Cholestasis

In medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. Bile formation is a secretory function of the liver. It begins in bile canaliculi that form between two adjacent surfaces of liver cells (hepatocytes) similar to the terminal branches of a tree. The canaliculi join each other to form larger and larger structures, sometimes referred to as Canals of Hering, which themselves join to form small bile ductules that have an epithelial surface. The ductules join to form bile ducts that eventually form either the right main hepatic duct that drains the right lobe of the liver and the left main hepatic duct draining the left lobe of the liver. The two ducts join to form the common hepatic duct, which in turn joins the cystic duct from the gall bladder, to give the common bile duct. This duct then enters the duodenum at the ampulla of Vater. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system such as can occur from a gallstone or malignancy and metabolic types of cholestasis which are disturbances in bile formation that can occur because of genetic defects or acquired as a side effect of many medications.

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Etiology

• gallstones
• abdominal mass (e.g. cancer)
• primary sclerosing cholangitis, associated with inflammatory bowel disease
• Primary biliary cirrhosis, secondary to autoimmune disorders
• congenital anomalies of the bilary tract
• biliary trauma
• some drugs, (e.g. Flucloxacillin and Erythromycin)
• in children, biliary atresia and other pediatric liver diseases
• Pregnancy, referred to as Intrahepatic Cholestasis of Pregnancy, or Obstetric Cholestasis

Histopathology

Under a microscope, the individual hepatocytes will have a brownish-green stippled appearance within the cytoplasm, representing bile that cannot get out of the cell. Canalicular bile plugs between individual hepatocytes or within bile ducts may also be seen, representing bile that has been excreted from the hepatocytes but cannot go any further due to the obstruction. When these plugs occur within the bile duct, sufficient pressure (caused by bile accumulation) can cause them to rupture, spilling bile into the surrounding tissue, causing hepatic necrosis. These areas are known as bile lakes, and are typically seen only with extra-hepatic obstruction.

Biochemical pathology

Cholestasis can be suspected when when there is an elevation of the protein GGT. GGT is elevated because it leaks out from the bile duct cells due to pressure from inside bile duct.

In a later stage of cholestasis AST, GLDH and bilirubin may be elevated due to liver damage as a secondary effect of cholestasis.

Symptoms

• Pale stools,
• dark urine,
• itchiness (pruritus) and
• jaundice.

Bile is secreted by the liver to aid in the digestion of fats. Drugs such as gold salts,nitrofurantoin, anabolic steroids, chlorpromazine, prochlorperazine, sulindac, cimetidine, erythromycin, can cause cholestasis and may result in damage to the liver.

See also

• Jaundice
• Liver function tests
• Lipoprotein-X - an abnormal low density lipoprotein found in cholestasis
• Intrahepatic Cholestasis of Pregnancy