Your liver makes a digestive juice called bile. Your gallbladder stores it between meals. When you eat, your gallbladder pushes the bile into tubes called bile ducts. They carry the bile to your small intestine. The bile helps break down fat. It also helps the liver get rid of toxins and wastes.

Different diseases can block the bile ducts and cause a problem with the flow of bile:

• Gallstones, which can increase pressure in the gallbladder and cause a gallbladder attack. The pain usually lasts from one to several hours.
• Cancer
• Infections
• Birth defects, such as biliary atresia. It is the most common reason for liver transplants in children in the United States.
• Inflammation, which can cause scarring. Over time, this can lead to liver failure.

Your liver makes a digestive juice called bile. Your gallbladder stores it between meals. When you eat, your gallbladder pushes the bile into tubes called bile ducts. They carry the bile to your small intestine. The bile helps break down fat. It also helps the liver get rid of toxins and wastes.

Bile duct cancer is rare. It can happen in the parts of the bile ducts that are outside or inside the liver. Cancer of the bile duct outside of the liver is much more common. Risk factors include having inflammation of the bile duct, ulcerative colitis, and some liver diseases.

Symptoms can include

• Jaundice
• Itchy skin
• Fever
• Abdominal pain

Tests to diagnose bile duct cancer may include a physical exam, imaging tests of the liver and bile ducts, blood tests, and a biopsy.

Treatments include surgery, radiation therapy, and chemotherapy.

Biliary atresia is a condition in infants in which the bile ducts—tubes inside and outside the liver—are scarred and blocked. Bile ducts carry bile from the liver to the gallbladder for storage, and to the first part of the small intestine, also called the duodenum, for use in digestion. In infants with biliary atresia, bile can’t flow into the intestine, so bile builds up in the liver and damages it. The damage leads to scarring, loss of liver tissue and function, and cirrhosis.

Biliary atresia is life-threatening, but with treatment, most infants with biliary atresia survive to adulthood.

Doctors have identified different types of biliary atresia.

Biliary atresia without birth defects

In the most common type of biliary atresia, infants have no other major birth defects. Doctors may call this type of biliary atresia perinatal or isolated biliary atresia. A recent North American study found that 84 percent of infants with biliary atresia have this type.

Biliary atresia with birth defects

Some infants have major birth defects—including problems with the heart, spleen, or intestines—along with biliary atresia. Doctors may call this fetal or embryonic biliary atresia. A recent North American study found that 16 percent of infants with biliary atresia have major birth defects.

Biliary atresia is rare and affects about 1 out of every 12,000 infants in the United States.

Primary sclerosing cholangitis is a condition that affects the bile ducts. These ducts carry bile (a fluid that helps to digest fats) from the liver, where bile is produced, to the gallbladder, where it is stored, and to the small intestine, where it aids in digestion. Primary sclerosing cholangitis occurs because of inflammation in the bile ducts (cholangitis) that leads to scarring (sclerosis) and narrowing of the ducts. As a result, bile cannot be released to the gallbladder and small intestine, and it builds up in the liver.

Primary sclerosing cholangitis is usually diagnosed around age 40, and for unknown reasons, it affects men twice as often as women. Many people have no signs or symptoms of the condition when they are diagnosed, but routine blood tests reveal liver problems. When apparent, the earliest signs and symptoms of primary sclerosing cholangitis include extreme tiredness (fatigue), discomfort in the abdomen, and severe itchiness (pruritus). As the condition worsens, affected individuals may develop yellowing of the skin and whites of the eyes (jaundice) and an enlarged spleen (splenomegaly). Eventually, the buildup of bile damages the liver cells, causing chronic liver disease (cirrhosis) and liver failure. Without bile available to digest them, fats pass through the body. As a result, weight loss and shortages of vitamins that are absorbed with and stored in fats (fat-soluble vitamins) can occur. A fat-soluble vitamin called vitamin D helps absorb calcium and helps bones harden, and lack of this vitamin can cause thinning of the bones (osteoporosis) in people with primary sclerosing cholangitis.

Primary sclerosing cholangitis is often associated with another condition called inflammatory bowel disease, which is characterized by inflammation of the intestines that causes open sores (ulcers) in the intestines and abdominal pain. However, the reason for this link is unclear. Approximately 70 percent of people with primary sclerosing cholangitis have inflammatory bowel disease, most commonly a form of the condition known as ulcerative colitis. In addition, people with primary sclerosing cholangitis are more likely to have an autoimmune disorder, such as type 1 diabetes, celiac disease, or thyroid disease, than people without the condition. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. People with primary sclerosing cholangitis also have an increased risk of developing cancer, particularly cancer of the bile ducts (cholangiocarcinoma).

