associated with damage to the lining or membrane of the SI (leaky gut syndrome, which I prefer to call leaky SI in this case). 

  • They consume some of our food which over time leads to deficiencies in their favorite nutrients such as iron and B12, causing anemia.
  • They consume food unable to be absorbed due to SI lining damage, which creates more bacterial overgrowth (a vicious cycle).
  • After eating our food, they produce gas/ expel flatus, within our SI.  The gas causes abdominal bloating, abdominal pain, constipation, diarrhea or both (the symptoms of IBS).  Excess gas can also cause belching and flatulence.
  • They decrease proper fat absorption by deconjugating bile leading to deficiencies of vitamins A & D and fatty stools.
  • Through the damaged lining, larger food particles not able to be fully digested, enter into the body which the immune system reacts to.  This causes food allergies/ sensitivities.
  • Bacteria themselves can also enter the body/bloodstream.  Immune system reaction to bacteria and their cell walls (endotoxin) causes chronic fatigue and body pain and burdens the liver.
  • Finally, the bacteria excrete acids which in high amounts can cause neurological and cognitive symptoms.
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Choledocholithiasis
Choledocholithiasis

 


What are the other Names for this Condition? (Also known as/Synonyms)

 

  • Bile Duct Stone
  • Common Bile Duct Stone
  • Gallstone in the Bile Duct

 

What is Choledocholithiasis? (Definition/Background Information)

 

  • Choledocholithiasis is the presence of stones (gallstones) in the common bile duct (CBD). The presence of even one stone in the CBD is called Choledocholithiasis
  • The liver is located on the upper right side of the abdomen. Among other functions the liver produces bile, which is important for the digestion of fat
    • The bile comes out of the liver through the common hepatic duct (hollow tube) and enters the gallbladder through the cystic duct
    • The gallbladder is a small sac located under the liver and its main function is to store bile and release it, as and when it is required
    • The cystic duct joins the common hepatic duct to form the common bile duct
    • The common bile duct carries bile into the duodenum (gastrointestinal tract). Bile in the gastrointestinal tract helps in the digestion of fat
  • The gallstones are made up of a mixture of bilirubin, calcium, and cholesterol. There are 4 types of gallstones
    • Cholesterol stones (the most common type)
    • Pigment stones – black: These stones are commonly found in individuals with hemolytic (destruction of red blood cells) anemia
    • Pigment stones – brown: These stones are commonly seen in Asians and are thought to arise due to infection of the bile duct. These type of stones are commonly formed in the common bile duct than in the gallbladder
    • Mixed stones: Contains a mixture of the above stone types
  • The process of gallstone formation in the gallbladder is called cholelithiasis. Some of the stones exit the gallbladder and gets trapped in the CBD to cause Choledocholithiasis (secondary stones). Up to 15% of individuals with gallstones (cholelithiasis) have associated Choledocholithiasis. Uncommonly, stones may be formed within the common bile duct itself (primary stones)
  • Choledocholithiasis may cause no symptoms or cause symptoms such as right upper abdominal pain, jaundice, etc.
  • The treatment options for Choledocholithiasis include the removal of the stones and removal of the gall bladder. The prognosis (outlook) is generally good with prompt diagnosis and early treatment

Who gets Choledocholithiasis? (Age and Sex Distribution)

 

  • Any individual who has gallstone disease (cholelithiasis) is at risk for Choledocholithiasis (or Gallstone in the Bile Duct). It is more common in the elderly adults, than in children or younger adults
  • Gallstone formation is more common in women than men
  • Cholesterol gallstone formation is more common in certain regions where there is high intake of dietary fat, such as in northern Europe, US, etc. Pigment gallstones-brown type formation is more common in Asia
  • Cholesterol gallstone formation is common in Native Indians than other races or ethnicities
  • Pigment gallstones-black type formation is more common in African-Americans than other races or ethnicities

 

What are the Risk Factors for Choledocholithiasis? (Predisposing Factors)

The risk factors of Choledocholithiasis include:

 

  • Individuals who have had their gallbladder removed (cholecystectomy) are at risk to develop Choledocholithiasis
  • Any individual with a history of gallstone disease (cholelithiasis) is also at risk to develop Choledocholithiasis

 

The following are the risk factors for gallstones formation:

 

  • Cholesterol gallstones: These gallstones are formed whenever there is too much cholesterol in the bile. The risk factors are:
    • Women gender (due to estrogen)
    • Obesity
    • Diabetes mellitus type 2
    • History of Crohn’s disease
    • Individuals with metabolic syndrome that includes insulin resistance, high blood sugar, obesity, low blood levels of good cholesterol (HDL), and high blood levels of triglycerides
    • Rapid weight loss with extreme calorie and fat restriction
    • Rapid weight loss followed by quick weight gain
    • Gastric bypass surgery performed for weight reduction purposes
    • Organ transplantation
    • High consumption of simple carbohydrates
    • High levels of triglycerides in blood
    • Decreased physical activity (and fitness)
    • Pregnancy
    • Conditions causing stasis of bile in the gallbladder
    • Native Indians are at risk due to LITH genes, which increase fat storage
    • Mutation in ABCG8 gene function increases one’s risk because excess cholesterol is pushed into the bile
    • Use of medications, such as estrogens (oral contraceptive pill), hormone replacement therapy (used in postmenopausal women), clofibrate (used for treating high triglyceride levels), somatostatin, thiazide diuretics, etc.
    • Prolonged intravenous feeding (used when an individual cannot take anything by mouth) increases one’s risk of getting gallstones
  • Individuals with increased red blood cell destruction, such as hemolytic anemias, are at increased risk to get pigment gallstones-black type. Individuals with scarred liver (cirrhosis) are also at risk
  • Individuals of Asian origin along with associated infection of the bile ducts, are at an increased risk to get pigment gallstones-brown type
  • There are other unknown genetic and environmental factors, such as inflammation, infection, etc., which increases one’s risk of gallstones

 

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Choledocholithiasis? (Etiology)

Choledocholithiasis occurs due to one of the two mechanisms outlined below:

 

  • Gallstones formed in the gallbladder move out and get trapped in the common bile duct (CBD)
  • Stones that get formed within the common bile duct itself, which is seen in individuals without a gallbladder (which was surgically removed through a procedure termed cholecystectomy) and in individuals with bile duct infection

 

There are four types of gallstones. Each type is formed due to various reasons:

 

  • Cholesterol gallstones are formed when there is too much cholesterol (super-saturation) in the bile. The factors that may increase cholesterol levels in the bile include estrogen (women), obesity, high levels of triglycerides in blood, genetic factors (such as in Native Indians), diabetes mellitus 2, etc.
  • Pigment stones-black type (calcium bilirubinate): Bilirubin, a yellow pigment derived from breakdown of heme (present in red blood cells) tends to form insoluble jet-black pigment stones along with calcium
  • Pigment stones-brown type: Bile is normally sterile, but in some unusual circumstances it may become colonized with bacteria. Bacteria break down lecithin (present in the bile) to release fatty acids which bind with calcium and precipitate to form brown pigment stones
  • Mixed stones are mixture of cholesterol stones and black stones (calcium bilirubinate)

 

What are the Signs and Symptoms of Choledocholithiasis?

Choledocholithiasis (Gallstones in the Common Bile Duct) and cholelithiasis (with or without infection of the gallbladder) frequently coexist. The signs and symptoms of Choledocholithiasis and cholelithiasis include:

 

  • Biliary colic: This is characterized by pain in the right upper abdomen (quadrant). The pain usually comes and goes, but sometimes it may be constant. The pain may be cramping or dull in nature. The pain may travel to the right shoulder tip or to the back. The pain may be worsened after having a heavy fatty meal
  • Jaundice
  • Clay-colored stools
  • Nausea and vomiting
  • Loss of appetite
  • Fever with or without chills
  • Tenderness of the right side of upper abdomen
  • Liver enlargement

 

How is Choledocholithiasis Diagnosed?

The following procedures may be used to diagnose Choledocholithiasis:

 

  • Thorough evaluation of the individual’s medical history and a thorough physical examination including the abdomen and skin
  • During history-taking the physicians may want to know the following:
    • When the symptoms began and whether they are becoming worse
    • List of prescription and over-the-counter medications currently being taken
    • About one’s personal and family history of gallbladder diseases, diet history, etc.
  • Consultation with a gastroenterologist may be necessary, as they are the experts in dealing with such health conditions
  • Stones in the common bile duct are detected using the following methods:
    • Abdominal ultrasound: It is a noninvasive and inexpensive test that is also safe during pregnancy
    • Endoscopic ultrasound or laparoscopic ultrasound may be used to better characterize the stones and the biliary duct
    • CT scan of the abdomen is useful in diagnostic challenges to characterize complications of gallbladder or bile duct disease
    • Endoscopic retrograde cholangiopancreatography (ERCP) permits radiographic imaging of bile ducts. It is the best test because it can help diagnose and the same time help remove a stone from the common bile duct. It is also helpful to visualize any associated pancreatic disease
    • PTC (percutaneous transhepatic cholangiography) may be the modality of choice when performing ERCP is difficult
    • MRI or MRCP (magnetic resonance cholangiopancreatography) is a good, non-invasive test to detect stones in the biliary tree
    • HIDA scintigraphy is a good test to detect cystic duct obstruction (cystic duct and hepatic duct join to form the common bile duct), and analyze how the bile is flowing through the liver, gallbladder, and biliary tree

 

  • Other tests that may be required in Choledocholithiasis to rule in or rule out associated diseases. They include:
    • Complete blood count with differential, liver function panel (bilirubin, transaminases [ALT, AST], alkaline phosphatase, protein), blood cultures, amylase, lipase, prothrombin time, etc.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis. 

choledocholithiasis-obstructive-jaundice-7-638[1]

What are the possible Complications of Choledocholithiasis?

The complications of Choledocholithiasis include:

 

  • Cholangitis: Whenever the bile duct is obstructed the bacteria from the intestine may ascend up and cause infection of the bile ducts and beyond
  • Secondarily biliary cirrhosis: Long-standing obstruction of the common bile duct can cause inflammation, destruction, and scarring of the smaller bile ducts inside the liver and cause liver failure
  • Pancreatitis (inflammation of the pancreas) can occur whenever there is obstruction of the distal part of the common bile duct
  • Gallstones ileus: Sometimes, the gallstone might reach the intestine and cause an obstruction
  • Associated cholelithiasis (stones in the gallbladder) can cause acute cholecystitis (infection of the gallbladder)

 

How is Choledocholithiasis Treated?

Stones in the Common Bile Duct (Choledocholithiasis) should be removed, even if there are no symptoms. The stones may be removed by one of the following methods:

 

  • Endoscopic sphincterotomy when an ERCP is performed
  • Simultaneous bile duct exploration when a laparoscopic cholecystectomy (removal of gallbladder) is performed
  • Balloon dilation of sphincter of Oddi, which is the site where the common bile duct attaches to the duodenum. This is usually reserved for individuals who have the tendency to bleed
  • Endoscopic ultrasound-guided drainage along with percutaneous trans-hepatic cholangiography (PTC) is done in individuals, if endoscopic sphincterotomy is not able to remove the stones
  • If the stone is large enough, then procedures such as lithotripsy (shockwaves to destroy stones), cholangioscopy (direct visualization of bile duct), or biliary tract stenting (placement of hollow tube) may be attempted at first
  • If there is an associated bile duct infection, then antibiotics may be given.

 

How can Choledocholithiasis be Prevented?

The preventative measures of Choledocholithiasis include:

 

  • Prevention of gallstone formation in the gallbladder through:
    • Low-fat diet
    • Exercise
    • Overweight individuals, if planning to lose weight should decrease their weight gradually, but by meeting appropriate nutritional requirements
    • Replacing saturated fats (animal fat) with monounsaturated fats (example olive oil) or omega-3 fatty acids products (example flaxseed, fish oil)
    • Scientists believe that the consumption of coffee, fruits, vegetables, nuts, and high fiber may prevent gallstone formation

 

  • Removal of gallstones formed in the gallbladder
    • The gallbladder may be removed (cholecystectomy), if there is associated symptomatic gallbladder disease, or if the gallstones are more than 3 cm in size, or calcification (calcium on the gallbladder wall) is observed. A laparoscopic cholecystectomy is preferred over an open cholecystectomy
    • Ursodeoxycholic acid medication can be used to dissolve the stones in selected individuals who refuse cholecystectomy
  • Treatment of infections affecting the biliary tree (bile carrying ducts)
  • Treatment of associated conditions that trigger gallstone formation

What is the Prognosis of Choledocholithiasis? (Outcomes/Resolutions)

 

  • With prompt diagnosis and treatment Choledocholithiasis has a favorable diagnosis
  • However, if diagnosis and treatment is delayed, it can cause complications and even lead to life-threatening situations

 

Additional and Relevant Useful Information for Choledocholithiasis:

Novel procedure Natural Orifice Transluminal Endoscopic Surgery (NOTES) for cholecystectomy is currently under review by the research community.

What are some Useful Resources for Additional Information?

American College of Gastroenterology (ACG)
4900 B South, 31st St. Arlington, VA 22206
Phone: (703) 820-7400
Fax: (703) 931-4520
Website: http://www.acg.gi.org

References and Information Sources used for the Article:

Nlm.nih.gov. Choledocholithiasis: MedlinePlus Medical Encyclopedia. 2015. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000274.htm. (accessed on 5/5/2015).

Papadakis M, McPhee S, Rabow M. Current Medical Diagnosis & Treatment 2015.; :699-705.

Helpful Peer-Reviewed Medical Articles:

Attasaranya S, Fogel E, Lehman G. Choledocholithiasis, Ascending Cholangitis, and Gallstone Pancreatitis. Medical Clinics of North America. 2008;92(4):925-960. doi:10.1016/j.mcna.2008.03.001.

London: National Institute for Health and Care Excellence (UK). Diagnosis and management of cholelithiasis, cholecystitis and choledocholithiasis. http://wwwncbinlmnihgov/pubmedhealth/. 2014. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0070643/pdf/TOC.pdf. Accessed February 5, 2015.

Chandran A, Sivarajan R, Srinivas M, Srinivasan V, Venkataraman J. Risk factors for choledocholithiasis in a south Indian population: A case–control study. Indian Journal of Gastroenterology. 2013;32(6):381-385. doi:10.1007/s12664-013-0354-x.

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 28, 2015
Last updated: Aug. 4, 2016


Source: https://www.dovemed.com/diseases-conditions/choledocholithiasis/

 

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Cholelithiasis (Gallstones)
Gallstones

Gallstones are marble-like deposits that form in the gallbladder, due to changes in the concentration of various components of bile. Bile is a fluid that is made by the liver and stored in the gallbladder.


What are the other Names for this Condition? (Also known as/Synonyms)

  • Cholelithiasis
  • Gallbladder Stones
  • Stones in the Gallbladder 

What is Gallstones? (Definition/Background Information)

  • Gallstones are marble-like deposits that form in the gallbladder, due to changes in the concentration of various components of bile. Bile is a fluid that is made by the liver and stored in the gallbladder
  • Gallstones are classified on the basis of their constituent material (what they are composed of). Most commonly these Gallbladder Stones are composed of cholesterol and less commonly are composed of a component of blood called bilirubin
  • The size of these stones can vary from that of a ‘peanut’ to the size of a ‘golf ball’. Majority of the times, Gallstones are found as an incidental finding, when they are not causing any symptoms
  • The symptoms arise when they obstruct the duct of the gallbladder and prevent the gallbladder from draining its fluid into the intestine. The common signs and symptoms of include intermittent pain in the right upper side of abdomen, aggravation of pain by fatty meals, nausea, and vomiting. An ultrasound of abdomen is the diagnostic test of choice
  • Removal of the gallbladder by surgery is the most effective treatment for Gallstones. Once the surgery is performed, the chances of developing the condition is practically nil 

 

Who gets Gallstones? (Age and Sex Distribution)

  • Women are more commonly affected by Gallstones than men, almost in the ratio of 2:1
  • The affected age group may vary from early 30s to late 50s. The chances of developing Gallstones increase with age
  • Gallstones are less commonly seen in the people of Africa and Asia, but are more common the western world, in North and South America

What are the Risk Factors for Gallstones? (Predisposing Factors)

Risk factors associated with Gallstones include:

  • Female gender
  • Advancing age: The older the age, the higher is the chance of developing Gallstones
  • Obese and overweight individuals
  • Pregnancy is a known condition to be associated with the development of Gallbladder Stones
  • Decreased motility of gallbladder: This occurs in individuals who are on intravenous nutrition for a long period of time
  • Individuals who regularly eat a diet high in fat and cholesterol, but low in fiber
  • The risk increases if family members are affected
  • Post-menopausal women taking hormone replacement
  • Certain conditions affecting the liver can also lead to the development of Gallstones. Conditions, such as liver cirrhosis and infections of the biliary tract, are associated with Gallstone formation
  • Individuals affected by chronic blood disorders, such as sickle cell anemia and thalassemia, are at an increased risk of developing bilirubin-type of Gallstones
  • Those who undergo fat reduction surgeries and those who lose weight very rapidly, while being on a low-calorie diet, also have a greater risk

 

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Gallstones? (Etiology)

The exact cause of Gallstone formation is not clear. However, the following factors are known to contribute to their formation:

  • Presence of excess cholesterol in the bile which may precipitate, leading to Gallstone formation
  • Presence of excess bilirubin in the bile, which may occur with certain blood disorders and infections of the biliary tract
  • Improper emptying of the Gallbladder may cause the bile to become concentrated, resulting in stone formation

 

Gallstones are broadly classified on the basis of their composition. They can be of the following types:

  • Cholesterol stones: These are composed of cholesterol, protein component, and may contain small amounts of calcium and bile pigment. They are the most common types of stones that are present in almost 80% of the patients. The cholesterol level of blood does not affect the development of these stone types
  • Pigment stones: They are seen in up to 20% of the cases presenting with gallbladder disease/condition. The majority of patients have underlying blood disorders that lead to the formation of pigmented Gallstones. The major component of these stone types is bilirubin
  • Mixed type: It is the least common variety of Gallstone. They can contain varied concentration of cholesterol, calcium, bilirubin, and other components

What are the Signs and Symptoms of Gallstones?

Most of the individuals with Gallstones are asymptomatic.

  • The symptoms may develop when a stone is large enough to block the duct draining the bile from the gallbladder to the first part of small intestine, duodenum
  • This leads to increased efforts of the gallbladder to push the bile out, which thus presents as a cramping type of pain in the right upper abdomen
  • This initial pattern presents as intermittent pain that subsides by itself. When it is complicated by some infection or other complication, it presents as continuous pain

 

The common signs and symptoms of Gallbladder Stones include:

  • Abdominal pain
    • The pain is located in the right upper part of the belly and may radiate to the right shoulder
    • The type of pain may vary from being sharp, dull, or cramping in nature
    • It may be constant or intermittent
    • The pain is typically aggravated by fatty diet
  • Fever and chills:
    • When there is an infection of the gallbladder, the patients may present with fever and chills
    • There may also be associated nausea and vomiting

How are Gallstones Diagnosed?

The diagnosis of Gallstones may involve the following tests and exams:

  • A complete evaluation of medical history along with a thorough physical exam
  • Various modalities of imaging are available to visualize the Gallstones, and these include:
    • Abdominal X-ray: It can only detect up to 10% of the Gallstones, which have high content of calcium and are thus seen on X-ray
    • Abdominal ultrasound: It is a test that uses high-frequency sound waves to detect the presence of Stones in the Gallbladder. It is the test of choice, when a patient presents with symptoms of Gallstones. This test may detect the presence of Gallstones in as many as 80% of the cases
    • HIDA scan: If an abdominal ultrasound does not detect the stones, but the clinical probability is high, then HIDA scans are generally used to confirm their presence. In this test, a dye is injected into the body and the movement of dye is followed through a series of images. This test has a high rate of detection of stones that are not seen on the ultrasound

Other less commonly used modalities in the detection of Gallstones include:

  • CT scan of abdomen: It is a high-resolution scan of the abdomen, which gives better images of the abdomen. It is mainly used for detecting the complications associated with Gallstones, if any
  • Cholangiography: It is a form of test that enables a direct visualization of the bile system. It can be performed by two methods:
    • Endoscopic retrograde cholangiopancreatography (ERCP: It is form of invasive test that serves the dual purpose of diagnosis and treatment
    • Magnetic resonance cholangiopancreatography (MRCP): It is a non-invasive form of test that is excellent to visualise the presence of stones in the biliary system. It is performed in patients who are poor candidates for ERCP

Blood tests to access the liver functions include:

  • Liver function tests:
    • Bilirubin level
    • Liver enzymes, which include aminotransferase and alkaline phosphatase
  • To assess the pancreatic function levels, enzymes secreted by the pancreas are measured that include:
    • Amylase
    • Lipase
  • To assess the blood abnormalities:
    • Complete blood count
    • Coagulation studies
    • Studies to assess hereditary disorders may also be ordered

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Gallstones?

The complications from Gallstones typically arise when they obstruct the ducts in the biliary system, or when they are associated with infections.

  • Infectious complications:
    • Acute cholecystitis: It occurs when Gallstones block the bile duct and infection occurs in the gallbladder. It is a form of surgical emergency, as the infection is fatal, if timely treatment is not provided
    • Cholangitis: It occurs when the stone leaves the gallbladder and gets stuck in the distal bile duct, and infection of the bile duct taking place. This infection may spread to the liver and can be fatal
  • Complications to obstruction in the biliary system:
    • Choledocholithiasis: When the stone reaches the common bile duct and gets stuck, it results in the obstruction of common bile duct, which may present as jaundice
    • Pancreatitis: It occurs when there is a blockage in the pancreatic ducts. The blockage is typically caused by a stone that leaves the gallbladder and enters the pancreatic system
    • Chronic cholecystitis: With repeated episodes of unresolved acute cholecystitis, a chronic form of the disease may develop. It is associated with decreased functioning of the gallbladder
  • Gallbladder cancer: There is a very small risk of cancer in the gallbladder due to Gallstones, but it is very rare

How are Gallstones Treated?

Only symptomatic patients need treatment for Gallstones. Since most of the asymptomatic Gallstones would not progress to become symptomatic, they may be only monitored.

  • The option to treat symptomatic Gallstones depends on the acuity of presentation
  • Surgery is the first line of treatment
  • If a patient is a poor candidate for surgery, medical management may be undertaken 

A surgical removal of the gallbladder is the treatment of choice. This can be achieved in two ways:

  • Laparoscopic removal (laparoscopic cholecystectomy) is the procedure of choice
    • It offers faster recovery
    • Less pain
    • Less complications
  • Open cholecystectomy, which is rarely performed nowadays, for it involves
    • Bigger incisions
    • More pain
    • Longer hospitalization period

Medical management:

  • It is reserved for the patients who cannot tolerate surgery
  • Medications, such as chenodeoxycholic acid or ursodeoxycholic acid, may be given to dissolve the stones
  • They take a long time to act and have inconsistent effects 

Lithotripsy:

  • For patients who are poor candidates of surgery and who do not respond to medical management
  • It is associated with a high recurrence rate 

How can Gallstones be Prevented?

Prevention of risk factors may be helpful in reducing the risk of Gallstones.

  • Having a healthy diet and proper exercise routine can reduce the chances of developing risk factors for this condition
  • Individuals who want to lose weight should do so progressively slowly and should not lose a considerable amount of weight within a short period of time

What is the Prognosis of Gallstones? (Outcomes/Resolutions)

  • Gallstones may be best treated through a surgery
  • Once the surgery is done the chances of developing the condition again is practically nil

Additional and Relevant Useful Information for Gallstones:

  • The most common indication for performing a laparoscopic cholecystectomy is symptomatic gallstones causing pain (biliary colic)

What are some Useful Resources for Additional Information?

American Gastroenterological Association (AGA)
4930 Del Ray Avenue Bethesda, MD 20814
Phone: (301) 654-2055
Fax: (301) 652-3890
Email: member@gastro.org
Website: http://www.gastro.org

References and Information Sources used for the Article:

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001318/ (accessed on 07/26/2015)

http://www.nlm.nih.gov/medlineplus/gallstones.html (accessed on 07/26/2015)

Mayo Clinic Gatroenterology and Hepatology Board Review (accessed on 07/26/2015)

Helpful Peer-Reviewed Medical Articles:

Casper, M., &Lammert, F. (2011). [Gallstone disease: basic mechanisms, diagnosis and therapy]. Praxis (Bern 1994), 100(23), 1403-1412. doi: 10.1024/1661-8157/a000721

Chuang, S. C., Hsi, E., & Lee, K. T. (2013).Genetics of gallstone disease.AdvClinChem, 60, 143-185.

Pronio, A., Piroli, S., Caporilli, D., Ciamberlano, B., Coluzzi, M., Castellucci, G., . . .Montesani, C. (2013). Recurrent gallstone ileus: case report and literature review. G Chir, 34(1-2), 35-37.

Ramamurthy, N. K., Rudralingam, V., Martin, D. F., Galloway, S. W., &Sukumar, S. A. (2013). Out of sight but kept in mind: complications and imitations of dropped gallstones. AJR Am J Roentgenol, 200(6), 1244-1253. doi: 10.2214/AJR.12.9430

Svensson, J., & Makin, E. (2012).Gallstone disease in children.SeminPediatrSurg, 21(3), 255-265. doi: 10.1053/j.sempedsurg.2012.05.008

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Aug. 2, 2015
Last updated: April 8, 2016


Source: https://www.dovemed.com/diseases-conditions/gallstones/

 

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Lithotripsy

Definition

Lithotripsy is the use of high-energy shock waves to fragment and disintegrate kidney stones. The shock wave, created by using a high-voltage spark or an electromagnetic impulse outside of the body, is focused on the stone. The shock wave shatters the stone, allowing the fragments to pass through the urinary system. Since the shock wave is generated outside the body, the procedure is termed extracorporeal shock wave lithotripsy (ESWL). The name is derived from the roots of two Greek words, litho , meaning stone, and trip , meaning to break.

Purpose

ESWL is used when a kidney stone is too large to pass on its own, or when a stone becomes stuck in a ureter (a tube that carries urine from the kidney to the bladder) and will not pass. Kidney stones are extremely painful and can cause serious medical complications if not removed.

Demographics

For an unknown reason, the number of persons in the United States developing kidney stones has been increasing over the past 20 years. White people are more prone to develop kidney stones than are persons of color. Although stones occur more frequently in men, the number of women who develop them has been increasing over the past 10 years, causing the ratio to change. Kidney stones strike most people between the ages of 20 and 40. Once persons develop more than one stone, they are more likely to develop others. Lithotripsy is not required for treatment in all cases of kidney stones.

Description

Lithotripsy uses the technique of focused shock waves to fragment a stone in the kidney or the ureter. The affected person is placed in a tub of water or in contact with a water-filled cushion. A sophisticated machine called Lithotripter produces the focused shock waves. A high-voltage electrical discharge is passed through a spark gap under water. The shock waves thus produced are focused on the stone inside the person’s body. The shock waves are created and focused on the stone with the help of a machine called C-Arm Image Intensifier. The wave shatters and fragments the stone. The resulting debris, called gravel, can then pass through the remainder of the ureter, through the bladder, and through the urethra during urination. There is minimal chance of damage to skin or internal organs because biologic tissues are resilient, not brittle, and because the shock waves are not focused on them.

The shock wave is characterized by a very rapid pressure increase in the transmission medium and is quite different from ultrasound. The shock waves are transmitted through a person’s skin and pass harmlessly through soft tissues. The shock wave passes through the
Kidney stones that are too big to pass through the ureter become very painful (B). During lithotripsy, the patient is put in a tub of water, or on a water-filled blanket. Shock waves are used to break up the stone (C). These smaller pieces are able to pass out of the body (D). (Illustration by GGS Inc.)

Kidney stones that are too big to pass through the ureter become very painful (B). During lithotripsy, the patient is put in a tub of water, or on a water-filled blanket. Shock waves are used to break up the stone (C). These smaller pieces are able to pass out of the body (D). (

Illustration by GGS Inc.

)

kidney and strikes the stone. At the edge of the stone, energy is transferred into the stone, causing small cracks to form on the edge of the stone. The same effect occurs when the shock wave exits the stone. With successive shock waves, the cracks open up. As more cracks form, the size of the stone is reduced. Eventually, the stone is reduced to small particles, which are then flushed out of the kidneys or ureter naturally during urination.

