LiverTheliver,hepar, is avital organpresent invertebratesand some other animals. It has a wide range of functions, includingdetoxification,protein synthesis, and production of biochemicals necessary fordigestion. The liver is necessary for survival; there is currently no way to compensate for the absence of liver function in the long term, although newliver dialysistechniques can be used in the short term.Thisorganplays a major role inmetabolismand has a number of functions in the body, includingglycogenstorage, decomposition of red blood cells,plasma proteinsynthesis,hormoneproduction, and detoxification. It lies below the diaphragm in the abdominal-pelvic region of the abdomen. It producesbile, an alkaline compound which aids indigestionvia theemulsificationoflipids. The liver's highly specializedtissuesregulate a wide variety of high-volume biochemical reactions, including the synthesis and breakdown of small and complex molecules, many of which are necessary for normal vital functions.[2]

AnatomyThe liver is a reddish brown organ with fourlobesof unequal size and shape. A human liver normally weighs 1.441.66 kg (3.23.7 lb),[3]and is a soft, pinkish-brown, triangular organ. It is both the largest internal organ (theskinbeing the largest organ overall) and the largestglandin the human body. It is located in theright upper quadrantof theabdominal cavity, resting just below thediaphragm. The liver lies to the right of the stomach and overlies thegallbladder. It is connected to two largeblood vessels, one called the hepatic artery and one called theportal vein. Thehepatic arterycarries blood from the aorta, whereas the portal vein carries blood containing digested nutrients from the entiregastrointestinal tractand also from thespleenandpancreas. These blood vessels subdivide into capillaries, which then lead to a lobule. Each lobule is made up of millions of hepatic cells which are the basic metabolic cells.Lobulesare the functional units of the liver.[edit]Cell typesTwo major types of cells populate the liver lobes: karat parenchymal and non-parenchymal cells. 80% of the liver volume is occupied by parenchymal cells commonly referred to ashepatocytes. Non-parenchymal cells constitute 40% of the total number of liver cells but only 6.5% of its volume. Sinusoidal endothelial cells,Kupffer cellsand hepatic stellate cells are some of the non-parenchymal cells that line the hepatic sinusoid.[4][edit]Blood flowThe liver gets a dual blood supply from thehepatic portal veinandhepatic arteries. Supplying approximately 75% of the liver's blood supply, the hepatic portal vein carriesvenous blooddrained from thespleen,gastrointestinal tract, and its associated organs. The hepatic arteries supplyarterial bloodto the liver, accounting for the remainder of itsblood flow. Oxygen is provided from both sources; approximately half of the liver's oxygen demand is met by the hepatic portal vein, and half is met by the hepatic arteries.[5]Blood flows through theliver sinusoidsand empties into the central vein of each lobule. Thecentral veinscoalesce into hepatic veins, which leave the liver.

The biliary treeThe termbiliary treeis derived from the arboreal branches of the bile ducts. Thebileproduced in the liver is collected inbile canaliculi, which merge to formbile ducts. Within the liver, these ducts are calledintrahepatic(within the liver) bile ducts, and once they exit the liver they are consideredextrahepatic(outside the liver). The intrahepatic ducts eventually drain into the right and lefthepatic ducts, which merge to form thecommon hepatic duct. Thecystic ductfrom thegallbladderjoins with thecommon hepatic ductto form thecommon bile duct.Bile either drains directly into theduodenumvia the common bile duct, or be temporarily stored in thegallbladdervia the cystic duct. The common bile duct and thepancreatic ductenter the second part of the duodenum together at theampulla of Vater.[edit]Surface anatomy[edit]Peritoneal ligamentsApart from a patch where it connects to thediaphragm(the so-called "bare area"), the liver is covered entirely byvisceralperitoneum, a thin, double-layeredmembranethat reducesfrictionagainst other organs. Theperitoneumfolds back on itself to form thefalciform ligamentand therightandleft triangular ligaments.These "lits" are in no way related to the trueanatomic ligamentsinjoints, and have essentially no known functional importance, but they are easily recognizable surface landmarks. An exception to this is the falciform ligament, which attaches the liver to the posterior portion of the anterior body wall.[edit]LobesTraditionalgross anatomydivided the liver into fourlobesbased on surface features. Thefalciform ligamentis visible on the front (anteriorside) of the liver. This divides the liver into aleft anatomical lobe, and aright anatomical lobe.If the liver is flipped over, to look at it from behind (thevisceralsurface), there are two additional lobes between the right and left. These are thecaudate lobe(the more superior) and thequadrate lobe(the more inferior).From behind, the lobes are divided up by theligamentum venosumandligamentum teres(anything left of these is the left lobe). Thetransverse fissure(orporta hepatis) divides thecaudatefrom thequadrate lobe, and the rightsagittal fossa, which theinferior vena cavaruns over, separates these two lobes from the right lobe.Each of the lobes is made up of lobules; a vein goes from the centre, which then joins to the hepatic vein to carry blood out from the liver.On the surface of the lobules, there are ducts, veins and arteries that carry fluids to and from them.[edit]Functional anatomyThe central area where thecommon bile duct,hepatic portal vein, andhepatic artery properenter is thehilumor "porta hepatis". The duct, vein, and artery divide into left and right branches, and the portions of the liver supplied by these branches constitute the functional left and right lobes.The functional lobes are separated by an imaginary plane (historically calledCantlie's line) joining the gallbladder fossa to the inferior vena cava. The plane separates the liver into the true right and left lobes. The middle hepatic vein also demarcates the true right and left lobes. The right lobe is further divided into ananteriorandposteriorsegment by the right hepatic vein. The left lobe is divided into themedialandlateralsegments by the left hepatic vein. The fissure for theligamentum teresalso separates the medial and lateral segments. The medial segment is also called thequadrate lobe. In the widely usedCouinaud(or "French") system, the functional lobes are further divided into a total of eight subsegments based on a transverse plane through the bifurcation of the main portal vein. Thecaudate lobeis a separate structure which receives blood flow from both the right- and left-sided vascular branches.[7][8][edit]In other animalsThe liver is found in allvertebrates, and is typically the largestvisceralorgan. Its form varies considerably in different species, and is largely determined by the shape and arrangement of the surrounding organs. Nonetheless, in most species it is divided into right and left lobes; exceptions to this general rule includesnakes, where the shape of the body necessitates a simple cigar-like form. The internal structure of the liver is broadly similar in all vertebrates.[9]An organ sometimes referred to as a liver is found associated with the digestive tract of the primitive chordateAmphioxus. However, this is an enzyme secreting gland, not a metabolic organ, and it is unclear how trulyhomologousit is to the vertebrate liver.[9][edit]PhysiologyThe various functions of the liver are carried out by the liver cells orhepatocytes. Currently, there is noartificial organor device capable of emulating all the functions of the liver. Some functions can be emulated byliver dialysis, an experimental treatment forliver failure. The liver is thought to be responsible for up to 500 separate functions, usually in combination with other systems and organs.[edit]