Primary sclerosing cholangitis (PSC) is a chronic liver disease in which the bile ducts inside and outside the liver become inflamed and scarred, and are eventually narrowed or blocked. When the bile ducts are narrowed or blocked, bile builds up in the liver and causes further liver damage. This damage can lead to cirrhosis and, eventually, liver failure. Medical experts believe PSC is an autoimmune disease, in which the immune system attacks normal, healthy bile duct cells.

An estimated 1 in 10,000 people have primary sclerosing cholangitis, and the condition is diagnosed in approximately 1 in 100,000 people per year worldwide.

People with PSC may have other health problems, including

• IBD
• gallstones
• autoimmune hepatitis
• other autoimmune diseases, such as type 1 diabetes, celiac disease, and thyroid diseases

About 7 out of 10 people who have PSC also have IBD.

A congenital anatomic malformation of a bile duct, including cystic dilatation of the extrahepatic bile duct or the large intrahepatic bile duct. Classification is based on the site and type of dilatation. Type I is most common.

Introduction

Cholestasis is defined as stagnation, or at least a marked reduction, in bile secretion and flow. Cholestasis can be due to a functional impairment of the hepatocytes in the secretion of bile and/or due to an obstruction at any level of the excretory pathway of bile, from the level of the hepatic parenchymal cells at the basolateral (sinusoidal) membrane of the hepatocyte to the ampulla of Vater in the duodenum. Cholestatic jaundice can thus be classified into intrahepatic or extrahepatic cholestasis, depending upon the level of obstruction to bile flow. Intrahepatic cholestasis or functional cholestasis can be due to a disease involving the liver parenchymal cells and/or the intrahepatic bile ducts. Intrahepatic cholestasis can be further subclassified as intralobular (disease of liver parenchymal cells and transporter molecules) and extralobular (disease involving intrahepatic bile ducts) cholestasis. Extrahepatic cholestasis or obstructive cholestasis is due to excretory block outside of the liver, along with the extrahepatic bile ducts.

Clinically, cholestasis leads to retention of the constituents of bile in blood. The 2 major constituents of bile are bilirubin and bile acids. Thus biochemically, cholestasis is marked by the elevation of predominantly serum alkaline phosphatase. Histologically, the retention of bilirubin in the hepatocytes, bile canaliculi, or bile ducts causes bilirubinostasis and is clinically manifested as jaundice. The stagnation of bile acids, on the other hand, causes typical changes in the periportal region of the liver which is termed as cholate stasis and presents clinically as pruritus. As the excretion of bilirubin follows hepatocellular pathways different from those of bile acids, serum bilirubin level may be normal in certain cases of severe cholestasis (anicteric cholestasis), and the patient may present with only pruritus but no jaundice. Prominent features of cholestasis are pruritus and malabsorption of fat and fat-soluble vitamins.

Etiology

Extrahepatic Cholestasis

• Choledocholithiasis

• Benign bile duct strictures

• Primary or secondary sclerosing cholangitis

• Mirizzi syndrome

• Cholangiocarcinoma

• Pancreatic cancer

• Ampullary adenoma/carcinoma

Intrahepatic Cholestasis

Hepatocellular Causes

• Viral hepatitis

• Acute alcoholic hepatitis

• Parenteral nutrition

• Intrahepatic atresia (infantile cholangiopathy)

• Zellweger syndrome

Canalicular Membrane Changes

• Medication (contraceptive pills, antibiotics, antithyroid drugs, sulphonamides)

• Cholestasis in pregnancy

Genetic Defects in Bile Transporters

• Benign recurrent intrahepatic cholestasis (BRIC)

• Progressive familial intrahepatic cholestasis (PFIC)

Canalicular/Ductular Luminal Obstruction

• Cholestasis due to sickle cell disease

• Hereditary protoporphyria

• Bacterial infections, sepsis

• Cystic fibrosis

Ductopenia

• Familial, drug-induced, chronic allograft rejection, Hodgkin disease, sarcoidosis, primary sclerosing cholangitis, primary biliary cholangitis

Epidemiology

Cholestasis is observed across all age groups. However, in the pediatric and adolescent age group is more susceptible to cholestasis owing to the immaturity of the liver. Also, there is no apparent difference in the prevalence of cholestatic jaundice between male and female. Females are at slightly higher risk of biliary atresia, drug-induced cholestasis, and intrahepatic cholestasis of pregnancy.