Diagnosis/Preparation

ESWL should not be considered for persons with severe skeletal deformities, people weighing more than 300 lb (136 kg), individuals with abdominal aortic aneurysms, or persons with uncontrollable bleeding disorders. Women who are pregnant should not be treated with ESWL. Individuals with cardiac pacemakers should be evaluated by a cardiologist familiar with ESWL. The cardiologist should be present during the ESWL procedure in the event the pacemaker needs to be overridden.

Prior to the lithotripsy procedure, a complete physical examination is performed, followed by tests to determine the number, location, and size of the stone or stones. A test called an intravenous pyelogram (IVP) is used to locate the stones, which involves injecting a dye into a vein in the arm. This dye, which shows up on x ray, travels through the bloodstream and is excreted by the kidneys. The dye then flows down the ureters and into the bladder. The dye surrounds the stones. In this manner, x rays are used to evaluate the stones and the anatomy of the urinary system. Blood tests are performed to determine if any potential bleeding problems exist. For women of childbearing age, a pregnancy test is done to make sure they are not pregnant. Older persons have an EKG test to make sure that no potential heart problems exist. Some individuals may have a stent placed prior to the lithotripsy procedure. A stent is a plastic tube placed in the ureter that allows the passage of gravel and urine after the ESWL procedure is completed.

The process of lithotripsy generally takes about one hour. During that time, up to 8,000 individual shock waves are administered. Depending on a person’s pain tolerance, there may be some discomfort during the treatment. Analgesicsmay be administered to relieve this pain.

Aftercare

Most persons pass blood in their urine after the ESWL procedure. This is normal and should clear after several days to a week. Lots of fluids should be taken to encourage the flushing of any gravel remaining in the urinary system. Treated persons should follow up with a urologist in about two weeks to make sure that everything is progressing as planned. If a stent has been inserted, it is normally removed at this time.

Risks

Abdominal pain is fairly common after ESWL, but it is usually not a cause for worry. However, persistent or severe abdominal pain may imply an unexpected internal injury. Occasionally, stones may not be completely fragmented during the first ESWL treatment and further lithotripsy procedures may be required.

Some people are allergic to the dye material used during an IVP, so it cannot be used. For these people, focused sound waves, called ultrasound, can be used to identify where the stones are located.

Normal results

In most cases, stones are reduced to gravel and passed within a few days. Individuals may return to work whenever they feel able.

Morbidity and mortality rates

Colicky renal pain is very common when gravel is being passed. Other problems may include perirenal hematomas (blood clots near the kidneys) in 66% of the cases; nerve palsies; pancreatitis (inflammation of the pancreas); and obstruction by stone fragments. Death is extremely rare and usually due to an undiagnosed associated or underlying condition that is aggravated by the lithotripsy procedure.

Alternatives

Before the advent of lithotripsy, surgery was used to remove kidney stones. This approach is uncommon today, but occasionally used when other conditions prevent the use of lithotripsy. Attempts are occasionally made to change the pH of urine so as to dissolve kidney stones. This treatment has limited success.

 

Resources

books

Field, Michael, David Harris, and Carol Pollock. The Renal System. London: Churchill Livingstone, 2001.

Parker, James N. The 2002 Official Patient’s Source Book on Kidney Stones. Logan, UT: ICON Health, 2002.

Tanagho, Emil A., and Jack W. McAninch. Smith’s General Urology, 15th ed. New York: McGraw-Hill, 2000.

Walsh, Patrick C., and Alan B. Retik. Campbell’s Urology, 8th ed. Philadelphia: Saunders, 2002.

periodicals

Ather, M. H., and M. A. Noor. “Does Size and Site Matter for Renal Stones Up to 30 mm in Size in Children Treated by Extracorporeal Lithotripsy?” Urology 61, no.1 (2003): 212–215.

Downey, P., and D. Tolley. “Contemporary Management of Renal Calculus Disease.” Journal of the Royal College of Surgery (Edinburgh) 47, no.5 (2002): 668–675.

Hochreiter, W. W., H. Danuser, M. Perrig, and U. E. Studer. “Extracorporeal Shock Wave Lithotripsy for Distal Ureteral Calculi.” Journal of Urology 169, no.3 (2003): 878–880.

Rajkumar, P., and G. F. Schmitgen. “Shock Waves Do More Than Just Crush Stones: Extracorporeal Shock Wave Therapy in Plantar Fasciitis.” International Journal of Clinical Practice 56, no.10 (2002): 735–737.

organizations

American Foundation for Urologic Disease. 1128 North Charles Street, Baltimore, MD 21201. (800) 242-2383 or (410) 468-1800. http://admin@afud.org. http://www.afud.org .

American Lithotripsy Society. 305 Second Avenue, Suite 200, Waltham, MA 02451.

American Medical Association. 515 N. State Street, Chicago, IL 60610. (312) 464-5000. http://www.ama-assn.org .

American Urological Association. 1120 North Charles Street, Baltimore, MD 21201-5559. (410) 727-1100. http://www.auanet.org/index_hi.cfm .

National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. (781) 895-9098. Fax: (781) 895-9088. E-mail: http://als@lithotripsy.org. http://www.kidney.org .

other

Case Western Reserve University. [cited March 17, 2003http://www.cwru.edu/artsci/dittrick/artifactspages/b-2lithotripsy.htm .

Global Lithotripsy Services. [cited March 17, 2003] http://www.gls-lithotripsy.com/Howdoes.html .

Lifespan. [cited March 17, 2003] http://www.lifespan.org/mininvasive/revised/patient/gallstones/lithotripsy.htm .

National Institute of Diabetes and Digestive and Kidney Diseases. [cited March 17, 2003] http://www.niddk.nih.gov/health/urolog/pubs/stonadul/stonadul.htm#whogets .

National Library of Medicine. [cited March 17, 2003] http://www.nlm.nih.gov/medlineplus/ency/article/007113.htm .

L. Fleming Fallon, Jr, MD, DrPH

WHO PERFORMS THE PROCEDURE AND WHERE IS IT PERFORMED?


Lithotripsy is performed by a technician or other individual with specialized training under the supervision of a physician. The physician in charge usually has specialized training in urology. Lithotripsy is most often performed as an outpatient procedure in a facility affiliated with a hospital.

Source Read more: http://www.surgeryencyclopedia.com/La-Pa/Lithotripsy.html#ixzz53XzP0D6h

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Cystic duct

Cystic duct

The gallbladder stores bile produced in the liver. In order to enter into the duodenum, bile must travel out of the gallbladder, through the cystic duct’s spiral valve, and into the common bile duct. Along with fluid from the pancreas, the bile enters the duodenum through the ampulla of vater.

While there is no other use for the cystic duct, health problems can result when it develops obstructions. If gallstones become lodged in the spiral valve or other parts of the duct, the movement of bile becomes impeded or blocked completely. Should this happen, bile will become trapped within the gallbladder. The bile will build up to the point where the gallbladder will swell. In the worst case scenario, the gallbladder will rupture, leading to a surgical emergency.

Gallbladder


Source: https://www.healthline.com/human-body-maps/cystic-duct

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Role of Bile Acids In Digestion

Role of Bile Acids In Digestion
Bile is a complex fluid containing water, electrolytes and a battery of organic molecules including bile acids, cholesterol, phospholipids and bilirubin that flows through the biliary tract into the small intestine. There are two fundamentally important functions of bile in all species:

Bile contains bile acids, which are critical for digestion and absorption of fats and fat-soluble vitamins in the small intestine.
Many waste products, including bilirubin, are eliminated from the body by secretion into bile and elimination in feces.
Adult humans produce 400 to 800 ml of bile daily, and other animals proportionately similar amounts. The secretion of bile can be considered to occur in two stages:

Initially, hepatocytes secrete bile into canaliculi, from which it flows into bile ducts. This hepatic bile contains large quantities of bile acids, cholesterol and other organic molecules.
As bile flows through the bile ducts it is modified by addition of a watery, bicarbonate-rich secretion from ductal epithelial cells.
In species with a gallbladder (man and most domestic animals except horses and rats), further modification of bile occurs in that organ. The gall bladder stores and concentrates bile during the fasting state. Typically, bile is concentrated five-fold in the gall bladder by absorption of water and small electrolytes – virtually all of the organic molecules are retained.

Secretion into bile is a major route for eliminating cholesterol. Free cholesterol is virtually insoluble in aqueous solutions, but in bile, it is made soluble by bile acids and lipids like lecithin. Gallstones, most of which are composed predominantly of cholesterol, result from processes that allow cholesterol to precipitate from solution in bile.

Role of Bile Acids in Fat Digestion and Absorption
Bile acids are derivatives of cholesterol synthesized in the hepatocyte. Cholesterol, ingested as part of the diet or derived from hepatic synthesis is converted into the bile acids cholic and chenodeoxycholic acids, which are then conjugated to an amino acid (glycine or taurine) to yield the conjugated form that is actively secreted into cannaliculi.
Bile acids are facial amphipathic, that is, they contain both hydrophobic (lipid soluble) and polar (hydrophilic) faces. The cholesterol-derived portion of a bile acid has one face that is hydrophobic (that with methyl groups) and one that is hydrophilic (that with the hydroxyl groups); the amino acid conjugate is polar and hydrophilic.

Their amphipathic nature enables bile acids to carry out two important functions:

Emulsification of lipid aggregates: Bile acids have detergent action on particles of dietary fat which causes fat globules to break down or be emulsified into minute, microscopic droplets. Emulsification is not digestion per se, but is of importance because it greatly increases the surface area of fat, making it available for digestion by lipases, which cannot access the inside of lipid droplets.
Solubilization and transport of lipids in an aqueous environment: Bile acids are lipid carriers and are able to solubilize many lipids by forming micelles – aggregates of lipids such as fatty acids, cholesterol and monoglycerides – that remain suspended in water. Bile acids are also critical for transport and absorption of the fat-soluble vitamins.
Role of Bile Acids in Cholesterol Homeostasis
Hepatic synthesis of bile acids accounts for the majority of cholesterol breakdown in the body. In humans, roughly 500 mg of cholesterol are converted to bile acids and eliminated in bile every day. This route for elimination of excess cholesterol is probably important in all animals, but particularly in situations of massive cholesterol ingestion.

Interestingly, it has recently been demonstrated that bile acids participate in cholesterol metabolism by functioning as hormones that alter the transcription of the rate-limiting enzyme in cholesterol biosynthesis.

Enterohepatic Recirculation
Large amounts of bile acids are secreted into the intestine every day, but only relatively small quantities are lost from the body. This is because approximately 95% of the bile acids delivered to the duodenum are absorbed back into blood within the ileum.

Venous blood from the ileum goes straight into the portal vein, and hence through the sinusoids of the liver. Hepatocytes extract bile acids very efficiently from sinusoidal blood, and little escapes the healthy liver into systemic circulation. Bile acids are then transported across the hepatocytes to be resecreted into canaliculi. The net effect of this enterohepatic recirculation is that each bile salt molecule is reused about 20 times, often two or three times during a single digestive phase.


It should be noted that liver disease can dramatically alter this pattern of recirculation – for instance, sick hepatocytes have decreased ability to extract bile acids from portal blood and damage to the canalicular system can result in escape of bile acids into the systemic circulation. Assay of systemic levels of bile acids is used clinically as a sensitive indicator of hepatic disease.

Pattern and Control of Bile Secretion
The flow of bile is lowest during fasting, and a majority of that is diverted into the gallbladder for concentration. When chyme from an ingested meal enters the small intestine, acid and partially digested fats and proteins stimulate secretion of cholecystokinin and secretin. As discussed previously, these enteric hormones have important effects on pancreatic exocrine secretion. They are both also important for secretion and flow of bile:

Cholecystokinin: The name of this hormone describes its effect on the biliary system – cholecysto = gallbladder and kinin = movement. The most potent stimulus for release of cholecystokinin is the presence of fat in the duodenum. Once released, it stimulates contractions of the gallbladder and common bile duct, resulting in delivery of bile into the gut.
Secretin: This hormone is secreted in response to acid in the duodenum. Its effect on the biliary system is very similar to what was seen in the pancreas – it simulates biliary duct cells to secrete bicarbonate and water, which expands the volume of bile and increases its flow out into the intestine.


 

Source:  http://www.vivo.colostate.edu/hbooks/pathphys/digestion/liver/bile.html

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Gallstones (expanded)

A male adult pointing to a liver outline and painted gallbladder on his abdomen.

Gallstones facts

  • Gallstones are “stones” that form in the gallbladder or bile ducts.
  • The common types of gallstones are cholesterol, black pigment, and brown pigment.
  • Cholesterol gallstones occur more frequently in several ethnic groups and are associated with female gender, obesity, pregnancy, oral hormonal therapy, rapid loss of weight, elevated blood triglyceride levels, and Crohn’s disease.
  • Black pigment gallstones occur when there is increased destruction of red blood cells, while brown pigment gallstones occur when there is reduced flow and infection of bile.
  • The majority of gallstones do not cause symptoms.
  • The most common symptoms of gallstones are biliary colic and cholecystitis. Gallstones do not cause intolerance to fatty foods, belching, abdominal distention, or gas.
  • Complications of gallstones include cholangitis, gangrene of the gallbladder, jaundice, pancreatitis, sepsis, fistula, and ileus.
  • Gallbladder sludge is associated with symptoms and complications of gallstones; however, like gallstones, sludge usually does not cause problems.
  • The best single test for diagnosing gallstones is transabdominal ultrasonography. Other tests include endoscopic ultrasonography, magnetic resonance cholangio-pancreatography (MRCP), cholescintigraphy (HIDA scan), endoscopic retrograde cholangio-pancreatography(ERCP), liver and pancreatic blood tests, duodenal drainage, oral cholecystogram (OCG), and intravenous cholangiogram (IVC).
  • Gallstones are managed primarily with observation (no treatment) or removal of the gallbladder (cholecystectomy). Less commonly used treatments include sphincterotomy and extraction of gallstones, dissolution with oral medications, and extra-corporeal shock-wave lithotripsy (ESWL). Prevention of cholesterol gallstones also is possible with oral medications.
  • Symptoms of gallstones should stop following cholecystectomy. If they do not, it is likely that gallstones were left in the ducts, there is a second problem within the bile ducts, or there is sphincter of Oddi dysfunction.
  • Many dietary recommendations have been made for the prevention or treatment of gallstones and to prevent their symptoms, but none of them have been shown to be effective.
  • Many home remedies have been suggested for eliminating gallstones, but none have been shown to be effective
  • Continuing research is directed at uncovering the genes that are responsible for the formation of gallstones.
Illustration of the digestive system with gallstones and close up of gallstones in the gallbladder a stone that has also passed in to the cystic duct.

What are gallstones, and how do they form?

Gallstones (often misspelled as gall stones) are stones that form in the gall (bile) within the gallbladder. (The gallbladder is a pear-shaped organ just below the liver that stores bile secreted by the liver.) Gallstones reach a size of between a sixteenth of an inch and several inches.

  • Bile is a watery liquid made by the cells of the liver that is important for digesting food in the intestine, particularly fat, and eliminating toxic substances from the body.
  • Liver cells secrete the bile into small canals within the liver referred to as canaliculi.
  • The bile flows through the canaliculi and into larger collecting ducts within the liver referred to as intrahepatic bile ducts.
  • The bile then flows through merged intrahepatic bile ducts out of the liver as extrahepatic (outside the liver) bile ducts, ( first into the two hepatic bile ducts, then into the single common hepatic duct, and finally, after the common hepatic duct is joined by the cystic duct coming from the gallbladder, into the common bile duct.

From the common bile duct, there are two different directions that bile can flow.

  • The first direction is through the common bile duct and directly into the intestine where the bile mixes with food and promotes digestion of food. At the same time toxic substances that are removed by the liver from the blood are eliminated into the intestine.
  • The second direction is into a off-shoot of the common bile duct, the cystic duct, and from there into the gallbladder.
Illustration showing gallstones in the gallbladder as well as in the distal common bile duct.

What are gallstones and how do they form?

Once in the gallbladder, bile is concentrated by the removal (absorption) of water. During a meal, the muscle that makes up the wall of the gallbladder contracts and squeezes the concentrated bile in the gallbladder back through the cystic duct into the common bile duct and then into the intestine. (Concentrated bile is much more effective for digestion than the un-concentrated bile that goes from the liver straight into the intestine.) The timing of gallbladder contraction – during a meal – allows the concentrated bile from the gallbladder to mix with food.

Gallstones usually form in the gallbladder; however, they also may form anywhere there is bile – in the intrahepatic, hepatic, common bile, and cystic ducts.

Gallstones also may move about in the bile, for example, from the gallbladder into the cystic or the common duct.

 

What causes gallstones, and who gets them?

Gallstones are common; they occur in approximately 20% of women in the US, Canada and Europe, but there is a large variation in the prevalence among different ethnic groups. For example, gallstones occur 1 ½ to 2 times more commonly in Scandinavians and Mexican-Americans. Among American Indians, gallstone prevalence is more than 80%. These differences probably are accounted for by genetic (hereditary) factors. First-degree relatives (parents, siblings, and children) of individuals with gallstones are 1 ½ times more likely to have gallstones than if they do not have a first-degree relative with gallstones. Further support for a genetic predisposition comes from twin studies. Thus, among non-identical pairs of twins (who share 50% of their genes with one another), both individuals in a pair have gallstones 8% of the time. Among identical pairs of twins (who share 100% of their genes with one another), both individuals have gallstones 23% of the time.

There are several conditions that are associated with the formation of gallstones, and the way in which they cause gallstones can vary. (Please see the section on risks for gallstones in this article.)

 

Small gallstones made up largely of cholesterol.

What are the types of gallstones?

There are several types of gallstones, and each type has a different cause.

Cholesterol gallstones

Cholesterol gallstones are primarily made up of cholesterol. They are the most common type of gallstone, comprising 80% of gallstones in individuals in Europe and the Americas. Cholesterol is one of the substances (chemicals) that liver cells secrete into bile. Secretion of cholesterol into bile is an important mechanism by which the liver eliminates excess cholesterol from the body.

In order for bile to carry cholesterol, the cholesterol must be dissolved in the bile. Cholesterol is a fat, however, and bile is an aqueous or watery solution; fats do not dissolve in watery solutions. In order to make the cholesterol dissolve in bile, the liver also secretes two detergents, bile acids and lecithin, into the bile. These detergents, just like dish-washing detergents, dissolve the fatty cholesterol so that it can be carried by bile through the ducts. If the liver secretes too much cholesterol for the amount of bile acids and lecithin it secretes, some of the cholesterol does not stay dissolved. Similarly, if the liver does not secrete enough bile acids and lecithin, some of the cholesterol does not stay dissolved. In either case, the undissolved cholesterol sticks together and forms particles of cholesterol that grow in size and eventually become gallstones.

There are two other processes that promote the formation of cholesterol gallstones though neither process is able to cause cholesterol gallstones to form. The first is an abnormally rapid formation and growth of cholesterol particles into gallstones. Thus, with the same concentrations of cholesterol, bile acids and lecithin in the bile, patients with gallstones form particles of cholesterol more rapidly than individuals without gallstones. The second process that promotes the formation and growth of gallstones is reduced contraction and emptying of the gallbladder that allows bile to stay in the gallbladder longer than normally so that there is more time for cholesterol particles to form and grow into gallstones.

 

A man experiences pain from biliary colic.

What are the symptoms of gallstones?

The majority of people with gallstones have no signs or symptoms and are unaware of their gallstones. (The gallstones are “silent.”) These gallstones often are found as a result of tests (for example, ultrasoundor X-ray examination of the abdomen) performed while evaluating medical conditions other than gallstones. Symptoms can appear later in life, however, after many years without symptoms. Thus, over a period of five years, approximately 10% of people with silent gallstones will develop symptoms. Once symptoms develop, they are likely to continue and often will worsen.

Gallstones are blamed for many symptoms they do not cause. Among the symptoms gallstones do not cause are:

  • dyspepsia (including abdominal bloating and discomfort after eating),
  • intolerance to fatty foods,
  • belching, and
  • flatulence (passing gas or farting).

When signs and symptoms of gallstones occur, they virtually always occur because the gallstones obstruct the bile ducts.

The most common symptom of gallstones is biliary colic. Biliary colic is a very specific type of pain, occurring as the primary or only symptom in 80% of people with gallstones who develop symptoms. Biliary colic occurs when the bile ducts (cystic, hepatic ducts or common bile duct) are suddenly blocked by a gallstone. Slowly-progressing obstruction, as from a tumor, does not cause biliary colic. Behind the obstruction, fluid accumulates and distends the ducts and gallbladder. In the case of hepatic duct or common bile duct obstruction, this is due to continued secretion of bile by the liver. In the case of cystic duct obstruction, the wall of the gallbladder secretes fluid into the gallbladder. It is the distention of the ducts or gallbladder that causes biliary colic.

Characteristically, biliary colic comes on suddenly or builds rapidly to a peak over a few minutes.

  • It is a constant pain; it does not come and go, though it may vary in intensity while it is present. IT is not cramp-like.
  • It lasts for 15 minutes to 4-5 hours. If the pain lasts more than 4-5 hours, it means that a complication – usually cholecystitis – has developed.
  • The pain usually is severe, but movement does not make the pain worse. In fact, patients experiencing biliary colic often walk about or writhe (twist the body in different positions) in bed trying to find a comfortable position.
  • Biliary colic often is accompanied by nausea.
  • Most commonly, biliary colic is felt in the middle of the upper abdomen just below the sternum.
  • The second most common location for pain is the right upper abdomen just below the margin of the ribs.
  • Occasionally, the pain also may be felt in the back at the lower tip of the scapula on the right side.
  • On rare occasions, the pain may be felt beneath the sternum and is mistaken for angina or a heart attack.
  • An episode of biliary colic subsides gradually once the gallstone shifts within the duct so that it is no longer causing obstruction.

Biliary colic is a recurring symptom. Once the first episode occurs, there are likely to be other episodes. Also, there is a pattern of recurrence for each individual, that is, in some individuals the episodes tend to remain frequent while in others they are infrequent. The majority of people who develop biliary colic do not go on to develop cholecystitis or other complications. There is a misconception that contraction of the gallbladder is what causes the obstruction of the ducts and biliary colic. Eating, even fatty foods, does not cause biliary colic; most episodes of biliary colic occur during the night, long after the gallbladder has emptied.

 

A doctor examining a gallstone patient.

What are the complications of gallstones?

Biliary colic is the most common symptom of gallstones, but, fortunately, it is usually a self-limited symptom. There are, however, more serious complications of gallstones.

Cholecystitis

Cholecystitis means inflammation of the gallbladder. Like biliary colic, it too is caused by sudden obstruction of the ducts, usually the cystic duct by a gallstone. In fact, cholecystitis may begin with an episode of biliary colic. Obstruction of the cystic duct causes the wall of the gallbladder to begin secreting fluid, but for unclear reasons, inflammation sets in. At first the inflammation is sterile, that is, there is no infection with bacteria; however, over time the bile and gallbladder become infected with bacteria that travel through the bile ducts from the intestine.

With cholecystitis, there is constant pain in the right upper abdomen. Inflammation extends through the wall of the gallbladder, and the right upper abdomen becomes particularly tender when it is pressed or even tapped. Unlike with biliary colic, however, it is painful to move around. Individuals with cholecystitis usually lie still. There is fever, and the white blood cell count is elevated, both signs of inflammation. Cholecystitis usually is treated with antibiotics, and most episodes will resolve over several days. Even without antibiotics, cholecystitis often resolves. As with biliary colic, movement of the gallstone out of the cystic duct and back into the gallbladder relieves the obstruction and allows the inflammation to resolve.

Cholangitis

Cholangitis is a condition in which bile in the common, hepatic, and intrahepatic ducts becomes infected. Like cholecystitis, the infection spreads through the ducts from the intestine after the ducts become obstructed by a gallstone. Patients with cholangitis are very sick with high fever and elevated white blood cell counts. Cholangitis may result in an abscess within the liver or sepsis. (See discussion of sepsis that follows.)

Gangrene

Gangrene of the gallbladder is a condition in which the inflammation of cholecystitis cuts off the supply of blood to the gallbladder. Without blood, the tissues forming the wall of the gallbladder die, and this makes the wall very weak. The weakness combined with infection often leads to rupture of the gallbladder. The infection then may spread throughout the abdomen, though often the rupture is confined to a small area around the gallbladder (a confined perforation).

Yellowish eyes are a symptom of jaundice.

What are the complications of gallstones? (Continued)

Jaundice

Jaundice is a condition in which bilirubin accumulates in the body. Bilirubin is brownish-black in color but is yellow when it is not too concentrated. A build-up of bilirubin in the body turns the skin and whites of the eye (sclera) yellow. Jaundice occurs when there is prolonged obstruction of the bile ducts. The obstruction may be due to gallstones, but it also may be due to many other causes, for example, tumors of the bile ducts or surrounding tissues. (Other causes of jaundice are a rapid destruction of red blood cells that overwhelms the ability of the liver to remove bilirubin from the blood or a damaged liver that cannot remove bilirubin from the blood normally.) Jaundice, by itself, generally does not cause problems.

Pancreatitis

Pancreatitis means inflammation of the pancreas. The two most common causes of pancreatitis are alcoholism and gallstones. The pancreas surrounds the common bile duct as it enters the intestine. The pancreatic duct that drains the digestive juices from the pancreas joins the common bile duct just before it empties into the intestine. If a gallstone obstructs the common bile duct just after the pancreatic duct joins it, the flow of pancreatic juice from the pancreas is blocked. This results in inflammation within the pancreas. Pancreatitis due to gallstones usually is mild, but it may cause serious illness and even death. Fortunately, severe pancreatitis due to gallstones is rare.

Sepsis

Sepsis is a condition in which bacteria from any source within the body, including the gallbladder or bile ducts, enter into the blood stream and spread throughout the body. Although the bacteria usually remain within the blood, they also may spread to distant tissues and lead to the formation of abscesses (localized areas of infection with formation of pus). Sepsis is a feared complication of any infection. The signs of sepsis include high fever, high white blood cell count, and, less frequently, rigors (shaking chills) or a drop in blood pressure.

Fistula

A fistula is an abnormal tract through which fluid can flow between two hollow organs or between an abscess and a hollow organ or skin. Gallstones cause fistulas when the hard gallstone erodes through the soft wall of the gallbladder or bile ducts. Most commonly, the gallstone erodes into the small intestine, stomach, or common bile duct. This can leave a tract that allows bile to flow from the gallbladder to the small intestine, stomach, or the common bile duct. If the fistula enters the distal part of the small intestine, the concentrated bile can lead to problems such as diarrhea. Rarely, the gallstone erodes into the abdominal cavity. The bile then leaks into the abdominal cavity and causes inflammation of the lining of the abdomen (peritoneum), a condition called bile peritonitis.

Ileus

Ileus is a condition in which there is an obstruction to the flow of food, gas, and liquid within the intestine. It may be due to a mechanical obstruction, for example, a tumor within the intestine, or a functional obstruction, for example, inflammation of the intestine or surrounding tissues that prevents the muscles of the intestine from working normally and propelling intestinal contents. If a large gallstone erodes through the wall of the gallbladder and into the stomach or small intestine, it will be propelled through the small intestine. The narrowest part of the small intestine is the ileo-cecal valve, which is located at the site where the small intestine joins the colon. If the gallstone is too large to pass through the valve, it can obstruct the small intestine and cause an ileus. Gallstones also may cause ileus if there are other abnormal narrowings in the intestine such as a tumor or scarring.

Cancer

Cancer of the gallbladder almost always is associated with gallstones, but it is not clear which comes first, that is, whether the gallstones precede the cancer and, therefore, could potentially be the cause of the cancer or the gallstones form because cancer is present. Cancer of the gallbladder arises in less than 1% of individuals with gallstones. Therefore, concern about future development of cancer is by itself not a good reason for removing the gallbladder when gallstones are present.

 

Longitudinal and axial scans through the gallbladder show layering of sludge (S) in the gallbladder.

What is the relationship of sludge to gallstones?

Sludge is a common term that is applied to an abnormality of bile that is seen with ultrasonography of the gallbladder. Specifically, the bile within the gallbladder is seen to be of two different densities with the denser bile on the bottom. The bile is denser because it contains microscopic particles, usually cholesterol or pigment, embedded in mucus. (The mucus is secreted by the gallbladder.) Over time, sludge may remain in the gallbladder, it may disappear and not return, or it may come and go. As discussed previously, these particles may be precursors of gallstones, and they occur often in some situations in which gallstones frequently appear, for example, rapid weight loss, pregnancy, and prolonged fasting.

Nevertheless, it appears that sludge goes on to become gallstones in only a minority of individuals. Just to make matters more difficult, it is not clear how often – if at all – sludge alone causes problems. Sludge has been blamed for many of the same symptoms as gallstones-biliary colic, cholecystitis, and pancreatitis, but often these symptoms and complications are caused by very small gallstones that are missed by ultrasonography. Thus, there is some uncertainty about the importance of sludge.