A CT scan in which the liver and portal vein are shown. A large part ofamino acid synthesis The liver performs several roles incarbohydrate metabolism: Gluconeogenesis(the synthesis ofglucosefrom certainamino acids,lactateorglycerol) Glycogenolysis(the breakdown ofglycogenintoglucose) Glycogenesis(the formation of glycogen from glucose)(muscle tissues can also do this) The liver is responsible for the mainstay of proteinmetabolism, synthesis as well as degradation. The liver also performs several roles inlipidmetabolism: Cholesterolsynthesis Lipogenesis, the production oftriglycerides(fats). A bulk of the lipoproteins are synthesized in the liver. The liver producescoagulation factorsI(fibrinogen),II(prothrombin),V,VII,IX,XandXI, as well asprotein C,protein Sandantithrombin. In the first trimesterfetus, the liver is the main site ofred blood cellproduction. By the 32nd week ofgestation, thebone marrowhas almost completely taken over that task. The liver produces and excretesbile(a yellowish liquid) required for emulsifying fats. Some of the bile drains directly into theduodenum, and some is stored in thegallbladder. The liver also producesinsulin-like growth factor 1(IGF-1), apolypeptideproteinhormone that plays an important role in childhood growth and continues to haveanabolic effectsin adults. The liver is a major site ofthrombopoietinproduction. Thrombopoietin is aglycoproteinhormone that regulates the production ofplateletsby thebone marrow.[edit]Breakdown The breakdown ofinsulinand otherhormones The liverglucoronidatesbilirubin, facilitating its excretion intobile. The liver breaks down or modifiestoxicsubstances (e.g., methylation) and most medicinal products in a process calleddrug metabolism. This sometimes results intoxication, when the metabolite is more toxic than its precursor. Preferably, the toxins areconjugatedto avail excretion in bile or urine. The liver convertsammoniatourea(urea cycle).[edit]Other functions The liver stores a multitude of substances, including glucose (in the form ofglycogen),vitamin A(12 years' supply),vitamin D(14 months' supply)[citation needed],vitamin B12(13 years' supply),vitamin K,iron, andcopper. The liver is responsible for immunological effectsthereticuloendothelial systemof the liver contains many immunologically active cells, acting as a 'sieve' for antigens carried to it via theportal system. The liver producesalbumin, the majorosmolarcomponent ofblood serum. The liver synthesizesangiotensinogen, a hormone that is responsible for raising theblood pressurewhen activated byrenin, an enzyme that is released when thekidneysenseslow blood pressure.[edit]Relation to medicine and pharmacologyThe oxidative capacity of the liver decreases with aging and therefore,benzodiazepines(BZDs) that require oxidation are more likely to accumulate to toxic levels. Therefore, those with shorter half-lives, such aslorazepamandoxazepamare preferred when benzodiazepines are required in regards togeriatric medicine.[edit]Diseases of the liverMain article:Liver disease

Left lobe liver tumorThe liver supports almost every organ in the body and is vital for survival. Because of its strategic location and multidimensional functions, the liver is also prone to many diseases.[10]The most common include: Infections such ashepatitis A, B, C, D, E,alcoholdamage,fatty liver,cirrhosis,cancer, drug damage (particularly byacetaminophen(paracetamol) and cancer drugs).Many diseases of the liver are accompanied byjaundicecaused by increased levels ofbilirubinin the system. The bilirubin results from the breakup of thehemoglobinof deadred blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.There are also many pediatric liver diseases includingbiliary atresia,alpha-1 antitrypsin deficiency,alagille syndrome,progressive familial intrahepatic cholestasis, andLangerhans cellhistiocytosis, to name but a few.Diseases that interfere with liver function will lead to derangement of these processes. However, the liver has a great capacity toregenerateand has a large reserve capacity. In most cases, the liver only produces symptoms after extensive damage.Liver diseases may be diagnosed byliver function tests, for example, by production ofacute phase proteins.[edit]Disease symptomsThe classic symptoms of liver damage include the following: Pale stoolsoccur whenstercobilin, a brown pigment, is absent from the stool. Stercobilin is derived from bilirubin metabolites produced in the liver. Dark urineoccurs when bilirubin mixes with urine Jaundice(yellow skin and/or whites of the eyes) This is wherebilirubindeposits in skin, causing an intenseitch. Itching is the most common complaint by people who have liver failure. Often this itch cannot be relieved by drugs. Swellingof the abdomen, ankles and feet occurs because the liver fails to makealbumin. Excessive fatigueoccurs from a generalized loss of nutrients,mineralsand vitamins. Bruisingand easy bleeding are other features of liver disease. The liver makes substances which help prevent bleeding. When liver damage occurs, these substances are no longer present and severe bleeding can occur.[11][edit]DiagnosisThe diagnosis of liver function is made byblood tests. Liver function tests can readily pinpoint the extent of liver damage. Ifinfectionis suspected, then otherserologicaltests are done. Sometimes, one may require anultrasoundor aCT scanto produce an image of the liver.Physical examination of the liver is not accurate in determining the extent of liver damage. It can only reveal presence of tenderness or the size of liver, but in all cases, some type of radiological study is required to examine it.[12][edit]Biopsy / scanDamage to the liver is sometimes determined with abiopsy, particularly when the cause of liver damage is unknown. In the 21st century they were largely replaced by high-resolution radiographic scans. The latter do not require ultrasound guidance, lab involvement, microscopic analysis, organ damage, pain, or patient sedation; and the results are available immediately on a computer screen.In a biopsy, a needle is inserted into the skin just below the rib cage and a tissue sample obtained. The tissue is sent to the laboratory, where it is analyzed under amicroscope. Sometimes, a radiologist may assist the physician performing aliver biopsyby providing ultrasound guidance.[13][edit]RegenerationThe liver is the only internal human organ capable of naturalregenerationof losttissue; as little as 25% of a liver can regenerate into a whole liver[14]. This is, however, not true regeneration but rathercompensatory growth.[15]The lobes that are removed do not regrow and the growth of the liver is a restoration of function, not original form. This contrasts with true regeneration where both original function and form are restored.This is predominantly due to thehepatocytesre-entering thecell cycle. That is, the hepatocytes go from the quiescentG0 phaseto theG1 phaseand undergo mitosis. This process is activated by thep75receptors.[16]There is also some evidence ofbipotentialstem cells, called hepatic oval cells or ovalocytes (not to be confused with oval red blood cells ofovalocytosis), which are thought to reside in thecanals of Hering. These cells can differentiate into eitherhepatocytesorcholangiocytes, the latter being the cells that line thebile ducts.Scientific and medical works about liver regeneration often refer to the GreekTitanPrometheuswho was chained to a rock in the Caucasus where, each day, his liver was devoured by an eagle, only to grow back each night. Some think the myth indicates theancient Greeksknew about the livers remarkable capacity for self-repair, though this claim has been challenged.[17][edit]Liver transplantationMain article:Liver transplantationHuman liver transplants were first performed byThomas Starzlin theUnited StatesandRoy CalneinCambridge,Englandin 1963 and 1965, respectively.Liver transplantationis the only option for those with irreversible liver failure. Most transplants are done for chronic liver diseases leading tocirrhosis, such as chronichepatitis C,alcoholism, autoimmune hepatitis, and many others. Less commonly, liver transplantation is done forfulminant hepatic failure, in which liver failure occurs over days to weeks.Liverallograftsfortransplantusually come from donors who have died from fatalbrain injury.Living donor liver transplantationis a technique in which a portion of a living person's liver is removed and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20 percent of an adult's liver (Couinaud segments 2 and 3) is needed to serve as a liver allograft for an infant or small child.More recently, adult-to-adult liver transplantation has been done using the donor's right hepatic lobe, which amounts to 60 percent of the liver. Due to the ability of the liver toregenerate, both the donor and recipient end up with normal liver function if all goes well. This procedure is more controversial, as it entails performing a much larger operation on the donor, and indeed there have been at least two donor deaths out of the first several hundred cases. A recent publication has addressed the problem of donor mortality, and at least 14 cases have been found.[18]The risk of postoperative complications (and death) is far greater in right-sided operations than that in left-sided operations.With the recent advances of noninvasive imaging, living liver donors usually have to undergo imaging examinations for liver anatomy to decide if the anatomy is feasible for donation. The evaluation is usually performed by multidetector rowcomputed tomography(MDCT) andmagnetic resonance imaging(MRI). MDCT is good in vascular anatomy and volumetry. MRI is used for biliary tree anatomy. Donors with very unusual vascular anatomy, which makes them unsuitable for donation, could be screened out to avoid unnecessary operations.

