Gallbladder Stone
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A gallstone is a
stone In geology, rock (or stone) is any naturally occurring solid mass or aggregate of minerals or mineraloid matter. It is categorized by the minerals included, its Chemical compound, chemical composition, and the way in which it is formed. Rocks ...
formed within the
gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow Organ (anatomy), organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath t ...
from
precipitated In an aqueous solution, precipitation is the "sedimentation of a solid material (a precipitate) from a liquid solution". The solid formed is called the precipitate. In case of an inorganic chemical reaction leading to precipitation, the chemic ...
bile Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...
components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and
choledocholithiasis Common bile duct stone, also known as choledocholithiasis, is the presence of gallstones in the common bile duct (CBD) (thus '' choledocho-'' + '' lithiasis''). This condition can cause jaundice and liver cell damage. Treatments include choledocho ...
refers to the presence of migrated gallstones within
bile duct A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. The bile duct is separated into three main parts: the fundus (superior), the body (middle), and the neck (inferior). Bile is requ ...
s. Most people with gallstones (about 80%) are asymptomatic. However, when a gallstone obstructs the bile duct and causes acute
cholestasis Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are: * obstructive type of cholestasis, where there is a mechanical blockage in the duct system that can occur from a gallston ...
, a
reflex In biology, a reflex, or reflex action, is an involuntary, unplanned sequence or action and nearly instantaneous response to a stimulus. Reflexes are found with varying levels of complexity in organisms with a nervous system. A reflex occurs ...
ive
smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...
spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ, such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a musc ...
often occurs, resulting in an intense
cramp A cramp is a sudden, involuntary, painful skeletal muscle contraction or overshortening associated with electrical activity. While generally temporary and non-damaging, they can cause significant pain and a paralysis-like immobility of the aff ...
-like
visceral pain Visceral pain is defined as pain that results from the activation of nociceptors of the thoracic, pelvic, or abdominal viscera (organs) in the human body. Visceral structures are highly sensitive to distension (stretch), ischemia and inflammation, ...
in the right upper part of the
abdomen The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...
known as a
biliary colic Biliary colic, also known as symptomatic cholelithiasis, a gallbladder attack or gallstone attack, is when a colic (sudden pain) occurs due to a gallstone temporarily blocking the cystic duct. Typically, the pain is in the right upper part of t ...
(or "gallbladder attack"). This happens in 1–4% of those with gallstones each year. Complications from gallstones may include inflammation of the gallbladder (
cholecystitis Cholecystitis is inflammation of the gallbladder. Symptoms include Right upper quadrant (abdomen), right upper abdominal pain, pain in the right shoulder, nausea, vomiting, and occasionally fever. Often gallbladder attacks (biliary colic) precede ...
), inflammation of the
pancreas The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...
(
pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormone A hormone (from the Ancient Greek, Greek participle , "se ...
),
obstructive jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
, and infection in bile ducts ( cholangitis). Symptoms of these complications may include pain that lasts longer than five hours,
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
, yellowish skin, vomiting, dark
urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
, and pale stools. Risk factors for gallstones include
birth control pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. It is the oral form of combined hormonal contra ...
s,
pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...
, a
family history Genealogy () is the study of families, family history, and the tracing of their lineages. Genealogists use oral interviews, historical records, genetic analysis, and other records to obtain information about a family and to demonstrate kins ...
of gallstones,
obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
,
diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
,
liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...
, or rapid weight loss. The bile components that form gallstones include
cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...
,
bile salts Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...
, and
bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...
. Gallstones formed mainly from cholesterol are termed ''cholesterol stones'', and those formed mainly from bilirubin are termed ''pigment stones''. Gallstones may be suspected based on symptoms. Diagnosis is then typically confirmed by
ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...
. Complications may be detected using blood tests. The risk of gallstones may be decreased by maintaining a healthy weight with exercise and a
healthy diet A healthy diet is a diet that maintains or improves overall health. A healthy diet provides the body with essential nutrition: fluid, macronutrients such as protein, micronutrients such as vitamins, and adequate fibre and food energy. A he ...
. If there are no symptoms, treatment is usually not needed. In those who are having gallbladder attacks, surgery to remove the gallbladder is typically recommended. This can be carried out either through several small incisions or through a single larger incision, usually under
general anesthesia General anaesthesia (UK) or general anesthesia (US) is medically induced loss of consciousness that renders a patient unarousable even by painful stimuli. It is achieved through medications, which can be injected or inhaled, often with an analgesi ...
. In rare cases when surgery is not possible, medication can be used to dissolve the stones or
lithotripsy Lithotripsy is a procedure involving the physical destruction of hardened masses like kidney stones, bezoars or gallstones, which may be done non-invasively. The term is derived from the Greek words meaning "breaking (or pulverizing) stones" ( lit ...
can be used to break them down. In
developed countries A developed country, or advanced country, is a sovereign state that has a high quality of life, developed economy, and advanced technological infrastructure relative to other less industrialized nations. Most commonly, the criteria for eval ...
, 10–15% of adults experience gallstones. Gallbladder and biliary-related diseases occurred in about 104 million people (1.6% of people) in 2013 and resulted in 106,000 deaths. Gallstones are more common among women than men and occur more commonly after the age of 40. Gallstones occur more frequently among certain ethnic groups than others. For example, 48% of Native Americans experience gallstones, whereas gallstone rates in many parts of Africa are as low as 3%. Once the gallbladder is removed, outcomes are generally positive.