It is clear, however, that sludge is not the equivalent of gallstones. The practical implication of this uncertainty is that unless an individual’s symptoms are typical of gallstones, sludge should not be considered as a possible cause of the symptoms.

 

A female doctor sits next to an ultrasound machine.

What kind of doctor treats gallstones?

Gallstones usually are diagnosed by a gastroenterologist, a medical subspecialist who deals with diseases of the intestine, liver, pancreas and gallbladder. General surgeons also may be involved in the diagnosis of gallstones but usually are the doctors who treat gallstones because the common treatment is surgical removal of the gallbladder.

How are gallstones diagnosed?

Gallstones are diagnosed in one of two situations.

  1. When there are symptoms or signs that suggest the presence of gallstones and the diagnosis of gallstones is being pursued.
  2. Coincidentally while a non-gallstone-related medical problem is being evaluated.

Ultrasonography is the most important means of diagnosing gallstones. Standard computerized tomography (CT or CAT scan) and magnetic resonance imaging (MRI) may occasionally demonstrate gallstones; however, they are not as useful compared to ultrasonography because they miss gallstones.

Ultrasonography

Ultrasonography is a radiological technique that uses high-frequency sound waves to produce images of the organs and structures of the body. The sound waves are emitted from a device called a transducer and are sent through the body’s tissues. The sound waves are reflected by the surfaces and interiors of internal organs and structures as “echoes.” These echoes return to the transducer and are transmitted onto a viewing monitor. On the monitor, the outline of organs and structures can be determined as well as their consistency, for example, liquid or solid.

There are two types of ultrasonographic techniques that can be used for diagnosing gallstones: transabdominal ultrasonography and endoscopic ultrasonography.

Transabdominal ultrasonography

For transabdominal ultrasonography, the transducer is placed directly on the skin of the abdomen. The sound waves travel through the skin and then into the abdominal organs. Transabdominal ultrasonography is painless, inexpensive, and without risk to the patient. In addition to identifying 97% of gallstones in the gallbladder, abdominal ultrasonography can identify many other abnormalities related to gallstones. It can identify:

  • A thickened wall of the gallbladder when there is cholecystiti and inflammation has thickened the wall
  • Enlarged gallbladder and bile duct due to obstruction by gallstones
  • Pancreatitis
  • Fluid surrounding the gallbladder (a possible sign of inflammation) sludge

Transabdominal ultrasonography also may identify diseases not related to gallstones that may be the cause of the patient’s problem, for example, appendicitis. The limitations of transabdominal ultrasonography are that it can only identify gallstones larger than 4-5 millimeters in size, and it is poor at identifying gallstones in the bile ducts.

MRCP image showing stones in the common bile duct: (a) Gallbladder with stones (b) Stone in bile duct (c) Pancreatic duct (d) Duodenum.

How are gallstones diagnosed? (Part 2)

Endoscopic ultrasonography (EUS)

For endoscopic ultrasonography, a long flexible tube – the endoscope – is swallowed by the patient after he or she has been sedated with intravenous medication. The tip of the endoscope is fitted with an ultrasound transducer. The transducer is advanced into the duodenum where ultrasonographic images are obtained.

Endoscopic ultrasonography can identify gallstones and the same abnormalities as transabdominal ultrasonography; however, since the transducer is much closer to the structures of interest – the gallbladder, bile ducts, and pancreas – better images are obtained than with transabdominal ultrasonography. Thus, it is possible to visualize smaller gallstones with EUS than transabdominal ultrasonography. EUS also is better in identifying gallstones in the common bile duct.

Although endoscopic ultrasonography is in many ways better than transabdominal ultrasonography, it is expensive, not available everywhere, and carries a small risk of complications such as those associated with the use of intravenous sedation, and intestinal perforation by the endoscope. Fortunately, transabdominal ultrasonography usually gives most of the information that is necessary, and endoscopic ultrasonography is needed only infrequently. Endoscopic ultrasonography also is a better way than transabdominal ultrasonography to evaluate the pancreas for pancreatitis or its complications.

Magnetic resonance cholangio-pancreatography (MRCP)

Magnetic resonance cholangio-pancreatography or MRCP is a modification of magnetic resonance imaging (MRI) that allows the bile and pancreatic ducts to be examined.

  • For MRCP, the patient is placed in a strong magnetic field that through its energy-carrying radio waves aligns (magnetizes) the protons in the molecules of water in the tissues. (Protons are parts of the atoms that make up water molecules. All tissues in the body contain water though they contain different amounts of water.)
  • Energy-carrying radio waves are passed through the tissues, and the energy is absorbed by the water’s protons.
  • The radio waves are turned off, and the protons release the energy they had absorbed.
  • The released energy is used to form an image of the tissues and organs of the body.
  • The MRI separates tissues and organs based on their concentration of water. Since different tissues contain different amounts of water, MRCP is very good at providing images of organs and tissues.
  • Since bile is mostly water, MRCP gives an excellent image of bile within the gallbladder and bile ducts. The pancreatic duct, which, like the bile ducts, is filled with a watery fluid, also is seen well.
  • Often an intravenous injection of a dye is used to better delineate the bile and pancreatic ducts.

The procedure is called cholangio- (referring to the bile ducts) pancreatography (referring to the pancreatic duct) because it can demonstrate the bile and pancreatic ducts.

MRCP has in many instances replaced other procedures such as cholescintigraphy (HIDA scan) and endoscopic retrograde cholangiopancreatography (ERCP) for evaluating the bile ducts. It can identify gallstones in the bile ducts, obstruction of the ducts, and leaks of bile. There are no risks to the patient with MRCP except for very rare reactions to the injected dye.

 

Normal hepatobiliary scan (HIDA scan) showing a series of scans done over time to see where bile is excreted and/or accumulated.

How are gallstones diagnosed? (Part 3)

Cholescintigraphy (HIDA scan)

Cholescintigraphy is a procedure done by nuclear medicine physicians. It also is referred to as a HIDA scan or a gallbladder scan.

  • For a HIDA scan, a radioactive chemical is injected intravenously into a patient.
  • The radioactive chemical is removed from the blood by the liver and secreted into the bile.
  • The chemical then disperses everywhere that the bile goes-into the bile ducts, the gallbladder, the intestine, and any place else that bile goes.
  • A camera that senses radioactivity (like a Geiger counter) is then placed over the patient’s abdomen and a “picture” of the liver, bile ducts, and gallbladder is obtained which corresponds to where the radioactive chemical has traveled within, or outside of the bile-filled bile ducts, and gallbladder.

HIDA scans are used to identify obstruction of the bile ducts, for example, by a gallstone. They also may identify bile leaks and fistulas. There are no risks to the patient with HIDA scans.

Cholescintigraphy also is used to study the emptying of the gallbladder. Some patients with gallstones have had gallbladder inflammation due to recognized or unrecognized episodes of cholecystitis. (There also are uncommon, non-gallstone-related causes of inflammation of the gallbladder.) The inflammation can result in scarring of the gallbladder’s wall and muscle, which reduces the ability of the gallbladder to contract. As a result, the gallbladder does not empty normally. During cholescintigraphy, a synthetic hormone related to cholecystokinin (the hormone the body produces and releases during a meal to cause the gallbladder to contract) can be injected intravenously to cause the gallbladder to contract and squeeze out its bile and radioactivity into the intestine. If the gallbladder does not empty the bile and radioactivity normally, it is assumed that the gallbladder is diseased as a result of gallstones or non-gallstone related inflammation.

The problem with interpreting a gallbladder emptying study is that many people with normal gallbladders have abnormal emptying of the gallbladder. Therefore, it is hazardous to base a diagnosis of a diseased gallbladder on abnormal gallbladder emptying alone.

Doctor performs an endoscopic retrograde cholangio-pancreatography (ERCP) on a woman for gallstones.

How are gallstones diagnosed? (Part 4)

Endoscopic retrograde cholangio-pancreatography (ERCP)

ERCP is a combined endoscope and X-ray procedure performed to examine the duodenum (the first portion of the small intestine), the papilla of Vater (a small nipple-like structure where the common bile and pancreatic ducts enter the duodenum), the bile ducts, the gallbladder and the pancreatic duct.

The procedure is performed by using a long, flexible, side viewing instrument (a duodenoscope, a type of endoscope) about the diameter of a fountain pen. The duodenoscope is flexible and can be directed and moved around the many bends of the stomach and intestine. The video-endoscope is the most common type of duodenoscope, and uses chip at the tip of the instrument to transmit video images to a TV screen.

  • First the patient is sedated with intravenous drugs.
  • The duodenoscope is inserted through the mouth, to the back of the throat, down the food pipe (esophagus), through the stomach and into the first portion of the small intestine (duodenum).
  • Once the papilla of Vater is identified, a small plastic catheter (cannula) is passed through a channel in the duodenoscope into the papilla of Vater, and into the bile ducts and the pancreatic duct.
  • Contrast material (dye) is injected, and x-rays are taken of the bile ducts, gallbladder and/or the pancreatic duct.

ERCP can identify; 1) gallstones in the gallbladder (though it is not particularly good at this) and 2) blockage of the bile ducts, for example, by gallstones, and 3) bile leaks. ERCP also may identify diseases not related to gallstones that may be the cause of the patient’s problem, for example, pancreatitis or pancreatic cancer.

An important advantage of ERCP is that instruments can be passed through the same channel as the cannula used to inject the dye to extract gallstones stuck in the common and hepatic ducts. This can save the patient from having an operation. ERCP has several risks associated with it, including the drugs used for sedation, perforation of the duodenum by the duodenoscope, and pancreatitis (due to damage to the pancreas). If gallstones are extracted, bleeding also may occur as a complication.

A doctor holding an anatomical model of the human liver and pointing to a gallstone.

How are gallstones diagnosed? (Part 5)

Liver and pancreatic blood tests

When the liver or pancreas becomes inflamed or their ducts become obstructed and enlarged, the cells of the liver and pancreas release some of their enzymes into the blood. The most commonly-measured liver enzymes in blood are aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The most commonly-measured pancreatic enzymes in blood are amylase and lipase. Many medical conditions that affect the liver or pancreas cause these blood tests to become abnormal, so these abnormalities alone cannot be used to diagnose gallstones. Nevertheless, abnormalities of these tests suggest there is a problem with the liver, bile ducts, or pancreas, and gallstones are a common cause of such abnormal tests, particularly during sudden obstruction of the bile ducts or pancreatic ducts. Thus, abnormal liver and pancreatic blood tests direct attention to the possibility that gallstones may be causing the acute problem.

Duodenal biliary drainage

Duodenal biliary drainage is a procedure that occasionally can be useful in diagnosing gallstones; however, it is not often used. As previously discussed, gallstones begin as microscopic particles of cholesterol or pigment that grow in size. It is clear that some people who develop biliary colic, cholecystitis, or pancreatitis have only these particles in their gallbladders, yet the particles are too small to obstruct the ducts. There are two potential explanations for how obstruction might occur in this situation. The first is that a small gallstone initially caused an obstruction before passing through the bile ducts into the intestine. The second is that particles passing through the bile ducts can “irritate” the ducts, causing spasm of the muscle within the walls of the ducts (which obstructs the flow of bile) or inflammation of the duct that causes the wall of the duct to swell (and also obstructs the duct).

  • For duodenal drainage, a thin plastic or rubber tube with several holes at its tip is passed through a patient’s anesthetized nostril, down the back of the throat, through the esophagus and stomach, and into the duodenum where the bile and pancreatic ducts enter the small intestine. This is done with the help of x-ray (fluoroscopy).
  • Once the tube is in place, a synthetic hormone related to cholecystokinin, the hormone that is normally released after a meal to cause the gallbladder, is injected intravenously. As a result, the gallbladder contracts and squeezes out its concentrated bile into the duodenum.
  • The bile is sucked through the tube in the duodenum and examined for the presence of small cholesterol and pigment particles under a microscope.

The risks to the patient of duodenal drainage are minimal. (There have been no reports of reactions to the synthetic hormone.) Nevertheless, duodenal drainage is uncomfortable.

A modification of duodenal drainage involves collection of bile through an endoscope at the time of an upper gastrointestinal endoscopy-either esophago-gastro-duodenoscopy (EGD) or ERCP.

Oral cholecystogram (OCG)

The oral cholecystogram or OCG is a radiologic (X-ray) procedure for diagnosing gallstones.

  • The patient takes iodine-containing tablets for one or two nights in a row and then has an X-ray of the abdomen.
  • The iodine is absorbed from the intestine into the blood, removed from the blood by the liver, and excreted into bile.
  • In the gallbladder, the iodine becomes concentrated along with the bile.
  • On the X-ray, the iodine, which is dense and stops X-rays, fills the gallbladder and outlines the gallstones which are not dense, and allow X-rays to pass through them. The ducts cannot be seen on the x-ray because the iodine is not concentrated in the ducts.

The OCG is an excellent procedure for diagnosing gallstones; it finds 95% of them. The OCG has been replaced, however, by ultrasonography because ultrasonography is slightly better at finding gallstones and can be done immediately without waiting one or two days for the iodine to be absorbed, excreted, and concentrated.

Unlike ultrasonography, the OCG also cannot give information about the presence of non-gallstone related diseases. As would be expected, ultrasonography sometimes finds gallstones that are missed by the OCG. Less frequently, the OCG finds gallstones that are missed by ultrasonography. For this reason, if there is a strong suspicion that gallstones are present but ultrasonography does not show them, it is reasonable to consider doing an OCG; however, EUS has mostly replaced the OCG in this situation. An OCG should not be done in individuals who are allergic to iodine.

Intravenous cholangiogram (IVC)

The intravenous cholangiogram or IVC is a radiologic (X-ray) procedure that is used primarily for looking at the larger intrahepatic and the extrahepatic bile ducts. It can be used to locate gallstones within these ducts.

An iodine-containing dye is injected intravenously into the blood. The dye is removed from blood by the liver and excreted into bile. Unlike the iodine used in the OCG, the iodine in the IVC is concentrated sufficiently enough in the bile ducts to outline the ducts and any gallstones within them. The IVC is rarely used because it has been replaced by MRI cholangiography and endoscopic ultrasound. Moreover, occasional serious reactions to the iodine-containing dye can occur, which rarely may result in the death of the patient.

A senior male patient and doctor.

What are the potential pitfalls of diagnosing gallstones?

Usually, it is not difficult to diagnose gallstones. Problems arise, however, because of the high prevalence of silent gallstones and the occasional gallstone that is difficult to diagnose.

If a patient has symptoms that are typical for gallstones, for example, biliary colic, cholecystitis, or pancreatitis, and has gallstones on ultrasonography, little else usually needs to be done to demonstrate that the gallstones are causing the symptoms unless the patient has other complicating medical issues.

If symptoms are not typical for gallstones there is a possibility that the gallstones are innocent bystanders (silent), and most importantly, removing the gallbladder surgically will resolve the patient’s problem or prevent further symptoms. In addition, the real cause of the symptoms will not be pursued. In such a situation, there is a need to obtain further evidence, other than their mere presence, that the gallstones are causing the problem. Such evidence can be obtained during an acute episode or shortly thereafter.

If ultrasonography can be done during an acute episode of pain or inflammation caused by gallstones, it may be possible to demonstrate an enlarged gallbladder or bile duct caused by obstruction of the ducts by the gallstone. This is likely to require ultrasonography again after the episode has resolved in order to demonstrate that the gallbladder indeed was larger during the episode than before or after the episode. It is easier to obtain the necessary ultrasonography if the episode lasts several hours, but it is much more difficult to obtain ultrasonography rapidly enough if the episode lasts only 15 minutes.

Another approach is to test the blood for abnormal liver and pancreatic enzymes. The advantage here is that the enzymes, though not always elevated, can be elevated during an acute attack and for several hours after an episode of gallstone-related pain or inflammation, so they may be abnormal even after the episode has subsided. It is important to remember, however, that the enzymes are not specific for gallstones, and it is necessary to exclude other liver and pancreatic causes for abnormal enzymes.

Sometimes, episodes of pain or inflammation may be more or less typical of gallstones, but transabdominal ultrasonography may not demonstrate either gallstones or another cause of the episodes. In this situation, it is necessary to decide whether suspicion is high or low for gallstones as a cause of the episodes. If suspicion is low because of lack of typical symptoms, it may be reasonable only to repeat the ultrasonography, obtain an OCG, and/or test for abnormalities of liver or pancreatic enzymes. If suspicion is high because of more typical symptoms, it is reasonable to investigate even further with endoscopic ultrasonography, ERCP, and duodenal drainage. Prior to these “invasive” procedures, some physicians recommend MRCP.

 

X-Ray during laparoscopic cholecystectomy.

How are gallstones treated?

Observation

Most gallstones are silent, and do not need treatment.

  • If silent gallstones are discovered in an individual at age 65 (or older), the chance of developing symptoms from the gallstones is only 20% (or less) assuming a life span of 75 years. In this instance, it is reasonable not to treat the individual.
  • In younger individuals, no treatment also may be appropriate if the individuals have serious, life-threatening diseases, for example, serious heart disease, that are likely to shorten their life span.
  • On the other hand, in healthy young individuals, treatment should be considered even for silent gallstones because the individuals’ chances of developing symptoms from the gallstones over a lifetime will be higher. Once symptoms begin, treatment should be recommended since further symptoms are likely and more serious complications can be prevented.

Cholecystectomy

Cholecystectomy (removal of the gallbladder surgically) is the standard treatment for gallstones in the gallbladder. Surgery may be done through a large abdominal incision, laparoscopically or robotically through small punctures in the abdominal wall. Laparoscopic surgery results in less pain and a faster recovery. Robot-assisted laparoscopic surgery has 3D visualization. Cholecystectomy has a low rate of complications, but serious complications such as damage to the bile ducts and leakage of bile occasionally occur. There also is risk associated with the general anesthesia that is necessary for either type of surgery. Problems following removal of the gallbladder are few. Digestion of food is not affected, and no change in diet is necessary. Nevertheless, chronic diarrhea occurs in approximately 10% of patients.

Sphincterotomy and extraction of gallstones

Sometimes a gallstone may be stuck in the hepatic or common bile ducts. In such situations, there usually are gallstones in the gallbladder as well, and cholecystectomy is necessary. It may be possible to remove the gallstone stuck in the duct at the time of surgery, but this may not always be possible. An alternative means for removing gallstones in the duct before or after cholecystectomy is with sphincterotomy followed by extraction of the gallstone.

Sphincterotomy involves cutting the muscle of the common bile duct (sphincter of Oddi) at the junction of the common bile duct and the duodenum in order to allow easier access to the common bile duct. The cutting is done with an electrosurgical instrument passed through the same type of endoscope that is used for ERCP. After the sphincter is cut, instruments may be passed through the endoscope and into the hepatic and common bile ducts to grab and pull out the gallstone or to crush the gallstone. It also is possible to pass a lithotripsy instrument that uses high frequency sound waves to break up the gallstone. Complications of sphincterotomy and extraction of gallstones include risks associated with general anesthesia, perforation of the bile ducts or duodenum, bleeding, and pancreatitis.

Oral dissolution therapy

It is possible to dissolve some cholesterol gallstones with medication taken orally. The medication is a naturally-occurring bile acid called ursodeoxycholic acid or ursodiol (Actigall, Urso). Bile acids are one of the detergents that the liver secretes into bile to dissolve cholesterol. Although one might expect therapy with ursodiol to work by increasing the amount of bile acids in bile and thereby cause the cholesterol in gallstones to dissolve, the mechanism of ursodiol’s action actually is different. Ursodiol reduces the amount of cholesterol secreted in bile. The bile then has less cholesterol and becomes capable of dissolving the cholesterol in the gallstones.

There are important limitations to the use of ursodiol:

  • It is only effective for cholesterol gallstones and not pigment gallstones.
  • It works only for small gallstones, less than 1-1.5 cm in diameter.
  • It takes one to two years for the gallstones to dissolve, and many of the gallstones reform following cessation of treatment.

Due to these limitations, ursodiol generally is used only in individuals with smaller gallstones that are likely to have a very high cholesterol content and who are at high risk for surgery because of ill health. It also is reasonable to use ursodiol in individuals whose gallstones were perhaps formed because of a transient event, for example, rapid loss of weight, since the gallstones would not be expected to recur following successful dissolution. Another use of ursodiol is to prevent the formation of gallstones in patients who will lose weight rapidly.

Extracorporeal shock-wave lithotripsy

Extracorporeal shock-wave lithotripsy (ESWL) is an infrequently used method for treating gallstones, particularly those lodged in bile ducts. ESWL generators produce shock waves outside of the body that are then focused on the gallstone. The shock waves shatter the gallstone, and the resulting pieces of the gallstone either drain into the intestine on their own or are extracted endoscopically. Shock waves also can be used to break up gallstones via special catheters passed through an endoscope at the time of ERCP.

 

A doctor discusses gallstone prevention and possible after effects of removal with a patient in the hospital.

Can gallstones be prevented?

Ideally, it would be better if gallstones could be prevented rather than treated. Prevention of cholesterol gallstones is feasible since ursodiol, the bile acid medication that dissolves some cholesterol gallstones, also prevents them from forming. The difficulty is to identify individuals who are at a high risk for developing cholesterol gallstones over a relatively short period of time so that the duration of preventive treatment can be limited. One such group is obese individuals losing weight rapidly with very low calorie diets or with surgery. The risk of gallstones in this group is as high as 40% to 60%. In fact, ursodiol has been shown in several studies to be very effective at preventing gallstones in these individuals. It is important to stress that no dietary changes have been shown to treat or prevent gallstones.

Can symptoms continue after gallstones are removed?

Removal of the gallbladder (cholecystectomy) should eliminate all gallstone-related symptoms except in three situations:

  1. gallstones were left in the ducts,
  2. there were problems with the bile ducts in addition to gallstones, and
  3. gallstones were not the cause of the symptoms.

The possibility of gallstones in the ducts can be pursued with MRCP, endoscopic ultrasound, and ERCP. Rarely, gallstone-like symptoms can be caused by a condition called sphincter of Oddi dysfunction, discussed below.

The common bile duct has a muscular wall. The last several centimeters of the common bile duct’s muscle immediately before the duct joins the duodenum comprise the sphincter of Oddi. The sphincter of Oddi controls the flow of bile. Since the pancreatic duct usually joins the common bile duct shortly before it enters the duodenum, the sphincter also controls the flow of fluid from the pancreatic duct. When the muscle of the sphincter tightens, it shuts off the flow of bile and pancreatic fluid. When it relaxes, bile and pancreatic fluid again flow into the duodenum, for example, after a meal. The sphincter may become scarred, and the duct is narrowed by the scarring. (The cause of the scarring is unknown.) The sphincter also may go into spasm intermittently. In either case, the flow of bile and pancreatic fluid may intermittently stop abruptly, mimicking the effects of a gallstone causing biliary colic and pancreatitis.

The diagnosis of sphincter of Oddi dysfunction can be difficult to make. The best diagnostic test requires an endoscopic procedure with the same type of endoscope as ERCP. Instead of filling the ducts with dye, however, the pressure within the sphincter is measured. If the pressure is abnormally high, scarring or spasm of the sphincter are likely. The treatment for sphincter of Oddi dysfunction is sphincterotomy (described previously). The measurement of liver and pancreatic enzymes in the blood also may be useful in diagnosing sphincter dysfunction.

Bandages cover a patient's laparoscopic gallstone surgery scars.

What’s new with gallstones?

It is clear that genetic factors are important in determining who develops gallstones. Current scientific studies are directed at uncovering the specific genes that are responsible for gallstones. To date, 8-10 genes have been identified as being associated with cholesterol gallstones, at least in animals that develop cholesterol gallstones. Not surprisingly, the products of many of these genes control the production and secretion (by the liver) of cholesterol, bile acids, and lecithin. The long-term goal is to be able to identify individuals who are genetically at very high risk for cholesterol gallstones and to offer them preventive treatment. An understanding of the exact mechanism(s) of gallstone formation also may result in new therapies for treatment and prevention.

Surgery for gallstones has undergone a major transition from requiring large abdominal incisions to requiring only tiny incisions for laparoscopic instruments (laparoscopic cholecystectomy). It is possible that there will be another transition. Surgeons are experimenting with a technique called natural orifice transluminal endoscopic surgery (NOTES). NOTES is a new technique for accomplishing standard intraabdominal surgery, but access to the abdomen is through a natural orifice – the mouth, anus or vagina.

For NOTES, a flexible endoscopic instrument is similar to the flexible endoscopes presently being used widely is introduced through the chosen orifice, through an incision somewhere inside the orifice (for example, the stomach), and into the abdominal cavity. Thus, the only incision is within the body and not visible on the body’s surface. There are potential advantages to this type of surgery, but it is in the early stages of development, and it is unclear what the future role of NOTES will be in gallbladder surgery. Nevertheless, several series of patients have already been described who have had their gallbladders removed via NOTES primarily through the vagina.


 

Source: https://www.medicinenet.com/gallstones/article.htm

 

  • Medical Author: Jay W. Marks, MD
  • Medical Editor: Bhupinder S. Anand, MBBS, MD, DPHIL (OXON)

 

Print Friendly, PDF & Email
Gallstones (Beyond the Basics)
Patient education: Gallstones (Beyond the Basics)
Author:
Salam F Zakko, MD, FACP, AGAF
Section Editor:
Sanjiv Chopra, MD, MACP
Deputy Editor:
Shilpa Grover, MD, MPH, AGAF
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2018. | This topic last updated: Feb 21, 2018.

GALLSTONES OVERVIEW

Gallstones are solid, pebble-like concretions that form inside the gallbladder. The gallbladder is located in the upper right abdomen, under the liver (figure 1).

More than one million Americans are diagnosed with gallstones (cholelithiasis) every year, joining about 38 million who already have the disorder. Fortunately, most people with gallstones do not have symptoms and do not require treatment. In some cases, however, gallstones cause pain or other complications and must be treated, usually by removing the entire gallbladder with its stones.

More detailed information about gallstones is available by subscription. (See “Approach to the patient with incidental gallstones” and “Uncomplicated gallstone disease in adults” and “Treatment of acute calculous cholecystitis” and “Nonsurgical treatment of gallstones”.)

THE GALLBLADDER

The gallbladder is a pear-shaped sac-like organ with a muscular wall that is about three to six inches (7.5 to 15 cm) long, located in the right upper side of the abdomen, under the liver (figure 1). It is connected to the liver and intestine through small tubes called bile ducts.

The primary purpose of the gallbladder is to store and concentrate bile, a greenish-brown fluid that is produced by the liver. Bile carries waste products out of the liver but it is also needed to digest and absorb fatty foods, and to absorb important fat-soluble vitamins. Between meals, the gallbladder is relaxed, allowing bile to flow into it, where bile is stored and concentrated (figure 1). With meals, the fat content of foods in the small intestine cause the gallbladder to contract (squeeze) and partially empty into the intestine. A few hours later, the gallbladder relaxes and begins to store bile again.

WHAT ARE GALLSTONES?

Gallstones are solid concretions that form inside the gallbladder. Gallstones may be as small as tiny specks or as large as the gallbladder itself. The vast majority, however, are smaller than one inch (2.5 cm) and are one of two major types, cholesterol or pigment. Gallstone type is important since cholesterol stones are more likely to respond to non-surgical treatments than pigment stones.

?Cholesterol gallstones account for approximately 80 percent of gallstones in developed countries, including the United States.

 

?Pigment stones account for about 20 percent of gallstones.

 

RISK FACTORS FOR GALLSTONES

Experts do not know for sure why gallstones develop. However, many people have bile with an abnormally high concentration of cholesterol and/or calcium from which stones may develop. There are a number of factors that increase the risk of developing gallstones

?Sex – Gallstones are more common in women.

 

?Age – The risk of gallstones increases with age. The condition is extremely rare in children and becomes progressively more frequent over time, especially after the age of 40 years.

 

?Family history and genetics – Gallstones are more common in certain families, suggesting that genetics has a role in gallstone development.

 

?Other factors – Other conditions can increase the risk of developing gallstones, including:

 

Pregnancy

Use of medicines that contain estrogen (such as birth control pills)

Obesity

Frequent fasting

Rapid weight loss (including patients who have surgical weight loss treatments)

Lack of physical activity

Diabetes mellitus

Sickle cell disease (and other conditions associated with rapid destruction of red blood cells, such as in patients with mechanical heart valves)

Cirrhosis or severe scarring of the liver

Certain medicines

 

GALLSTONE SYMPTOMS

Silent gallstones — The majority of people who have gallstones do not have symptoms; their stones remain “silent.” Silent gallstones are often found on an ultrasound or CT scan done for other reasons. Silent stones do not need to be treated since the first symptoms of gallstones are usually mild and there are risks involved in removing the gallbladder.