The liver is a large, meaty organ that sits on the right side of the belly. Weighing about 3 pounds, the liver is reddish-brown in color and feels rubbery to the touch. Normally you can't feel the liver, because it's protected by the rib cage.The liver has two large sections, called the right and the left lobes. The gallbladder sits under the liver, along with parts of the pancreas and intestines. The liver and these organs work together to digest, absorb, and process food.The liver's main job is to filter the blood coming from the digestive tract, before passing it to the rest of the body. The liver also detoxifies chemicals and metabolizes drugs. As it does so, the liver secretes bile that ends up back in the intestines. The liver also makes proteins important for blood clotting and other functions.Liver Conditions Hepatitis: Inflammation of the liver, usually caused by viruses like hepatitis A, B, and C. Hepatitis can have non-infectious causes too, including heavy drinking, drugs, allergic reactions, or obesity. Cirrhosis: Long-term damage to the liver from any cause can lead to permanent scarring, called cirrhosis. The liver then becomes unable to function well. Liver cancer: The most common type of liver cancer, hepatocellular carcinoma, almost always occurs after cirrhosis is present. Liver failure: Liver failure has many causes including infection, genetic diseases, and excessive alcohol. Ascites: As cirrhosis results, the liver leaks fluid (ascites) into the belly, which becomes distended and heavy. Gallstones: If a gallstone becomes stuck in the bile duct draining the liver, hepatitis and bile duct infection (cholangitis) can result. Hemochromatosis: Hemochromatosis allows iron to deposit in the liver, damaging it. The iron also deposits throughout the body, causing multiple other health problems. Primary sclerosing cholangitis: A rare disease with unknown causes, primary sclerosing cholangitis causes inflammation and scarring in the bile ducts in the liver. Primary biliary cirrhosis: In this rare disorder, an unclear process slowly destroys the bile ducts in the liver. Permanent liver scarring (cirrhosis) eventually develops.Liver TestsBlood Tests: Liver function panel: A liver function panel checks how well the liver is working and consists of many different blood tests. ALT (Alanine Aminotransferase): An elevated ALT helps identify liver disease or damage from any number of causes, including hepatitis. AST (Aspartate Aminotransferase): Along with an elevated ALT, the AST checks for liver damage. Alkaline phosphatase: Alkaline phosphatase is present in bile-secreting cells in the liver; it's also in bones. High levels often mean bile flow out of the liver is blocked. Bilirubin: High bilirubin levels suggest a problem with the liver. Albumin: As part of total protein levels, albumin helps determine how well the liver is working. Ammonia: Ammonia levels in the blood rise when the liver is not functioning properly. Hepatitis A tests: If hepatitis A is suspected, the doctor will test liver function as well as antibodies to detect the hepatitis A virus. Hepatitis B tests: Your doctor can test antibody levels to determine if you have been infected with the hepatitis B virus. Hepatitis C tests: In addition to checking liver function, blood tests can determine if you have been infected with the hepatitis C virus. Prothrombin Time (PT): A prothrombin time, or PT, is commonly done to see if someone is taking the correct dose of the blood thinner warfarin (Coumadin). It also checks for blood clotting problems. Partial Thromboplastin Time (PTT): A PTT is done to check for blood clotting problems.Imaging Tests: Ultrasound: An abdominal ultrasound can test for many liver conditions, including cancer, cirrhosis, or problems from gallstones. CT scan (computed tomography): A CT scan of the abdomen gives detailed pictures of the liver and other abdominal organs. Liver biopsy: A liver biopsy is most commonly done after another test, such as a blood test or ultrasound, indicates a possible liver problem. Liver and spleen scan: This nuclear scan uses radioactive material to help diagnose a number of conditions, including abscesses, tumors, and other liver function problems.Liver Treatments Hepatitis A treatment: Hepatitis A usually goes away with time. Hepatitis B treatment: Chronic hepatitis B often requires treatment with antiviral medication. Hepatitis C treatment: Treatment for hepatitis C depends on several factors. Liver transplant: A liver transplant is needed when the liver no longer functions adequately, whatever the cause. Liver cancer treatment: While liver cancer is usually difficult to cure, treatment consists of chemotherapy and radiation. In some cases, surgical resection or liver transplantation is performed. Paracentesis: When severe ascites -- swelling in the belly from liver failure -- causes discomfort, a needle can be inserted through the skin to drain fluid from the abdomen. ERCP (Endocscopic retrograde cholangiopancreatography): Using a long, flexible tube with a camera and tools on the end, doctors can diagnose and even treat some liver problems.The liver is the largest internal organ in the body.Its main functions are to: metabolize most of the nutrients that are absorbed by the intestine store nutrients produce proteins detoxify blood by removing medications, alcohol, and potentially harmful chemicals from the bloodstream and treating them chemically so they can be excreted by digestive or urinary systemsBecause the liver comes in close contact with many harmful substances, it is protected against diseasein two main ways. First, it can regenerate itself by repairing or replacing injured tissue. Second, the liver has many cell units responsible for the same task. Therefore, if one area is injured, other cells will perform the functions of the injured section indefinitely or until the damage has been repaired.Different types of liver disordersinclude hepatitis, cirrhosis, liver tumours, and liver abscess (collection of pus),just to name a few. The focus here will be the two most common forms:hepatitisandcirrhosis.There is more than one type of hepatitis, and although they have similar symptoms, they're contracted in very different ways.Hepatitis Ais the most common and the most infectious, spreading easily from person to person like most other viruses. It affects millions around the world and is responsible for more than 2 million deaths a year.Hepatitis Bis acquired through exposure to infected blood, vaginal fluids, or semen. It's estimated that about 0.5% to 1% of Canadians have hepatitis B.Hepatitis Caffects about 3.5 million North Americans. About 15% of those with hepatitis C may have been exposed to infected blood products before widespread blood testing began.Hepatitis Dis unique because it can only affect those that already have hepatitis B.The second type of liver disorder is called cirrhosis.It's a major cause of death in Canadian men aged 25 to 64. It is twice as common in men as in women and 30 times as common among heavy drinkers.Causes of Liver DisordersHepatitis is an inflammation of the liver that can be caused by a virus, by inherited disorders, and sometimes by certain medications or toxins such as alcohol and drugs. Scientists have identified four main types of viral hepatitis: hepatitis A, hepatitis B, hepatitis C, and hepatitis D. A fifth type, hepatitis E, is generally not found in North America.Hepatitis Ais waterborne and spread mainly via sewage and contaminated food and water.Hepatitis Bis transmitted by contact with infected semen, blood, or vaginal secretions, and from mother to newborn. Hepatitis B is most commonly spread by unprotected sex and by sharing of infected needles (including those used for tattooing, acupuncture, and ear piercing).Hepatitis Cspreads via direct blood-to-blood contact.Hepatitis Dis spread by infected needles and blood transfusions.Improved screening of donated blood has greatly reduced the risk of catching hepatitis B or C from blood transfusions. Both hepatitis B and C can be spread through sharing of razors, toothbrushes, and nail clippers.The main cause of cirrhosis is chronic infection with the hepatitis C virus.Other causes include: long-term, excessive alcohol consumption chronic infection with hepatitis B virus inherited disorders of iron and copper metabolism severe reactions to certain medications fatty liver caused by obesity infections from bacteria and parasites usually found in the tropics repeated episodes of heart failure with liver congestion and bile-duct obstructionWith cirrhosis, the liver tissue is irreversibly and progressively destroyed as a result of infection, poison, or some other disease. Normal liver tissue is replaced by scars and areas of regenerating liver cells.Symptoms and Complications of Liver DisordersBoth hepatitis and cirrhosis show few warning signs.In the acute phase of most forms of hepatitis, there are flu-like symptoms such as tiredness, fever, nausea, loss of appetite, and pain (usually under the ribs on the right side of the abdomen). There may also be some jaundice (yellowing of the skin and whites of the eyes.)Following the acute stage, hepatitis A will be cleared from the body and lifelong immunity develops. In hepatitis B and C, viral particles may linger in the body producing a chronic infection that lasts for years. This can eventually lead to liver cirrhosis and, in some cases, liver cancer.Signs and symptoms of cirrhosis include: abdominal pain general fatigue intestinal bleeding itching jaundice (yellowing of the skin and eyes) loss of interest in sex nausea and vomiting small red, spider-like blood vessels under the skin or easy bruising swelling in the abdomen and legs caused by fluid accumulation weakness weight lossIf you have cirrhosis, you should seek emergency help if you experience any of the following: mental confusion rectal bleeding vomiting bloodDiagnosing Liver DisordersDoctors diagnose hepatitis with blood tests and a complete personal history.They will ask if you have: used intravenous drugs recently eaten shellfish from polluted waters travelled to countries where hepatitis infections are common had a blood transfusion or been in contact with fresh blood had potentially risky sexual practices taken certain medications in the past few monthsDiagnosing cirrhosis is based on your clinical or medical historyand appearance, and blood test results. A liver biopsy may also be performed to confirm the diagnosis.Treating and Preventing Liver DisordersThere is no specific treatment for acute hepatitis.Bed rest isn't always essential, although you may feel better if you limit your amount of physical activity. It is important to maintain an adequate intake of calories. Your doctor may recommend small, frequent high-calorie meals, with plenty of fluids. Alcohol should be avoided or limited in order to help the liver recover. If you are unable to eat or drink, you may be hospitalized.Some people with chronic hepatitis B or C may benefit from medications that can slow the replication (reproduction) of the virus to decrease the amount of virus in the body. The risks and benefits of these medications should be discussed with your doctor.With hepatitis B or C, your doctor may check blood periodically for a few months to watch for any continuing signs of inflammation in the liver. It isn't usually necessary to isolate people with hepatitis, but those who are close to someone with hepatitis should be aware of how the virus spreads. Hand-washing after going to the bathroom is very important.There are a number of ways that governments and health professionals are fighting the spread of hepatitis.For example, there's an effective vaccination for hepatitis A. Global immunization programs exist against hepatitis B, and screening of blood donations is now common practice to check for hepatitis C. In Canada, hepatitis B vaccination is recommended for the entire population and is included as one of the primary series of vaccinations for infants. If you are travelling to countries where hepatitis is common, check with your doctor or travel medicine clinic to see if you are a candidate for hepatitis A or B immunization. There is no immunization against hepatitis C.To prevent the spread of viral hepatitis, thorough hand-washing by medical personnel who come into contact with contaminated utensils, bedding, or clothing is critical. Health care workers should be vaccinated, as they are at higher risk for infection due to exposure to people who are infected.While there are no effective treatments for liver cirrhosis, its progression can be greatly reduced by complete abstinence from alcohol. Caution should also be taken when considering the use of medications that can worsen liver disease. For example, people with cirrhosis should discuss with their doctor how much acetaminophen* they can take safely because acetaminophen is metabolized by the liver. Sometimes anti-inflammatory medications need to be avoided.Treatment is mainly focused on complications and may include salt restriction to combat fluid retention, diuretic medications ("water pills" that help get rid of excess water in the body), at times a low-protein diet, and vitamin supplements such as vitamins K, A, and D. Itching may be controlled with special medications. Laxatives may be prescribed to speed up removal of toxins from the system. In some cases, a liver transplant may be necessary.