Definition

Gallstone disease refers to the condition where gallstones are either in the gallbladder or common bile duct. The presence of stones in the gallbladder is referred to as ''cholelithiasis'', from the Greek (, 'bile') + (, 'stone') + (, 'process'). The presence of gallstones in the
common bile duct The common bile duct (also bile duct) is a part of the biliary tract. It is formed by the union of the common hepatic duct and cystic duct. It ends by uniting with the pancreatic duct to form the ampulla of Vater (hepatopancreatic ampulla). ...
is called ''
choledocholithiasis Common bile duct stone, also known as choledocholithiasis, is the presence of gallstones in the common bile duct (CBD) (thus '' choledocho-'' + '' lithiasis''). This condition can cause jaundice and liver cell damage. Treatments include choledocho ...
'', from the Greek (, 'bile-containing', from + , 'duct') + + . Choledocholithiasis is frequently associated with obstruction of the bile ducts, which can lead to '' cholangitis'', from the Greek: + (, 'vessel') + (, 'inflammation'), a serious infection of the bile ducts. Gallstones within the
ampulla of Vater The ampulla of Vater, hepatopancreatic ampulla or hepatopancreatic duct is the common duct that is usually formed by a union of the common bile duct and the pancreatic duct within the wall of the duodenum. This common duct usually features a di ...
can obstruct the
exocrine Exocrine glands are glands that secrete substances onto an epithelial surface by way of a duct. Examples of exocrine glands include sweat, salivary, mammary, ceruminous, lacrimal, sebaceous, prostate and mucous. Exocrine glands are one of t ...
system of the
pancreas The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...
and can result in
pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormone A hormone (from the Ancient Greek, Greek participle , "se ...
.


Signs and symptoms

Gallstones, regardless of size or number, are asymptomatic in 60–80% of patients. These "silent stones" do not require treatment and can remain asymptomatic even years after they form.


Biliary colic

Biliary
colic Colic or cholic () is a form of pain that starts and stops abruptly. It occurs due to muscular contractions of a hollow tube (small and large intestine, gall bladder, ureter, etc.) in an attempt to relieve an obstruction by forcing content ou ...
, also known as symptomatic cholelithiasis, is what patients consider to be a " gallstone attack". These attacks occur when a gallstone blocks the opening to the cystic duct or the cystic duct itself, increasing the pressure inside the gallbladder as it contracts, which leads to pain. Patients typically experience sudden, severe pain in the right upper side of their abdomen or in the
epigastric In anatomy, the epigastrium (or epigastric region) is the upper central region of the abdomen. It is located between the costal margins and the subcostal plane. Pain may be referred to the epigastrium from damage to structures derived from the fo ...
area (the upper, center part of the abdomen). This pain typically peaks approximately 1 hour after the onset and usually subsides completely within 5 hours. Sometimes, the pain may be referred to the right shoulder; this is called "Collin's sign". Patients may also experience nausea and vomiting. These attacks often occur after eating a fatty meal or at night. Of note, laboratory studies of AST, ALT, alkaline phosphatase, direct
bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...
, amylase, lipase, and
white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
count are normal.