Pathophysiology

Cholestasis can occur either in a hepatocellular pattern where there is an impairment in bile synthesis. Bile is a highly complex, water-soluble medium. Bile formation included multiple different mechanisms of conjugation with multilevel regulation. The content of bile is transported in canaliculus via transported protein which creates a chemical and osmotic gradient through which water enters the canaliculi. Identification of abnormalities within some of these transporter proteins has led to an understanding mechanism of certain diseases better such as benign recurrent intrahepatic cholestasis (F1C1 locus gene) and progressive familial intrahepatic cholestasis (F1C2 locus gene). Failure to transport this bile salts lead to its accumulation within the liver. The strong detergent-like effect of the bile salts causes membrane injury and impairment of membrane function. Another mechanism of cholestasis is the physical obstruction to bile flow at the level of extrahepatic biliary ducts. Retained bile similarly causes hepatotoxicity.

Histopathology

The histologic findings are disease specific. However, in general, in hepatocellular causes of cholestasis, histology shows the presence of bile within hepatocytes and canaliculi spaces along with diffuse cholestatic injury pattern. While in the obstructive cholestatic pattern, histology shows bile plugging of interlobular bile ducts, portal expansion, and bile duct proliferation with mainly a centrilobular pattern of cholestatic injury. Retention of bilirubin (bilirubinostasis) can lead to stagnation of bile and bilirubin along cytoplasmic, canalicular, ductular or ductal regions, depending on the severity and duration of biliary obstruction. Cholate stasis corresponds to the peculiar changes in the periportal hepatocytes due to stagnation of bile acids and their detergent effects. There is hydropic swelling of hepatocytes with a clearing of their cytoplasm, and the concentration of the remaining cytoplasm in the perinuclear region with the formation of Mallory bodies and accumulation of copper-binding proteins (stained by orcein) in autophagic vacuoles. Acute complete obstruction of the extrahepatic bile ducts is manifested as portal edema and centrilobular bilirubinostasis in the early stage, followed by cholangitis (neutrophilic inflammation around the periportal ductules) and parenchymal bilirubinostasis which extends into the periportal areas. Chronic complete obstruction reveals all of the classic features of cholestasis, which eventually leads to secondary biliary cirrhosis. Chronic incomplete cholestasis, on the other hand, reveals the periportal and parenchymal features of cholestasis, depending on the duration of obstruction. Bilirubinostasis, however, may remain absent for long periods in chronic incomplete obstruction.

History and Physical

The onset is critical. Acute, sudden, and rapid onset is suggestive of acute pathology as opposed to chronic, insidious onset, which might be concerning for malignancy or other chronic etiology. While a good history is vital in a patient with new onset of jaundice, following are some of the features in history that can point toward a specific etiology.

• Presence of pain, specifically epigastric or right upper quadrant pain before the onset of jaundice might suggest choledocholithiasis or cholecystitis causing Mirrizi syndrome

• Presence of fever is highly suggestive of cholangitis

• The onset of jaundice after any hepatobiliary surgery might indicate, bile duct injury, bile duct leak. Jaundice is not always present in cholestasis

• Any history of critical illness or shock that can cause cholestasis of sepsis

• Any recent new medication use, especially antibiotics which can cause cholestasis

• Insidious onset of jaundice with nausea, vomiting, and prodrome phase is suggestive of viral hepatitis. History of prior travel, sexual contact, blood transfusion, and major surgery as well as the history of intravenous (IV) drug use can support this diagnosis

• Family or personal history of any autoimmune disease can point toward PSC or PBC

Other clinical features observed in patients with chronic cholestasis:

• Itching: The itching may be misdiagnosed as being due to a primary dermatological condition, particulalrly when there is no jaundice in some patients with cholestasis. Itching is typical in chronic cholestasis. Better in the morning and gets worse throughout the day after intake of food in the morning. During night time, fasting permits concentration of biliary elements decreases leading to improvement of itching in the morning.