*All medications have both common (generic) and brand names. The brand name is what a specific manufacturer calls the product (e.g., Tylenol). The common name is the medical name for the medication (e.g., acetaminophen). A medication may have many brand names, but only one common name. This article lists medications by their common names.For information on a given medication, check our Drug Information database.For more information on brand names, speak with your doctor or pharmacist.Liver disease is any condition that causes liver inflammation or tissue damage and affects liver function. The liver is a vital organ located in the upper right-hand side of the abdomen. It is as large as a football, weighs 2-3 pounds, and performs numerous functions for the body: converting nutrients derived from food into essential blood components, storing vitamins and minerals, regulating blood clotting, producingproteinsandenzymes, maintaininghormonebalances, and metabolizing and detoxifying substances that would otherwise be harmful to the body. The liver makes factors that help the human immune system fight infection, removesbacteriafrom the blood, and makes bile, which is essential for digestion.Bile, a greenish-yellow fluid consisting of bile acids or salts and waste products such as bile pigments, flows through small bile ducts inside the liver. The bile moves from these small ducts into larger ones, like streams into a river, eventually converging into the common bile duct and exiting the liver. Some of the bile flows directly to theduodenum; the rest is stored and concentrated in the gallbladder. After a person eats, the gallbladder, a fist-sized organ that sits next to the liver, releases some of the stored bile into the small intestine, where it helps to digest fats.What is liver disease?Liver disease is categorized both by the cause and the effect it has on the liver. Causes may include infection, injury, exposure to drugs or toxic compounds, an autoimmune process, or a genetic defect that leads to the deposition and build-up of damaging substances such as iron or copper. Effects may include inflammation, scarring, obstructions, clotting abnormalities, and liver failure. The following table summarizes some types of liver disease. The links lead to more information about the various types.Type of Liver DiseaseDescriptionExamples of Causes/Conditions

Acute liver failureRapid decrease in liver functionDrugs, toxins, a variety of liver diseases

Autoimmune-associatedThe body produces an inappropriate immune response against itself; sometimes developsantibodiesagainst own liver tissuePBC (Primary biliary cirrhosis), PSC (Primary sclerosing cholangitis),Autoimmune hepatitis

Budd-Chiari syndromeBlood clots impede blood flow from the liver; symptoms such asascites, enlarged liver,jaundice, and abdominal pain can developHypercoagulable disorders, liver injury, cancer,parasiticinfection

CirrhosisScarring of liver tissue leads to decreased liver functionCan be caused by a variety of conditions but usually a result of chronic hepatitis,alcoholism, or chronic bile duct obstruction

GeneticGenemutationscan lead to liver damage, disease; relatively rare conditionsHemochromatosis,Alpha-1 antitrypsin deficiency,Wilson's disease

HepatitisAcuteorchronicliver inflammationViruses, alcohol abuse, drugs, toxins, autoimmune,nonalcoholic fatty liver disease (NAFLD)

InfectionsCertain infections can cause various degrees of liver damage, blockage of bile ductsViral hepatitis, Parasitic infection

Liver cancerA cancer that originates in the liverIncreased risk with cirrhosis and chronic hepatitis; hepatocellular carcinoma (HCC) is most common primary liver tumor

Obstruction of bile ductsComplete or partial blockage of bile ductsTumors, gallstones, inflammation, trauma

Signs and SymptomsLiver disease may not cause any symptoms at first or the symptoms may be vague, like weakness and loss of energy. Inacuteliver disease, symptoms related to problems handling bilirubin, including yellow skin and eyes (jaundice), dark urine, and light stools, along with loss of appetite, nausea, vomiting, and diarrhea are the most common.Chronicliver disease symptoms may include jaundice, dark urine, abdominal swelling (due toascites),pruritus, unexplained weight loss or gain, and abdominal pain; these symptoms may not be present until the disease has reached an advanced stage.