Complications


Acute cholecystitis

Acute cholecystitis, or inflammation of the gallbladder, is caused by gallstones in 90–95% of cases. It presents very similarly to biliary colic: a sudden onset of severe pain in the right upper side of the abdomen or epigastric area. However, this pain differs from a gallstone attack because it lasts more than 6 hours and does not subside like a normal attack would. In addition, patients also experience fever, decreased appetite, nausea, and vomiting. On physical exam, the patient can have an increased temperature,
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...
(fast heart rate greater than 100 beats per minute), tenderness in the right upper quadrant (RUQ) of the abdomen, and a positive
Murphy's sign In medicine, Murphy's sign (also known as Sweeney’s sign) is a maneuver during a physical examination as part of the abdominal examination. It is useful for differentiating pain in the right upper quadrant. Typically, it is positive in cholec ...
. Murphy's sign, which is specific for acute cholecystitis, is the sudden stoppage of inspiration when deep pressure is applied to the RUQ. Laboratory studies typically show a moderately increased white blood cell count and normal to slightly elevated AST, ALT, alkaline phosphatase, and direct bilirubin.


Choledocholithiasis

Choledocholithiasis Common bile duct stone, also known as choledocholithiasis, is the presence of gallstones in the common bile duct (CBD) (thus '' choledocho-'' + '' lithiasis''). This condition can cause jaundice and liver cell damage. Treatments include choledocho ...
refers to a gallstone obstructing the
common bile duct The common bile duct (also bile duct) is a part of the biliary tract. It is formed by the union of the common hepatic duct and cystic duct. It ends by uniting with the pancreatic duct to form the ampulla of Vater (hepatopancreatic ampulla). ...
. Patients typically experience right upper quadrant pain, back pain,
jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
(or yellowing of the skin), decreased appetite, nausea, vomiting, and fever. However, choledocholithiasis, just like gallstones, can also be asymptomatic. If the patient has symptoms, the physical exam is similar to that of acute cholecystitis. Laboratory studies show an increase in direct (conjugated) bilirubin, gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase. AST and ALT can be elevated or normal.


Ascending cholangitis

Ascending cholangitis Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct, usually caused by bacteria ascending from Ampulla of Vater, its junction with the duodenum (first part of the small intestine). It ten ...
is a complication of choledocholithiasis. When a gallstone obstructs the common bile duct, inflammation and infection of the biliary tree can occur. Approximately 2/3 of patients present with the classic Charcot's triad: jaundice, fever or chills, and right upper quadrant pain. This can progress to septic shock, which presents as Reynold's pentad (Charcot's triad plus hypotension and altered mental status). Laboratory studies show an increase in white blood cell count, direct bilirubin, alkaline phosphatase, AST, and ALT.


Gallstone (biliary) pancreatitis

Pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormone A hormone (from the Ancient Greek, Greek participle , "se ...
is the inflammation of the pancreas. Gallstone pancreatitis occurs when a gallstone slips down the biliary tree and gets stuck in either the
pancreatic duct The pancreatic duct or duct of Wirsung (also, the major pancreatic duct due to the existence of an accessory pancreatic duct) is a duct joining the pancreas to the common bile duct. This supplies it with pancreatic juice from the exocrine pancre ...
or at the
ampulla of Vater The ampulla of Vater, hepatopancreatic ampulla or hepatopancreatic duct is the common duct that is usually formed by a union of the common bile duct and the pancreatic duct within the wall of the duodenum. This common duct usually features a di ...
. Gallstone pancreatitis presents the same as acute pancreatitis: a sudden onset of epigastric pain that moves towards the back, decrease in appetite, nausea, and vomiting. Laboratory studies will show an elevated lipase, amylase, and white blood cell count.


Gallstone ileus

Large gallstones can potentially erode through the gallbladder wall and into the neighboring small intestine. This large stone then travels through the small intestine until it is too narrow for the stone to continue, causing a
small bowel obstruction Bowel obstruction, also known as intestinal obstruction, is a mechanical or Ileus, functional obstruction of the Gastrointestinal tract#Lower gastrointestinal tract, intestines which prevents the normal movement of the products of digestion. Ei ...
. This obstruction often occurs at previous surgical sites or at the
ileocecal valve In many Animalia, including humans, an ileocolic structure or problem is something that concerns the region of the gastrointestinal tract from the ileum to the large intestine, colon. In Animalia that have cecum, ceca, the ileocecal region is a sub ...
(the portion of the bowel where the small intestine meets the large intestine). The patient presents with the inability to defecate or pass gas, nausea, vomiting, and severe abdominal pain.