If you have silent gallstones, you should be aware of the initial symptoms of gallstone disease because you may need treatment if you develop symptoms (see ‘Biliary colic’ below). (See “Approach to the patient with incidental gallstones”.)

Biliary colic — Biliary colic, also known as gallstone pain or biliary pain, is the most common initial symptom of gallstones. It manifests as attacks of abdominal pain, often located in the right upper belly just under the lower ribs. Sometimes it is felt in the upper center of the abdomen or even in the lower chest, causing it to be confused with angina or a heart attack. You may also feel nausea, and vomiting, and pain in the right shoulder or back.

Biliary colic usually happens when the gallbladder contracts in response to a fatty meal. This compresses the stones against the gallbladder outlet, blocking its opening. As the gallbladder relaxes several hours after the meal, the pain subsides. In some people, the pain happens without having eaten anything and many times it starts around or after midnight.

Once you have a first attack of biliary colic, there is a good chance you will have more symptoms in the future. Such recurrent symptoms are usually more severe and occasionally associated with complications.

Complications of gallstones

Acute cholecystitis — Acute cholecystitis refers to inflammation of the gallbladder. This happens when there is a complete blockage of the gallbladder, caused by a gallstone. Unlike biliary colic, which resolves within a few hours, pain is constant with acute cholecystitis and fever is common.

Acute cholecystitis is a serious condition that requires immediate medical treatment in the hospital. Treatment includes IV fluids, pain medicine, and usually antibiotics. Surgery to remove the gallbladder along with its contained stones is usually recommended during the hospitalization or shortly thereafter. If not treated, acute cholecystitis can lead to gallbladder rupture, a life-threatening condition. (See “Treatment of acute calculous cholecystitis”.)

Choledocholithiasis — This complication can develop if one or more gallstones leave the gallbladder to the main bile ducts and block the area where bile exits into the intestine. It may lead to:

?Jaundice, which is a yellow discoloration of the skin and eyes.

 

?Acute cholangitis, which is an infection of the bile ducts that causes pain, chills, and fever. This is a life-threatening condition that requires prompt treatment, usually involving removal of the blocking gallstone with a non-surgical procedure known as endoscopic retrograde cholangiopancreatography, or ERCP. (See “Patient education: ERCP (endoscopic retrograde cholangiopancreatography) (Beyond the Basics)”.)

 

?Acute pancreatitis, which is sudden inflammation of the pancreas, leading to severe abdominal pain. (See “Patient education: Acute pancreatitis (Beyond the Basics)”.)

 

GALLSTONE DIAGNOSIS

There are two parts to diagnosing gallstones: determining if gallstones are present, and determining if gallstones are the cause of symptoms.

Gallstones are usually found using ultrasound imaging, a painless test that uses sound waves to create an image of the gallbladder. An ultrasound is the most sensitive test with which to find gallbladder stones, but gallstones can also be seen on other imaging tests

Having gallstones does not mean that the gallstones are the cause of your symptoms. Thus, other tests may be recommended if there is doubt about the relationship of the gallstones to your symptoms.

GALLSTONE TREATMENT

There are three general options for people with gallstones; the best option depends upon your individual situation.

?Expectant management: Do nothing, wait and watch

?Surgical therapy: Remove the gallbladder and stones

?Non-surgical therapy: Eliminate the stones while preserving the gallbladder

 

Surgical treatment

Cholecystectomy — Cholecystectomy is a surgery that removes the gallbladder. It is one of the most commonly performed surgeries in the United States. The surgery is done in an operating room after you are given anesthesia.

The gallbladder is an important organ, but you can live without it. Removing the gallbladder does not usually cause serious complications. However, about half of people who have their gallbladder removed develop loose stools, gas, and bloating; in most people these symptoms are mild, do not require treatment, and improve with time.

Surgery may be done through an open incision (cut) in the skin and abdominal wall. However, in most people, the surgery is done using small instruments and a video camera, which are inserted into the abdomen through several small puncture holes in lieu of the larger cut. This is called laparoscopic cholecystectomy.

Non-surgical treatments — Nonsurgical treatments are available for some people with gallstones, mainly those who cannot undergo cholecystectomy. These treatments get rid of the gallstones while preserving the gallbladder. The main disadvantage is that the stones can come back over time. (See “Nonsurgical treatment of gallstones”.)

Bile acid pill — A bile acid pill (ursodeoxycholic acid or ursodiol) is a medicine that can dissolve and break down the cholesterol type of gallstones. About two-thirds of people who take it become symptom free within two to three months after starting treatment. However, it may take several years for the stones to disappear completely. The treatment is safe and well tolerated. Some people develop mild, temporary diarrhea.

Because of its slow action, bile acid treatment is not practical in people who are having recurrent gallstone symptoms. Bile acid treatments are most effective for people with small cholesterol stones and a functioning gallbladder, which may be determined by using imaging studies. Even then, it may fail to eliminate the stones in some patients.

Extracorporeal shock wave lithotripsy — Extracorporeal shock wave lithotripsy (ESWL) is widely used for kidney stones but has fallen out of favor for the treatment of gallbladder stones. Only a few centers worldwide continue to offer it. It uses shock waves to break gallstones into smaller fragments and “sand,” which can then be dissolved more easily with an oral bile acid pill. It is most effective in people who have a normal body weight (not obese), fewer than three stones, and who have good gallbladder function.

The procedure may be uncomfortable, but a sedative can be given to reduce discomfort, and occasionally it may cause attacks of biliary pain as broken stone fragments pass through the bile duct.

Since bile acid therapy is needed to clear the fractured stones and residue, lithotripsy is mostly used to treat cholesterol stones. The success of lithotripsy for gallstones varies, with experienced centers successfully treating 90 to 100 percent of people with one stone and up to 67 percent of people with two or three stones.

Percutaneous removal — When a patient at high surgical risk due to multiple medical conditions is found to have life-threatening acute cholecystitis, the patient is often treated with a temporizing percutaneous catheter drainage in lieu of the surgical removal of the gallbladder, which may not be tolerated. This is done by inserting a small plastic tube (catheter), the size of a spaghetti strand, into the gallbladder to drain and relieve the obstruction caused by the stones. In highly specialized centers, the hole through which the catheter is placed is gradually enlarged over a few weeks and the stones are extracted through the hole leaving the gallbladder behind. This procedure is not recommended for otherwise healthy gallstone patients since it requires many weeks to accomplish and the gallstones commonly recur over a few years.

Gallstone recurrence — The main disadvantage of the non-surgical treatments is that gallstones can come back, since the gallbladder is still in place. With bile acid treatment, stones come back in about 50 percent of people in the first five years. However, symptoms do not always come back and retreatment is not always needed. After cholecystectomy, gallstones may recur in the bile duct in a small percentage of patients. (See “Endoscopic management of bile duct stones: Standard techniques and mechanical lithotripsy”.)

Gallstone prevention — To try to prevent gallstones from coming back, it is recommended that you try to stay at a healthy body weight by eating an appropriate number of calories and exercising for at least 30 minutes five days per week. If you are planning a rapid weight-loss program, such as weight loss surgery, your doctor or nurse should monitor you. Bile acid pills may be recommended to prevent gallstones from developing as you lose weight.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Gallstones (The Basics)
Patient education: Gallbladder removal (cholecystectomy) (The Basics)
Patient education: Gallbladder cancer (The Basics)
Patient education: Jaundice in adults (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: ERCP (endoscopic retrograde cholangiopancreatography) (Beyond the Basics)
Patient education: Acute pancreatitis (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Approach to the patient with incidental gallstones
Acute cholecystitis: Pathogenesis, clinical features, and diagnosis
Endoscopic management of bile duct stones: Standard techniques and mechanical lithotripsy
Epidemiology of and risk factors for gallstones
Gallbladder cancer: Epidemiology, risk factors, clinical features, and diagnosis
Nonsurgical treatment of gallstones
Patient selection for the nonsurgical treatment of gallstone disease
Treatment of acute calculous cholecystitis
Uncomplicated gallstone disease in adults

The following organizations also provide reliable health information.

?National Library of Medicine

 

(www.nlm.nih.gov/medlineplus/ency/article/000273.htm, available in Spanish)

?National Institutes Diabetes and Digestive and Kidney Diseases

 

(http://digestive.niddk.nih.gov/ddiseases/pubs/gallstones/)

?The American Gastroenterological Association (AGA)

 

(http://www.gastro.org/info_for_patients/2013/6/6/understanding-gallstones)

[1,2]

Topic 4578 Version 17.0
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Gallstones – Nonsurgical treatment
Nonsurgical treatment of gallstones
Author:
Salam F Zakko, MD, FACP, AGAF
Section Editor:
Sanjiv Chopra, MD, MACP
Deputy Editor:
Shilpa Grover, MD, MPH, AGAF

INTRODUCTION

Over the past several decades, four modalities for the nonsurgical treatment of gallbladder stones were evaluated and gained some popularity at various times. These included: 

?Oral medical dissolution with bile acids

?Percutaneous cholecystostomy with stone extraction

?Percutaneous or transnasal topical solvent dissolution

?Extracorporeal shock wave lithotripsy

To continue reading this article, you must log in with your personal, hospital, or group practice subscription.
Literature review current through: Mar 2018. | This topic last updated: Jan 15, 2018.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of UpToDate content is governed by the UpToDate Terms of Use. ©2018 UpToDate, Inc. All rights reserved.

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Gallstones

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Definition

gallstone is a solid crystal deposit that forms in the gallbladder, which is a pear-shaped organ that stores bile salts untilthey are needed to help digest fatty foods. Gallstones can migrate to other parts of the digestive tract and cause severepain with life-threatening complications.

Description

Gallstones vary in size and chemical structure. A gallstone may be as tiny as a grain of sand or as large as a golf ball.Eighty percent of gallstones are composed of cholesterol. They are formed when the liver produces more cholesterol thandigestive juices can liquefy. The remaining 20% of gallstones are composed of calcium and an orange-yellow wasteproduct called bilirubin. Bilirubin gives urine its characteristic color and sometimes causes jaundice.
Gallstones are the most common of all gallbladder problems. They are responsible for 90% of gallbladder and bile ductdisease, and are the fifth most common reason for hospitalization of adults in the United States. Gallstones usuallydevelop in adults between the ages of 20 and 50; about 20% of patients with gallstones are over 40. The risk ofdeveloping gallstones increases with age-at least 20% of people over 60 have a single large stone or as many as severalthousand smaller ones. The gender ratio of gallstone patients changes with age. Young women are between two and sixtimes more likely to develop gallstones than men in the same age group. In patients over 50, the condition affects menand women with equal frequency. Native Americans develop gallstones more often than any other segment of thepopulation; Mexican-Americans have the second-highest incidence of this disease.

Definitions

Gallstones can cause several different disorders. Cholelithiasis is defined as the presence of gallstones within thegallbladder itself. Choledocholithiasis is the presence of gallstones within the common bile duct that leads into the firstportion of the small intestine (the duodenum). The stones in the duct may have been formed inside it or carried there fromthe gallbladder. These gallstones prevent bile from flowing into the duodenum. Ten percent of patients with gallstoneshave choledocholithiasis, which is sometimes called common-duct stones. Patients who don’t develop infection usuallyrecover completely from this disorder.
Cholecystitis is a disorder marked by inflammation of the gallbladder. It is usually caused by the passage of a stone fromthe gallbladder into the cystic duct, which is a tube that connects the gallbladder to the common bile duct. In 5-10% ofcases, however, cholecystitis develops in the absence of gallstones. This form of the disorder is called acalculouscholecystitis. Cholecystitis causes painful enlargement of the gallbladder and is responsible for 10-25% of all gallbladdersurgery. Chronic cholecystitis is most common in the elderly. The acute form is most likely to occur in middle-aged adults.
Cholesterolosis or cholesterol polyps is characterized by deposits of cholesterol crystals in the lining of the gallbladder.This condition may be caused by high levels of cholesterol or inadequate quantities of bile salts, and is usually treated bysurgery.
Gallstone ileuswhich results from a gallstone’s blocking the entrance to the large intestine, is most common in elderlypeople. Surgery usually cures this condition.
Narrowing (stricture) of the common bile duct develops in as many as 5% of patients whose gallbladders have beensurgically removed. This condition is characterized by inability to digest fatty foods and by abdominal pain, whichsometimes occurs in spasms. Patients with stricture of the common bile duct are likely to recover after appropriatesurgical treatment.

Causes and symptoms

Gallstones are caused by an alteration in the chemical composition of bile. Bile is a digestive fluid that helps the bodyabsorb fat. Gallstones tend to run in families. In addition, high levels of estrogen, insulin, or cholesterol can increase aperson’s risk of developing them.
Pregnancy or the use of birth control pills can slow down gallbladder activity and increase the risk of gallstones. So candiabetes, pancreatitisand celiac diseaseOther factors influencing gallstone formation are:
  • infection
  • obesity
  • intestinal disorders
  • coronary artery disease or other recent illness
  • multiple pregnancies
  • high-fat, low-fiber diet
  • smoking
  • heavy drinking
  • rapid weight loss
Gallbladder attacks usually follow a meal of rich, high-fat foods. The attacks often occur in the middle of the night,sometimes waking the patient with intense pain that ends in a visit to the emergency room. The pain of a gallbladderattack begins in the abdomen and may radiate to the chest, back, or the area between the shoulders. Other symptoms ofgallstones include:
  • inability to digest fatty foods
  • low-grade fever
  • chills and sweating
  • nausea and vomiting
  • indigestion
  • gas
  • belching.
  • clay-colored bowel movements

Diagnosis

Gallstones may be diagnosed by a family doctor, a specialist in digestive problems (a gastroenterologist), or a specialist ininternal medicine. The doctor will first examine the patient’s skin for signs of jaundice and feel (palpate) the abdomen forsoreness or swelling. After the basic physical examinationthe doctor will order blood counts or blood chemistry tests todetect evidence of bile duct obstruction and to rule out other illnesses that cause fever and pain, including stomachulcers, appendicitisand heart attacks.
More sophisticated procedures used to diagnose gallstones include:
  • Ultrasound imaging. Ultrasound has an accuracy rate of 96%.
  • Cholecystography (cholecystogram, gallbladder series, gallbladder x ray). This type of study shows how thegallbladder contracts after the patient has eaten a high-fat meal.
  • Fluoroscopy. This imaging technique allows the doctor to distinguish between jaundice caused by pancreatic cancerand jaundice caused by gallbladder or bile duct disorders.
Gallstones form in the gallbladder but can migrate to other parts of the body via the bileduct.

(Illustration by Argosy Inc.)
  • Endoscopy (ERCP). ERCP uses a special dye to outline the pancreatic and common bile ducts and locate the positionof the gallstones.
  • Radioisotopic scan. This technique reveals blockage of the cystic duct.

Treatment

Watchful waiting

One-third of all patients with gallstones never experience a second attack. For this reason many doctors advise watchfulwaiting after the first episode. Reducing the amount of fat in the diet or following a sensible plan of gradual weight lossmay be the only treatments required for occasional mild attacks. A patient diagnosed with gallstones may be able tomanage more troublesome episodes by:
  • applying heat to the affected area
  • resting and taking occasional sips of water
  • using non-prescription forms of acetaminophen (Tylenol or Anacin-3)
doctor should be notified if pain intensifies or lasts for more than three hours; if the patient’s fever rises above 101 °F(38.3 °C); or if the skin or whites of the eyes turn yellow.

Surgery

Surgical removal of the gallbladder (cholecystectomy) is the most common conventional treatment for recurrent attacks.Laparoscopic surgery, the technique most widely used, is a safe, effective procedure that involves less pain and a shorterrecovery period than traditional open surgery. In this technique, the doctor makes a small cut (incision) in the patient’sabdomen and removes the gallbladder through a long tube called a laparoscope.

Nonsurgical approaches

LITHOTRIPSYShock wave therapy (lithotripsyuses high-frequency sound waves to break up the gallstones. Thepatient can then take bile salts to dissolve the fragments. Bile salt tablets are sometimes prescribed without lithotripsy todissolve stones composed of cholesterol by raising the level of bile acids in the gallbladder. This approach requires long-term treatment, since it may take months or years for this method to dissolve a sizeable stone.
CONTACT DISSOLUTION. Contact dissolution can destroy gallstones in a matter of hours. This minimally invasiveprocedure involves using a tube (catheter) inserted into the abdomen to inject medication directly into the gallbladder.

Alternative treatment

Alternative therapies, like non-surgical treatments, may provide temporary relief of gallstone symptoms. Alternativeapproaches to the symptoms of gallbladder disorders include homeopathy, Chinese traditional herbal medicine, and acupunctureDietary changes may also help relieve the symptoms of gallstones. Since gallstones seem to develop moreoften in people who are obese, eating a balanced diet, exercising, and losing weight may help keep gallstones fromforming.

Prognosis

Forty percent of all patients with gallstones have “silent gallstones” that produce no symptoms. Silent stones, discoveredonly when their presence is indicated by tests performed to diagnose other symptoms, do not require treatment.
Gallstone problems that require treatment can be surgically corrected. Although most patients recover, some developinfections that must be treated with antibiotics.
In rare instances, severe inflammation can cause the gallbladder to burst. The resulting infection can be fatal.

Prevention

The best way to prevent gallstones is to minimize risk factors. In addition, a 1998 study suggests that vigorous exercise may lower a man’s risk of developing gallstones by as much as 28%. The researchers have not yet determined whetherphysical activity benefits women to the same extent.

Key terms

Acalculous cholecystitis — Inflammation of the gallbladder that occurs without the presence of gallstones.
Bilirubin — A reddish-yellow waste product produced by the liver that colors urine and is involved in the formation ofsome gallstones.
Celiac disease — Inability to digest wheat protein (gluten), which causes weight loss, lack of energy, and pale, foul-smelling stools.
Cholecystectomy — Surgical removal of the gallbladder.
Cholecystitis — Inflammation of the gallbladder.
Choledocholithiasis — The presence of gallstones within the common bile duct.
Cholelithiasis — The presence of gallstones within the gallbladder.
Cholesterolosis — Cholesterol crystals or deposits in the lining of the gallbladder.
Common bile duct — The passage through which bile travels from the cystic duct to the small intestine.
Gallstone ileus — Obstruction of the large intestine caused by a gallstone that has blocked the intestinal opening.
Lithotripsy — A nonsurgical technique for removing gallstones by breaking them apart with high-frequency sound waves.

Resources

Organizations

National Digestive Diseases Clearinghouse (NDDIC). 2 Information Way.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Building 31, Room 9A04, 31 Center Drive,MSC 2560, Bethesda, MD 208792-2560. (301) 496-3583. http://www.niddk.nih.gov.
Gale Encyclopedia of Medicine. Copyright 2008 The Gale Group, Inc. All rights reserved.

gallstones

Round, oval or faceted masses of cholesterol, chalk (calcium carbonate), calcium bilirubinate, or amixture of these. Gallstones vary in size, from less than a millimetre to several centimetres, and are often present butunsuspected. They are commoner in women than in men and are more likely if the composition of the bile is abnormal orthere is infection or blockage of outflow of bile. They tend to cause inflammation of the gall bladder (cholecystitis) and can befragmented by LITHOTRIPSY.

Collins Dictionary of Medicine © Robert M. Youngson 2004, 2005
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Gallstones
Gabriel E Njeze

Abstract

Gallstone disease is a worldwide medical problem, but the incidence rates show substantial geographical variation, with the lowest rates reported in African populations. Publications in English language on gallstones which were obtained from reprint requests and PubMed database formed the basis for this paper. Data extracted from these sources included authors, country, year of publication, age and sex of patients, pathogenesis, risk factors for development of gallstones, racial distribution, presenting symptoms, complications and treatment. Gallstones occur worldwide, however it is commonest among North American Indians and Hispanics but low in Asian and African populations. High biliary protein and lipid concentrations are risk factors for the formation of gallstones, while gallbladder sludge is thought to be the usual precursor of gallstones. Biliary calcium concentration plays a part in bilirubin precipitation and gallstone calcification. Treatment of gallstones should be reserved for those with symptomatic disease, while prophylactic cholecystectomy is recommended for specific groups like children, those with sickle cell disease and those undergoing weight-loss surgical treatments. Treatment should be undertaken for a little percentage of patients with gallstones, as majority of those who harbor them never develop symptoms. The group that should undergo cholecystectomy include those with symptomatic gallstones, sickle cell disease patients with gall stones, and patients with morbid obesity who are undergoing laparotomy for other reasons.

KeywordsCholecystectomy, dissolution therapy, gallstones, risk factors
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Introduction

Gallstones are hardened deposits of the digestive fluid bile, that can form within the gallbladder. They vary in size and shape from as small as a grain of sand to as large as a golf ball.[1] Gallstones occur when there is an imbalance in the chemical constituents of bile that result in precipitation of one or more of the components.

Gallstone disease is often thought to be a major affliction in modern society.[2] However, gallstones must have been known to humans for many years, since they have been found in the gallbladders of Egyptian mummies dating back to 1000 BC.[3,4] This disease is however, a worldwide medical problem, even though there are geographical variations in gallstone prevalence[5,6,7,8,9,10,11] Gallstones are becoming increasingly common; they are seen in all age groups, but the incidence increases with age;[12] and about a quarter of women over 60 years will develop them.[13] In most cases they do not cause symptoms, and only 10% and 20% will eventually become symptomatic within 5 years and 20 years of diagnosis.[14,15] Thus the average risk of developing symptomatic disease is low, and approaches 2.0-2.6%/year.[15]

This article gives a clinically useful review of the literature on gallstones disease and focuses on current information about the pathogenesis, risk factors, investigations, and treatment of gallstones. The paper is intended to make readers aware of current thinking in this field.

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Methods

Publications in English language on gallstones up to 2012 were obtained from both reprint requests and by searching PubMed database. Data extracted from these papers included authors, country, year of publication, age and sex of patients, pathogenesis, risk factors for development of gallstones, racial distribution, presenting symptoms, complications and treatment.

Pathogenesis

Gallstones are composed mainly of cholesterol, bilirubin, and calcium salts, with smaller amounts of protein and other materials.[16,17,18,19] There are three types of gallstones[20] (i) Pure cholesterol stones, which contain at least 90% cholesterol, (ii) pigment stones either brown or black, which contain at least 90% bilirubin and (iii) mixed composition stones, which contain varying proportions of cholesterol, bilirubin and other substances such as calcium carbonate, calcium phosphate and calcium palmitate.[21] Brown pigment stones are mainly composed of calcium bilirubinate whereas black pigment stones contain bilirubin, calcium and/or tribasic phosphate.[22] In Western societies[23] and in Pakistan[24] more than 70% of gallstones are composed primarily of cholesterol, either pure or mixed with pigment, mucoglycoprotein, and calcium carbonate.[25] Pure cholesterol crystals are quite soft, and protein contributes importantly to the strength of cholesterol stones.[26]

In the simplest sense, cholesterol gallstones form when the cholesterol concentration in bile exceeds the ability of bile to hold it in solution, so that crystals form and grow as stones.[27] Cholesterol is virtually insoluble in aqueous solution, but in bile it is made soluble by association with bile salts and phospholipids in the form of mixed micelles and vesicles.

Three types of abnormalities have been considered to be responsible for cholesterol gallstone formation. Cholesterol supersaturation, the essential requirement for cholesterol gallstone formation, might occur via excessive cholesterol biosynthesis, which is the main lithogenic mechanism in obese persons. In the non-obese, defective conversion of cholesterol to bile acids, due to a low or relatively low activity of cholesterol 7? hydroxylase, the rate limiting enzyme for bile acid biosynthesis and cholesterol elimination could result in excessive cholesterol secretion. Finally, interruption of the enterohepatic circulation of bile acids could increase bile saturation. Temporary interruption of the enterohepatic bile acid circulation during overnight fasting leads to a higher cholesterol/phospholipid ratio in the vesicles secreted by the liver. Estrogen treatment also reduces the synthesis of bile acid in women.[7]

Pigment stones occur when red blood cells are being destroyed, leading to excessive bilirubin in the bile. Black pigment stones are more common in patients with cirrhosis or chronic hemolytic conditions such as the thalassemias, hereditary spherocytosis, and sickle cell disease, in which bilirubin excretion is increased.[28,29] Primary bile-duct stones, defined as stones that originate in the bile ducts, are usually brown pigment stones associated with infection. Bacteria in the biliary system release ?-glucuronidases, which hydrolyze glucuronic acid from conjugated bilirubin. The resulting unconjugated bilirubin precipitates as its calcium salts. Primary brown pigment stones of the bile ducts often occur in Asians, associated with decreased biliary secretory Immunogloblin A (IgA.)[30] About 15% of gallstones are calcified enough to be seen on a plain abdominal radiograph, and of these, two thirds are pigment stones.[31]

High biliary protein and lipid concentrations are risk factors for the formation of gallstones. Gallbladder sludge, i.e., thickened gallbladder mucoprotein with tiny entrapped cholesterol crystals is thought to be the usual precursor of gallstones.[32] Sludge can sometimes cause biliary pain, cholecystitis, or acute pancreatitis,[33] but sludge may also resolve without treatment. The sources of sludge are pregnancy,[34] prolonged total parenteral nutrition,[35] starvation, or rapid weight loss.[36,37] The antibiotic ceftriaxone can also precipitate in the gallbladder as sludge[38] and rarely, as gallstones.[39]

The biliary calcium concentration plays a part in bilirubin precipitation and gallstone calcification.[40,41] Many patients with gallstones have increased biliary calcium, with supersaturation of calcium carbonate.[42]

Impaired motility of the gallbladder as seen in patient with high spinal cord injury[43] or with the use of the somatostatin analogue octreotide, has been cited as another contributing factor in the development of gallstones.[43] In theory, microscopic cholesterol crystals would regularly be washed out of the gallbladder if its contractions were effective enough. Intestinal hypomotility has been recently recognised as a primary factor in cholesterol lithogenesis.[25] Fiber may protect against gallstone formation by speeding intestinal transit and reducing the generation of secondary bile acids such as deoxycholate[44,45,46] which has been associated with increased cholesterol saturation of the bile.[47,48]

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Epidemiology of Gallstones

Epidemiological studies have suggested a marked variation in overall prevalence between different populations. Gallstone is one of the diseases prevalent in developed nations, but it is less prevalent in the developing populations that still consume traditional diets.[49] Its prevalence is especially high in the Scandinavian countries and Chile and among Native Americans.[50] Gallstones are more common in North America, Europe, and Australia, and are less prevalent in Africa, India, China, Japan, Kashmir, and Egypt.[2,7,51,52,53,54,55,56,57]

Factors influencing gallstone disease

Age

All epidemiological studies showed that increasing age was associated with an increased prevalence of gallstones. Gallstones are 4-10 times more frequent in older than younger subjects. Biliary cholesterol saturation increases with age, due to a decline in the activity of cholesterol 7? hydroxylase, the rate limiting enzyme for bile acid synthesis.[58] Deoxycholic acid proportion in bile increases with age through enhanced 7? dehydroxylation of the primary bile acids by the intestinal bacteria.[59]

Gender, parity, and oral contraceptives

In all populations of the world, regardless of overall gallstone prevalence, women during their fertile years are almost twice as likely as men to experience cholelithiasis. This preponderance persists to a lesser extent into the postmenopausal period, but the sex difference narrows with increasing age.[26] 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.[60]

Genetics

Both necropsy and population studies have clearly shown the existence of racial differences that cannot completely be explained by environmental factors. Cholesterol gallstone prevalence varies widely, from extremely low (<5%) in Asian and African populations, to intermediate (10-30%) in European and Northern American populations, and to extremely high (30-70%) in populations of Native American ancestry (Pima Indians in Arizona, Mapuche Indians in Chile).[53]

The Pima tribe of Arizona has the highest gallstone prevalence in the world: More than 70% of Pima women older than 25 years had gallstones or a history of cholecystectomy. High rates of gallstone prevalence have been also reported in other North American Indian tribes, including the Chippewas, Navajo, Micmacs, and Cree-Ojibwas.[25] Certain Hispanic populations in the USA are above average risk for gallbladder disease. Some studies strongly support the existence of Amerindian lithogenic genes in Mexican-Americans.