Laboratory TestsThe goals with testing for liver disease are to screen for and detect liver injury, to evaluate its severity, diagnose the cause, and to monitor the liver's status over time. Screening and early detection are important since significant liver damage may occur with few or no symptoms. Diagnosing the cause of liver disease helps to guide Types. The liver is often capable of repairing injuries and resolving inflammation, but conditions that cause obstruction of the bile ducts and/or lead tocirrhosiscan cause permanent progressive liver damage. Monitoring the status of a person's liver over time allows measures to be taken to preserve liver function.Screening, detection, and monitoringSeveral liver tests are performed routinely as part of general health screening in aCMP (Comprehensive Metabolic Panel). Essentially the same liver tests may be ordered as aliver panelwhen someone has symptoms that may be due to liver injury or is at risk for developing liver disease. These tests measure the levels of specific enzymes, bilirubin, or protein that are abnormal when liver injury is present. Tests such asbilirubinmay also be ordered individually to monitor a person with a liver disease. If any of the liver tests are abnormal, then they indicate the need for additional evaluation and the use of diagnostic testing that is targeted at what liver condition(s) the doctor suspects a person may have. Screening and detection tests include: Alanine aminotransferase (ALT) an enzyme found mainly in the liver; best test to detecthepatitis Alkaline phosphatase (ALP) an enzyme related to the bile ducts; often increased when they are blocked Aspartate aminotransferase (AST) an enzyme found in the liver and a few other places, particularly the heart and other muscles Gamma-glutamyl transferase (GGT) an enzyme found mainly in the liver; very sensitive to changes in liver function Total bilirubin measures all the bilirubin in the blood; increased with many liver diseases Direct bilirubin measures a form conjugated (combined with another compound) in the liver Albumin measures the main protein made by the liver and tells how well the liver is making this protein Total protein measures albumin and all other proteins in blood, includingantibodiesmade to help fight off infections (antibodies are not made in the liver)Diagnosis and monitoringOther tests may be ordered to help diagnose the cause of liver dysfunction. Some are also used to monitor disease status and/or effectiveness of treatment. Testing may include: Liverbiopsy a tiny sample of liver tissue is taken to evaluate the structure and cells of the liver; used to help diagnose a wide range of liver diseases Hepatitis tests [seeHepatitis A,Hepatitis B,Hepatitis C] to detectviral hepatitis Alfa-fetoprotein (AFP) may be elevated withliver cancer Des-gamma-carboxy prothrombin (DCP) may be elevated with liver cancer Prothrombin time (PT) to evaluate clotting function Iron tests whenhemochromatosisis suspected Copperandceruloplasmin whenWilson diseaseis suspected Alpha-1 antitrypsin for alpha-1 antitrypsin deficiency Antimitochondrial Antibody (AMA) to help diagnosePBC (primary biliary cirrhosis) Acetaminophen leveland/or otherEmergency and Overdose Drug Testing whenacute liver failuredue to drugs or toxins is suspected Complete blood count (CBC) to evaluate the patient's white and red blood cells and plateletsFor more information on laboratory tests used for specific types of liver disease, see the links found in the Table on theOverviewpage.Non-Laboratory Tests Ultrasound CT (computed tomography) scan MRI (magnetic resonance imaging) MRCP (magnetic resonance cholangiopancreatography) PTC (percutaneous transhepatic cholangiogram) ERCP (endoscopic retrograde cholangiopancreatography)TreatmentThe most important treatment for liver disease is prevention.Vaccinesare available for hepatitis A and B, and many cases of hepatitis can be prevented by avoiding the risk factors that lead to their spread. Although liver inflammation may resolve over time, liver damage may also become permanent. Treatment of liver disease involves protecting and supporting remaining liver function, minimizing further damage and complications, and addressing the underlying cause of the damage. It may range from taking specific medications to surgery to, in severe cases, liver transplantation. Patients who are diagnosed with liver disease will often require long-term monitoring and should talk to their doctors to determine the best treatment options for their condition.