Cancer

Rarely,
gallbladder cancer Gallbladder cancer is a relatively uncommon cancer, with an incidence of fewer than 2 cases per 100,000 people per year in the United States. It is particularly common in central and South America, central and eastern Europe, Japan and northern Ind ...
may occur as a complication in the setting of chronic gallstones.


Risk factors

Gallstone risk increases for females (especially before menopause) and for people near or above 40 years; the condition is more prevalent among people of European or American Indigenous descent than among other ethnicities. A lack of
melatonin Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...
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. Gilbert syndrome has been linked to an increased risk of gallstones. Researchers believe that gallstones may be caused by a combination of factors, including inherited body chemistry,
body weight Human body weight is a person's mass or weight. Strictly speaking, body weight is the measurement of mass without items located on the person. Practically though, body weight may be measured with clothes on, but without shoes or heavy accessori ...
, gallbladder
motility Motility is the ability of an organism to move independently using metabolism, metabolic energy. This biological concept encompasses movement at various levels, from whole organisms to cells and subcellular components. Motility is observed in ...
(movement), and low-calorie diet. The absence of such risk factors does not, however, preclude the formation of gallstones. Nutritional factors that may increase risk of gallstones include
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...
; eating fewer meals per day; low intake of the nutrients
folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
,
magnesium Magnesium is a chemical element; it has Symbol (chemistry), symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 ...
,
calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
, and
vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits, berries and vegetables. It is also a generic prescription medication and in some countries is sold as a non-prescription di ...
; low fluid consumption; and, at least for men, a high intake of
carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...
, a high
glycemic load The glycemic load (GL) of food is a number that estimates how much the food will raise a person's blood glucose level after it is eaten. One unit of glycemic load approximates the effect of eating one gram of glucose. Glycemic load accounts for ho ...
, and high
glycemic index The glycemic (glycaemic) index (GI; ) is a number from 0 to 100 assigned to a food, with pure glucose arbitrarily given the value of 100, which represents the relative rise in the blood glucose level two hours after consuming that food. The GI of ...
diet. Wine and whole-grained bread may decrease the risk of gallstones. Rapid weight loss increases risk of gallstones. The weight loss drug
orlistat Orlistat, sold under the brand name Xenical among others, is a medication used to treat obesity. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake. It ...
is known to increase the risk of gallstones. Cholecystokinin deficiency caused by
celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine. Patients develop intolerance to gluten, which is present in foods such as wheat, rye, spel ...
increases risk of gallstone formation, especially when diagnosis of celiac disease is delayed. Pigment gallstones are most commonly seen in the developing world. Risk factors for pigment stones include
hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonl ...
s (such as from
sickle-cell disease Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the oxygen-carrying ...
and
hereditary spherocytosis Hereditary spherocytosis (HS) is a congenital hemolytic disorder wherein a genetic genetic mutation, mutation coding for a structural membrane protein phenotype causes the red blood cells to be sphere-shaped (spherocytosis), rather than the norma ...
),
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
, and biliary tract infections. People with
erythropoietic protoporphyria Erythropoietic protoporphyria (or commonly called EPP) is a form of porphyria, which varies in severity and can be very painful. It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the ...
(EPP) are at increased risk to develop gallstones. Additionally, prolonged use of
proton pump inhibitors Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of gastric acid, stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase, H+/K+ ATPase proton pump. The body ...
has been shown to decrease gallbladder function, potentially leading to gallstone formation. Cholesterol modifying medications can affect gallstone formation.
Statin Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...
s inhibit cholesterol synthesis and there is evidence that their use may decrease the risk of getting gallstones.
Fibrate In pharmacology, the fibrates are a class of amphipathic carboxylic acids and esters. They are derivatives of fibric acid (phenoxyisobutyric acid). They are used for a range of metabolic disorders, mainly hypercholesterolemia (high choles ...
s increase cholesterol concentration in bile and their use has been associated with an increased risk of gallstones. Bile acid malabsorption may also be a risk.