• Fatigue: About 70% to 80% patients with chronic fatigue suffer from fatigue. Underlying abnormal serotonergic neurotransmission or neuroendocrine defects in the corticotrophin hormone axis are believed to be underlying etiology.

• Fat-soluble vitamins: Bile is necessary for absorption of ingested fat-soluble vitamins (A, D, E, and K). In chronic cholestasis, deficiency of these vitamins occurs leading to clinical features of their deficiency.

• Xanthomas: Flat or slightly raised yellow skin deposits are usually present around the eyes but can be present in palmar creases and other parts of the body.

Physical Examination

The extent of jaundice can assess the degree of hyperbilirubinemia. Examination of icterus should be done in the conjunctiva, oral mucosa, as well as skin throughout the body.

General Examination

Cachexia or wasting indicate either cancer or cirrhosis. Findings of diffuse lymphadenopathy especially Virchow’s nodes can be suggestive of underlying malignancy.

Skin Examination

In chronic cholestasis scratch marks due to pruritus, melanin pigmentation, as well as xanthomas over eyelids, extensor surfaces, and palmar creases can be found. Findings of chronic liver disease, for example, spider angiomas might suggest cirrhosis. Findings of needle track markers might suggest intravenous (IV) drug use.

Abdominal Examination

Large, nodular liver suggests possible hepatic metastasis. Tender hepatomegaly can be seen in viral hepatitis, congestive heart failure, and alcoholic hepatitis. In choledocholithiasis and cholecystitis, right upper quadrant (RUQ) tenderness is appreciated. Palpable, enlarged, painless gallbladder can suggest pancreatic cancer. Splenomegaly can be seen due to massive hemolysis or portal HTN. Ascites can be observed in cirrhosis due to portal HTN.

Evaluation

Laboratory

Liver Chemistry Panel

• Serum total and fractioned direct bilirubin should be obtained. In cholestasis, predominantly direct hyperbilirubinemia (more than 50% of total bilirubin) is observed. Serum alkaline phosphatase is also evaluated 3 times more than the upper normal limit in cholestasis, while normal or mild elevation in transaminases (ALT/AST) is a pure form of cholestatic jaundice. Serum albumin is usually normal except in cirrhosis and chronic liver disease where albumin is decreased.

Hematology

• Leukocytosis is found in cholangitis, alcoholic hepatitis, and underlying malignancy.

• Acute severe anemia can be found due to hemolysis. Evaluation of peripheral smear, reticulocyte count can help to differentiate. Chronic anemia can be seen in cirrhosis or underlying malignancy.

• Elevated prothrombin time can be seen with cholestasis which rapidly reverses with vitamin K supplementation as opposed to patients with cirrhosis.

Radiological Evaluation

• Abdominal ultrasound can help to identify if there is any biliary ductal dilation and help differentiate hepatocellular causes of cholestasis (where ducts will be normal size) versus biliary obstruction (where ducts will be dilated).

• If dilated biliary ducts are encountered on initial ultrasound, then magnetic resonance cholangiopancreatography can be used to assess bile ducts to identify stone, stricture vs. malignancy. CT scan can be helpful as well; however, MRI has better sensitivity.

Liver Biopsy

• Helpful in intrahepatic cholestasis to evaluate for various possible underlying etiologies.

Treatment / Management

Management of cholestatic jaundice widely depends upon underlying etiology and type of cholestasis. Usually, the mainstay of obstructive cholestasis is biliary decompression. Management of hepatocellular cholestasis includes symptomatic treatment of associated symptoms while specific treatment for the underlying disease process is attempted.

Biliary Decompression

• In common bile duct stones, endoscopic sphincterotomy with or without stent placement can relieve the obstruction. Similarly, in benign CBD strictures, stricture dilation and stent placement can relieve the obstruction.

• In malignant obstruction, depending upon the stage of disease and the operative candidacy of the patient, surgical resection of the obstructive lesion is preferred. If complete resection is not possible, surgical hepaticojejunostomy and the Roux-en-Y bypass is an option. If a patient is not a surgical candidate, either palliative CBD stent is placed endoscopically (usually metal stent). If endoscopic stent placement is not successful, a percutaneous transhepatic cholangiography tube can be placed for biliary decompression. Antibiotics are considered in pre and post biliary decompression phase to reduce the risk of sepsis.

Medical Management

Pruritus

In cases of obstructive physiology, pruritus is relieved within 24 to 48 hours of biliary decompression. For other cases. The following medications can be attempted for symptomatic control.