Obesity and body fat distribution

Obesity is an important risk factor for gallstone disease, more so for women than for men. It raises the risk of cholesterol gallstones by increasing biliary secretion of cholesterol, as a result of an increase in 3-hydroxy-3-mthylglutaryl coenzyme A (HMGCoA) reductase activity. Epidemiological studies have found that the lithogenic risk of obesity is strongest in young women, and that slimness protects against cholelithiasis.[26]

Rapid weight loss

Rapid weight loss is associated with occurrence of sludge and gallstones in 10-25% of patients in a few weeks of initiating the slimming procedures.[61] If a person loses weight too quickly, the liver secretes extra cholesterol; in addition there is rapid mobilization of cholesterol from adipose tissue stores. In fasting associated with severely fat restricted diets, gallbladder contraction is reduced, and the accompanying gallbladder stasis favors gallstone formation. Enhancing gallbladder emptying by inclusion of a small amount of dietary fat inhibits gallstone formation in patients undergoing rapid weight loss.[62] Fasting in the short term increases the cholesterol saturation of gallbladder bile and in the longer term, causes gallbladder stasis which can lead to sludge, and eventually gallstone formation. Younger women with gallstones were shown to be more prone to skip breakfast than controls.[63] A shorter overnight fasting is protective against gallstones in both sexes.[64]

Diet

Nutritional exposure to western diet, i.e., increase intake of fat, refined carbohydrates and decrease in fibre content is a potent risk factor for development of gallstones.[65,66] Calcium intake seems to be inversely associated with gallstone prevalence.[67] Dietary calcium decreases cholesterol saturation of gallbladder bile by preventing the reabsorption of secondary bile acids in the colon. Vitamin C influences 7? hydroxylase activity in the bile and it was shown that ascorbic acid might reduce lithogenic risk in adults.[68] Coffee consumption seems to be inversely correlated with gallstone prevalence, due to an increased enterohepatic circulation of bile acids. Coffee components stimulate cholecystokinin release,[69] enhance gallbladder motility, inhibit gallbladder fluid absorption, decrease cholesterol crystallization in bile[70] and perhaps increase intestinal motility.[71,72]

Physical activity

Regular exercise, in addition to facilitating weight control, alone or in combination with dieting, improves several metabolic abnormalities related to both obesity and cholesterol gallstones. In contrast, sedentary behaviour, is positively associated with the risk of cholecystectomy.[17]

Drugs

All fibric acid derivatives increase biliary cholesterol saturation while lowering serum cholesterol. Clofibrate is a potent inhibitor of hepatic acyl-CoA cholesterol acyltransferase (ACAT). ACAT inhibition leads to an increased availability of free or unesterified cholesterol for secretion into bile, favouring gallstone formation.[24] Additionally, prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to gallstone formation.[73] The lithogenic role of ceftriaxone, had earlier been mentioned.[36,37]

Diabetes

People with diabetes generally have high levels of fatty acids called triglycerides. These fatty acids may increase the risk of gallstones. Gallbladder function is impaired in the presence of diabetic neuropathy, and regulation of hyperglycaemia with insulin seems to raise the lithogenic index.[24] 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.[74]

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Clinical Presentations of Gallstone Disease

For practical purpose gallbladder disease can be equated with gallstones as these are present in the large majority of patients.[75] Most patients with gallstones have no symptoms.[25] These gallstones are called “silent stones” and may not require treatment.

Patients with symptomatic stones most often present with recurrent episodes of right-upper-quadrant or epigastric pain, probably related to the impaction of a stone in the cystic duct.[76] They may experience intense pain in the upper-right side of the abdomen, often accompanied by nausea and vomiting, that steadily increases for approximately 30 min to several hours. A patient may also experience referred pain between the shoulder blades or below the right shoulder region (Boas’ sign). Often, attacks occur after a particularly fatty meal and almost always happen at night.[77]

Some patients with gallstones present with acute cholecystitis, and often secondary infection by intestinal microorganisms, predominantly Escherichia coli and Bacteroides species. Inflammation of the gallbladder wall causes severe abdominal pain, especially in the right upper quadrant, with nausea, vomiting, fever, and leucocytosis.[27] This condition may remit temporarily without surgery, but it sometimes progresses to gangrene and perforation. Less commonly, gallstones can become lodged in the common bile duct (choledocholithiasis), sometimes with obstruction of the common bile duct and symptoms of cholestasis.[77] Obstruction leading to jaundice though commonly caused by a stone migrating into the common bile duct, can be due to compression of the common hepatic duct by a stone in the neck of the gall bladder or cystic duct (Mirrizi syndrome).[78] Infection in the bile ducts (cholangitis) can occur even with a seemingly minor degree of obstruction to bile flow. Stones in the common bile duct usually cause pain in the epigastrium or right upper quadrant, but may be painless. The passage of common-bile-duct stones can provoke acute pancreatitis, probably by transiently obstructing the main pancreatic duct where it passes near the common bile duct at the ampulla of Vater.[26] Gallstones may fistulate directly into the duodenum from the gallbladder during a period of silent inflammation.[79] This stone can impact in the duodenum leading to duodenal obstruction (Bouveret’s syndrome) Alternatively, gallstones can impact at the narrowest portion of healthy small, bowel causing an obstruction termed gallstone ileus.[80,81]

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The Diagnosis of Gallstone Disease

This disorder is usually diagnosed by history of recurrent episodes of right-upper-quadrant or epigastric pain, suggesting biliary colic and Boas’ sign. There may be fever, tender right upper quadrant with or without Murphy’s sign, tenderness when the hand taps the right costal arch (Ortner’s sign).

The three primary methods used to diagnose gallbladder disease are ultrasonography, nuclear scanning (cholescintigraphy), and oral cholecystography. Today, ultrasonography is the method most often used to detect cholelithiasis and cholecystitis. Occasionally gallstones are diagnosed during plain X-rays. Ultrasonography has a specificity and sensitivity of 90-95%, and can detect stones as small as 2 mm in diameter.[26] It can demonstrate the presence of common-bile-duct stones, show bile-duct dilatation and detect thickening of the gallbladder wall.

In cholescintigraphy, a patient is injected with a small amount of non-harmful radioactive material that is absorbed by the gallbladder, which is stimulated to contract if intravenous injection of cholecystokinin is given in addition.[82] The short-lived isotope technetium-99 m, which is bound to one of several radioactive HIDA (iminodiacetic acids such as (hepatic iminodiacetic acid) or DISIDA (disopropyl iminodiacetic acid,) that are excreted into the bile ducts, can provide functional information about gallbladder contraction. It can detect total obstruction of the bile duct, but cannot provide anatomical information, and cannot identify gallstones. It permits the rapid assessment of gallbladder function in a patient with suspected acute cholecystitis. Gamma rays emitted by the tracer are used to make an image of the bile ducts and gallbladder. Failure of the tracer to enter the gallbladder suggests obstruction of the neck of the gallbladder, as occurs in acute cholecystitis. Cholescintigraphy has a sensitivity and specificity of about 95% for acute cholecystitis, in the setting of upper abdominal pain with signs of inflammation.

In oral cholecystography, an iodinated contrast agent such as iopanoic acid (Telepaque) is given orally the day before the examination.[83] The contrast agent is absorbed from the gut, taken up by the liver, conjugated with glucuronic acid, and secreted into bile, where it is concentrated in the gallbladder. It is still useful in patients who have suspected gallbladder symptoms but a negative or equivocal ultrasound examination. On oral cholecystography the gallbladder may be seen to contain stones, polyps, or sludge, or it may simply not be visualized because contrast material is reabsorbed through an inflamed gallbladder wall or because the cystic duct is obstructed.[84]

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Treatment

Treatment of gallstones depends partly on whether they are causing symptoms or not. Recurrent episodes of upper abdominal pain related to gallstones are the most common indication for the treatment of gallstones.[80] Delaying elective cholecystectomy until repeated episodes of pain occur results in a minimal decrease in life expectancy.[85]

Prophylactic cholecystectomy for gallstones has been recommended in specific groups, such as children, because symptoms develop in almost all patients.[84] It has also been recommended in sickle cell disease patients with gallstones, because the symptoms of gallstones can mimic those of sickle cell crisis, and elective cholecystectomy is much safer than emergency cholecystectomy in this group.[86] Incidental cholecystectomy for cholelithiasis is often performed concomitantly with surgery for morbid obesity, in view of the high incidence of symptomatic gallstones during rapid weight loss.[87] Some surgeons have recommended incidental cholecystectomy for cholelithiasis in patients undergoing other abdominal surgery.[73]

Prophylactic cholecystectomy is also recommended in certain high-risk groups to prevent gallbladder cancer. These include native Americans who have gallstones,[88] patients in the general population with longstanding stone or stones greater than 3 cm in diameter[89] and patients with a calcified gallbladder wall, or “porcelain” gallbladder.[90]

Prophylactic cholecystectomy was recommended for diabetic patients with gallstones because of an increased risk of acute cholecystitis and increased mortality with emergency cholecystectomy. Recent studies show that diabetic patients have increased operative risk with elective as well as emergency gallbladder surgery[91] related to risk of cardiovascular disease and other coexisting conditions rather than to diabetes mellitus itself.[79] Most authorities do not recommend cholecystectomy in diabetic patients without symptoms of gallstones.

Open cholecystectomy was formerly the gold standard of treatment for gallstones, until the advent of laparoscopic cholecystectomy.[92] Open cholecystectomy in an otherwise healthy, good-risk candidate requires hospital stay for some days, and has mortality of less than 1%.[93,94] The greatest drawbacks to open cholecystectomy are the resulting pain and weeks of disability.[26] Laparoscopic cholecystectomy has become widely used since it was first performed in 1988[95,96] with a complication rate probably at least as good as that of the open procedure.[97] However a patient who has undergone abdominal surgery a number of times may not be a suitable candidate for Laparoscopic cholecystectomy because of extensive adhesions around the gallbladder.[26] A patient who is medically too unstable to undergo open cholecystectomy is also not a good candidate for Laparoscopic cholecystectomy either. The evaluation and treatment of suspected stones in the common bile duct can be carried out by endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy.[98] If common-bile-duct stones are unexpectedly found by cholangiography during laparoscopic cholecystectomy,[99] an open exploration of the common bile duct may be needed.

The laparoscopic procedure requires more operating time than the open procedure, but usually only one night in the hospital postoperatively; postoperative pain is greatly reduced, and the patients can usually return to work early, i.e., in one to 2 weeks, as compared with 4-6 weeks after open cholecystectomy.[100]

Attempts to use oral bile salts to dissolve gallstones began more than 30 years ago because of those who refuse or are poor risks for surgery.[101,102] Chenodeoxycholic acid (chenodiol) and ursodeoxycholic acid (ursodiol) are known to dissolve gallstones, but chenodiol causes diarrhoea and abnormal aminotransferase levels, while ursodiol does not. Therapy with bile salts is suitable for only a minority of patients with symptomatic cholesterol gallstones.[103] It is not suitable for patients with acute cholecystitis or stones in the common bile duct, who need urgent action. Candidates for treatment with bile salts should have a patent cystic duct and noncalcified cholesterol gallstones. Gallstones frequently recur after oral bile salts are stopped.

Contact dissolution therapy of cholesterol gallstones rapidly is possible by instilling solvents like the organic solvent methyl tert-butyl ether into the gallbladder through a percutaneous catheter placed through the liver.[104,105,106,107] Alternatively, a nasobiliary catheter can be endoscopically guided into the gallbladder can be used for instilling the organic solvent.[108] This is a technically difficult and hazardous procedure, and should be performed only by experienced doctors in hospitals where research on this treatment is being done. Serious side effects include severe burning pain.

Finally a mixture of plant terpenes may also be useful for dissolving radiolucent gallstones, particularly when used in combination with a bile acid.[109]

Footnotes

Source of Support: Nil.

Conflict of Interest: None declared.

References

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62. Gebhard RL, Prigge WF, Ansel HJ, Schlasner L, Ketover SR, Sande D, et al. The role of gallbladder emptying in gallstone formation during diet-induced rapid weight loss. Hepatology. 1996;24:544–8.[PubMed]
63. Capron JP, Delamarre J, Herve MA, Dupas JL, Poulain P, Descombes P. Meal frequency and duration of overnight fast: A role in gall-stone formation? Br Med J (Clin Res Ed) 1981;283:1435.[PMC free article] [PubMed]
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74. Koppisetti S, Jenigiri B, Terron MP, Tengattini S, Tamura H, Flores LJ, et al. Reactive oxygen species and the hypomotility of the gall bladder as targets for the treatment of gallstones with melatonin: A review. Dig Dis Sci. 2008;53:2592–603. [PubMed]
75. Burkitt DP, Tunstall M. Gall-stones: Geographical and chronological features. J Trop Med Hyg. 1975;78:140–4. [PubMed]
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77. Fitzgerald JE, Fitzgerald LA, Maxwell-Armstrong CA, Brooks AJ. Recurrent gallstone ileus: Time to change our surgery? J Dig Dis. 2009;10:149–51. [PubMed]
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81. Fink-Bennett D, DeRidder P, Kolozsi WZ, Gordon R, Jaros R. Cholecystokinin cholescintigraphy: Detection of abnormal gallbladder motor function in patients with chronic acalculous gallbladder disease. J Nucl Med. 1991;32:1695–9. [PubMed]
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85. Ware R, Filston HC, Schultz WH, Kinney TR. Elective cholecystectomy in children with sickle hemoglobinopathies. Successful outcome using a preoperative transfusion regimen. Ann Surg. 1988;208:17–22. [PMC free article] [PubMed]
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94. Gilliland TM, Traverso LW. Modern standards for comparison of cholecystectomy with alternative treatments for symptomatic cholelithiasis with emphasis on long-term relief of symptoms. Surg Gynecol Obstet. 1990;170:39–44. [PubMed]
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Postcholecystectomy Syndrome (PCS)

The Postcholecystectomy Syndrome (PCS): is a heterogeneous group of diseases and symptoms presenting following gallbladder removal. Symptoms occur in about 5 to 40 percent of patients who undergo cholecystectomy, and can be transient, persistent or lifelong. The chronic condition is diagnosed in approximately 10% of postcholecystectomy cases.

Post-cholecystectomy Syndrome may include: 

  • Diarrhoea as a troublesome problem range from 9 to 12% of which bile acid malabsorption (BAM) , 65% of these patients. [1]
  • Depression disorders occurring in 0.9%-3.0% of patients[2]
  • Bile (duodenogastric) reflux occurring in 20%-30% of patients[3,4,5].  Likely damage attributable to chronic bile exposure post-cholecystectomy includes:
    • cellular damage to esophagogastric junction
    • bile induced Gastroesophageal Mucosal Injury (Protective barrier that constrains the acidic reflux)
    • increase the incidence of gastric and esophageal cancer
  • Sphincter of Oddi dysfunction (SOD) is seen in 1% of patients after cholecystectomy, but in 14%-23% of patients with the post-cholecystectomy syndrome [6]
  • increased Body Mass Index (weight gain) with metabolic syndrome, gastritis, liposoluble vitamin deficiency. Cholecystectomy can have nutritional and metabolic consequences and in the long-term[7]

The onset of symptoms may range from 2 days to 25 years.  There may also be gender-specific risk factors for developing symptoms after cholecystectomy. In one study, the incidence of recurrent symptoms among female patients was 43%, compared to 28% of male patients.”

Patients with cholecystectomy had more comorbidities, particularly chronic fatigue syndrome, fibromyalgia, depression, and anxiety. Postcholecystectomy gastroparesis patients had increased health care utilization and had a worse quality of life.

Postcholecystectomy Syndrome in more detail

Absence of the gallbladder leads to development of functional biliary hypertension and dilatation of common bile duct and the common hepatic duct. The dilatation of right and left hepatic ducts may be formed within 3-5 years after cholecystectomy. Functional hypertension in the common bile duct leads to development of functional hypertension in Wirsung’s pancreatic duct accompanied by chronic pancreatitis symptoms.

During this period in some patients this is accompanied by chronic pancreatitis progression, dysfunction of the sphincter of Oddi and duodeno-gastral reflux. Duodeno-gastral reflux causes the development of atrophic (bile-acid-depen­dent) antral gastritis . After cholecystectomy 40% to 60% of patients suffer from dyspeptic disorders, 5% to 40% from pains of different localizations. Up to 70% of patients show symptoms of chronic “bland” intrahepatic cholestasis, chronic cholestatic hepatitis and compensatory bile-acid-dependent apoptosis of hepatocytes. In some of cholecystectomized patients with high concentration of hydrophobic hepatotoxic co-cancerogenic deoxycholic bile acid in serum and/or feces high risk of the colon cancer is found.

Not disclosed to patients, specialist medical opinion and studies list the following expected risks, side effects, diseases, syndromes and conditions after the removal of the gallbladder and its function. The majority of these problems are not accepted by the HDC as a risk and are blocked from disclosure to patients during the informed consent process, or advised during post-operative follow-ups.

They are but not exclusive to:

Anatomy Etiology
Biliary track Biliary injury
Cholangitis
Choledochoduodenal fistula
Choledocholithiasis
Clip migration / Inaccurate clip placement
Dyskinesia
Nonspecific dilatation or hypertension
Obstruction
Strictures
Stump cholelithiasis
Adhesions
Cyst
Dilation without obstruction
Fistula
Hypertension or nonspecific dilation
Malignancy and cholangiocarcinoma
Trauma
Bone Arthritis
Colon Adhesions; incisional hernia; irritable bowel diseaseConstipationDiarrhoea
Incisional hernia
Duodenum AdhesionsDuodenal diverticulaIrritable bowel disease
Peptic ulcer disease
Perforation
Esophagus AchalasiaAerophagiaDiaphragmatic hernia
Esophagitis
Hiatal hernia
Gallbladder and cystic Duct remnant InflammationLeakMirizzi’s syndrome
Mucocele
Neuroma (Amputation ), suture granuloma
Residual or reformed gallbladder
Stump cholelithiasis
Liver Chronic idiopathic jaundiceCirrhosisCyst
Dubin-Johnson syndrome
Fatty liver; hepatitis; cirrhosis; idiopathic jaundice
Gilbert disease
Hepatitis
Hydrohepatosis
Liver abscess
Sclerosing cholangitis
Nerve Intercostal lesionsIntercostal neuralgiaNeuroma
Neurosis
Psychic tension or anxiety
Spinal nerve lesions
Sympathetic imbalance
Pancreas Benign tumorsFunctional pancreatic sphincter disorderPancreatic cysts
Pancreatic stone
Pancreatitis
Stone
Tumors
Periampullary PapillomaSphincter of Oddi dysfunction (Functional biliary sphincter disorder); spasm; hypertrophyspasm; hypertrophySphincter of Oddi stricture
Stricture
Small bowel AdhesionsAdhesions; incisional hernia; irritable bowel diseaseIncisional hernia
Irritable bowel disease
Stomach Bile gastritisPeptic ulcer disease
Subcutaneous tissue AbscessHematoma
Vascular Coronary anginaInjury to hepatic artery, portal vein (pseudoaneurysm, portal vein thrombosis)Intestinal angina
Mesenteric ischemia
Miscellaneous Dropped GallstonesParasitic infestation (Ascariasis)Thermal injury
Trocar site hernia
Other AnxietyBacteria overgrowth in the stomachBarrett’s oesophagusBezoars
Bile Acid Malabsorption
Bile Reflux
Bloating
Celiac Disease
Cramps
Decrease in bile secretion
Depression
Diabetes
Dumping of bile Syndrome
Foreign bodies, including gallstones and surgical clips
Gas
Gastroparesis
GERD Reflux
Heartburn
Irritable Bowel Syndrome
Nausea
Pain – right upper abdomen
Pain – shoulders and abdomen
Thyrotoxicosis
Weight gain
Weight loss

Evidence based medical studies confirming statistically significant increased risk of cancer following cholecystectomy, required by law but never disclosed by doctors during the informed consent process listed as:

Anatomy

Etiology

Other
Biliary tract
Liver
Colon
Esophagus
Stomach
Liver
Liver
Pancreas
Periampullary
Other
Adrenal cancer
Ampulla of Vater cancer
Cholangiocarcinoma cancer
Colorectal cancer (Colon / Bowl)
Esophageal cancer
Gastric cancer
Hepatocellular carcinoma cancer
Liver cancers
Pancreatic cancer
Periampullary cancer
Smallintestine carcinoid cancer

Source references:

  1. M. Farahmandfar, M. Chabok, M. Alade, A. Bouhelal and B. Patel, Post Cholecystectomy Diarrhoea—A Systematic Review, Surgical Science, Vol. 3 No. 6, 2012, pp. 332-338. http://dx.doi.org/10.4236/ss.2012.36065
  2. Tsai M-C, Chen C-H, Lee H-C, Lin H-C, Lee C-Z (2015) Increased Risk of Depressive Disorder following Cholecystectomy for Gallstones. PLoS ONE 10(6): e0129962. https://doi.org/10.1371/journal.pone.0129962
  3. Nudo R, Pasta V, Monti M, Vergine M, Picardi N. Correlation between post-cholecystectomy syndrome and biliary reflux gastritis. Endoscopic study. https://www.ncbi.nlm.nih.gov/pubmed/2699712
  4. Lorusso D1, Pezzolla F, Montesani C, Giorgio P, Caruso ML, Cavallini A, Guerra V, Misciagna G. Duodenogastric reflux and gastric histology after cholecystectomy with or without sphincteroplasty https://www.ncbi.nlm.nih.gov/pubmed/2253017
  5. Shah Gilani SN1, Bass GA1, Kharytaniuk N2, Downes MR3, Caffrey EF3, Tobbia I3, Walsh TN4. Gastroesophageal Mucosal Injury after Cholecystectomy: An Indication for Surveillance? https://doi.org/10.1016/j.jamcollsurg.2016.12.003
  6. Bistritz, L., & Bain, V. G. (2006). Sphincter of Oddi dysfunction: Managing the patient with chronic biliary pain. World Journal of Gastroenterology?: WJG, 12(24), 3793–3802. http://doi.org/10.3748/wjg.v12.i24.3793
  7. Donato F. Altomare, Maria T. Rotelli, Nicola Palasciano. Diet After Cholecystectomy http://www.eurekaselect.com/node/152535/article
  8. Wikipedia,  Postcholecystectomy syndrome.  https://en.wikipedia.org/wiki/Postcholecystectomy_syndrome
  9. Steen W Jensen, MD; Chief Editor: John Geibel, MD, DSc, MSc, AGAF Postcholecystectomy Syndrome [medscape.com]
  10. S.S.JaunooS MohandasL.M.Almond. Postcholecystectomy syndrome (PCS) [ScienceDirect]
  11. Sureka B, Mukund A. Review of imaging in post-laparoscopy cholecystectomy complications. Indian J Radiol Imaging 2017;27:470-81  [Indian Journal of Radiology and Imaging]
  12. Murshid KR. The postcholecystectomy syndrome: A review. Saudi J Gastroenterol [serial online] 1996 [cited 2018 Jan 15];2:124-37. Available from:  http://www.saudijgastro.com/text.asp?1996/2/3/124/34017
  13. Girometti, R., Brondani, G., Cereser, L., Como, G., Del Pin, M., Bazzocchi, M., & Zuiani, C. (2010). Post-cholecystectomy syndrome: spectrum of biliary findings at magnetic resonance cholangiopancreatography[The British Journal of Radiology, 83(988), 351–361]
  14. Jacob L. Turumin, Victor A. Shanturov, Helena E. Turumina. Irkutsk Institute of Surgery, Irkutsk Regional Hospital, Irkutsk 664079. The role of the gallbladder in human [ScienceDirect]
  15. Dr. Jacob L. Turumin, MD, PhD, DMSci Biliary Diseases Laparoscopic Cholecystectomy. Postcholecystectomy Syndromehttp://www.drturumin.com/en/index.html#sthash.Y35Uey8C.dpuf
  16. Martin, Walton. “RECENT CONTROVERSIAL QUESTIONS IN GALL-BLADDER SURGERY.” Annals of Surgery 79.3 (1924): 424–443. Print. [PMC]
  17. The NIDDK Gastroparesis Clinical Research Consortium (GpCRC). “Cholecystectomy and Clinical Presentations of Gastroparesis.” Digestive diseases and sciences 58.4 (2013): 1062–1073. [PMC]
  18. Yong Zhang , Hao Liu , Li Li , Min Ai , Zheng Gong, Yong He, Yunlong Dong, Shuanglan Xu, Jun Wang , Bo Jin, Jianping Liu, Zhaowei Teng Cholecystectomy can increase the risk of colorectal cancer: A meta-analysis of 10 cohort studies Published: August 3, 2017 https://doi.org/10.1371/journal.pone.0181852
  19. Mearin, F., De Ribot, X., Balboa, A. Duodenogastric bile reflux and gastrointestinal motility in pathogenesis of functional dyspepsia. Role of cholecystectomy.  Digest Dis Sci (1995) 40: 1703. https://doi.org/10.1007/BF02212691
  20. Simona Manea, Georgeta & Carol, Stanciu. (2008). DUODENOGASTROESOPHAGEAL REFLUX AFTER CHOLECYSTECTOMY. Jurnalul de Chirurgie. 4 [Researchgate]

Another opinion not accepted by NZ Laparoscopic Surgeons or heath consumer watch dog Health and Disability Commissioner and as such never presented to patients when legally obtaining informed consent for gallbladder surgery (Cholecystectomy)

The body is permanently damaged and cannot be healthy without a gallbladder and its function. You can live, but in many cases you will be miserable. Some common side effects of gallbladder removal are an upset stomach, nausea, and vomiting. Gas, bloating, and diarrhoea. Persistent pain in the upper right abdomen.

It is gross medical negligence to send a patient home after surgery and pretend there are no side effects and can lead a perfectly normal life without a gallbladder and its purpose. Due to the considerable numbers of affected New Zealand patients, under United Nations Universal Declaration of Human Rights, Article 5 and 25 an ongoing crime is occurring.

Article 5: No one shall be subjected to cruel, inhuman or degrading treatment

Article 25: Everyone has the right to a standard of living adequate for the health and well-being of himself and of his family, including food, clothing, housing and medical care and necessary social services, and the right to security in the event of unemployment, sickness, disability, or other lack of livelihood in circumstances beyond his control.

Most patients suffer permanent impairments of the digestive system as a consequence of cholecystectomy, and develop various disorders as a result of poor digestion. The gall bladder is a vital organ with a crucial role in the absorption of fat and fat-soluble vitamins A, D, E and K and in essential fatty acids (omega-3 and omega-6), and poor cholesterol metabolism. In the long run, this may contribute to fatty liver. The absence of the gall bladder affects not only the process of food digestion but a wide range of other internal processes as well. In time, patients who have suffered cholecystectomy are also exposed to a high risk of developing heart disease, diabetes and disorders of the nervous system. This is due to inappropriate synthesis and assimilation of vital nutrients, vitamins and minerals.

Vitamin deficiency

Symptoms and Conditions

Vitamin A deficiency signs include Dry eyes
Drying, scaling, and follicular thickening of the skin
Night blindness
Red or white acne-like bumps (on your cheeks, arms, thighs, and buttocks)
Respiratory infections
Vitamin D deficiency linked to a strikingly diverse array of common chronic diseases, including: Alzheimer’s disease
Asthma
Autism
Cancer
Cavities
Cold and fly
Crohn’s disease
Cystic fibrosis
Diabetes 1 and 2
Dementia
Depression
Eczema & Psoriasis
Hearing loss
Hypertension
Heart disease
Infertility
Inflammatory Bowel Disease
Insomnia
Macular degeneration
Migraines
Multiple Sclerosis
Muscle pain
Obesity
Osteoporosis
Periodontal disease
Preeclampsia
Red or white acne-like bumps (on your cheeks, arms, thighs, and buttocks)
Rheumatoid arthritis
Septicemia
Seizures
Schizophrenia
Signs of aging
Tuberculosis
Vitamin E deficiency signs include: asthma and allergies
brain damage
cancer
cognitive decline
high oxidized LDL cholesterol levels
hot flashes
menstrual pain
poor circulation
prostate and breast cancers
Vitamin K deficiency can lead to: Arterial calcification
Cardiovascular disease
Dementia
Infectious diseases such as pneumonia
Leukemia
Liver cancer
Lung cancer
Osteoporosis
Prostate cancer
Tooth decay
Varicose veins
Deficiencies in essential fatty acids Allergies
Alzheimer’s disease
Asthma
Bone weakness
Brittle or soft nails
Cancer
Cracked skin on heals or fingertips
Dandruff or dry hair
Dry eyes
Dry Eye Syndrome
Dry, flaky skin, alligator skin, or “chicken skin” on backs of arms
Fatigue
Frequent urination or excessive thirst
Gallstones
Heart disease
Lowered immunity, frequent infections
Lupus erythematosus and other autoimmune diseases
Multiple sclerosis
Parkinson’s disease
Peripheral artery disease
Poor attention span, hyperactivity, or irritability
Poor mood
Poor wound healing
Postpartum depression
Premature birth
Problems learning
Red or white acne-like bumps (on your cheeks, arms, thighs, and buttocks)
Rheumatoid arthritis
Schizophrenia
Tissues and organ inflammation
Ulcerative colitis
Vascular complications from type 2 diabetes

Source references:

  1. National Research Council. 1989. Diet and Health: Implications for Reducing Chronic Disease Risk. Washington, DC: The National Academies Press. https://doi.org/10.17226/1222https://www.nap.edu/read/1222/chapter/14#317
  2. Mike Adams. What conventional medicine won’t dare tell you about gall bladder removal surgery. http://www.naturalnews.com/007733_gall_bladder_surgery.html
  3. Barbara Bolen, PhD. Emmy Ludwig, MD. What to Do About IBS After Gallbladder Removalhttp://ibs.about.com/od/relatedconditions/a/IBS-After-Gallbladder-Removal.htm

Alternative opinions not accepted continued

The postcholecystectomy syndrome may occur in two weeks or two decades following gallbladder surgery. The symptoms can be mild and just diminish of person’s quality of life. For some patients, PCS makes life miserable. Mostly, it does not depend on upon the surgical techniques, equipment, or experience of the surgeon. Just absence of gallbladder causes this problem.

