With cholestasis, the flow of bile (the digestive fluid produced by the liver) is impaired at some point between the liver cells (which produce bile) and the duodenum (the first segment of the small intestine). When bile flow is stopped, the pigment bilirubin (a waste product formed when old or damaged red blood cells are broken down) escapes into the bloodstream and accumulates. Normally, bilirubin joins with bile in the liver, moves through the bile ducts into the digestive tract, and is eliminated from the body. Most bilirubin is eliminated in stool, but a small amount is eliminated in urine.
Overview of Cholestasis
The portal vein receives blood from the entire intestine and from the spleen, pancreas, and gallbladder and carries that blood to the liver. After entering the liver, the portal vein divides into right and left branches and then into tiny channels that run through the liver. When blood leaves the liver, it flows back into the general circulation through the hepatic vein.
The causes of cholestasis are divided into two groups: those originating within the liver and those originating outside the liver.
Causes include acute hepatitis, alcoholic liver disease, primary biliary cholangitis with inflammation and scarring of the bile ducts, cirrhosis due to viral hepatitis B or C (also with inflammation and scarring of the bile ducts), certain drugs (eg, amoxicillin/clavulanate, chlorpromazine, azathioprine, and oral contraceptives), hormonal effects on bile flow during pregnancy (a condition called cholestasis of pregnancy), and cancer that has spread to the liver.
Causes include a stone in a bile duct, narrowing (stricture) of a bile duct, cancer of a bile duct, cancer of the pancreas, and inflammation of the pancreas (pancreatitis).
Jaundice, dark urine, light-colored stools, and generalized itchiness are characteristic symptoms of cholestasis. Jaundice results from excess bilirubin deposited in the skin, and dark urine results from excess bilirubin excreted by the kidneys. The skin itches, possibly because bile products accumulate in the skin. Scratching can damage the skin. Stools may become light-colored because the passage of bilirubin into the intestine is blocked, preventing it from being eliminated from the body in stool. Stools may contain too much fat (a condition called steatorrhea) because bile cannot enter the intestine to help digest fat in foods. Fatty stools may be foul-smelling.
The lack of bile in the intestine also means that calcium and vitamin D are poorly absorbed. If cholestasis persists, a deficiency of these nutrients can cause loss of bone tissue. Vitamin K, which is needed for blood clotting, is also poorly absorbed from the intestine, causing a tendency to bleed easily.
Prolonged jaundice due to cholestasis produces a muddy skin color and fatty yellow deposits in the skin. Whether people have other symptoms, such as abdominal pain, loss of appetite, vomiting, or fever, depends on the cause of cholestasis.
A doctor suspects cholestasis in people who have jaundice and tries to determine whether the cause is within or outside the liver on the basis of symptoms and the results of a physical examination.
Recent use of drugs that can cause cholestasis suggests a cause within the liver. Small spiderlike blood vessels visible in the skin (called spider angiomas), an enlarged spleen, and accumulation of fluid within the abdomen (ascites)—which are signs of chronic liver disease—also suggest a cause within the liver.
Findings that suggest a cause outside the liver include certain kinds of abdominal pain (such as intermittent pain in the upper right side of the abdomen and sometimes also in the right shoulder) and an enlarged gallbladder (felt during the physical examination or detected by imaging studies).
Some findings do not indicate whether the cause is within or outside the liver. They include consumption of large amounts of alcohol, loss of appetite, nausea, and vomiting.
Typically, blood tests are done to measure levels of two enzymes (alkaline phosphatase and gamma-glutamyl transpeptidase) that are very high in people with cholestasis. A blood test that measures the level of bilirubin indicates the severity of the cholestasis but not its cause.
An imaging study, usually ultrasonography, is almost always done if blood test results are abnormal. Computed tomography (CT) or sometimes magnetic resonance imaging (MRI) may be done in addition to or instead of ultrasonography. If the cause appears to be within the liver, a liver biopsy may be done and usually establishes the diagnosis.
If the cause appears to be blockage of the bile ducts, more precise images of these ducts are usually needed. Typically, one of the following is done:
A blockage of the bile ducts can usually be treated with surgery or endoscopy (using a flexible viewing tube with surgical instruments attached).
A blockage within the liver may be treated in various ways depending on the cause. If a drug is the suspected cause, the doctor stops its use. If acute hepatitis is the cause, cholestasis and jaundice usually disappear when hepatitis has run its course. People with cholestasis are advised to avoid or stop using any substance that is toxic to the liver, such as alcohol and certain drugs.
Cholestyramine, taken by mouth, can be used to treat itchiness. This drug binds with certain bile products in the intestine, so they cannot be reabsorbed to irritate the skin.
Unless the liver is severely damaged, taking vitamin K can improve blood clotting.
Supplements of calcium and vitamin D are often taken if the cholestasis persists, but they are not very effective in preventing loss of bone tissue.