Cholestyramine: Should be taken with breakfast. Pruritus is the least in the morning as pruritus factor is stored in gallbladder overnight during the morning. The dose can be repeated after breakfast depending upon response. Required dose can vary from 4 gm daily to 12 gm maximum dose daily. Patients should be kept on the minimal required dose to avoid side effects such as nausea and oily stool. Fat-soluble vitamins should be supplemented.

Ursodeoxycholic acid can be used in doses of 13 to 15 mg/kg per day to reduce itching in patients with cholestasis due to PBC and possibly in drug-associated cholestasis. Use is not studied in other causes of cholestasis.

Antihistamine medications can be used especially at night mostly for sedative effect.

Phenobarbitone can be used to relieve itching resistant to other modes of therapy.

Naloxone is an opioid antagonist is currently experimental has shown to relieve itching due to cholestasis in a randomized control trial.

Non-pharmacological treatment options include bright light therapy (based on the circadian pattern of pruritus associated with cholestasis) and plasmapheresis.

Surgical resection of greater than 15% of terminal ileum to prevent enterohepatic circulation (bile salt reabsorption) can be effective in intractable pruritus.

Finally, in cases of PBC/PSC and other causes leading to end-stage liver disease, liver transplantation can cure intractable pruritus.

Differential Diagnosis

• Acute liver failure

• Acute hepatitis

• Acute pancreatitis

• Amyloidosis

• Autoimmune hepatitis

• Biliary obstruction

• Cardiac cirrhosis

• Cholangitis

• Cholecystitis

• Cirrhosis

Enhancing Healthcare Team Outcomes

Because there are many causes of cholestatic jaundice, most of which are serious, the disorder is best managed by an interprofessional team that includes the primary care provider, nurse practitioner, gastroenterologist, general surgeon, radiologist, and the pathologist. Management of cholestatic jaundice widely depends upon underlying etiology and type of cholestasis. Usually, the mainstay of obstructive cholestasis is biliary decompression. Management of hepatocellular cholestasis includes symptomatic treatment of associated symptoms while specific treatment for the underlying disease process is attempted. The outcomes of patients with cholestatic jaundice depend on the cause. For those with a benign cause like a gallstone the outcomes are good but in those with malignancy, the outcomes are somewhat grave

Complication of CHOLELITHIASIS characterized by OBSTRUCTIVE JAUNDICE; abdominal pain, and fever.

A motility disorder characterized by biliary COLIC, absence of GALLSTONES, and an abnormal GALLBLADDER ejection fraction. It is caused by gallbladder dyskinesia and/or SPHINCTER OF ODDI DYSFUNCTION.

Your gallbladder is a pear-shaped organ under your liver. It stores bile, a fluid made by your liver to digest fat. As your stomach and intestines digest food, your gallbladder releases bile through a tube called the common bile duct. The duct connects your gallbladder and liver to your small intestine.

Your gallbladder is most likely to give you trouble if something blocks the flow of bile through the bile ducts. That is usually a gallstone. Gallstones form when substances in bile harden. Gallstone attacks usually happen after you eat. Signs of a gallstone attack may include nausea, vomiting, or pain in the abdomen, back, or just under the right arm.

Gallstones are most common among older adults, women, overweight people, Native Americans and Mexican Americans.

Gallstones are often found during imaging tests for other health conditions. If you do not have symptoms, you usually do not need treatment. The most common treatment is removal of the gallbladder. Fortunately, you can live without a gallbladder. Bile has other ways to reach your small intestine.

Gallstones are hard, pebble-like pieces of material, usually made of cholesterol or bilirubin, that form in your gallbladder. Gallstones can range in size from a grain of sand to a golf ball. The gallbladder can make one large gallstone, hundreds of tiny stones, or both small and large stones.

When gallstones block the bile ducts of your biliary tract, the gallstones can cause sudden pain in your upper right abdomen. This pain is called a gallbladder attack, or biliary colic. If your symptoms continue and they’re left untreated, gallstones can cause serious complications.

However, most gallstones don’t cause blockages and are painless, also called “silent” gallstones. Silent gallstones usually don’t need medical treatment.

Types of gallstones

The two main types of gallstones are

• cholesterol stones
• pigment stones

Cholesterol stones are usually yellow-green in color and are made of mostly hardened cholesterol. In some countries, cholesterol stones make up about 75 percent of gallstones.