The typical symptoms of the postcholecystectomy syndrome include

  • Intolerance of some foods, mostly fatty foods
  • Upper abdominal pain
  • Constant gas, bloating, flatulence
  • Nausea, vomiting
  • Stubborn heartburn
  • Constipation
  • Chronic diarrhea
  • Symptoms, which are very far from stomach such as depression, anxiety, low memory, skin dryness or itchiness, yellowish skin, blurred vision, bruises, tingling and numbness, often colds and more

The problem is that there is no conventional treatment of the PCS. The patients are under the care of the variety of doctors and medical practitioners with different skills, knowledge, and viewpoint on the postcholecystectomy syndrome. There are three kinds of situations.

The first one is when the symptoms happen rarely, and the entire lab and visual tests are normal. Patient has symptomatic treatment with the painkillers or gets a referral to a pain management clinic, or sends to a psychiatrist for depression and anxiety. Frequently PCS misdiagnosed with gastroesophageal reflux disease, food poison or food sensitivity, gastritis, dyspepsia, IBS, dumping syndrome, etc.

The second situation, the lab, and visual tests demonstrate increases in the pancreatic or liver enzymes, presence of the dilatation of the common bile duct. Symptoms become chronic. That is followed by numerous diagnostic tests, which are often insecure, visits to the countless doctors, hospitals, and taking all sorts of medications.

The third scenario, the individual underwent many tests that revealed severe structural changes in the bile duct, pancreas, liver, duodenum, and sphincter of Oddi. At this time, patients have numerous doctor visits, medications, ER admissions, consultations of specialists, and endoscopic surgeries.

These three situations are not separate disorders; these are the different stages of the sphincter of Oddi dysfunction, chronic biliary pancreatitis, metabolic acidosis, dysbiosis, and adhesion syndrome. Biliary means connection to bile system. The health of the bile, bile ducts, sphincter of

Oddi, and gallbladder is inextricably bound to the health of the pancreas, small, large intestines, and stomach.

Like all chronic diseases, there are the functional stage, structural stage, and advanced stage of the postcholecystectomy syndrome

Source : https://www.biotherapy-clinic.com/article/postcholecystectomy-syndrome-pain-and-indigestion-after-gallbladder-surgery

“In 12 years of practice, I have rarely met any ‘cholecystectomy patient’ who didn’t have to make changes to feel better afterwards. Sooner or later their underlying nutritional deficiencies caught up to them and affected their health.”

Dr. Miranda Jorgenson, licensed Chiropractic Physician

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Gallbladder role and fucntion

Functions of the Gallbladder

The gallbladder stores and concentrates bile between meals. Gallbladder motor function is regulated by bile acids via the membrane bile acid receptor, TGR5, and by neurohormonal signals linked to digestion, for example, cholecystokinin and FGF15/19 intestinal hormones, which trigger gallbladder emptying and refilling, respectively. The cycle of gallbladder filling and emptying controls the flow of bile into the intestine and thereby the enterohepatic circulation of bile acids. The gallbladder also largely contributes to the regulation of bile composition by unique absorptive and secretory capacities. The gallbladder epithelium secretes bicarbonate and mucins, which both provide cytoprotection against bile acids. The reversal of fluid transport from absorption to secretion occurs together with bicarbonate secretion after feeding, predominantly in response to an adenosine 3′,5′-cyclic monophosphate (cAMP)-dependent pathway triggered by neurohormonal factors, such as vasoactive intestinal peptide. Mucin secretion in the gallbladder is stimulated predominantly by calcium-dependent pathways that are activated by ATP present in bile, and bile acids. The gallbladder epithelium has the capacity to absorb cholesterol and provides a cholecystohepatic shunt pathway for bile acids. Changes in gallbladder motor function not only can contribute to gallstone disease, but also subserve protective functions in multiple pathological settings through the sequestration of bile acids and changes in the bile acid composition. Cholecystectomy increases the enterohepatic recirculation rates of bile acids leading to metabolic effects and an increased risk of nonalcoholic fatty liver disease, cirrhosis, and small-intestine carcinoid, independently of cholelithiasis.

Housset C1,2, Chrétien Y1,2, Debray D1,3, Chignard N1. Functions of the Gallbladder. https://doi.org/10.1002/cphy.c150050

 

 

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 Uncomplicated gallstone disease

Author

Salam F Zakko, MD, FACP  Section Editor

Sanjiv Chopra, MD  Deputy Editor

Peter A L Bonis, MD

Last literature review version 17.1: January 2009 | This topic last updated: January 28, 2008 (More)

INTRODUCTION — The most significant challenge in the evaluation of patients with upper digestive symptoms who are found to have gallstones, is whether the stones are the cause of the symptoms (ie, gallstone disease) or are an incidental finding. Making this distinction is important because both gallstones and upper digestive symptoms are common in the general population but are not always related. While cholecystectomy can be curative in those whose symptoms are related to gallstones, it exposes the rest to unnecessary risk, delays definitive treatment for the actual cause of symptoms, and incurs unnecessary expense.

This topic review will provide an overview of the evaluation of patients with possible, uncomplicated gallstone-related disease. An approach to asymptomatic patients found to have gallstones is presented separately. (See “Approach to the patient with incidental gallstones”). Complications related to gallstones are discussed on their corresponding topic reviews.

CLINICAL FEATURES — When considering gallstone disease it is helpful to categorize patients into the following clinical groups: Gallstones on imaging studies but without symptoms (category 1) Typical biliary symptoms and gallstones on imaging studies (category 2) Atypical symptoms and gallstones on imaging studies (category 3) Typical biliary symptoms but without gallstones on imaging studies (category 4)

As will be discussed below, the approach to patients in category 1 and 2 is generally straightforward. Patients in category 1 should generally be left alone, while those in category 2 should undergo treatment aimed at eliminating the gallstones. By contrast, optimal approaches to patients who fall into the last two categories (3 and 4) are less clear. Management of such patients should be individualized but depends largely upon the likelihood (based upon clinical features and diagnostic testing) that the patient’s symptoms are related to the gallstones. The following discussion provides guidance to aid in this process.

Biliary type symptoms — In most patients, the first symptoms experienced from gallstones are recurrent pain attacks generated by the gallstones (biliary colic). Less frequently, the initial symptoms are those of one of the complications of gallstones (most commonly acute cholecystitis, acute biliary pancreatitis, acute cholangitis, or choledocholithiasis with extrahepatic cholestasis).

Biliary colic — Biliary colic is usually caused by the gallbladder contracting in response to hormonal or neural stimulation usually due to a fatty meal, forcing a stone (or possibly sludge or microlithiasis) against the gallbladder outlet or cystic duct opening, and leading to increased intragallbladder pressure and pain. The stones often fall back from the cystic duct as the gallbladder relaxes. As a result, the discomfort progresses in less than an hour to a steady plateau that ranges from moderate to excruciating and remains constant for more than an hour, then slowly subsides over several hours. In most patients the pain is not very severe which is why it takes several attacks before a patient seeks medical attention. The frequency of recurrent attacks is variable ranging from years to hours [1] .

Despite the term “colic”, the pain is usually constant and not colicky. The classic attack is described as an intense dull pressure-like discomfort in the right upper or mid abdomen or in the chest that may radiate to the back and the right shoulder blade [2,3] . The pain classically follows ingestion of a fatty meal (about one to two hours after) and usually does not occur during fasting. However, the pain may be unrelated to meals in a substantial proportion of patients [4] . One group suggested that the pain had a circadian pattern, peaking at 9:30 PM [4,5] . In most cases the pain has a characteristic pattern and timing for individual patients.

The pain is often associated with diaphoresis, nausea and vomiting. It is not exacerbated by movement and not relieved by squatting, bowel movements, or flatus [1] . After the attack, the physical examination is usually normal with the possible exception of residual upper abdominal tenderness.

Although many patients are not symptomatic when they are undergoing medical evaluation, some patients present during an attack of symptoms. In such cases, biliary colic must be distinguished from the more serious complication of acute cholecystitis, which is associated with gallbladder wall inflammation, fever and an elevated white cell blood count. Prolonged or recurrent cystic duct blockage can progress to total obstruction causing acute cholecystitis. An episode of prolonged right upper quadrant pain (greater than four to six hours), especially if associated with fever, should arouse suspicion for acute cholecystitis as opposed to an attack of simple biliary colic. (See “Clinical features and diagnosis of acute cholecystitis”). Other acute abdominal pain diagnoses must also be considered in such patients. (See “Differential diagnosis of abdominal pain in adults”).

PREDICTIVE VALUE OF SYMPTOMS — Multiple studies have evaluated the association of gallstones with symptoms [2,6-14] . A consistent observation has been that the most specific feature pointing toward gallstones as the cause of symptoms was biliary colic. However, up to 80 percent of patients with gallstones referred for cholecystectomy had other abdominal symptoms [8] . At least two systematic reviews have provided estimates of the strength of the association between symptoms and gallstones: One systematic review focused on a total of 24 relevant studies that evaluated the association between seven abdominal symptoms and the presence of gallstones on ultrasonography or oral cholecystography as the reference standard [8] . The presence of biliary colic (diagnostic odds ratio {OR} 2.6, 95 percent CI 2.4 to 2.9), radiating pain (OR 2.8, 95 percent CI 2.2 to 3.7) and use of analgesics (OR 2, 95 percent CI 1.6 to 2.5) were consistently related to the presence of gallstones. However, the magnitude of these associations was notably weak. Similar conclusions were reached in an earlier systematic review that included 21 controlled studies evaluating an association between gallstones and dyspeptic symptoms [7] . Upper abdominal pain was most consistently associated with the presence of gallstones (OR 2.0). A weaker association was found with nausea and vomiting (OR 1.4). In contrast, there was no significant association with other symptoms such as flatulence, heartburn, acid regurgitation, bloating and belching.

A limitation of these studies is that the reference standard chosen was the presence of gallstones on imaging tests. A more clinically relevant reference standard may be whether symptoms were relieved following cholecystectomy, a question that has also been addressed in several reports [10,11,14] .

An illustrative study focused on 92 patients who had undergone cholecystectomy for symptomatic gallstones and were followed for a mean of 31 months [10] . Abdominal pain continued to be present (or arose de novo) in 30 percent of patients. A pain-free outcome was significantly associated with a preoperative diagnosis of biliary colic, fatty food intolerance, and a thick-walled gallbladder on ultrasound.

Interestingly, several other symptoms appeared to be improved after cholecystectomy including abdominal bloating, dyspepsia, heartburn, fat intolerance, nausea and vomiting. However, these observations should not be interpreted as suggesting that gallstones are a possible cause of all these complaints. Relief of symptoms may have been due to the natural history of some of these disorders, a placebo response, or other nonspecific effect of the procedure. Furthermore, it is notable that abdominal symptoms continued or developed in one-third of patients, despite this being a highly selected group of patients whose symptoms had implicated gallstones to an extent that warranted cholecystectomy.

Similar findings were noted in a second study that included 225 patients who had undergone laparoscopic cholecystectomy, 91 percent of whom had biliary pain [11] . Pain was relieved in 82 percent of such patients when stones were documented preoperatively. However, pain was also relieved in 52 percent of patients without gallstones preoperatively (patients thought to have acalculous cholecystitis), in 80 percent of patients with atypical pain, and in 44 percent of patients with non-pain syndromes.

A third report included 2481 patients who had undergone elective cholecystectomy at one of several centers [14] . The mean number of abdominal symptoms per patient decreased significantly. However, 27 percent of patients who had identified a symptom that was most bothersome before surgery, still had that symptom six months after surgery. Symptom persistence rates ranged for 6 percent (for vomiting) to 40 percent (for gas and flatulence). The authors concluded that symptoms categorized as dyspeptic were more likely to persist compared with the more typical biliary symptoms, although the prevalence of all symptoms decreased after cholecystectomy.

Conclusion — In aggregate, these data suggest that in patients with gallstones, no single clinical feature or combination of features confidently predicts that symptoms will be relieved following cholecystectomy. Symptom relief is most likely in patients whose principal symptom is biliary colic. Non-specific atypical symptoms like indigestion, abdominal bloating, and belching, although commonly reported by patients with gallstones, are less likely to be caused by cholelithiasis since they are least likely to disappear after cholecystectomy. As will be discussed below, additional testing has been proposed to better discriminate those with symptoms attributable to gallstones. However, none has been proven to be superior to clinical judgment.

DIAGNOSIS — The diagnosis of uncomplicated gallstone disease should be suspected based upon the clinical features described above (ie, principally biliary colic). Such patients should then undergo evaluation to diagnose the presence of gallbladder stones or sludge.

Gallstone disease is usually considered as part of the differential diagnosis of patients presenting with upper abdominal symptoms. Thus, the decision to implicate the gallbladder has to be made based upon clinical suspicion for a varied group of disorders that include peptic ulcer disease, cardiac chest pain, esophageal chest pain, gastroesophageal reflux disease, nonulcer dyspepsia, irritable bowel syndrome, sphincter of Oddi dyskinesia, hepatitis, and chronic pancreatitis.

It is important to consider that many of these diagnoses are common in the general population and thus may coexist but be unrelated to the gallstones. Thus, a hunting expedition with imaging studies to look for gallstones in patients with nonspecific or atypical symptoms is discouraged. Such patients should be considered to have dyspepsia, and undergo appropriate evaluation and/or treatment based upon the predominant symptoms and suspicion for particular diagnoses. (See “Approach to the patient with dyspepsia”).

As discussed earlier, biliary colic is the most accurate predictor of gallstone disease, but while imaging studies can detect gallstones, there is no clinical or laboratory test that can make the diagnosis of biliary colic. The diagnosis is based upon a meticulous history; questioning should focus on eliciting a history consistent with biliary colic as described above.

Physical examination — Patients with simple biliary colic are not usually ill appearing and do not have fever or tachycardia. The pain is characteristically dull and not severe enough to bring the patient to the emergency department, but, if a patient does present during a pain episode, the abdominal examination is generally benign and non-revealing. There are no peritoneal signs since the pain is purely visceral without gallbladder inflammation. However, voluntary guarding may be encountered depending upon the severity of the pain.

Physical examination can also help distinguish patients with acute cholecystitis. While biliary-type pain is present in both uncomplicated biliary colic and in acute cholecystitis, the pain in uncomplicated biliary colic is entirely visceral in origin since the gallbladder wall is not inflamed. Thus, it is generally less well localized and patients do not exhibit a positive “Murphy” sign on physical examination. A Murphy’s sign is elicited by palpating the area of the gallbladder fossa just beneath the liver edge while the patient is asked to inspire deeply, causing the gallbladder to descend toward the examining fingers. Patients with acute cholecystitis commonly experience increased discomfort and may have an associated inspiratory arrest (a positive Murphy’s sign). (See “Clinical features and diagnosis of acute cholecystitis”).

Laboratory studies — Laboratory studies should be normal in patients with uncomplicated biliary colic both during asymptomatic periods and during attacks of symptoms. However, laboratory studies can be helpful for excluding other diagnoses. Although the choice and order of testing varies depending upon the clinical presentation and suspicion for a particular diagnosis, the following are reasonable screening tests: Liver biochemical tests (serum AST, ALT, total bilirubin, alkaline phosphatase). (See “Approach to the patient with abnormal liver function tests”). Serum amylase and lipase (to evaluate for pancreatitis) Complete blood count (to evaluate for leukocytosis and anemia) Urine analysis

IMAGING STUDIES — Imaging studies are useful for confirming the presence of gallstones or sludge in a patient with a history suggestive of biliary colic. They may also be useful for excluding other diagnoses.

Ultrasonography — Ultrasonography is generally considered to be the most useful test to detect the presence of gallstones since it is non-invasive, readily available, relatively inexpensive, and does not subject the patient to ionizing radiation. As noted above, it should generally be requested in patients suspected of having gallstones based upon a history of biliary colic.

Multiple studies have evaluated test characteristics of ultrasonography in determining the presence of gallstones. A systematic review estimated that the sensitivity was 84 percent (95 percent CI 76 to 99 percent) and specificity was 99 percent (95 percent CI 97 to 100 percent) [15] .

However, it is important to recognize that precise estimates of sensitivity and specificity are difficult to determine since surgical confirmation of a negative sonogram is unlikely. In a study that compared ultrasonography with direct percutaneous mini-endoscopy in patients who had undergone topical gallstone dissolution, ultrasonography was negative in 12 of 13 patients in whom endoscopy demonstrated 1 to 3 mm stones or fragments [16] (show endoscopy 1).

Furthermore, the accuracy of ultrasonography is operator dependent. The ultrasound examination must be conducted with the patient having fasted for at least eight hours, because stones are best seen in a distended gallbladder when they are surrounded with bile. The entire gallbladder must be examined axially and sagittally. Every effort should be made to examine the outlet of the gallbladder (Hartmann’s pouch), where gallstones may be hidden. The gallbladder neck must be traced all the way into the porta hepatis to exclude stones in this region. If an out-pouching from the gallbladder (phrygian cap) is present, the redundant portion of the fundus must not be overlooked.

Even with an experienced operator, it is generally accepted that ultrasound is not highly sensitive for determining the number or size of stones in the gallbladder. This is especially true for very small stones approaching 1 or 2 mm in diameter that frequently, when present in large numbers, can appear on ultrasonography as one large stone.

Characteristics of stones on ultrasound — On ultrasonography, gallstones appear as an echogenic focus that casts an acoustic shadow (show radiograph 1) and seeks gravitational dependency [17,18] :

Two additional ultrasonographic entities that are frequently described are sludge and gravel. Gravel is the appearance of multiple small stones that are echogenic and cast a shadow. Sludge is echogenic in appearance but does not cast an acoustic shadow. It also is more viscous and does not move to the dependent portion of the gallbladder as rapidly as gravel [19,20] . If the gallbladder is totally filled with stones, or if it is contracted around many stones, it may be confused with gas in a partially collapsed duodenal bulb, emphysematous cholecystitis, porcelain gallbladder, or a calcified hepatic artery aneurysm. The ultrasonographer performing the procedure regularly uses specific maneuvers and techniques to identify and distinguish gallstones from some of these other appearances, further underscoring the degree to which ultrasonography is operator dependent.

Gallstones must be distinguished from gallbladder polyps, which can produce similar sonographic images. This is usually done by examining the patient in different positions to demonstrate the movement of stones to the dependent region of the gallbladder. Occasionally, vigorous rolling of the patient or pressure on the gallbladder in sharp jerky movements may be necessary to make the distinction. In addition, stones cast an acoustic shadow while polyps do not. (See “Gallbladder polyps and cholesterolosis”).

Plain abdominal X-ray — Plain abdominal x-rays are generally not useful in looking for gallstones in symptomatic patients. Only about 10 percent of gallstones have enough calcium in their composition to make them sufficiently radio-opaque to be visible on a plain radiograph (show radiograph 2).

Oral cholecystography — Oral cholecystography (OCG), once used commonly to diagnose gallstones and measure gallbladder function, is now used only rarely since it is less sensitive and specific compared with ultrasonography [15,21] . It is still occasionally used in patients in whom a high quality ultrasound examination cannot be obtained (such as in obese patients), to confirm the presence of adenomyomatosis of the gallbladder, and to evaluate patients who are being considered for medical dissolution therapy with ursodeoxycholic acid, in whom it is important to demonstrate stone number and size, relative density of the stones to bile, cystic duct patency and the gallbladder’s concentrating ability. (See “Patient selection for the nonsurgical treatment of gallstone disease”).

OCG is based upon an orally administered contrast agent that is absorbed through the intestine, taken up by the liver, and secreted into bile. Gallstones appear as filling defects within the contrast (show radiograph 3). Several contrast agents have been used; in the United States the most frequently used is iopanoic acid (Telepaque, Winthrop Pharmaceuticals, New York, New York). The standard dose of contrast is 3 grams (six tablets) of Telepaque. If the gallbladder shows no visualization, then a repeat dose of another six tablets is given the next evening and the x-ray examination is repeated the following morning. Other available similar agents are sodium tyropanoate (Bilopaque, Winthrop Pharmaceuticals), and calcium ipodate (Oragraffin, Squibb, Princeton, New Jersey).

False negative results can occur due to poor absorption from the intestine (due to malabsorption syndromes, inflammatory bowel disease, and ileal bypass), diminished liver function (such as in patients with hepatitis or cirrhosis, where the dye may not be adequately conjugated and excreted), or extrahepatic biliary obstruction. It is unlikely that the gallbladder will visualize when the serum bilirubin is greater than 2 to 3 mg/dL.

An approximation of gallbladder motor function can also be obtained if the patient is given a fatty meal following which the decrease in gallbladder size is estimated on serial x-rays. However, this is not recommended in patients who have known gallbladder stones since it may induce biliary colic.

Computed tomography — The sensitivity of computed tomography (CT) for gallstones is poor since most stones are isodense with bile and thus not visible on CT scanning [22,23] . CT can be useful for screening patients in whom medical dissolution therapy is being considered since the presence of calcifications within gallstones (readily apparent on CT) makes it unlikely that such therapy will be successful. (See “Patient selection for the nonsurgical treatment of gallstone disease”)

Cholescintigraphy — Cholescintigraphy has no role in the diagnosis of gallstones but is very useful in excluding acute cholecystitis in patients who present with acute biliary colic. (See “Clinical features and diagnosis of acute cholecystitis”).

APPROACH TO THE PATIENT — As noted above, the approach to the patient can be understood based upon the categorization described above.

Patients with gallstones but no symptoms (category 1) — Patients who are asymptomatic but found to have incidental gallstones on an imaging test should be left alone since the risk of developing life threatening severe complications is arguably less than the likelihood of developing such complications from prophylactic treatment. This recommendation is based upon studies showing that the rate of progression from asymptomatic to symptomatic gallstones is very low (about 1 percent per year). Furthermore, when patients do become symptomatic, the initial presenting symptoms are usually not severe. (See “Approach to the patient with incidental gallstones”).

As a result, patients with incidental gallstones can be educated about potentially concerning symptoms, allowing the uncommon patient destined to develop symptoms to seek treatment before severe complications arise. Thus, prophylactic cholecystectomy is not advised. (See “Approach to the patient with incidental gallstones”)

Patients with biliary symptoms and gallstones (category 2) — In contrast to patients with incidental gallstones, prophylactic treatment should be advised to patients of category 2 who have or had biliary type symptoms (see “Biliary colic” abovesee “Biliary colic” above) or complications (such as cholangitis, pancreatitis, cholecystitis, choledocholithiasis, gallstone ileus and Mirizzi syndrome) clearly related to gallstones, since such patients are likely to have recurrent and more severe symptoms. The National Cooperative Gallstone Study (one of the most definitive studies on the subject) showed that the risk of further symptoms and complications in such patients was approximately 70 percent within two years after initial presentation [24] .

Patients with gallstones but atypical symptoms (category 3) — Atypical symptoms in patients with gallstones (category 3) are unlikely to be caused by the gallstones. Thus, a careful search for other causes of symptoms is prudent. However, symptoms as described by patients are highly subjective and often change. As a result, it is always useful to review the symptoms on more than one occasion to see if any particular patient can be assigned to one of the other categories with the understanding that the less consistent the symptoms are, the higher the likelihood that they will not respond to treating the gallstones.

An empiric trial of oral dissolution therapy with ursodeoxycholic acid is reasonable if other serious illnesses such as cardiac disease or peptic ulcer disease have been excluded and the patient is a candidate for medical gallstone dissolution therapy. (See “Nonsurgical treatment of gallstone disease”). If the symptoms were indeed from the gallstones, ursodeoxycholic acid therapy relieves the symptoms in most patients within three months, long before the stones have dissolved [25] . Thus, a response to therapy may be helpful in guiding further management.

Patients with typical biliary symptoms but without gallstones on ultrasonography (category 4) — Patients in this category have either small stones (microlithiasis) or sludge that were missed on conventional imaging studies or other causes of biliary symptoms unrelated to gallstones such as sphincter of Oddi dysfunction. There is now increasing evidence that sludge can produce symptoms [26-28] and that it represents lithogenic bile containing cholesterol monohydrate crystals, bilirubin granules, and a mucus glycoprotein gel [29] . The conversion of ultrasonographic sludge into macroscopic gallstones has been documented in several studies [30,31] .

It is important to confirm the presence of microlithiasis or sludge in patients of this category because while symptomatic sludge and microlithiasis will respond to cholecystectomy or medical therapy, cholecystectomy may worsen the symptoms of patients with sphincter of Oddi dysfunction [32] .

As noted earlier, ultrasonography may not detect small gallstones or biliary sludge. Sensitivity for small gallstones can be improved upon by repeating the examination at a later time [33] . Further evaluation for microlithiasis can be considered in patients whose repeat ultrasonography is unrevealing.

Microlithiasis, or microcrystalline disease, can cause symptoms and complications similar to those seen with larger gallstones including biliary colic, cholecystitis, cholangitis, obstructive jaundice, and acute pancreatitis [26-28,34,35] . The diagnosis can be established by bile microscopy and endoscopic ultrasonography, which, in patients with typical biliary symptoms, considered as the next step [36] . Both these tests are done through an upper endoscopy, which also serves to exclude other conditions such as peptic ulcer disease.

Bile microscopy — Bile microscopy is regarded as the reference standard for the diagnosis of microlithiasis with an overall sensitivity of 65 to 90 percent [37-41] . The test relies upon the theory that patients with cholesterol microlithiasis have bile that is supersaturated with cholesterol and thus have cholesterol monohydrate crystals (show figure 1) in their gallbladder bile while those with bilirubinate microlithiasis have amorphous reddish-brown bilirubinate granules in their gallbladder (show figure 2) [42,43] . However, the methods of performing the test have not been well standardized leading to a great deal of confusion regarding how to collect and process the bile samples for analysis and what constitutes a positive test.

Most available studies describe the test as it pertains to the detection of microlithiasis in patients with idiopathic recurrent pancreatitis, but even then, no two reports seem to have used the same technique for bile collection, bile processing, or microscopic crystal analysis. Nevertheless, most investigators agree that microcrystals are formed in the gallbladder where bile is concentrated and they produce biliary colic or pancreatitis as they pass through the cystic duct and/or ampulla. Thus, microcrystals should ideally be sought in gallbladder bile; hepatic bile is significantly less concentrated and thus has a lower yield for the detection of microlithiasis [28,38,44] .

Gallbladder bile can be collected using one of the following techniques: Through direct percutaneous puncture of the gallbladder under ultrasound or fluoroscopic guidance During ERCP either through selective gallbladder cannulation or by aspirating bile from the common bile duct after stimulating gallbladder contraction by an infusion of the CCK analogue sincalide During endoscopy during which bile is suctioned from the duodenum around the region of the ampulla after gallbladder stimulation with intravenous cholecystokinin (sincalide), which causes the gallbladder to contract

Collection during endoscopy is the simplest and most practical method. The procedure can be combined with endoscopic ultrasonography (see below) to further increase sensitivity [36,48] . At our center, if the endoscopic ultrasound examination is negative, then while the endoscope is still in the patient sincalide (Kinevac 0.03 microg/kg body weight) is given by intravenous drip over 45 minutes; the longer infusion is safer and more effective than a short bolus technique [45] . The tip of the endoscope is positioned next to the ampulla and the bile is aspirated. Bile flow usually starts to accelerate within five minutes of the start of the CCK infusion. The first 5 to 10 minutes of bile flow is normally light in color representing common bile duct and hepatic bile. Gallbladder bile is the darker bile that starts flowing several minutes later.

