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Cholestasis

Cholestasis

Definition

Cholestasis is a condition caused by rapidly developing (acute) or long-term (chronic) interruption in the excretion of bile (a digestive fluid that helps the body process fat). The term is taken from the Greek chole, bile, and stasis, standing still.

Description

Cholestasis is caused by obstruction within the liver (intrahepatic) or outside the liver (extrahepatic). The obstruction causes bile salts, the bile pigment bilirubin, and fats (lipids) to accumulate in the blood stream instead of being eliminated normally.

Intrahepatic cholestasis is characterized by widespread blockage of small ducts or by disorders, such as hepatitis, that impair the body's ability to eliminate bile. Extrahepatic cholestasis can occur as a side effect of many medications. It can also occur as a complication of surgery, serious injury, tissue-destroying infection, or intravenous feeding. Extrahepatic cholestasis can be caused by conditions such as tumors and gallstones that block the flow of bile from the gallbladder to the first part of the small intestine (duodenum).

Pregnancy increases the sensitivity of the bile ducts to estrogen, and cholestasis often develops during the second and third trimesters of pregnancy. This condition is the second most common cause of jaundice during pregnancy, but generalized itching (pruritus gravidarum) is the only symptom most women experience. Cholestasis of pregnancy tends to run in families. Symptoms usually disappear within two to four weeks after the baby's birth but may reappear if the woman becomes pregnant again.

A similar condition affects some women who take birth control pills. Symptoms disappear after the woman stops using oral contraceptives. This condition does not lead to chronic liver disease. A woman who develops cholestasis from either of these causes (pregnancy or birth control hormones) has an increased risk of developing cholestasis from the other.

Benign familial recurrent cholestasis is a rare condition characterized by brief, repeated episodes of itching and jaundice. Symptoms often disappear. This condition does not cause cirrhosis.

Drug-induced cholestasis may be a complication of chemotherapy or other medications. The two major types of drug-induced cholestasis are direct toxic injury and reactions unique to an individual (idiosyncratic reactions). In direct toxic injury, the severity of symptoms parallels the amount of medication involved. This condition:

  • develops a short time after treatment begins
  • follows a predictable pattern
  • usually causes liver damage

Direct toxic reactions develop in 1% of all patients who take chlorpromazine (Thorazine), a tranquilizer and antinausea drug. Idiosyncratic reactions may occur at the onset of treatment or at a later time. Allergic responses are varied and are not related to the amount of medication being taken.

Causes and symptoms

Intrahepatic cholestasis is usually caused by hepatitis or by medications that can produce symptoms resembling hepatitis. Phenothiazine-derivative drugs, including chlorpromazine, can cause sudden fever and inflammation. Symptoms usually disappear after use of the drug(s) is stopped. In rare cases, a condition resembling chronic biliary cirrhosis (a progressive disease characterized by destruction of small bile ducts) persists even after the medication is stopped. Some patients experience a similar reaction in response to tricyclic antidepressants (amitriptyline, imipramine), phenylbutazone (Butazolidin), erythromycin estolate (Estomycin, Purmycin), and other drugs. Intrahepatic cholestasis may also be caused by alcoholic liver disease, primary biliary cirrhosis, cancer that has spread (metastasized) from another part of the body, and a number of rare disorders.

Extrahepatic cholestasis is most often caused by a stone obstructing the passage through which bile travels from the gallbladder to the small intestine (common bile duct) or by pancreatic cancer. Less often, the condition occurs as a result of non-cancerous narrowing of the common duct (strictures), ductal carcinoma, or disorders of the pancreas.

Cholestasis caused by the use of steroids causes little, if any, inflammation. Symptoms develop gradually and usually disappear after the drug is discontinued. Other drugs that can cause cholestasis include:

  • allopurinol (Zyloprim)
  • amitriptyline (Elavil)
  • azathioprine (Imuran)
  • benoxaprofen (Oraflex)
  • capotril (Capoten)
  • carbamazepine (Tegretol)
  • cimetidine (Tagamet)
  • hydralazine hydrochloride (Apresoline Hydrochloride)
  • imipramine (Tofranil)
  • penicillin
  • quinidine sulfate (Quinidex)
  • ranitidine (Zantac)
  • sulfonamides (Apo-Sulfatrim, sulfamethoxazole)
  • sulindac (Clinoril, Saldac)

Symptoms of both intrahepatic and extrahepatic cholestasis include a yellow discoloration of the skin (jaundice), dark urine, and pale stools. Itching over the skin may be severe if the condition is advanced.

Symptoms of chronic cholestasis include:

  • skin discoloration
  • scars or skin injuries caused by scratching
  • bone pain
  • yellowish fat deposits beneath the surface of the skin (xanthoma) or around the eyes (xanthelasma)

Patients with advanced cholestasis feel ill, tire easily, and are often nauseated. Abdominal pain and such systemic symptoms as anorexia, vomiting, and fever are usually due to the underlying condition that causes cholestasis.

Diagnosis

Determining whether obstruction exists inside or outside the liver is the essential part of diagnosis. A history of hepatitis or heavy drinking, recent use of certain drugs, and symptoms like ascites (abnormal abdominal swelling) and splenomegaly (enlarged spleen) suggest intrahepatic cholestasis. Pain or rigidity in the gallbladder or pancreas suggest an extrahepatic form.