What are normal levels of AST and ALT? The normal range of values for AST (SGOT) is from 5 to 40 units per liter of serum (the liquid part of the blood). The normal range of values for ALT (SGPT) is from 7 to 56 units per liter of serum.The ranges of AST and ALT numbers may differ slightly depending on the technique and protocols used by different laboratories. However, normal reference ranges are routinely provided by each laboratory and printed in the report.What do elevated liver tests (AST and ALT) mean?AST (SGOT) and ALT (SGPT) are sensitive indicators of liver damage or injury from different types of diseases. But it must be emphasized that higher-than-normal levels of these liver enzymes should not be automatically equated withliver disease. They may mean liver problems or they may not. For example, elevations of these enzymes can occur with muscle damage. The interpretation of elevated AST and ALT levels depends upon the entire clinical evaluation of an individual, and so it is best done by physicians experienced in evaluating liver disease and muscle disease.Moreover, the precise levels of these enzymes do not correlate well with the extent of liver damage or the prognosis (outlook). Thus, the exact levels of AST (SGOT) and ALT (SGPT) cannot be used to determine the degree of liver disease or predict the future. For example, individuals with acuteviral hepatitis Amay develop very high AST and ALT levels (sometimes in the thousands of units/liter range). But most people with acute viral hepatitis A recover fully without residual liver disease. Conversely, people with chronichepatitis C infectiontypically have only a little elevation in their AST and ALT levels while having substantial liver injury and even advanced scarring of the liver (cirrhosis).Biliary tractThebiliary tract(orbiliary tree) is the commonanatomicalterm for the path by whichbileis secreted by theliverthen transported to the first part of thesmall intestine, also known as theduodenum. A structure common to most members of themammalfamily, it is referred to as a tree because it begins with many small branches which end in the common bile duct, sometimes referred to as the trunk of the biliary tree. The duct, the branches of thehepatic arteryand theportal veinform the central axis of theportal triad. Bile flows in the direction opposite to that of the blood present in the other two channels.The name usually excludes theliver,[1]but sometimes does include it.[2]Clinical significancePressure inside in the biliary tree can give rise togallstonesand lead tocirrhosis of the liver.Blockage can causejaundice.[3]The biliary tract can also serve as a reservoir for intestinal tract infections. Since the biliary tract is an internal organ, it has nosomatic nerve supply, and colicky pain due to infection and inflammation of the biliary tract is not a somatic pain. Rather, pain may be caused by luminal distension, which causes stretching of the wall. This is the same mechanism that causes pain inbowel obstructions.[citation needed][edit]PathThe path is as follows: Bile canaliculi>>Canals of Hering>> bile ductules (in portal tracts) >> intrahepatic bile ducts >> left and right hepatic ducts >> merge to form>>common hepatic duct>> exits liver and joins>>cystic duct(fromgall bladder) >> forming>>common bile duct>>joins with>>pancreatic duct>> forming>>ampulla of Vater>>enters duodenum[edit]PathologyAn obstruction of the biliary tract can result injaundice, a yellowing of the skin and whites of the eyes.Biliary atresiaEmail this page to a friendShare on facebookShare on twitterBookmark & SharePrinter-friendly versionBiliary atresia is a blockage in the tubes (ducts) that carry a liquid called bile from the liver to the gallbladder.CausesBiliary atresia occurs when the bile ducts inside or outside the liver do not develop normally. It is not known why the biliary system fails to develop normally.The bile ducts help remove waste from the liver and carry salts that help the small intestine break down (digest) fat.In babies with biliary atresia, bile flow from the liver to the gallbladder is blocked. This can lead to liver damage and cirrhosis of the liver, which is deadly if not treated.SymptomsNewborns with this condition may appear normal at birth. However, jaundice (a yellow color to the skin and mucous membranes) develops by the second or third week of life. The infant may gain weight normally for the first month, but then will lose weight and become irritable, and have worsening jaundice.Other symptoms may include: Dark urine Enlarged spleen Floating stools Foul-smelling stools Pale or clay-colored stools Slow growth Slow or no weight gainExams and TestsThe health care provider will perform a physical exam, which includes feeling the patient's belly area. The doctor may feel an enlarged liver.Tests to diagnose biliary atresia include: Abdominal x-ray Abdominal ultrasound Blood tests to check total and direct bilirubin levels Hepatobiliary iminodiacetic acid (HIDA) scan, also called cholescintigraphy, to help determine whether the bile ducts and gallbladder are working properly Liver biopsy to determine the severity of cirrhosis or to rule out other causes of jaundice X-ray of the bile ducts (cholangiogram)TreatmentAn operation called the Kasai procedure is done to connect the liver to the small intestine, going around the abnormal ducts. It is most successful if done before the baby is 8 weeks old. However, a liver transplant may still be needed.Outlook (Prognosis)Early surgery will improve the survival of more than a third of babies with this condition. The long-term benefit of liver transplant is not yet known, but is expected to improve survival.Possible Complications Infection Irreversible cirrhosis Liver failure Surgical complications, including failure of the Kasai procedureGallstonesEmail this page to a friendShare on facebookShare on twitterBookmark & SharePrinter-friendly versionGallstones are hard, pebble-like deposits that form inside the gallbladder. Gallstones may be as small as a grain of sand or as large as a golf ball.See also: Acute cholecystitis CholedocholithiasisCausesThe cause of gallstones varies. There are two main types of gallstones: Stones made of cholesterol, which are by far the most common type. Cholesterol gallstones have nothing to do with cholesterol levels in the blood. Stones made of bilirubin, which can occur when red blood cells are being destroyed (hemolysis). This leads to too much bilirubin in the bile. These stones are called pigment stones.Gallstones are more common in women, Native Americans, Hispanics, and people over age 40. Gallstones may also run in families.The following also make you more likely to develop gallstones: Bone marrowor solid organ transplant Diabetes Failure of the gallbladder to empty bile properly (this is more likely to happen during pregnancy) Liver cirrhosisand biliary tract infections (pigmented stones) Medical conditions that cause the liver to make too much bilirubin, such as chronichemolytic anemia, includingsickle cell anemia Rapid weight loss from eating a very low-calorie diet, or after bariatric surgery Receiving nutrition through a vein for a long period of time (intravenous feedings)SymptomsMany people with gallstones have never had any symptoms. The gallstones are often found during a routine x-ray, abdominal surgery, or other medical procedure.However, if a large stone blocks either the cystic duct or common bile duct (calledcholedocholithiasis), you may have a cramping pain in the middle to right upper abdomen. This is known as biliary colic. The pain goes away if the stone passes into the first part of the small intestine (the duodenum).Symptoms that may occur include: Pain in the right upper or middle upper abdomen: May be constant May be sharp, cramping, or dull May spread to the back or below the right shoulder blade Fever Yellowing of skin and whites of the eyes (jaundice)Other symptoms that may occur with this disease include: Clay-colored stools Nausea and vomitingIt is important to see a doctor if you have symptoms of gallstones.Exams and TestsTests used to detect gallstones or gallbladder inflammation include: Abdominal ultrasound Abdominal CT scan Endoscopic retrograde cholangiopancreatography (ERCP) Gallbladder radionuclide scan Endoscopic ultrasound Magnetic resonance cholangiopancreatography (MRCP) Percutaneous transhepatic cholangiogram(PTCA)Your doctor may order the following blood tests: Bilirubin Liver function tests Pancreatic enzymesTreatmentSURGERYSome people have gallstones and have never had any symptoms. The gallstones may not be found until an ultrasound is done for another reason. Surgery is usually not needed unless symptoms begin. One exception is in patients who have weight-loss surgery.In general, patients who have symptoms will need surgery either right away, or after a short period of time. A technique calledlaparoscopic cholecystectomyis most commonly used now. This procedure uses smaller surgical cuts, which allow for a faster recovery. Patients are often sent home from the hospital on the same day as surgery, or the next morning. In the past, opencholecystectomy(gallbladder removal) was the usual procedure for uncomplicated cases. However, this is done less often now.Endoscopic retrograde cholangiopancreatography (ERCP) and a procedure called a sphincterotomy may be done to find or treatgallstones in the common bile duct.MEDICATIONMedicines called chenodeoxycholic acids (CDCA) or ursodeoxycholic acid (UDCA, ursodiol) may be given in pill form to dissolve cholesterol gallstones. However, they may take 2 years or longer to work, and the stones may return after treatment ends.Rarely, chemicals are passed into the gallbladder through a catheter. The chemical rapidly dissolves cholesterol stones. This treatment is not used very often, because it is difficult to perform, the chemicals can be toxic, and the gallstones may return.LITHOTRIPSYElectrohydraulic shock wave lithotripsy (ESWL) of the gallbladder has also been used for certain patients who cannot have surgery. Because gallstones often come back in many patients, this treatment is not used very often anymore.Outlook (Prognosis)Gallstones develop in many people without causing symptoms. The chance of symptoms or complications from gallstones is low. Nearly all patients who have gallbladder surgery do not have their symptoms return (if the symptoms were actually caused by gallstones).Possible ComplicationsBlockage of the cystic duct or common bile duct by gallstones may cause the following problems: Acute cholecystitis Cholangitis Cholecystitis - chronic Choledocholithiasis PancreatitisWhen to Contact a Medical ProfessionalCall for an appointment with your health care provider if you have: Pain in the upper part of your abdomen Yellowing of the skin or whites of the eyesPreventionIn most people, gallstones cannot be prevented. In people who are obese, avoiding rapid weight loss could prevent gallstones.Cholelithiasis is the medical name for hard deposits (gallstones) that may form in the gallbladder. Cholelithiasis is very common in the United States, especially in women over age 40.Gallbladder Problems Spotlight Cholelithiasis? Join the DiscussionThe cause of cholelithiasis is not completely understood, but it is thought to have multiple factors. The gallbladder stores bile and releases it into the small intestine when it is needed for digestion. Gallstones can develop if the bile contains too muchcholesterolor too much bilirubin (one of the components of bile), or if the gallbladder is dysfunctional and cannot release the bile.Different types of gallstones form in cholelithiasis. The most common type, called a cholesterol stone, results from the presence of too much cholesterol in the bile. Another type of stone, called a pigment stone, is formed from excess bilirubin, a waste product created by the breakdown of the red blood cells in the liver. The size and number ofgallstonesvaries in cholelithiasis; the gallbladder can form many small stones or one large stone.The course of cholelithiasis varies among individuals. Some people with cholelithiasis have no symptoms at all, while others may have severe abdominal pain,nauseaand vomiting, and complete blockage that may pose the risk of infection. Cholelithiasis can lead to cholecystitis, inflammation of the gallbladder. Acute gallstone attacks may be managed with intravenous medications. Chronic (long-standing) cholelithiasis is treated by surgical removal of the gallbladder.Left untreated, cholelithiasis can lead to serious complications such as tissue damage, tears in the gallbladder, and infection that spreads to other parts of your body.Seek immediate medical care (call 911)for serious symptoms, such as highfever(higher than 101 degrees Fahrenheit), severe abdominal pain, abdominal swelling, and nausea with or withoutvomiting.Seek prompt medical care if you are being treated for cholelithiasis, but mild symptoms recur or are persistent.SYMPTOMSWhat are the symptoms of cholelithiasis?Cholelithiasis may cause irritation and inflammation of the gallbladder (cholecystitis) that can result in a number of symptoms. The symptoms can vary in intensity among individuals....Read More About Cholelithiasis SymptomsCAUSESWhat causes cholelithiasis?In most cases, cholelithiasis is caused by excessive amounts of cholesterol in the bile that is stored in the gallbladder. The cholesterol hardens to form stone-like substances. Increased body weight and older age are associated with increased levels of cholesterol in the bile. Thus, gallstones are more likely to occur in women, in people who are obese, and in older individuals....Read More About Cholelithiasis CausesTREATMENTSHow is cholelithiasis treated?Treatment of cholelithiasis begins with seeking medical care from your health care provider. To determine if you have cholelithiasis, your health care provider may ask you to provide blood samples and undergo diagnostic tests....Read More About Cholelithiasis TreatmentsAgallstoneis acrystallineconcretionformed within thegallbladderby accretion ofbilecomponents. Thesecalculiare formed in the gallbladder but maydistallypass into other parts of thebiliary tractsuch as thecystic duct,common bile duct,pancreatic duct, or theampulla of Vater. Rarely, in cases of severe inflammation, gallstones may erode through the gallbladder into adherent bowel potentially causing an obstruction termedgallstone ileus.[1]Presence of gallstones in the gallbladder may lead to acutecholecystitis, aninflammatorycondition characterized byretention of bile in the gallbladderand often secondaryinfectionbyintestinal microorganisms, predominantlyEscherichia coliandBacteroidesspecies. Presence of gallstones in other parts of the biliary tract can cause obstruction of thebile ducts, which can lead to serious conditions such asascending cholangitisorpancreatitis. Either of these two conditions can be life-threatening and are therefore considered to bemedical emergencies.[edit]DefinitionsPresence of stones in the gallbladder is referred to as cholelithiasis (from the Greekchol- (bile) +lith- (stone) +iasis- (process). If gallstones migrate into the ducts of the biliary tract, the condition is referred to as choledocholithiasis, from the Greekchol- (bile) +docho- (duct) +lith- (stone) +iasis- (process). Choledocholithiasis is frequently associated with obstruction of the biliary tree, which in turn can lead to acuteascending cholangitis, from the Greek:chol- (bile) +ang- (vessel) +itis- (inflammation), a serious infection of the bile ducts. Gallstones within the ampulla of Vater can obstruct theexocrinesystem of thepancreas, which in turn can result in pancreatitis.