Pigment stones are dark in color and are made of bilirubin. Some people have a mix of both kinds of stones.

Gallstones are very common, affecting 10 to 15 percent of the U.S. population, which is almost 25 million people. About a quarter of the nearly 1 million people diagnosed with gallstones each year will need to be treated, usually with surgery.

Your biliary tract, which is made up of your gallbladder and bile ducts, helps with digestion by releasing bile.

The gallbladder is a small, pear-shaped organ that stores bile and is located in your upper right abdomen, below your liver.

The bile ducts of your biliary tract include the hepatic ducts, common bile duct, and cystic duct. Bile ducts also carry waste and digestive juices from the liver and pancreas to the duodenum.

Your liver produces bile, which is mostly made of cholesterol, bile salts, and bilirubin. Your gallbladder stores the bile until it’s needed. When you eat, your body signals your gallbladder to empty bile into your duodenum to mix with food. The bile ducts carry the bile from your gallbladder to the duodenum.

Most of us give little thought to the gallbladder, a pear-sized organ that sits just under the liver and next to the pancreas. The gallbladder may not seem to do all that much. But if this small organ malfunctions, it can cause serious problems. Gallbladder disorders rank among the most common and costly of all digestive system diseases. By some estimates, up to 20 million Americans may have gallstones, the most common type of gallbladder disorder.

The gallbladder stores bile, a thick liquid that’s produced by the liver to help us digest fat. When we eat, the gallbladder’s thin, muscular lining squeezes bile into the small intestine through the main bile duct. The more fat we eat, the more bile the gallbladder injects into the digestive tract.

Bile has a delicate chemical balance. It’s full of soluble cholesterol produced by the liver. This is a different type of cholesterol than the kind related to cardiovascular disease. If the chemical balance of bile gets slightly off, the cholesterol can crystalize and stick to the wall of the gallbladder. Over time, these crystals can combine and form gallstones.

Gallstones can range from the size of a grain of sand to that of a golf ball. When the gallbladder injects bile into the small intestine, the main bile duct can become blocked by these crystalline stones. That may cause pressure, pain, and nausea, especially after meals. Gallstones can cause sudden pain in the upper right abdomen, called a gallbladder attack (or biliary colic). In most cases, though, people with gallstones don’t realize they have them.

The causes of gallstones are unclear, but you’re more likely to have gallstone problems if you have too much body fat, especially around your waist, or if you’re losing weight very quickly. Women, people over age 40, people with a family history of gallstones, American Indians, and Mexican Americans are also at increased risk for gallstones.

“For the average person with an average case, the simplest way to diagnose a gallstone is by an ultrasound,” says Dr. Dana Andersen, an NIH expert in digestive diseases.

If left untreated, a blocked main bile duct and gallbladder can become infected and lead to a life-threatening situation. Gallbladder removal, called a cholecystectomy, is the most common way to treat gallstones. The gallbladder isn’t an essential organ, which means you can live normally without it.

Gallbladder removal can be done with a laparoscope, a thin, lighted tube that shows what’s inside your abdomen. The surgeon makes small cuts in your abdomen to insert the surgical tools and take out the gallbladder. The surgery is done while you are under general anesthesia, asleep and pain-free. Most people go home on the same day or the next.

Researchers have long investigated medications that can prevent gallstones from forming, but these therapies are currently used only in special situations.

It’s uncommon for the gallbladder to cause problems other than gallstones. Gallbladder cancer is often difficult to treat, as it’s usually diagnosed at an advanced stage. But such cancers are relatively rare.

While the gallbladder may not be the star of the digestive system, it still plays an important role. Treat it well by maintaining a healthy diet and getting regular exercise, and the little bag of bile should do its job. Don’t ignore pain or symptoms, and see your doctor if you’re in discomfort, especially after eating.

Symptoms of a Gallstone Attack

Talk with your doctor if you have:

• severe pain in the upper-right side of the abdomen that starts suddenly and lasts from 30 minutes to many hours.
• pain under the right shoulder or in the right shoulder blade.
• indigestion after eating foods high in fat or protein, including desserts and fried foods.

Seek help right away if you have these signs of a serious attack:

• abdominal pain that lasts more than 5 hours.
• nausea and vomiting.
• fever or chills.
• yellowish color of the skin or the whites of the eyes.
• dark urine or light-colored stools.