Gallstone disease

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For patient information click here Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2] Prashanth Saddala M.B.B.S

Synonyms and related keywords: Cholecystolithiasis; choleliths; cholelithiasis; Biliary colic; Gall stones; Gallbladder calculus

Overview

Gallstones is the presence of gallstones (cholelithiasis) within the gallbladder. Gallstones are crystalline bodies formed within the body by accretion or concretion of normal or abnormal bile components. is Gallstones can occur anywhere within the biliary tree, including the gallbladder and the common bile duct. Obstruction of the common bile duct is choledocholithiasis; obstruction of the biliary tree can cause jaundice; obstruction of the outlet of the pancreatic exocrine system can cause pancreatitis. Cholelithiasis is the presence of stones in the gallbladder—chole- means "bile", lithia means "stone", and -sis means "process".

The characteristics of gallstones are various. Independent of appearance, however, gallstones from animals are valuable on the market.

Gallstones are, oddly, a valuable by-product of meat processing, fetching up to US$32 per gram in their use as a purported antipyretic and antidote in the herbal medicine of some cultures, particularly in China. The finest gallstones tend to be sourced from old dairy cows, which are called Niu-Huang (yellow thing of oxen) in Chinese. Those got from dogs, called Gou-Bao (treasure of dogs) in Chinese, are also used today. Much as in the manner of diamond mines, slaughterhouses carefully scrutinize offal department workers for gallstone theft.

Classification

Size

A gallstone's size varies and may be as small as a sand grain or as large as a golf ball. The gallbladder may develop a single, often large, stone or many smaller ones. May occur in any part of the biliary system

Content

Gallstones have different appearance, depending of their contents. On the basis of their contents, gallstones can be subdivided into the two following types:

Cholesterol stones

Cholesterol stones are usually green, but are sometimes white or yellow in color and account for about 80 percent of gallstones. They are made primarily of cholesterol.

Pigment stones

Pigment stones are small, dark stones made of bilirubin and calcium salts that are found in bile. They account for the other 20 percent of gallstones. Risk factors for pigment stones include cirrhosis, biliary tract infections, and hereditary blood cell disorders, such as sickle cell anemia and spherocytosis. Stones of mixed origin also occur.

Pathophysiology

Asymptomatic stones: 16-26% of patients develop gallstone-related symptoms in 10 years. Prophylactic cholecystectomy not indicated UNLESS increased risk of gallbladder (gb) cancer:

• Pima Indian
• calcified gb
• gb polyp >10 mm
• gallstones >2.5 cm
• Salmonella carrier

Diagrams shown below are courtesy of Wikisurgery.com

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Symptomatic stones

38-50% of patients have pain recurrence/year after 1 episode biliary colic. 1-2% of patients have complication rate/year.

Causes

Gall bladder opened to show numerous gallstones. Their brownish to greenish color suggest they are cholesterol calculi.

Progress has been made in understanding the process of gallstone formation. Researchers believe that gallstones may be caused by a combination of factors, including inherited body chemistry, body weight, gallbladder motility (movement), and perhaps diet. Additionally, people with erythropoietic protoporphyria (EPP) are at increased risk to develop gallstones.

Cholesterol gallstones develop when bile contains too much cholesterol and not enough bile salts. Besides a high concentration of cholesterol, two other factors seem to be important in causing gallstones. The first is how often and how well the gallbladder contracts; incomplete and infrequent emptying of the gallbladder may cause the bile to become overconcentrated and contribute to gallstone formation. The second factor is the presence of proteins in the liver and bile that either promote or inhibit cholesterol crystallization into gallstones.

In addition, increased levels of the hormone estrogen as a result of pregnancy, 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.

No clear relationship has been proven between diet and gallstone formation. However, low-fiber, high-cholesterol diets, and diets high in starchy foods have been suggested as contributing to gallstone formation. Other nutritional factors that may increase risk of gallstones include rapid weight loss, constipation, eating fewer meals per day, eating less fish, and low intakes of the nutrients folate, magnesium, calcium, and vitamin C. On the other hand, wine and whole grain bread may decrease the risk of gallstones.