Blood tests and liver function tests can reveal the pattern and extent of liver injury, indicate functional abnormalities, and establish the cause of the condition. However, most misdiagnoses occur when physicians rely more on laboratory analysis than on detailed medical history and the results of a thorough physical examination. Special attention should be paid to three liver function tests. Levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) can indicate whether the patient's condition is caused by an obstructive condition like cholestasis or a disease of the liver cells (hepatocellular disease) like viral hepatitis or cancer. ALP levels more than three times greater than normal indicate cholestasis. High levels of AST and particularly of ALT, which is found predominantly in liver cells, indicate hepatocellular disease.

KEY TERMS

Bile A bitter yellow-green substance produced by the liver. Bile breaks down fats in the small intestine so that they can be used by the body. It is stored in the gallbladder and passes from the gallbladder through the common bile duct to the top of the small intestine (duodenum) as needed to digest fat.

Biliary Of bile or of the gallbladder and bile ducts that transport bile and make up the biliary system or tract.

Computed tomography scans (CT) An imaging technique in which cross-sectional x rays of the body are compiled to create a three-dimensional image of the body's internal structures.

Endoscopic retrograde cholangiopancreatography A diagnostic procedure for mapping the pancreatic and common bile ducts. A flexible tube with a light transmitter (fiberoptics) is placed in the duct. A contrast dye is instilled directly into the duct and a series of x-ray images are taken.

Hepatic Of the liver, from the Greek hepar.

Liver function tests Tests used to evaluate liver metabolism, storage, filtration, and excretion. The tests include alkaline phosphatase and serum alanine aminotransferase and aspartate aminotransferase.

Magnetic resonance imaging (MRI) An imaging technique that uses a large circular magnet and radio waves to generate signals from atoms in the body. These signals are used to construct images of internal structures.

Percutaneous transhepatic cholangiography An x-ray examination of the bile ducts. A needle is passed through the skin (percutaneous) across or over the liver (transhepatic) and directly into a bile duct to inject a contrast dye. The dye enhances the x-ray image mapping the system of bile ducts (cholangiography).

Phenothiazine-derivative drugs A large family of drugs derived from phenothiazine, a compound that in itself is too poisonous for human consumption. Phenothiazine derivatives include tranquilizers, medications that prevent vomiting, antihistamines, and drugs used to enhance the effectiveness of anesthesia.

Ultrasonography A test using sound waves to measure blood flow. Gel is applied to a hand-held transducer that is pressed against the patient's body. Images are displayed on a monitor.

Once the disease pattern has been established, ultrasound may be performed to determine whether obstruction of the large duct has caused widening of small ducts located close to it. Computed tomography scans (CT) and magnetic resonance imaging (MRI) can provide more detailed information about the source of the obstruction. If these procedures that do not enter the patient's body (non-invasive procedures) do not provide the information a family physician, internist, or gastroenterologist needs to make a diagnosis of cholestasis, one of these procedures may be performed:

  • direct cholangiography, an x-ray map of the bile ducts, enhanced by the use of contrast dye
  • percutaneous transhepatic cholangiography, used to identify obstructions that impede the flow of bile from the liver to the digestive system, takes x-ray images of the bile ducts after a contrast dye has been injected by a needle passed directly into a hepatic duct
  • endoscopic retrograde cholangiopancreatography (ERCP), which uses a special dye to outline the pancreatic and common bile ducts and highlight the position of any obstruction; a special tube with a light transmitter is inserted into the duct and a series of x-ray images is taken

A doctor who thinks a physical obstruction is responsible for progressive deterioration of a patient's condition may consider an exploratory surgical procedure (diagnostic laparotomy). Liver biopsy is sometimes performed if imaging tests do not indicate why a duct is enlarged, but results of a single biopsy may not represent the status of the entire organ.

Treatment

The goal of treatment is to eliminate or control the patient's symptoms. Discontinuing the use of certain drugs can restore normal liver function, but surgery may be needed to drain or remove obstructions or to widen affected ducts.

Rifampin (Rifadin, Rimactane), an antibacterial drug; phenobarbital, a barbiturate anticonvulsant; and other drugs are sometimes prescribed to cleanse the system and eliminate bile salts and other toxic compounds.

Patients who have chronic cholestasis and have trouble digesting fat may have to restrict the amount of fat in their diet and take calcium and water-soluble vitamin supplements. A liver transplant may become necessary if complications occur.

Prognosis

Symptoms almost always disappear after the underlying condition is controlled.

Some patients who have cholestasis experience symptoms only after infection develops, but chronic bile-duct obstruction always leads to cirrhosis. It may also cause osteoporosis (fragile bones) or osteomalacia (soft bones).

Emergency care is not required unless inflammation of the bile ducts (cholangitis ) develops. Cancer should be considered when an adult suddenly develops cholestasis after the age of 50.

Resources

ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar Grove, NJ 07009. (800) 223-0179. http://www.liverfoundation.org.

National Organization for Rare Disorders. P.O. Box 8923, New Fairfield, CT 06812-8923. (800) 999-6673. http://www.rarediseases.org.

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cholestasis

cholestasis (koli-stay-sis) n. failure of normal amounts of bile to reach the intestine, resulting in obstructive jaundice. The symptoms are jaundice with dark urine, pale faeces, and usually itching (pruritus).

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cholestasis

cholestasis Failure of normal amounts of bile to reach the intestine, resulting in obstructive jaundice. May be caused by bile stones or liver disease.

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