Big GallstoneGallstones can vary in size and shape from as small as a grain of sand to as large as a golf ball.[2]The gallbladder may contain a single large stone or many smaller ones. Pseudoliths, sometimes referred to as sludge, are thicksecretionsthat may be present within the gallbladder, either alone or in conjunction with fully formed gallstones. The clinical presentation is similar to that of cholelithiasis.[citation needed]The composition of gallstones is affected by age, diet, andethnicity.[3]On the basis of their composition, gallstones can be divided into the following types:Cholesterol stonesCholesterolstones vary from light yellow to dark green or brown and are oval, between 2 and 3cm 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).[4]Pigment stonesPigment stones are small and dark and comprisebilirubinandcalciumsaltsthat are found in bile. They contain less than 20% of cholesterol (or 30%, according to the Japanese-classification system).[4]Mixed stonesMixed gallstones typically contain 2080% cholesterol (or 3070%, according to the Japanese- classification system).[4]Other common constituents arecalcium carbonate,palmitatephosphate, bilirubin, and otherbile pigments. Because of their calcium content, they are oftenradiographicallyvisible.CTof a gallstone. Image acquisition done using "CT Alpha" by "Procon X-Ray GmbH", Garbsen, Germany. Visualization done with "VG Studio Max 2.0" by "Volume Graphics", Heidelberg, Germany[edit]Cholelithiasis[edit]SymptomsGallstones may be asymptomatic, even for years. These gallstones are called "silent stones" and do not require treatment.[5][6]Symptoms commonly begin to appear once the stones reach a certain size (>8mm).[7]A characteristic symptom of gallstones is a"gallstone attack", in which a person may experience intense pain in the upper-right side of the abdomen, often accompanied by nausea and vomiting, that steadily increases for approximately 30 minutes to several hours. A patient may also experiencereferred painbetween theshoulder bladesor below the right shoulder. These symptoms may resemble those of a"kidney stone attack". Often, attacks occur after a particularly fatty meal and almost always happen at night.A positiveMurphy's signis a common finding onphysical examination.[edit]CausesGallstone risk increases for females (especially before menopause) and for people near or above 40 years;[8]the condition is more prevalent among both North and South Amerindians and among those of European descent than among other ethnicities. A lack ofmelatonincould 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.[9]Researchers believe that gallstones may be caused by a combination of factors, including inherited body chemistry,body weight, gallbladder motility (movement), and perhaps diet[citation needed]. The absence of such risk factors does not, however, preclude the formation of gallstones.No clear relationship has been proved between diet and gallstone formation; however, low-fiber and high-cholesterol diets have been suggested as contributing to gallstone formation[citation needed]. Other nutritional factors that may increase risk of gallstones include rapid weight loss, constipation, eating fewer meals per day, and low intake of the nutrients folate, magnesium, calcium, and vitamin C.[10]On the other hand, wine and whole-grained bread may decrease the risk of gallstones.[11]Pigment gallstones are most commonly seen in the developing world. Risk factors for pigment stones includehemolytic anemias(such assickle-cell diseaseandhereditary spherocytosis),cirrhosis, and biliary tract infections.[12]People witherythropoietic protoporphyria(EPP) are at increased risk to develop gallstones.[13][14]Additionally, prolonged use ofproton pump inhibitorshas been shown to decrease gallbladder function, potentially leading to gallstone formation.[15][edit]PathophysiologyCholesterol gallstones develop when bile contains too much cholesterol and not enough bile salts. 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.[16]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 hormoneestrogen, as a result ofpregnancyorhormone therapy, or the use of combined (estrogen-containing) forms ofhormonal contraception, may increase cholesterol levels in bile and also decrease gallbladder movement, resulting in gallstone formation.[edit]TreatmentMedicalCholesterol gallstones can sometimes be dissolved by oralursodeoxycholic acid, but it may be necessary for the patient to take this medication for up to two years.[17]Gallstones may recur, however, once the drug is stopped. Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy (ERS) followingendoscopic retrograde cholangiopancreatography(ERCP). Gallstones can be broken up using a procedure calledextracorporeal shock wave lithotripsy(often simply called "lithotripsy"),[17]which is a method of concentrating ultrasonic shock waves onto the stones to break them into tiny pieces. They are then passed safely in the feces. However, this form of treatment is suitable only when there is a small number of gallstones.SurgicalCholecystectomy(gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. Surgery is only indicated in symptomatic patients. The lack of a gallbladder may have no negative consequences in many people. However, there is a portion of the population between 10 and 15% who develop a condition calledpostcholecystectomy syndrome[18]which may cause gastrointestinal distress and persistent pain in the upper-right abdomen, as well as a 10% chance of developing chronicdiarrhea.[19]There are two surgical options for cholecystectomy: Open cholecystectomy is performed via an abdomenal incision (laparotomy) below the lower right ribs. Recovery typically requires 35 days of hospitalization, with a return to normal diet a week after release and to normal activity several weeks after release.[5] Laparoscopiccholecystectomy, introduced in the 1980s,[20]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.[5]Laparoscopic cholecystectomy patients can, in general, resume normal diet and light activity a week after release, with some decreased energy level and minor residual pain continuing 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 bycholangiogramprior to the procedure so that they can all be removed.[citation needed]Alternative medicineA regimen called a "gallbladder flush" or "liver flush" is a popular remedy in alternative medicine.[21]In this treatment, often self-administered, the patient drinks four glasses of pure apple juice (not cider) and eats five apples (or applesauce) per day for five days, then fasts briefly, takes magnesium, and then drinks large quantities of lemon juice mixed with olive 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. Apples are a source ofpectin, which has been shown to sequester bile and facilitate its elimination in the stool.[22]A brief communication in The Lancet[23]presents a case report of such a treatment where the patient released many soft stones. According to the letter, "At the university hospital the stones were recognized as fatty stones". In another case report, a patient with ultrasonography-confirmed gallstones drank olive oil and lemon juice, suffered diarrhea and intense abdominal pain, and released several gallstones. After that treatment, the gallbladder was empty, as confirmed by ultrasonography.[24]On the other hand, a couple of case reports challenge whether the stones retrieved from the stool after the "gallbladder flush" really come from the gallbladder. 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,[25]demonstrating that they are little more than hardened olive oil. Despite the gallbladder flush, the patient still required surgical removal of multiple true gallstones. A similar case report in The Lancet,[26]accompanied by a simple chemical experiment, concludes that the observed stones from a typical gallbladder flush actually are a consequence of the flush: they form in the stomach under the action of digestive enzymes on the mix of olive oil and lemon.Finally, drinking an infusion of "Chanca Piedra", or "Break Stones" (Phyllanthus niruri), a plant that is native to the Amazon, has long been used in South American traditional medicine to maintain kidney, liver, and gallbladder health and to treat gallstones and kidney stones and jaundice.Other patients have anecdotally reported that symptoms can be temporarily reduced by drinking several glasses of water when experiencing gallstone pain. There is no known evidence backing this claim, and this approach will not eliminate the gallstones or improve the patient's condition in the long term.