Pathophysiology

Cholesterol gallstones develop when bile contains too much cholesterol and not enough
bile salts Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...
. Besides a high concentration of cholesterol, two other factors are important in causing gallstones. The first is how often and how well the gallbladder contracts; incomplete and infrequent emptying of the gallbladder may cause the bile to become overconcentrated and contribute to gallstone formation. This can be caused by high resistance to the flow of bile out of the gallbladder due to the complicated internal geometry of the cystic duct. 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 Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
, as a result of
pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...
or
hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are hormonal therap ...
, or the use of combined (estrogen-containing) forms of
hormonal contraception Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original ...
, may increase cholesterol levels in bile and also decrease gallbladder motility, resulting in gallstone formation.


Composition

The composition of gallstones is affected by age, diet and
ethnicity An ethnicity or ethnic group is a group of people with shared attributes, which they Collective consciousness, collectively believe to have, and long-term endogamy. Ethnicities share attributes like language, culture, common sets of ancestry, ...
. On the basis of their composition, gallstones can be divided into the following types: cholesterol stones, pigment stones, and mixed stones. An ideal classification system is yet to be defined.


Cholesterol stones

Cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...
stones vary from light yellow to dark green or brown or chalk white and are oval, usually solitary, between 2 and 3 cm long, each often having a tiny, dark, central spot. To be classified as such, they must be at least 80% cholesterol by weight (or 70%, according to the Japanese classification system). Between 35% and 90% of stones are cholesterol stones.


Pigment stones

Bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...
("pigment", "black pigment") stones are small, dark (often appearing black), and usually numerous. They are composed primarily of bilirubin (insoluble bilirubin pigment polymer) and
calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
(calcium phosphate)
salts In chemistry, a salt or ionic compound is a chemical compound consisting of an assembly of positively charged ions ( cations) and negatively charged ions (anions), which results in a compound with no net electric charge (electrically neutral). ...
that are found in bile. They contain less than 20% of cholesterol (or 30%, according to the Japanese classification system). Between 2% and 30% of stones are bilirubin stones.


Mixed stones

Mixed ( brown pigment stones) typically contain 20–80% cholesterol (or 30–70%, according to the Japanese classification system). Other common constituents are
calcium carbonate Calcium carbonate is a chemical compound with the chemical formula . It is a common substance found in Rock (geology), rocks as the minerals calcite and aragonite, most notably in chalk and limestone, eggshells, gastropod shells, shellfish skel ...
,
palmitate Palmitic acid (hexadecanoic acid in IUPAC nomenclature) is a fatty acid with a 16-carbon chain. It is the most common saturated fatty acid found in animals, plants and microorganisms.Gunstone, F. D., John L. Harwood, and Albert J. Dijkstra. The Li ...
phosphate, bilirubin and other bile pigments (calcium bilirubinate, calcium palmitate and
calcium stearate Calcium stearate is a carboxylate salt of calcium, classified as a calcium soap. The salt is a component of some lubricants, surfactants, as well as many foodstuffs. It is a white waxy powder. Production and occurrence Calcium stearate is produc ...
). Because of their calcium content, they are often radiographically visible. They typically arise secondary to infection of the biliary tract which results in the release of β-glucuronidase (by injured
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, bi ...
s and bacteria) which hydrolyzes bilirubin
glucuronide A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides. Glucuronidation, the conversion of chemical compounds to glucu ...
s and increases the amount of unconjugated bilirubin in bile. Between 4% and 20% of stones are mixed. Gallstones can vary in size and shape from as small as a grain of sand to as large as a golf ball. The gallbladder may contain a single large stone or many smaller ones. Pseudoliths, sometimes referred to as sludge, are thick
secretion Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...
s that may be present within the gallbladder, either alone or in conjunction with fully formed gallstones. File:Gallstones.JPG, Gallbladder opened to show small cholesterol gallstones File:Gallstone µCT.jpg, X-ray microtomograph of a gallstone File:Gallstones.jpg, The large, yellow stone is largely cholesterol, while the green-to-brown stones are mostly composed of bile pigments File:Gallenstein FRONT.OGG, CT images of gallstones File:Big Gallstone.JPG, Large gallstone File:Human gallstones 2015 G1.jpg, Numerous small gallstones made up largely of
cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...