Causes by Organ System

Cardiovascular	No underlying causes
Chemical / poisoning	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	Ceftriaxone, Clofibrate, Combined oral contraceptive pill, Hormonal contraception, Lanreotide, Pasireotide, Proton pump inhibitors, Somatostatin
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	No underlying causes
Gastroenterologic	No underlying causes
Genetic	No underlying causes
Hematologic	No underlying causes
Iatrogenic	No underlying causes
Infectious Disease	No underlying causes
Musculoskeletal / Ortho	No underlying causes
Neurologic	No underlying causes
Nutritional / Metabolic	No underlying causes
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Opthalmologic	No underlying causes
Overdose / Toxicity	Ceftriaxone, Clofibrate, Combined oral contraceptive pill, Hormonal contraception, Lanreotide, Pasireotide, Proton pump inhibitors, Somatostatin
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal / Electrolyte	No underlying causes
Rheum / Immune / Allergy	No underlying causes
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	No underlying causes

Causes in Alphabetical Order

Aging Ceftriaxone Clofibrate Clonorchiasis Combined oral contraceptive pill Crohn's disease Cystic fibrosis Diabetes Dieting Erythropoietic protoporphyria Fasting Hemochromatosis Hemoglobin E disease Hemolytic anemia Hereditary spherocytosis Hormonal contraception Hypercalcaemia

Infection in the gallbladder Lanreotide Liver cirrhosis Long term intravenous nutrition Low-fibre, high-cholesterol diets Obesity Pasireotide Pregnancy Proton pump inhibitors Rapid weight loss Sickle cell disease Somatostatin Somatostatinoma Ulcerative colitis Weight loss surgery Williams Syndrome

Risk Factors

• More common in females.
• Obesity
• Common amongst Pima Indians, North Americans and Chileans.
• Generally Japanese have the lowest incidence of stones.
• Sudden weight loss
• Prolonged fasting.
• Pregnancy
• Presence of Crohn's disease.
• Cystic fibrosis
• Diabetes,
• Liver cirrhosis
• Increasing age
• Extensive bowel resection
• Use of contraceptives and other medications like largactil, octreotide, and clofibrate

Diagnosis

History and Symptoms

Gallstones usually remain asymptomatic initially. They start developing symptoms once the stones reach a certain size (>8mm). A main symptom of gallstones is commonly referred to as a gallstone "attack", also known as biliary colic, in which a person will experience intense pain in the upper abdominal region that steadily increases for approximately thirty minutes to several hours. A victim may also encounter pain in the back, ordinarily between the shoulder blades, or pain under the right shoulder. In some cases, the pain develops in the lower region of the abdomen, nearer to the pelvis, but this is less common.

Biliary colic

Biliary colic is pain associated with irritation of the viscera secondary to cholecystitis and gallstones. Unlike renal colic, the phrase 'biliary colic' refers to the actual cholelithiasis.

Though unlike renal colic, the phrase 'biliary colic' refers to the actual cholelithiasis. Although it is frequently described as a colic, the pain is steady, starts rapidly and lasts at least 30 minutes and up to several hours. Many patients complain of right upper quadrant pain, rt flank pain, or even mid chest pain with cholelithiasis. There may be irradiation to the back and shoulders and other concomitant symptoms such as vomiting and diarrhea. Fatty foods can provoke biliary pain, but this association is relatively non-specific.

Biliary pain can be associated with objective findings (dilation of the biliary tract, elevation of plasma liver enzyme concentration, elevation of bilirubin, gamma-GT and alkaline phosphatase).

Causes

Biliary pain is most frequently caused by obstruction of the common bile duct or the cystic duct by a gallstone. However, the presence of gallstones is a frequent incidental finding and does not always necessitate treatment, in the absence of identifiable disease. Furthermore, biliary pain may be associated with functional disorders of the biliary tract, so called acalculous biliary pain, and can even be found in patients post-cholecystectomy (removal of the gallbladder), possibly as a consequence of dysfunction of the biliary tree and the sphincter of oddi.

Differential Diagnosis

• Amoebic liver abscess
• Perforated peptic ulcer
• Upper small bowel obstruction.

Complications

The more serious complication is total blockage of the bile duct which leads to jaundice, which if it is not corrected naturally or by a surgical procedure can be fatal as it causes liver damage.

The presence of gallstones can lead to infection of the gall bladder (cholecystitis) or the biliary tree (cholangitis) or acute inflammation of the pancreas (pancreatitis). Rarely, an impacted gallstone can obstruct the bowel, causing gallstone ileus (mechanical ileus).

Biliary pain in the absence of gallstones may severely impact the patient's quality of life, even in the absence of disease progression.

Presentation

This condition causes crescendos of severe pain in the right upper abdomen and sometimes through to the upper back and/or right shoulder. The pain relates to the obstruction of the passage of bile and can be associated with eating fatty foods. There is usually an inflammatory component to the pain as the characteristic colic is not completely relieved between crescendos.

Often, these attacks occur after a particularly fatty meal and almost always happen at night.

Treatment

These attacks are intensely painful, similar to that of a kidney stone attack. One way to alleviate the abdominal pain is to drink a full glass of water at the start of an attack to regulate the bile in the gallbladder, but this does not work in all cases. Another way is to take magnesium followed by a bitter liquid such as coffee or swedish bitters an hour later. Bitter flavors stimulate bile flow. A study has found lower rates of gallstones in coffee drinkers.