[edit]CholedocholithiasisCholedocholithiasis is the presence of gallstones in thecommon bile duct. This condition causesjaundiceand liver cell damage, and requires treatment by cholecystectomy and/or ERCP.[edit]Signs and symptomsA positiveMurphy's signis a common finding onphysical examination. Jaundice of the skin or eyes is an important physical finding in biliary obstruction. Jaundice and/or clay-colored stool may raise suspicion of choledocholithiasis or even gallstone pancreatitis.[5]If the above symptoms coincide withfeverand chills, the diagnosis of ascending cholangitis may also be considered.[edit]CausesWhile stones can frequently pass through the common bile duct (CBD) into theduodenum, some stones may be too large to pass through the CBD and may cause an obstruction. One risk factor for this is duodenaldiverticulum.[edit]PathophysiologyThis obstruction may lead to jaundice, elevation inalkaline phosphatase, increase inconjugatedbilirubin in the blood and increase in cholesterol in the blood. It can also cause acutepancreatitisand ascendingcholangitis.[edit]DiagnosisCholedocholithiasis (stones in common bile duct) is one of the complications of cholelithiasis (gallstones), so the initial step is to confirm the diagnosis of cholelithiasis. Patients with cholelithiasis typically present with pain in the right-upper quadrant of the abdomen with the associated symptoms of nausea and vomiting, especially after a fatty meal. The physician can confirm the diagnosis of cholelithiasis with an abdominal ultrasound that shows the ultrasonic shadows of the stones in the gallbladder.The diagnosis of choledocholithiasis is suggested when the liver function blood test shows an elevation in bilirubin and serum transaminases. Other indicators include raised indicators of ampulla of vater (pancreatic duct obstruction) such as lipases and amylases. In prolonged cases theINRmay change due to a decrease in vitamin K absorption. (It is the decreased bile flow which reduces fat breakdown and therefore absorption of fat soluble vitamins). The diagnosis is confirmed with either an MRCP (magnetic resonance cholangiopancreatography), anERCP, or an intraoperative cholangiogram. If the patient must have the gallbladder removed for gallstones, the surgeon may choose to proceed with the surgery, and obtain a cholangiogram during the surgery. If the cholangiogram shows a stone in the bile duct, the surgeon may attempt to treat the problem by flushing the stone into the intestine or retrieve the stone back through the cystic duct.On a different pathway, the physician may choose to proceed with ERCP before surgery. The benefit of ERCP is that it can be utilized not just to diagnose, but also to treat the problem. During ERCP the endoscopist may surgically widen the opening into the bile duct and remove the stone through that opening. ERCP, however, is an invasive procedure and has its own potential complications. Thus, if the suspicion is low, the physician may choose to confirm the diagnosis with MRCP, a non-invasive imaging technique, before proceeding with ERCP or surgery.[edit]TreatmentFluoroscopicimage taken duringERCP. Multiple gallstones are present in the gallbladder andcystic duct. The common bile duct andpancreatic ductappear to be patent.Treatment involves removing the stone using ERCP. Typically, the gallbladder is then removed, an operation called cholecystectomy, to prevent a future occurrence of common bile duct obstruction or other complications.[27]GallstonesCholelithiasis; Gallbladder attack; Biliary colic; Gallstone attack; Biliary calculusLast reviewed: August 11, 2011.Gallstones are hard, pebble-like deposits that form inside the gallbladder. Gallstones may be as small as a grain of sand or as large as a golf ball.See also: Acute cholecystitis CholedocholithiasisCauses, incidence, and risk factorsThe cause of gallstones varies. There are two main types of gallstones: Stones made of cholesterol, which are by far the most common type. Cholesterol gallstones have nothing to do with cholesterol levels in the blood. Stones made of bilirubin, which can occur when red blood cells are being destroyed (hemolysis). This leads to too much bilirubin in the bile. These stones are called pigment stones.Gallstones are more common in women, Native Americans, Hispanics, and people over age 40. Gallstones may also run in families.The following also make you more likely to develop gallstones: Bone marrowor solid organ transplant Diabetes Failure of the gallbladder to empty bile properly (this is more likely to happen during pregnancy) Liver cirrhosisand biliary tract infections (pigmented stones) Medical conditions that cause the liver to make too much bilirubin, such as chronichemolytic anemia, includingsickle cell anemia Rapid weight loss from eating a very low-calorie diet, or after bariatric surgery Receiving nutrition through a vein for a long period of time (intravenous feedings)SymptomsMany people with gallstones have never had any symptoms. The gallstones are often found during a routine x-ray, abdominal surgery, or other medical procedure.However, if a large stone blocks either the cystic duct or common bile duct (calledcholedocholithiasis), you may have a cramping pain in the middle to right upper abdomen. This is known as biliary colic. The pain goes away if the stone passes into the first part of the small intestine (the duodenum).Symptoms that may occur include: Pain in the right upper or middle upper abdomen: May be constant May be sharp, cramping, or dull May spread to the back or below the right shoulder blade Fever Yellowing of skin and whites of the eyes (jaundice)Other symptoms that may occur with this disease include: Clay-colored stools Nausea and vomitingIt is important to see a doctor if you have symptoms of gallstones.Signs and testsTests used to detect gallstones or gallbladder inflammation include: Abdominal ultrasound Abdominal CT scan Endoscopic retrograde cholangiopancreatography (ERCP) Gallbladder radionuclide scan Endoscopic ultrasound Magnetic resonance cholangiopancreatography (MRCP) Percutaneous transhepatic cholangiogram(PTCA)Your doctor may order the following blood tests: Bilirubin Liver function tests Pancreatic enzymesTreatmentSURGERYSome people have gallstones and have never had any symptoms. The gallstones may not be found until an ultrasound is done for another reason. Surgery is usually not needed unless symptoms begin. One exception is in patients who have weight-loss surgery.In general, patients who have symptoms will need surgery either right away, or after a short period of time. A technique calledlaparoscopic cholecystectomyis most commonly used now. This procedure uses smaller surgical cuts, which allow for a faster recovery. Patients are often sent home from the hospital on the same day as surgery, or the next morning. In the past, opencholecystectomy(gallbladder removal) was the usual procedure for uncomplicated cases. However, this is done less often now.Endoscopic retrograde cholangiopancreatography (ERCP) and a procedure called a sphincterotomy may be done to find or treatgallstones in the common bile duct.MEDICATIONMedicines called chenodeoxycholic acids (CDCA) or ursodeoxycholic acid (UDCA,ursodiol) may be given in pill form to dissolve cholesterol gallstones. However, they may take 2 years or longer to work, and the stones may return after treatment ends.Rarely, chemicals are passed into the gallbladder through a catheter. The chemical rapidly dissolves cholesterol stones. This treatment is not used very often, because it is difficult to perform, the chemicals can be toxic, and the gallstones may return.LITHOTRIPSYElectrohydraulic shock wave lithotripsy (ESWL) of the gallbladder has also been used for certain patients who cannot have surgery. Because gallstones often come back in many patients, this treatment is not used very often anymore.Expectations (prognosis)Gallstones develop in many people without causing symptoms. The chance of symptoms or complications from gallstones is low. Nearly all patients who have gallbladder surgery do not have their symptoms return (if the symptoms were actually caused by gallstones).ComplicationsBlockage of the cystic duct or common bile duct by gallstones may cause the following problems: Acute cholecystitis Cholangitis Cholecystitis - chronic Choledocholithiasis Pancreatitis