Diagnosis

Diagnosis is typically confirmed by
abdominal ultrasound Abdominal ultrasonography (also called abdominal ultrasound imaging or abdominal sonography) is a form of medical ultrasonography (medicine, medical application of ultrasound technology) to visualise abdomen, abdominal anatomy, anatomical structu ...
. Other imaging techniques used are ERCP and MRCP. Gallstone complications may be detected on blood tests. On abdominal ultrasound, sinking gallstones usually have posterior acoustic shadowing. In floating gallstones, reverberation echoes (or comet-tail artifact) is seen instead in a clinical condition called adenomyomatosis. Another sign is wall-echo-shadow (WES) triad (or double-arc shadow) which is also characteristic of gallstones. A positive
Murphy's sign In medicine, Murphy's sign (also known as Sweeney’s sign) is a maneuver during a physical examination as part of the abdominal examination. It is useful for differentiating pain in the right upper quadrant. Typically, it is positive in cholec ...
is a common finding on
physical examination In a physical examination, medical examination, clinical examination, or medical checkup, a medical practitioner examines a patient for any possible medical signs or symptoms of a Disease, medical condition. It generally consists of a series of ...
during a gallbladder attack. File:Gallstones.PNG, A 1.9 cm gallstone impacted in the neck of the gallbladder and leading to cholecystitis as seen on
ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...
. There is 4 mm gall bladder wall thickening. File:Ultrasonography of sludge and gallstones, annotated.jpg,
Biliary sludge A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. The bile duct is separated into three main parts: the fundus (superior), the body (middle), and the neck (inferior). Bile is requ ...
and gallstones. There is borderline thickening of the gallbladder wall. File:StonesXray.PNG, Gallstones as seen on plain X-ray File:LargeGstoneMark.png, Large gallstone as seen on CT File:UOTW 8 - Ultrasound of the Week 1.webm, A normal gallbladder on ultrasound with bowel peristalsis creating the false appearance of stones


Prevention

Maintaining a healthy weight by getting sufficient exercise and eating a
healthy diet A healthy diet is a diet that maintains or improves overall health. A healthy diet provides the body with essential nutrition: fluid, macronutrients such as protein, micronutrients such as vitamins, and adequate fibre and food energy. A he ...
that is high in
fiber Fiber (spelled fibre in British English; from ) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often inco ...
may help prevent gallstone formation.
Ursodeoxycholic acid Ursodeoxycholic acid (UDCA), also known as ursodiol, is a secondary bile acid, produced in humans and most other species from metabolism by intestinal bacteria. It is synthesized in the liver in some species, and was first identified in bile o ...
(UDCA) appears to prevent formation of gallstones during weight loss. A high fat diet during weight loss also appears to prevent gallstones.


Treatment


Lithotripsy

Extracorporeal shock wave lithotripsy Extracorporeal shockwave therapy (ESWT) is a treatment using powerful acoustic pulses which is mostly used to lithotripsy, treat kidney stones and in physical therapy and orthopedics. Medical uses The most common use of extracorporeal shock ...
is a non-invasive method to manage gallstones that uses high-energy sound waves to disintegrate them first applied in January 1985. Side effects of extracorporeal shock wave lithotripsy include biliary pancreatitis and liver haematoma. The term is derived from the Greek words meaning 'breaking (or pulverizing) stones': + , ).