Pain management is an important part of treating biliary colic. Treatment is often with NSAIDs such as ketorolac (Toradol) and diclofenac (Voltaren). Hyoscine butylbromide (Buscopan) is occasionally used but is less effective than analgesics.

Other symptoms

Other symptoms include

• Jaundice
• Nausea and vomiting
• Diarrhea
• Bleeding caused by continuous vomiting
• Dehydration caused by the nausea and diarrhea.
• Abdominal bloating
• Intolerance of fatty foods
• Belching
• Indigestion.

If the above symptoms coincide with chills, lowgrade fever, yellowing of the skin or eyes, and/or clay-colored stool, a doctor should be consulted immediately.

Some people who have gallstones are asymptomatic and do not feel any pain or discomfort. These gallstones are called "silent stones" and do not affect the gallbladder or other internal organs. They do not need treatment.

Ultrasound

Test of choice

• 95% sensitivity and specificity for gallstones >2 mm diameter
• stones better visualized if patient is fasting

Other Imaging Findings

• Endoscopic Retrograde Cholangiopancreatography (ERCP): most sensitive/specific for common bile duct (CBD) stones
• Magnetic Resonance Cholangiopancreatography (MRCP): diagnostic accuracy equivalent to ERCP, but not therapeutic
• Hepatobiliary Iminodiacetic Acid (HIDA) scan: highly sensitive for acute cholecytitis

Patient #1: Gallstone on MRI

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Patient #2: A large gallstone in a patient with Autosomal dominant polycystic kidney disease

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Treatment

Nonoperative management is suboptimal (ursodiol, lithotripsy). Cholecystectomy is the therapy of choice.

Medical therapy

Cholesterol gallstones can sometimes be dissolved by oral ursodeoxycholic acid. Gallstones may recur however, once the drug is stopped. Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphinceterotomy (ERS) following endoscopic retrograde cholangiopancreatography (ERCP). A common misconception is that the use of ultrasound (Extracorporeal Shock Wave Lithotripsy) can be used to break up gallstones. Although this treatment is highly effective against kidney stones, it can only rarely be used to break up the softer and less brittle gallstones.

Surgery

Cholecystectomy (gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. Only symptomatic patients must be indicated to surgery. The lack of a gall bladder does not seem to have any negative consequences in many people. However, there is a significant proportion of the population, between 5-40%, who develop a condition called postcholecystectomy syndrome. Symptoms include gastrointestinal distress and persistent pain in the upper right abdomen.

There are two surgery options: open procedure and laparoscopic: see the cholecystectomy article for more details.

• Open cholecystectomy procedure: This involves a large incision into the abdomen (laparotomy) below the right lower ribs. A week of hospitalization, normal diet a week after release and normal activity a month after release.
• Laparoscopic cholecystectomy: 3-4 small puncture holes for camera and instruments (available since the 1980s). Typically same-day release or one night hospital stay, followed by a week of home rest and pain medication. Can resume normal diet and light activity a week after release. (Decreased energy level and minor residual pain for a month or two.) Studies have shown that this procedure is as effective as the more invasive open cholecystectomy, provided the stones are accurately located by cholangiogram prior to the procedure so that they can all be removed. The procedure also has the benefit of reducing operative complications such as bowel perforation and vascular injury.

Alternative medicine

A regimen called a "gallbladder flush" or "liver flush" is a popular remedy in alternative medicine. In this treatment, often self-administered, the patient drinks four glasses of apple cider and eats five apples per day for five days, then fasts briefly, takes magnesium, and then drinks large quantities of lemon or grapefruit juice mixed with olive oil or other oil before bed; the next morning, they painlessly pass a number of green and brown pebbles purported to be stones flushed from the biliary system. A New Zealand hospital analyzed stones from a typical gallbladder flush and found them to be composed of fatty acids similar to those in olive oil, with no detectable cholesterol or bile salts, demonstrating that they are little more than hardened olive oil. Despite the gallbladder flush, the patient still required surgical removal of multiple true gallstones. The note concluded: "The gallbladder flush may not be entirely worthless, however; there is one case report in which treatment with olive oil and lemon juice resulted in the passage of numerous gallstones, as demonstrated by ultrasound examination."

In the case mentioned, ultrasound confirmed multiple gallstones, but after waiting months for a surgical option, the patient underwent a treatment with olive oil and lemon juice resulting in the passage of four 2.5 cm by 1.25 cm stones and twenty pea-sized stones. Two years later symptoms returned, and ultrasound showed a single large gallstone; the patient chose to have this removed surgically.

External links

• Gallbladder removal - series from Nuggets Medical Encyclopedia
• "Gall Stones and Gall Bladder Surgery" Information for this article was located from the University of Florida, Medical Library in Gainesville, Florida, and researched by Richard Pressinger (M.Ed.) and Jerry Abraham (M.B.A)
• Diagram of pain radiation