The darker bile is collected in a separate collecting tube and kept for analysis. The bile is incubated at 37 degrees C for 24 hours, then centrifuged at 3,000 G for 30 minutes [46] . The supernatant is discarded and the sediment is made to mix into the liquid remaining at the bottom of the tube. A drop of that liquid is placed on a slide and examined using a polarizing microscope; a polarizing filter facilitates identification of cholesterol crystals, which exhibit birefringence (they shine against the dark background of the polarizing microscope). The test is considered positive if any cholesterol crystals or amorphous red brick bilirubinate granules are seen.

The proportion of patients found to have microcrystals has varied substantially in various reports. More recent studies seem to show a lower prevalence of microlithiasis (around 3.5 percent) [47] in patients of clinical category 4 compared to earlier reports in which the prevalence ranged from 33 to 90 percent [38,46] . This is thought to be in part due to the methods used to detect microcrystals and the definition of a positive test.

In earlier prospective studies, investigators inspected a drop of uncentrifuged bile on a slide and the test was considered positive if any cholesterol crystals or amorphous calcium bilirubinate granules were observed. These results correlated well with the presence or absence of gallstones in human subjects [38] . Subsequent studies demonstrated that the sensitivity of the test could be improved significantly if the bile was centrifuged and made to stand overnight at 37 degrees C [46] . While the presence of any cholesterol crystals is theoretically abnormal, to increase specificity, some of the newer reports considered the test to be positive only if more than three crystals were seen per high power field [47] . However, whether findings based upon this approach correlate with clinical outcomes has not been established. As a result, this methodology has not been widely accepted. Furthermore, improved sensitivity of extracorporeal ultrasonography for detection of small stones and sludge has reduced the need for microcrystal analysis, since relatively fewer patients are designated as having typical symptoms without gallstones (ie, clinical category 4).

In initial studies, for example, investigators inspected a drop of uncentrifuged bile on a slide. When any cholesterol crystals or amorphous calcium bilirubinate granules were observed, the test was considered positive; the results correlated well with the presence or absence of gallstones in human subjects [38] . Subsequent studies demonstrated that the sensitivity of the test could be improved significantly if the bile was centrifuged and made to stand overnight at 37 degrees C [46] .

While presence of any cholesterol crystals is theoretically abnormal, specificity can be increased by considering the test positive only if more than three crystals are seen per high power field [47] . This definition has been used in the relatively recent reports, which may explain why they have described a lower prevalence of microlithiasis (around 3.5 percent) in patients in clinical category 4 compared to earlier reports in which the prevalence ranged from 33 to 90 percent.

Endoscopic ultrasonography — Imaging of the gallbladder can be obtained by endoscopic ultrasound (EUS) during which an ultrasound transducer, on the tip of an endoscope, is placed into contact with the gastric antrum, which is in close proximity to the gallbladder, thereby allowing for its visualization without interference from bowel gas, subcutaneous tissue or the liver. As a result, EUS is more sensitive than extracorporeal ultrasonography for the detection of gallstones, particularly in patients who are obese or have other anatomic considerations limiting views with transabdominal ultrasonography [48,49] .

Several studies have demonstrated EUS can be useful for the detection of small stones and microcrystals as illustrated by the following examples: In a study of 45 patients in whom there was a clinical suspicion of cholelithiasis but with at least two normal US examinations, EUS detected evidence of cholelithiasis in 26 patients and was more sensitive than microscopic examination of duodenal bile [48] . In a study of 89 patients with acute pancreatitis, EUS revealed small gallbladder stones (1 to 9 mm) in 14 patients who had otherwise negative standard imaging studies including ultrasonography [49] . Subsequent ERCP and cholecystectomy confirmed the presence of stones in all 14 patients. EUS detected microcrystals in 5 of 15 patients with pancreatitis but a negative ultrasound examination [37] . The sensitivity of EUS combined with bile microscopy in detecting microcrystals was 92 percent in 66 patients with biliary type pain and a negative abdominal ultrasound [36] . Resolution of symptoms after cholecystectomy was noted in 90 of these patients.

Because it is invasive, EUS is generally reserved for patients with biliary colic or suspected complications of gallstones (such as pancreatitis) who have a negative transabdominal ultrasound [36,50] . EUS also has a role in diagnosis of patients with suspected choledocholithiasis. (See “Endoscopic ultrasonography in patients with suspected choledocholithiasis”).

MANAGEMENT — There are two general considerations in the management of uncomplicated gallstone disease. Management of biliary colic Prophylactic treatment to prevent further attacks and/or the development of complications

Biliary colic — The management of acute biliary colic mainly involves pain control. Pain control can usually be achieved with intravenous administration of meperidine, which is preferred to morphine since it has less of an effect on sphincter of Oddi motility [51-53] . Patients should be instructed to remain NPO to prevent the release of cholecystokinin. Those with prolonged attacks (especially if accompanied by vomiting) should also receive intravenous hydration.

If the diagnosis is fairly certain there is increasing evidence that the use of nonsteroidal antiinflammatory drugs (NSAIDs) can produce effective analgesia for biliary colic, and may favorably alter its natural history. The latter benefit may reflect the role of prostaglandins in the development of acute cholecystitis. (See “Clinical features and diagnosis of acute cholecystitis”, section on Pathogenesis).

We use ketorolac (30 to 60 mg adjusted for age and renal function given in a single intramuscular dose) for patients who present to the emergency department with biliary colic. Treatment usually relieves symptoms within 20 to 30 minutes. Patients are then prescribed ibuprofen 400 mg orally to be taken during subsequent attacks, until definitive treatment can be accomplished. In a study comparing ketorolac with meperidine in 324 patients, the two agents were found to be equivalent for pain control but meperidine caused more adverse events mainly in the form of nausea and dizziness [54] .

Prophylactic treatment — When the acute attack of biliary colic subsides, definitive prophylactic therapy should be considered to remove the offending stones to prevent recurrent attacks of biliary colic and the occurrence of more severe complications. Several modalities are available ranging from the surgical removal of the gallbladder to the medical dissolution of the stones while sparing the gallbladder. The choice of the management pathway is generally based upon the patient’s surgical risk and preference.

Cholecystectomy is the most commonly recommended modality. The gallbladder along with its contained stones is removed under general anesthesia. This surgical procedure may be performed through an open right upper quadrant muscle cutting incision or laparoscopically. The latter has become popular since the early 1990s since it eliminates the need to cut the rectus abdominis muscle leading to significantly shortened hospital stay and convalescence.

However, the laparoscopic procedure has been associated with an increased risk of common bile duct injury [54,55] . In addition, the laparoscopic procedure has to be converted to an open procedure in about 10 percent of cases due to a variety of technical or patient issues. Ultimately, the choice of technique is based upon the experience and preference of the surgeon performing the procedure and the medical condition of the patient. (See “Complications of laparoscopic cholecystectomy”).

While removal of the gallbladder is commonly considered to have no lasting physiologic consequences, about 50 percent of patients note more frequent and less formed stools while 10 to 15 percent of patients develop frank diarrhea for which they seek medical attention [6] . An increased risk of right sided colon cancer in patients who have undergone cholecystectomy has also been suggested [56] .

In some cases, surgical removal of the gallbladder may not be feasible, usually because of patient comorbidities. Several nonsurgical techniques for treatment of gallstones have been developed. These include principally medical dissolution therapy with oral bile acids, topical chemical dissolution using solvents to lavage the gallbladder, and extracorporeal shock wave lithotripsy. While the development of laparoscopic cholecystectomy has generally reduced enthusiasm for these approaches, they remain reasonable options in selected patients. (See “Patient selection for the nonsurgical treatment of gallstone disease”).

SUMMARY AND RECOMMENDATIONS — When considering gallstone disease it is helpful to categorize patients into the following clinical categories.

Gallstones but without symptoms — These patients are unlikely to develop symptoms and when they do occur they are generally mild. Thus, patients should be educated about symptoms potentially related to gallstones (principally biliary colic) without recommending specific therapy to address the gallstones. (See “Approach to the patient with incidental gallstones”).

Typical biliary symptoms and gallstones — Such patients should generally undergo treatment (generally cholecystectomy) since they are likely to develop recurrent symptoms, which can be severe. The National Cooperative Gallstone Study (one of the most definitive studies on the subject) showed that the risk of further symptoms and complications in such patients was approximately 70 percent within two years after initial presentation [24] .

Atypical symptoms and gallstones — Such patients should undergo a search for non-gallstone-related causes of symptoms. If investigation is unrevealing, treatment of gallstones can be considered with the understanding that the rate of persistent symptoms is high. (See “Approach to the patient with dyspepsia”).

Typical biliary symptoms but without gallstones — Clinical suspicion for gallstone disease should be maintained in such patients. A repeat extracorporeal ultrasound should be obtained. If results are unrevealing, EUS and collection of duodenal bile for microscopy should be considered. If results continue to be unrevealing, a search for other causes of biliary pain is reasonable.

INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. (See “Patient information: Gallstones”). We encourage you to print or e-mail this topic review, or to refer patients to our public web site, www.uptodate.com/patients, which includes this and other topics.

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https://somepomed.org/articulos/contents/mobipreview.htm?14/53/15185/abstract/2,3,7-14

 

 

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Postcholecystectomy Syndrome (PCS) expanded with references

“The absence of the gallbladder leads to functional biliary hypertension and increased hepatic and common bile duct . 3-5 years after cholecystectomy increases right and left hepatic ducts equity.

Functional hypertension in the common bile duct contributes to the appearance of functional and hypertension in Wirsung’s pancreatic duct with the development of the phenomena of chronic pancreatitis . At the same time period in some patients this is accompanied by the progression of chronic pancreatitissphincter of Oddi dysfunction and duodenogastric (Biliary / bile ) reflux.

Duodenogastric reflux of mixture of bile with pancreatic juice promotes atrophic gastritis in the antral part of stomach.

From 40% to 60% of patients after cholecystectomy dyspeptic suffering from various disorders, from 20% to 40% of pains of different localization .

Up to 70% of patients after cholecystectomy have chronic effects of “bland” cholestasis, chronic cholestatic hepatitis and chronic compensatory bile acid-dependent apoptosis of hepatocytes.

Patients undergoing cholecystectomy had an increased prevalence of metabolic risk factors for cardiovascular disease, including type 2 diabetes mellitus, high blood pressure, and high cholesterol levels.

Part of patients after cholecystectomy with increased concentration of hydrophobic hepatotoxic co-carcinogenic deoxicholic bile acid in serum and/or feces with increased risk of colon cancer

 “Biliary Diseases Laparoscopic Cholecystectomy. Postcholecystectomy Syndrome Dr. Jacob L. Turumin (Iakov L. Tyuryumin), MD, PhD, DMSci”

 

  “The incidence of postcholecystectomy syndrome has been reported to be as high as 40% in one study, and the onset of symptoms may range from 2 days to 25 years.  There may also be gender-specific risk factors for developing symptoms after cholecystectomy. In one study, the incidence of recurrent symptoms among female patients was 43%, compared to 28% of male patients.”

 cholecystectomy is associated with several physiological changes in the upper gastrointestinal tract which may account for the persistence of symptoms or the development of new symptoms after gallbladder removal. The cholecyst sphincter of Oddi reflex, cholecyst-antral reflex, and cholecyst-oesophagal reflexes are all disrupted and some local upper gastrointestinal hormonal changes also occur after cholecystectomy. Thus, there is an increased incidence of gastritis, alkaline duodene gastric reflux and gastro-oesophageal reflux after cholecystectomy, all of which may be the basis for postcholecystectomy symptoms.”

 Postcholecystectomy syndrome (PCS), S. Mohandas, L.M. Almond, Department of General Surgery, Worcestershire Royal Hospital, Worcester, UK

 

Up to 15-20 % of cholecystectomized patients, continue to have a variety of gastrointestinal symptoms such as fatty food intolerance, nausea and vomiting, heartburn, flatulence, indigestion, diarrhea, mild occasional abdominal pain attacks and severe RUQ pain with extreme post-cholecystectomy distress. The term used to describe this condition is post-cholecystectomy syndrome (PCS). The reported frequency of postcholecystectomypain ranged from 14% to 34% in the reviewed literature, but postoperative dyspepsia was a more frequent symptom that occurred in up to 54% of cholecystectomized patients

It is obvious that irritable bowel syndrome (IBS) may occur after cholecystectomy, and, therefore, dyspeptic symptoms in patients with PCS may be caused by altered gut motility.

Sphincter of Oddi dysfunction (SOD), accounts for 1.5 – 3% of PCS patients

The majority of PCS patients suffered from dyspepsia with mild and occasional pain attacks that caused by functional motility disturbances of the upper gut and the sphincter of Oddi (SO). 2-5% of the PCS patients with continuous severe distress, intense right upper quadrant pain and recurrent cholangitis accounted from all cholecystectomized adults.

PCS symptoms could have several pathophysiological origins. The minority of PCS is caused by an organic disease of the gastrointestinal tract. In a substantial number of patients, no organic disease can be found as a cause of biliary type pain after cholecystectomy. Many patients in whom no organic abnormality can be found suffer from motility disorders of the biliary tract and the upper gut.

 Madacsy L, Dubravcsik Z, Szepes A (2015) Postcholecystectomy Syndrome: From Pathophysiology to Differential Diagnosis – A Critical Review. Pancreat Disord Ther 5:162. doi:10.4172/2165-7092.1000162 https://www.omicsonline.org/open-access/postcholecystectomy-syndrome-from-pathophysiology-to-differentialdiagnosis–a-critical-review-2165-7092-1000162.php?aid=63731

 

 Patients with cholecystectomy had more comorbidities, particularly chronic fatigue syndrome, fibromyalgia, depression, and anxiety. Postcholecystectomy gastroparesis patients had increased health care utilization and had a worse quality of life.

Cholecystectomy and Clinical Presentations of Gastroparesis, the NIDDK Gastroparesis Clinical Research Consortium (GpCRC)*

 

 “Cholecystectomy can have nutritional and metabolic consequences in the short-term (diarrhea, abdominal pain and bloating) and in the long-term (increased Body Mass Index with metabolic syndrome, gastritis, liposoluble vitamin deficiency). Pathogenic mechanisms behind these disturbances are reviewed and the need for an early post-operative nutritional intervention based on low-lipid, high-fibers diet, is highlighted. [7]

Altomare DF, Rotelli MT, Palasciano N. Diet after cholecystectomy.  https://doi.org/10.2174/0929867324666170518100053

 

Cholecystectomy itself is associated with many physiological changes in the upper gastrointestinal tract that may account for the persistence of the symptoms or the development of new symptoms after gallbladder removal. The cholecystosphincter of the Oddi reflex, cholecysto-antral reflex, and cholecyst-esophageal reflexes are all disrupted, and some local upper gastrointestinal hormonal changes often occur after cholecystectomy. Therefore, there is an increased incidence of gastritis, alkaline duodenogastric reflux, and gastro-esophageal reflux after cholecystectomy, which may be the basis for postcholecystectomy symptoms.18,19,20

Shirah, B. H., Shirah, H. A., Zafar, S. H., & Albeladi, K. B. (2018). Clinical patterns of postcholecystectomy syndrome. Annals of hepato-biliary-pancreatic surgery22(1), 52-57. https://dx.doi.org/10.14701%2Fahbps.2018.22.1.52

 

Source references:

  1. Farahmandfar, M. Chabok, M. Alade, A. Bouhelal and B. Patel, Post Cholecystectomy Diarrhoea—A Systematic Review, Surgical Science, Vol. 3 No. 6, 2012, pp. 332-338. http://dx.doi.org/10.4236/ss.2012.36065
  2. Tsai M-C, Chen C-H, Lee H-C, Lin H-C, Lee C-Z (2015) Increased Risk of Depressive Disorder following Cholecystectomy for Gallstones. PLoS ONE 10(6): e0129962. https://doi.org/10.1371/journal.pone.0129962
  3. Nudo R, Pasta V, Monti M, Vergine M, Picardi N.Correlation between post-cholecystectomy syndrome and biliary reflux gastritis. Endoscopic studyhttps://www.ncbi.nlm.nih.gov/pubmed/2699712
  4. Lorusso D1, Pezzolla F, Montesani C, Giorgio P, Caruso ML, Cavallini A, Guerra V, Misciagna G. Duodenogastric reflux and gastric histology after cholecystectomy with or without sphincteroplastyhttps://www.ncbi.nlm.nih.gov/pubmed/2253017
  5. Shah Gilani SN1, Bass GA1, Kharytaniuk N2, Downes MR3, Caffrey EF3, Tobbia I3, Walsh TN4. Gastroesophageal Mucosal Injury after Cholecystectomy: An Indication for Surveillancehttps://doi.org/10.1016/j.jamcollsurg.2016.12.003
  6. Bistritz, L., & Bain, V. G. (2006). Sphincter of Oddi dysfunction: Managing the patient with chronic biliary pain. World Journal of Gastroenterology?: WJG, 12(24), 3793–3802. http://doi.org/10.3748/wjg.v12.i24.3793
  7. Donato F. Altomare, Maria T. Rotelli, Nicola Palasciano. Diet After Cholecystectomyhttp://www.eurekaselect.com/node/152535/article
  8. Wikipedia, Postcholecystectomy syndrome.  https://en.wikipedia.org/wiki/Postcholecystectomy_syndrome
  9. Steen W Jensen, MD; Chief Editor: John Geibel, MD, DSc, MSc, AGAF Postcholecystectomy Syndrome[com]
  10. S.JaunooS MohandasL.M.Almond. Postcholecystectomy syndrome (PCS)[ScienceDirect]
  11. Sureka B, Mukund A.Review of imaging in post-laparoscopy cholecystectomy complications. Indian J Radiol Imaging 2017;27:470-81  [Indian Journal of Radiology and Imaging]
  12. Murshid KR. The postcholecystectomy syndrome: A review. Saudi J Gastroenterol [serial online] 1996 [cited 2018 Jan 15];2:124-37. Available from:  http://www.saudijgastro.com/text.asp?1996/2/3/124/34017
  13. Girometti, R., Brondani, G., Cereser, L., Como, G., Del Pin, M., Bazzocchi, M., & Zuiani, C. (2010). Post-cholecystectomy syndrome: spectrum of biliary findings at magnetic resonance cholangiopancreatography[The British Journal of Radiology, 83(988), 351–361]
  14. Jacob L. Turumin, Victor A. Shanturov, Helena E. Turumina. Irkutsk Institute of Surgery, Irkutsk Regional Hospital, Irkutsk 664079. The role of the gallbladder in human[ScienceDirect]
  15. Jacob L. Turumin, MD, PhD, DMSci Biliary Diseases Laparoscopic Cholecystectomy. Postcholecystectomy Syndromehttp://www.drturumin.com/en/index.html#sthash.Y35Uey8C.dpuf
  16. Martin, Walton. “RECENT CONTROVERSIAL QUESTIONS IN GALL-BLADDER SURGERY.” Annals of Surgery 79.3 (1924): 424–443. Print. [PMC]
  17. The NIDDK Gastroparesis Clinical Research Consortium (GpCRC). “Cholecystectomy and Clinical Presentations of Gastroparesis.” Digestive diseases and sciences 58.4 (2013): 1062–1073. [PMC]
  18. Yong Zhang , Hao Liu , Li Li , Min Ai , Zheng Gong, Yong He, Yunlong Dong, Shuanglan Xu, Jun Wang , Bo Jin, Jianping Liu, Zhaowei Teng Cholecystectomy can increase the risk of colorectal cancer: A meta-analysis of 10 cohort studies Published: August 3, 2017 https://doi.org/10.1371/journal.pone.0181852
  19. Mearin, F., De Ribot, X., Balboa, A. Duodenogastric bile reflux and gastrointestinal motility in pathogenesis of functional dyspepsia. Role of cholecystectomy. Digest Dis Sci (1995) 40: 1703. https://doi.org/10.1007/BF02212691
  20. Simona Manea, Georgeta & Carol, Stanciu. (2008). DUODENOGASTROESOPHAGEAL REFLUX AFTER CHOLECYSTECTOMY.Jurnalul de Chirurgie. 4 [Researchgate]
  1. A Shirah, B. H., Shirah, H. A., Zafar, S. H., & Albeladi, K. B. (2018). Clinical patterns of postcholecystectomy syndrome. Annals of hepato-biliary-pancreatic surgery, 22(1), 52-57. https://dx.doi.org/10.14701%2Fahbps.2018.22.1.52
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Uncomplicated gallstone disease in adults
Uncomplicated gallstone disease in adults
Author
Salam F Zakko, MD, FACP
Section Editor
Sanjiv Chopra, MD
Deputy Editor
Anne C Travis, MD, MSc, FACG
Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2013. This topic last updated: Mar 22, 2013.

INTRODUCTION  — Gallstones are common, particularly in Western populations ( table 1 ). In the United States, gallstones are seen in approximately 6 percent of men and 9 percent of women. Most individuals with gallstones are asymptomatic throughout their lives. When the stones start causing symptoms, the condition is referred to as gallstone disease. Uncomplicated gallstone disease refers to stones in the gallbladder that are associated with biliary colic in the absence of complications, such as acute cholecystitis, cholangitis, or gallstone pancreatitis.

Determining whether a patient’s upper digestive symptoms are the result of gallstones detected on imaging can be challenging. While both gallstones and upper digestive symptoms are common in the general population, they are not always related. Differentiating patients with uncomplicated gallstone disease from those with other disorders and an incidental finding of gallstones is important, since cholecystectomy is often curative in those with symptomatic gallstones, but it exposes those with incidental gallstones to unnecessary risk, delays appropriate treatment for the actual cause of symptoms, and incurs unnecessary expense.

This topic will review uncomplicated gallstone disease. The epidemiology of and risk factors for gallstones, the approach to patients with an incidental finding of gallstones, gallstone disease in pregnant women, and the complications of gallstone disease are discussed separately. (See “Epidemiology of and risk factors for gallstones” and “Approach to the patient with incidental gallstones” and “Gallstone disease in pregnant women” and “Pathogenesis, clinical features, and diagnosis of acute cholecystitis” and “Etiology of acute pancreatitis”, section on ‘Gallstones’ and “Acute cholangitis” and “Approach to the patient with suspected choledocholithiasis” .)

CATEGORIZATION OF PATIENTS  — When considering gallstone disease, we have found it helpful to categorize patients into the following clinical groups:

  • Category 1: Gallstones on imaging studies but without symptoms (incidental gallstones)
  • Category 2: Typical biliary symptoms and gallstones on imaging studies with no evidence of complications (uncomplicated gallstone disease)
  • Category 3: Atypical symptoms and gallstones on imaging studies
  • Category 4: Typical biliary symptoms but without gallstones on ultrasound

As will be discussed below, the approach to patients in categories 1 and 2 is generally straightforward. Patients in category 1 should generally be left alone, while those in category 2 should undergo treatment aimed at eliminating the gallstones. By contrast, optimal approaches to patients who fall into the last two categories (3 and 4) are less clear. Management of such patients should be individualized and depends largely upon the likelihood (based upon clinical features and diagnostic testing) that the patient’s symptoms are related to the gallstones. (See ‘Management’ below.)

NATURAL HISTORY  — The majority of patients with gallstones are asymptomatic. Of those with incidental (asymptomatic) gallstones, approximately 20 percent will develop symptoms over 15 years of follow-up, but their initial symptoms are typically not severe [ 1 ]. (See “Approach to the patient with incidental gallstones”, section on ‘Natural history of asymptomatic gallstones’ .)

Among patients with symptoms the natural history is variable, ranging from symptom resolution to the development of severe complications. This was demonstrated in a study that included 94 patients with mild symptoms and 119 patients with severe symptoms [ 2 ]. The patients were followed for a mean of 8.7 years. At the end of follow-up, 58 percent of the patients with mild symptoms were asymptomatic, 17 percent had mild symptoms, and 25 percent had severe symptoms. On the other hand, 52 percent of those with severe symptoms were asymptomatic, 17 percent had mild symptoms, and 31 percent had severe symptoms.

Complications that may develop in patients with gallstones include acute cholecystitis, choledocholithiasis with or without acute cholangitis, and gallstone pancreatitis. Acute cholecystitis is the most common complication. In a systematic review, it was seen in 6 to 11 percent of patients with symptomatic gallstones over a median followup of 7 to 11 years [ 3 ]. Rare complications include gallbladder cancer, gallstone ileus, and Mirizzi syndrome.

Patients with asymptomatic gallstones appear to have a slightly lower risk of complications than those with symptomatic gallstones. This was demonstrated in a study that followed 123 patients with asymptomatic gallstones and 298 patients with mild symptoms due to gallstones for up to 25 years [ 4 ]. It found that the cumulative probability of developing severe complications was lower among patients with asymptomatic gallstones compared with those with mild symptoms after 5, 10, 15, and 20 years of follow-up (4 versus 5 percent, 5 versus 12 percent, 10 versus 15 percent, and 16 versus 18 percent, respectively; p = 0.03).

CLINICAL FEATURES  — Patients with uncomplicated gallstone disease typically present with biliary colic, normal physical examination findings, and normal laboratory test results. Patients often report associated diaphoresis, nausea, and vomiting.

While patients may present with atypical symptoms, such as chest pain or nonspecific abdominal discomfort, the absence of biliary colic should prompt an investigation for alternative diagnoses. On the other hand, biliary colic that is associated with fevers, jaundice, or abnormal blood tests (leukocytosis, liver tests, pancreas tests) suggests the development of a complication of gallstone disease. (See ‘Differential diagnosis’ below.)

Biliary colic  — Despite the name, the pain of biliary colic is usually constant and not colicky. The classic description is of an intense, dull discomfort located in the right upper quadrant, epigastrium, or (less often) substernal area that may radiate to the back (particularly the right shoulder blade) [ 5,6 ]. The pain is often associated with diaphoresis, nausea, and vomiting. It is not exacerbated by movement and is not relieved by squatting, bowel movements, or passage of flatus [ 7 ].

Biliary colic is usually caused by the gallbladder contracting in response to hormonal or neural stimulation, forcing a stone (or possibly sludge) against the gallbladder outlet or cystic duct opening, leading to increased intra-gallbladder pressure. This increase in pressure then results in pain. Eating a fatty meal is a common trigger for gallbladder contraction, and many patients report postprandial pain. However, an association with meals is not universal, and in a significant proportion of patients the pain is nocturnal [ 8,9 ].

The pain typically lasts at least 30 minutes, plateauing within an hour. As the gallbladder relaxes, the stones often fall back from the cystic duct and the pain slowly subsides, with an entire attack usually lasting less than six hours [ 5 ]. In many patients, the pain is not severe, which is why patients often have had several attacks before seeking medical attention. The frequency of recurrent attacks is variable, ranging from hours to years, though most patients do not have symptoms on a daily basis [ 7 ]. Typically, the pain has a characteristic pattern and timing for an individual patient.

Atypical symptoms  — Numerous symptoms other than biliary colic have been reported in patients with gallstones, but their predictive value for the presence of gallstone disease is poor. In many cases they may coexist with biliary colic but may or may not be related to the gallstones [ 10-12 ]. Atypical symptoms seen in patients with gallstones include:

  • Chest pain
  • Nonspecific abdominal pain
  • Belching
  • Fullness after meals/early satiety
  • Fluid regurgitation
  • Abdominal distension/bloating
  • Epigastric or retrosternal burning
  • Nausea or vomiting without biliary colic

Whether atypical symptoms are due to the gallstones or due to a coexistent problem can be difficult to determine. Patients with atypical symptoms without associated biliary colic should be evaluated for alternative diagnoses, even if gallstones are demonstrated on imaging. (See ‘Differential diagnosis’ below.)

Physical examination  — Patients with biliary colic due to uncomplicated gallstone disease are usually not ill appearing and do not have fever or tachycardia. The pain is often not severe enough to bring the patient to the emergency department. If a patient does present during a pain episode, the abdominal examination is generally benign. Biliary colic is visceral pain and there are no peritoneal signs because the gallbladder is not inflamed. However, voluntary guarding may be encountered depending upon the severity of the pain.

Laboratory studies  — Laboratory studies should be normal in patients with uncomplicated gallstone disease, both during asymptomatic periods and during attacks of pain. Abnormal blood tests (leukocytosis, elevated liver or pancreas tests) suggest the development of a complication of gallstone disease, such as cholecystitis, cholangitis, or pancreatitis. (See “Pathogenesis, clinical features, and diagnosis of acute cholecystitis” and “Acute cholangitis”and “Clinical manifestations and diagnosis of acute pancreatitis” .)