Surgical

Cholecystectomy Cholecystectomy is the surgical removal of the gallbladder. Cholecystectomy is a common treatment of symptomatic gallstones and other gallbladder conditions. In 2011, cholecystectomy was the eighth most common operating room procedure performed i ...
(gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. The lack of a gallbladder has no negative consequences in most people, however 10 to 15% of people develop
postcholecystectomy syndrome Postcholecystectomy syndrome (PCS) describes the presence of abdominal symptoms after a cholecystectomy (gallbladder removal). Symptoms occur in about 5 to 40 percent of patients who undergo cholecystectomy, and can be transient, persistent or li ...
, which may cause nausea, indigestion, diarrhea, and episodes of abdominal pain. There are two surgical options for cholecystectomy: * Open cholecystectomy is performed via an abdominal incision (
laparotomy A laparotomy is a surgical procedure involving a surgical incision through the abdominal wall to gain access into the abdominal cavity. It is also known as a celiotomy. Origins and history The first successful laparotomy was performed without ...
) below the lower right ribs. Recovery typically requires 3–5 days of hospitalization, with a return to normal diet a week after release and to normal activity several weeks after release. *
Laparoscopic Laparoscopy () is an operation performed in the abdomen or human pelvis, pelvis using small Surgical incision, incisions (usually 0.5–1.5 cm) with the aid of a camera. The laparoscope aids diagnosis or therapeutic interventions with a few ...
cholecystectomy, introduced in the 1980s, is performed via three to four small puncture holes for a camera and instruments. Post-operative care typically includes a same-day release or a one-night hospital stay, followed by a few days of home rest and pain medication. Perforation of the gall bladder is not uncommon—it has been reported in the range of 10% to 40%. Unretrieved gallstone spillage has been reported as 6% to 30%, but gallstones that are not retrieved rarely cause complications (0.08%–0.3%). Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy (ERS) following
endoscopic retrograde cholangiopancreatography Endoscopic retrograde cholangiopancreatography (ERCP) is a technique that combines the use of endoscopy An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior ...
(ERCP). Surgery carries risks and some people continue to experience symptoms (including pain) afterwards, for reasons that remain unclear. An alternative option is to adopt a ‘watch and wait’ strategy before operating to see if symptoms resolve. A study compared the 2 approaches for uncomplicated gallstones and after 18 months, both approaches were associated with similar levels of pain. The watch and wait approach was also less costly (more than £1000 less per patient).


Medical

The medications
ursodeoxycholic acid Ursodeoxycholic acid (UDCA), also known as ursodiol, is a secondary bile acid, produced in humans and most other species from metabolism by intestinal bacteria. It is synthesized in the liver in some species, and was first identified in bile o ...
(UDCA) and
chenodeoxycholic acid Chenodeoxycholic acid (CDCA; also known as chenodesoxycholic acid, chenocholic acid and 3α,7α-dihydroxy-5β-cholan-24-oic acid) is a bile acid. Salts of this carboxylic acid are called chenodeoxycholates. Chenodeoxycholic acid is one of the ...
(CDCA) have been used in treatment to dissolve gallstones. A 2013 meta-analysis concluded that UDCA or higher dietary fat content appeared to prevent formation of gallstones during weight loss. Medical therapy with oral bile acids has been used to treat small cholesterol stones, and for larger cholesterol gallstones when surgery is either not possible or unwanted. CDCA treatment can cause diarrhea, mild reversible hepatic injury, and a small increase in the plasma cholesterol level. UDCA may need to be taken for years.


Use in alternative medicine

Gallstones can be a valued by-product of animals butchered for meat because of their use as an
antipyretic An antipyretic (, from ''anti-'' 'against' and ' 'feverish') is a substance that reduces fever. Antipyretics cause the hypothalamus to override a prostaglandin-induced increase in temperature. The body then works to lower the temperature, which r ...
and antidote in the
traditional medicine Traditional medicine (also known as indigenous medicine or folk medicine) refers to the knowledge, skills, and practices rooted in the cultural beliefs of various societies, especially Indigenous groups, used for maintaining health and treatin ...
of some cultures, particularly
traditional Chinese medicine Traditional Chinese medicine (TCM) is an alternative medicine, alternative medical practice drawn from traditional medicine in China. A large share of its claims are pseudoscientific, with the majority of treatments having no robust evidence ...
. The most highly prized gallstones tend to be sourced from old
dairy cows Dairy cattle (also called dairy cows) are cattle bred with the ability to produce large quantities of milk, from which dairy products are made. Dairy cattle generally are of the species '' Bos taurus''. Historically, little distinction was ...
, termed
calculus bovis ''Calculus bovis'', ''niu-huang'' () or cattle gallstones are dried gallstones of cattle used in Chinese herbology. In China and Japan it has been long used to treat various diseases, including high fever, convulsion and stroke. In Asian countri ...
or ''niu-huang'' (yellow thing of cattle) in Chinese. Some slaughterhouses carefully scrutinize workers for gallstone theft.


See also

*
Mirizzi's syndrome Mirizzi's syndrome is a rare complication in which a gallstone becomes impacted in the cystic duct or neck of the gallbladder causing compression of the common hepatic duct, resulting in obstruction and jaundice. The obstructive jaundice can be ca ...
* Porcelain gallbladder


References


External links

* {{Authority control Abdominal pain Articles containing video clips Gallbladder disorders Hepatology Steatorrhea-related diseases Wikipedia emergency medicine articles ready to translate Wikipedia medicine articles ready to translate