Imaging studies  — Most patients with uncomplicated gallstone disease will have gallstones demonstrated on transabdominal ultrasound. Other imaging studies, such as plain abdominal x-rays or computed tomography (CT) scanning of the abdomen are less sensitive than ultrasound, though patients may have had the tests as part of the general evaluation of their abdominal pain. (See ‘Transabdominal ultrasound’ below.)

Plain abdominal x-rays rarely reveal gallstones because only about 10 percent of gallstones contain enough calcium to make them sufficiently radio-opaque to be visible on a plain radiograph ( image 1 ). The sensitivity of CT scan for gallstones has been reported to be 55 to 80 percent. Gallstones may be missed on CT because many stones are isodense with bile [ 13,14 ].

DIAGNOSIS  — The diagnosis of uncomplicated gallstone disease should be suspected in a patient with biliary colic, a normal physical examination, and normal laboratory tests (complete blood count, aminotransferases, bilirubin, alkaline phosphatase, amylase, and lipase). Such patients should undergo an imaging study to determine if there are gallbladder stones or sludge. Typically, the evaluation begins with a transabdominal ultrasound since it is the most sensitive modality for detecting gallbladder stones. If the transabdominal ultrasound is negative in a patient with biliary colic, additional studies that may help with the diagnosis include endoscopic ultrasound (EUS) and bile microscopy.

Transabdominal ultrasound  — Transabdominal ultrasound is generally considered to be the most useful test to detect the presence of gallstones since it is non-invasive, readily available, relatively inexpensive, and does not subject the patient to ionizing radiation. The examination should be conducted with the patient having fasted for at least eight hours, because stones are best seen when surrounded by bile in a distended gallbladder.

Characteristics of stones on ultrasound  — Patients with uncomplicated gallstone disease may have ultrasound findings of gallstones, gravel, or sludge. Distinguishing among these three entities is generally not clinically important because they are managed identically. (See ‘Management’ below.)

On ultrasound, gallstones appear as echogenic foci that cast an acoustic shadow ( image 2 ) and seek gravitational dependency [ 15,16 ]. Gravel is the appearance of multiple small stones that are echogenic and cast shadows. Sludge is echogenic in appearance but does not cast an acoustic shadow. It is also more viscous and does not move to the dependent portion of the gallbladder as rapidly as gravel [ 17,18 ].

The sludge seen on ultrasound represents microlithiasis (lithogenic bile that contains cholesterol monohydrate crystals, bilirubin granules, and a mucus glycoprotein gel) [ 19,20 ]. Microlithiasis can produce biliary colic and lead to complications such as acute cholangitis and acute pancreatitis [ 21-25 ]. It may also progress to macroscopic gallstones [ 26,27 ].

False negative results may be obtained if the gallbladder is completely filled with stones or if it is contracted around many stones. In such cases, the findings may be confused with gas in a partially collapsed duodenal bulb, emphysematous cholecystitis, porcelain gallbladder, or a calcified hepatic artery aneurysm. False positive results may be seen if gallbladder polyps are present, since they produce sonographic images similar to those seen with gallstones, though they do not cast an acoustic shadow ( image 2 ). The ultrasonographer performing the procedure regularly uses specific maneuvers and techniques to identify and distinguish gallstones from some of these other entities. As a result, ultrasonography is highly operator-dependent. (See”Gallbladder polyps and cholesterolosis” .)

Test characteristics  — Multiple studies have evaluated the ability of transabdominal ultrasound to detect gallstones, though it is important to recognize that precise estimates of sensitivity and specificity are difficult to determine since surgical confirmation of a negative sonogram is unlikely.

A systematic review estimated that the sensitivity was 84 percent (95% confidence interval [CI] 76 to 99%) and specificity was 99 percent (95% CI 97 to 100%) [ 28 ]. Rarely, advanced scarring and contraction of the gallbladder around gallstones leads to nonvisualization of the gallbladder lumen, which has a specificity of 96 percent, but it should also raise the possibility of gallbladder cancer.

When compared with other cross-sectional imaging modalities and cholecystography, ultrasound has the highest sensitivity [ 29,30 ]. Modern sonographic equipment is able to detect stones as small as 1.5 to 2 mm in diameter [ 29 ]. Smaller stones may be missed, and the sensitivity falls to 50 to 60 percent for stones less than 3 mm in diameter [ 31-33 ].

The accuracy of transabdominal ultrasonography is operator dependent. The entire gallbladder must be examined axially and sagittally. Every effort should be made to examine the outlet of the gallbladder (Hartmann’s pouch), where gallstones may be difficult to detect. The gallbladder neck must be traced all the way into the porta hepatis to exclude stones in this region. If an out-pouching from the gallbladder (Phrygian cap) is present, the redundant portion of the fundus must not be overlooked.

Even with an experienced operator, it is difficult to determine the number or size of stones in the gallbladder with transabdominal ultrasound. This is especially true for very small stones (1 or 2 mm in diameter) that frequently, when present in large numbers, can appear on transabdominal ultrasound as one large stone.

Next steps if the ultrasound is negative  — For patients with symptoms that do not fit the classic description for biliary colic, an evaluation for non-biliary causes for the patient’s symptoms should be pursued. However, in a patient with classic biliary colic, if the initial transabdominal ultrasound was negative, additional testing to detect missed gallstones, sludge, or microlithiasis is indicated. (See ‘Differential diagnosis’ below.)

General approach  — In patients with typical biliary colic but no gallstones on ultrasonography, we usually repeat the transabdominal ultrasound in a few weeks. If the repeat transabdominal ultrasound is negative, the patient may have microlithiasis or may be a category 4 patient (typical biliary symptoms without gallstones on ultrasound). In such patients the next step is debatable. The approach depends on the patient’s preferences, age, and risk factors for adverse outcomes with invasive procedures.

The more definitive approach is to proceed with endoscopic ultrasonography (EUS) to look for missed stones or sludge and, if the EUS is negative, obtain samples of bile for bile microscopy to evaluate for microlithiasis. However, some centers recommend cholecystokinin-stimulated cholescintigraphy before an EUS with bile sampling. Cholescintigraphy is more widely available and less invasive. A positive result (low gallbladder ejection fraction) suggests functional gallbladder disorder, though it may also be seen in the setting of microlithiasis or sludge and microcrystals that are interfering with bile ejection through the cystic duct. Differentiating between the two entities is typically not required since both conditions are treated with cholecystectomy. If the cholescintigraphy is normal, EUS can then be pursued. (See “Functional gallbladder disorder in adults”, section on ‘CCK-stimulated cholescintigraphy’ .)

If medical dissolution therapy with oral bile acids is being considered, EUS with bile collection for microscopy should be done first to confirm the presence of microlithiasis or sludge. Many patients with microlithiasis will respond to a one- to two-year course of oral bile acid therapy. (See “Dissolution therapy for the treatment of gallstones”, section on ‘Bile acid therapy’ .)

Repeat transabdominal ultrasound  — Repeating the transabdominal ultrasound increases the sensitivity for detecting stones, particularly if they are smaller than 3 mm in diameter. A repeat examination should pay particular attention to regions of the gallbladder where stones are easily overlooked [ 34]. Patients with a negative repeat transabdominal ultrasound may still have microlithiasis or small stones that were missed. EUS and bile microscopy may identify missed stones or microlithiasis. These tests also both include an upper endoscopy, which also helps to exclude other conditions, such as peptic ulcer disease. If no stones are seen with EUS and bile microscopy, other disorders in the differential diagnosis of biliary colic (eg, sphincter of Oddi dysfunction or functional gallbladder disorder) should be considered. (See ‘Differential diagnosis’ below.)

It is important to thoroughly evaluate category 4 patients who have biliary colic but negative transabdominal ultrasounds because patients with missed stones or microlithiasis will typically respond to cholecystectomy. However, patients with other diagnoses, such as sphincter of Oddi dysfunction, peptic ulcer disease, dyspepsia, or irritable bowel syndrome, may not improve or may even worsen following cholecystectomy. (See “Clinical manifestations and diagnosis of sphincter of Oddi dysfunction” and “Approach to the patient with dyspepsia” and “Clinical manifestations and diagnosis of irritable bowel syndrome” and “Functional gallbladder disorder in adults” .)

Endoscopic ultrasound  — Imaging of the gallbladder can be obtained by EUS. During EUS, an ultrasound transducer on the tip of an endoscope is placed into contact with the gastric antrum, which is in close proximity to the gallbladder. This permits gallbladder visualization without interference from bowel gas, subcutaneous tissue, or the liver. As a result, EUS is more sensitive than transabdominal ultrasound for the detection of gallstones, particularly in patients who are obese or have other anatomic considerations that limit gallbladder visualization with transabdominal ultrasound [ 35,36 ].

Several studies have demonstrated that EUS is useful for the detection of small stones and microlithiasis [ 35-38 ]. In one study of 45 patients in whom there was a clinical suspicion of cholelithiasis but with at least two normal transabdominal ultrasound examinations, EUS detected evidence of cholelithiasis in 26 patients (58 percent). The sensitivity and specificity of EUS for detecting cholelithiasis were 96 and 86 percent, respectively [ 35 ].

In a second study of 89 patients with acute pancreatitis, EUS revealed small gallbladder stones (1 to 9 mm) in 14 of 18 patients who had otherwise negative standard imaging studies, including transabdominal ultrasound [ 36 ]. Subsequent endoscopic retrograde cholangiopancreatography (ERCP) and cholecystectomy confirmed the presence of stones in all 14 patients. None of the remaining four patients developed evidence of cholelithiasis during a median follow-up of 22 months.

Bile microscopy  — Bile microscopy detects microcrystals of cholesterol or amorphous bilirubinate as indirect evidence for the presence of microlithiasis in the bile. It has an overall sensitivity of 65 to 90 percent for identifying patients with gallstones [ 38-42 ]. Because of the improved sensitivity of transabdominal ultrasonography for detection of small stones and sludge, there is less need for microcrystal analysis. However, it still has a role in category 4 patients with biliary colic without gallstones on transabdominal ultrasound. However, because obtaining a sample for bile microscopy during endoscopy can take over 45 minutes, we reserve the procedure for patients with a negative EUS.

The test is based upon the theory that patients with cholesterol microlithiasis have bile that is supersaturated with cholesterol and thus have cholesterol monohydrate crystals in their gallbladder bile ( picture 1 ), while those with bilirubinate microlithiasis have amorphous reddish-brown bilirubinate granules in their gallbladders ( picture 2 ) [ 43,44 ]. However, the methods for performing the test have not been well standardized, which has led to confusion regarding how to collect and process the bile samples for analysis and what constitutes a positive test.

The proportion of patients with suspected gallstones but negative transabdominal ultrasound found to have microlithiasis varies substantially among reports. A systematic review found that microcrystals accounted for 7 to 79 percent of cases of idiopathic pancreatitis, 83 percent of patients with unexplained biliary-type pain, and 25 to 60 percent of patients with altered biliary and pancreatic sphincter function [ 45 ].

While the presence of any cholesterol crystals is theoretically abnormal, to increase specificity, some of the newer reports presume the test to be positive only if more than three crystals are seen per high power field [ 46 ]. However, whether findings based upon this approach correlate with clinical outcomes has not been established. As a result, this presumption has not been widely accepted.

Bile collection  — Most available studies describe the test as it pertains to the detection of microlithiasis in patients with idiopathic recurrent pancreatitis and have used variable techniques for bile collection, bile processing, and microscopic crystal analysis. Nevertheless, most investigators agree that crystals are formed in the gallbladder where bile is concentrated, so gallbladder bile rather than hepatic bile should be analyzed [ 23,39,47 ]. Hepatic bile is significantly less concentrated and thus has a lower yield for the detection of microlithiasis.

Gallbladder bile can be collected using the following techniques:

  • Through direct percutaneous puncture of the gallbladder under ultrasound or fluoroscopic guidance
  • During endoscopic retrograde cholangiopancreatography, either through selective gallbladder cannulation or by aspirating bile from the common bile duct after stimulating gallbladder contraction with a slow intravenous infusion of the cholecystokinin (CCK) analogue, sincalide
  • During endoscopy by suctioning bile from the duodenum in the region of the ampulla after gallbladder stimulation with sincalide

In most cases, collection during endoscopy is the simplest and most practical method. Since EUS includes an endoscopic examination, bile collection can be performed during the same session as an EUS, which increases the sensitivity for detecting gallstones over that of EUS alone [ 35,37 ]. (See ‘Endoscopic ultrasound’ above.)

Our approach in patients with biliary colic and a negative EUS is to collect a bile sample during the same endoscopic session as the EUS. Sincalide (0.03mcg/kg body weight) is given by intravenous drip over 45 minutes; the longer infusion is safer and more effective than a short bolus technique [ 48 ]. The tip of the endoscope is positioned next to the ampulla and the bile is aspirated. Bile flow usually starts to accelerate within five minutes of the start of the sincalide infusion. The first 5 to 10 minutes of bile flow is normally light in color and represents common bile duct and hepatic bile. Gallbladder bile is the darker bile that starts flowing several minutes later. We use a commercially available bile collecting catheter with a mushroom tip that we introduce through the working channel of the endoscope and connect to an external suction trap. Once we start to observe dark gallbladder bile being suctioned into the collecting trap, we empty the light colored bile from the trap and begin collecting the dark bile sample. When about 10 to 20 mL of bile has been collected, we stop the Sincalide infusion and conclude the procedure. This typically takes about 30 to 45 minutes from the start of the sincalide infusion to accomplish.

The darker bile is collected in a separate collecting tube and is incubated at 37 degrees C for 24 hours, then centrifuged at 3000 G for 30 minutes [ 49 ]. The supernatant is discarded and the sediment is mixed into the liquid remaining at the bottom of the tube. A drop of that liquid is placed on a slide and examined using a polarizing microscope; a polarizing filter facilitates identification of cholesterol crystals, which exhibit birefringence (they shine against the dark background of the polarizing microscope). The test is considered positive if any cholesterol crystals or amorphous red-brick colored bilirubinate granules are seen.

Tests that are rarely done

Oral cholecystography  — Oral cholecystography can diagnose gallstones and assess gallbladder function, but it has largely been replaced by more sensitive and specific tests, such as transabdominal ultrasound [ 28,50 ]. It is still occasionally used in patients in whom a high quality ultrasound examination cannot be obtained (such as in obese patients), to confirm the presence of adenomyomatosis of the gallbladder, and to evaluate patients who are being considered for medical dissolution therapy with ursodeoxycholic acid , in whom it is important to demonstrate stone number and size, relative density of the stones to bile, cystic duct patency, and the gallbladder’s concentrating ability. (See “Patient selection for the nonsurgical treatment of gallstone disease” .)

An orally administered contrast agent (eg, iopanoic acid, sodium tyropanoate, or calcium ipodate) is given and is absorbed through the intestine, taken up by the liver, and secreted into bile. Gallstones appear as filling defects within the contrast on plain x-rays ( image 3 ). Non-opacification of the gallbladder can occur due to poor absorption from the intestine, impaired liver function, or extrahepatic biliary obstruction. With the currently available oral contrast agents, it is unlikely that the gallbladder will be visualized if the serum bilirubin is greater than 2 to 3 mg/dL.

An approximation of gallbladder motor function can also be obtained using oral cholecystography. The patient is given a fatty meal and serial x-rays are obtained. If the gallbladder is functioning normally, there will be a decrease in gallbladder size over time. Evaluation of the gallbladder motor function is not recommended in patients who have known gallbladder stones since it may induce biliary colic or complications of gallstone disease.

DIFFERENTIAL DIAGNOSIS  — Many of the symptoms seen with uncomplicated gallstone disease may also be seen with other disorders or in patients who have developed complications from their gallstones. Hence, it is important to consider alternative diagnoses prior to making a diagnosis of uncomplicated gallstone disease.

Upper abdominal symptoms  — Gallstone disease is usually considered as part of the differential diagnosis of patients presenting with upper abdominal symptoms. Other disorders in the differential diagnosis include:

  • Esophageal chest pain
  • Gastroesophageal reflux disease
  • Peptic ulcer disease
  • Nonulcer dyspepsia
  • Hepatitis
  • Functional gallbladder disorder
  • Sphincter of Oddi dysfunction
  • Chronic pancreatitis
  • Irritable bowel syndrome
  • Ischemic heart disease
  • Pyelonephritis
  • Ureteral calculi
  • Complications of gallstone disease: acute cholecystitis, choledocholithiasis, acute pancreatitis, and acute cholangitis

It is important to remember that many of these diagnoses, such as irritable bowel syndrome, are common in the general population and thus may coexist with, but be unrelated to, gallstones. Because of this, an extensive search for gallstones in patients with nonspecific or atypical symptoms is discouraged. A general approach to the evaluation of patients with abdominal pain is discussed in detail elsewhere. (See “Diagnostic approach to abdominal pain in adults”and “Differential diagnosis of abdominal pain in adults” .)

An important feature for differentiating uncomplicated gallstone disease from non-biliary disorders is the presence of biliary colic, which has been shown to be predictive of the presence of gallstones on imaging [ 51,52 ]. However, biliary colic may be present in patients with other biliary disorders, such as acute cholecystitis, choledocholithiasis, sphincter of Oddi dysfunction, and functional gallbladder disorder. (See ‘Other disorders with biliary-type pain’below.)

Laboratory studies can be helpful for excluding other diagnoses and detecting complications of gallstone disease. The choice and order of testing varies depending upon the clinical presentation and suspicion for a particular diagnosis. Some commonly obtained tests include:

  • Liver biochemical tests (serum aminotransferases, total bilirubin, alkaline phosphatase), which may be abnormal in patients with hepatitis, biliary tract obstruction, or (less often) acute cholecystitis (see “Approach to the patient with abnormal liver biochemical and function tests” )
  • Serum amylase and lipase, which are elevated in acute pancreatitis
  • Complete blood count, which may show an elevated white blood cell count in patients with acute cholecystitis or acute cholangitis
  • Urine analysis, which may show evidence of a urinary tract infection or ureteral calculi

Other tests that may be indicated depending upon the patient’s symptoms and history include:

  • Upper endoscopy to look for peptic ulcer disease
  • Endoscopic ultrasonography to look for chronic pancreatitis
  • Endoscopic retrograde cholangiopancreatography (ERCP) with sphincter of Oddi manometry to look for sphincter of Oddi dysfunction
  • Cholescintigraphy with or without cholecystokinin (CCK)-stimulation to look for acute cholecystitis and functional gallbladder disorder, respectively
  • Testing for ischemic heart disease
  • Esophageal manometry to look for esophageal sources of chest pain, such as esophageal spasm

Other disorders with biliary-type pain  — Patients with acute cholecystitis, choledocholithiasis, sphincter of Oddi dysfunction, and functional gallbladder disorder may all present with biliary colic. Acute cholecystitis and choledocholithiasis typically present acutely and patients often seek urgent medical attention. Sphincter of Oddi dysfunction and functional gallbladder disorder, on the other hand, may occur intermittently and may not be severe enough to prompt the patient to seek urgent evaluation.

Acute cholecystitis  — Acute cholecystitis is the most common complication of gallstone disease and needs to be differentiated from uncomplicated gallstone disease in patients presenting with biliary colic. An episode of prolonged right upper quadrant pain (greater than four to six hours), especially if associated with fever, should arouse suspicion for acute cholecystitis as opposed to an attack of simple biliary colic. (See “Pathogenesis, clinical features, and diagnosis of acute cholecystitis” .)

Physical examination can help differentiate uncomplicated gallstone disease from acute cholecystitis. While biliary colic is present in both uncomplicated gallstone disease and in acute cholecystitis, the pain in uncomplicated gallstone disease is entirely visceral in origin since the gallbladder wall is not inflamed. Thus, it is less well localized and patients do not exhibit a positive Murphy’s sign on physical examination. A Murphy’s sign is elicited by palpating the area of the gallbladder fossa just beneath the liver edge while the patient is asked to inspire deeply, causing the gallbladder to descend toward the examining fingers. Patients with acute cholecystitis commonly experience increased discomfort and may have an associated inspiratory arrest (a positive Murphy’s sign). (See “Pathogenesis, clinical features, and diagnosis of acute cholecystitis” .)

Laboratory tests should be normal in patients with uncomplicated gallstone disease. On the other hand, patients with acute cholecystitis may have a leukocytosis and mild elevations in serum aminotransferases, bilirubin, and amylase. Transabdominal ultrasound findings that are not seen in patients with uncomplicated gallstone disease but that may be present with acute cholecystitis include gallbladder wall thickening or edema and a “sonographic Murphy’s sign” in which pain is reproduced when the gallbladder is compressed by the ultrasound probe under direct ultrasonic visualization. Cholescintigraphy (99mTc-heapto-iminodiacetic acid [HIDA] scanning) is not used in the diagnosis of gallstones, but is useful in excluding acute cholecystitis in patients who present with acute biliary colic. (See “Pathogenesis, clinical features, and diagnosis of acute cholecystitis”, section on ‘Diagnosis’ .)

A detailed discussion of the approach to patients with suspected acute cholecystitis is presented elsewhere. (See “Pathogenesis, clinical features, and diagnosis of acute cholecystitis” and “Treatment of acute cholecystitis” .)

Choledocholithiasis  — Patients with a stone in the common bile duct (choledocholithiasis) may have typical biliary colic. However, the pain is usually more prolonged than is seen with uncomplicated gallstone disease. Serum aminotransferases are normal with uncomplicated gallstone disease but are typically elevated early in the course of biliary obstruction. If the stone is not passed, a cholestatic pattern develops (increased bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase out of proportion to the elevation in the aminotransferases). Patients who have developed acute cholangitis may also present with fever, leukocytosis, hypotension, or mental status changes. (See “Approach to the patient with suspected choledocholithiasis”, section on ‘Laboratory evaluation’ and “Acute cholangitis”, section on ‘Clinical manifestations’ .)

Transabdominal ultrasound may reveal a stone in the common bile duct, but the sensitivity is poor for stones in the distal common bile duct. A dilated common bile duct supports a diagnosis of choledocholithiasis, but is not specific. Magnetic resonance cholangiopancreatography, endoscopic ultrasound, or ERCP may be required to confirm the diagnosis, and in the case of ERCP, provide therapy. (See “Approach to the patient with suspected choledocholithiasis”, section on ‘Imaging tests’ .)

The approach to the diagnosis and management of patients with choledocholithiasis is discussed in detail elsewhere. (See “Approach to the patient with suspected choledocholithiasis” .)

Sphincter of Oddi dysfunction  — The term sphincter of Oddi dysfunction (SOD) has been used to describe a clinical syndrome of biliary or pancreatic obstruction related to mechanical or functional abnormalities of the sphincter of Oddi. Patients with SOD may have biliary colic that lasts from about 30 minutes to several hours. Unlike patients with uncomplicated gallstone disease, patients with SOD may have elevations in their aminotransferases, alkaline phosphatase, amylase, or lipase. In addition, the common bile duct may appear dilated on transabdominal ultrasound. In some cases, sphincter of Oddi manometry may be required to confirm the diagnosis of SOD.

The approach to patients with suspected Sphincter of Oddi is discussed in detail elsewhere. (See “Clinical manifestations and diagnosis of sphincter of Oddi dysfunction” and “Treatment of sphincter of Oddi dysfunction” .)

Functional gallbladder disorder  — Functional gallbladder disorder is a diagnosis of exclusion. Patients with functional gallbladder disorder have biliary colic, but do not have gallstones, sludge, or microlithiasis. To differentiate functional gallbladder disorder from uncomplicated gallstone disease, patients must have a thorough evaluation for gallstones and other disorders that may cause upper abdominal symptoms. If this testing is negative, patients then undergo CCK-stimulated cholescintigraphy to determine the gallbladder ejection fraction, which is low in patients with functional gallbladder disorder. (See “Functional gallbladder disorder in adults”, section on ‘CCK-stimulated cholescintigraphy’ .)

Functional gallbladder disorder is discussed in detail elsewhere. (See “Functional gallbladder disorder in adults” .)

MANAGEMENT  — The approach to the management of patients with gallstones depends upon the patient’s symptoms, imaging test findings, and whether complications are present. In general, patients with sludge or microlithiasis are managed the same as patients with gallstones. Most asymptomatic patients are followed expectantly, whereas patients with recurrent severe symptoms are treated with pain control and cholecystectomy. The management of patients with atypical or mild symptoms and gallstones or with typical biliary colic but no gallstones is more complicated and may include empiric treatments for other disorders or, in appropriately selected patients, cholecystectomy.

We have found it useful to divide patients into four categories to help guide management:

  • Category 1: Patients with gallstones but no symptoms
  • Category 2: Patients with typical biliary symptoms and gallstones
  • Category 3: Patients with gallstones but atypical symptoms
  • Category 4: Patients with typical biliary symptoms but without gallstones on ultrasound

The management of patients with complications due to gallstones is discussed separately. (See “Treatment of acute cholecystitis” and “Approach to the patient with suspected choledocholithiasis”, section on ‘Approach to diagnosis and management’ and “Treatment of acute pancreatitis” and “Acute cholangitis” and “Gallstone ileus”, section on ‘Treatment’ and “Mirizzi syndrome”, section on ‘Treatment’ and “Surgical management of gallbladder cancer”and “Adjuvant treatment for localized, potentially resectable gallbladder cancer” and “Treatment of advanced, unresectable gallbladder cancer” .)

Category 1 patients (gallstones but no symptoms)  — Most patients who are asymptomatic but found to have incidental gallstones on an imaging test do not require treatment since the risk of developing life-threatening, severe complications is low. This recommendation is based upon studies showing that the rate of progression from asymptomatic to symptomatic gallstones is very low (about 1 percent per year). In addition, when patients do become symptomatic, the initial presenting symptoms are usually not severe, allowing for cholecystectomy at that time. As a result, most patients with incidental gallstones can be educated about potentially concerning symptoms, so they may seek medical attention before severe complications arise. (See “Approach to the patient with incidental gallstones” .)

However, some patients may be at increased risk for complications or cancer, and in such patients prophylactic cholecystectomy may be warranted. (See”Approach to the patient with incidental gallstones”, section on ‘Patients at increased risk of complications’ .)

Some data suggest that physical activity may reduce the risk of developing symptomatic gallstone disease. In a study of more than 60,000 women, women who were seated for less than six hours per week were less likely to undergo cholecystectomy compared with those who sat for 41 to 60 hours or more than 60 hours (relative risks 1.4 and 2.3, respectively) [ 53 ]. In a second study, there was a three-fold increase in gallstone disease among men who watched television for more than 40 hours per week compared with those who watched for less than six hours per week [ 54 ].

Category 2 patients (typical biliary symptoms and gallstones)  — In patients with a classic presentation of uncomplicated gallstone disease there are two general considerations when it comes to management:

  • Acute management of biliary colic.
  • Prophylactic treatment: In contrast to patients with incidental gallstones, prophylactic treatment to remove the offending stones (typically by cholecystectomy) is recommended for patients with gallstone disease, both to prevent future attacks of biliary colic and to prevent the complications of gallstone disease. Whether to perform prophylactic cholecystectomy in patients with mild symptoms depends upon factors such as the patient’s age, comorbid illnesses, and the frequency of attacks. (See ‘Natural history’ above.)

Pain management  — During an acute attack of biliary colic, management is focused on pain control. Pain control can usually be achieved with nonsteroidal antiinflammatory drugs (NSAIDs) or opioids. Those with prolonged attacks (especially if accompanied by vomiting) should also receive intravenous hydration.

We prefer ketorolac (30 to 60 mg adjusted for age and renal function given in a single intravenous or intramuscular dose) for patients who present to the emergency department with biliary colic. Treatment usually relieves symptoms within 10 to 30 minutes. Patients are then prescribed ibuprofen 400 mg orally for subsequent attacks that may occur while the patient is awaiting cholecystectomy. We reserve opioids for patients who have contraindications to NSAIDs or who do not achieve adequate pain relief with an NSAID.

The role for NSAIDs in the treatment of biliary colic was demonstrated in a meta-analysis of 11 randomized trials with 1076 patients that compared NSAIDs with no treatment, placebo, or other treatments [ 55 ]. NSAIDs were more likely to control pain than placebo (relative risk [RR] 3.8; 95% confidence interval [CI] 1.7-8.6) or antispasmodics (RR 1.5; 95% CI 1.0-2.1). In addition, there was no difference in pain control between NSAIDs and opioids (RR 1.1; 95% CI 0.8-1.3). NSAIDs may also favorably alter the natural history of biliary colic, possibly due to the role of prostaglandins in the development of acute