Cholestasis

Cholestasis
Micrograph showing bile (yellow) stasis, i.e. cholestasis. H&E stain.
Classification and external resources
Specialty	Gastroenterology
ICD-10	K71.0, K83.1
ICD-9-CM	576.2
DiseasesDB	9121
MedlinePlus	000215
eMedicine	ped/383
Patient UK	Cholestasis
MeSH	D002779

Cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system that 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.

Signs and symptoms

itchiness (pruritus). Pruritus is the primary symptom of cholestasis and is thought to be due to interactions of serum bile acids with opioidergic nerves. In fact, the opioid antagonist naltrexone is used to treat pruritus due to cholestasis.
jaundice. Jaundice is an uncommon occurrence in intrahepatic cholestasis, but is common in obstructive cholestasis.
pale stool. This symptom implies obstructive cholestasis.
dark urine

Causes

Possible causes:

Pregnancy
Androgens
Birth Control pills
Antibiotics (such as, TMP/SMX)
abdominal mass (e.g. cancer)
biliary atresia and other pediatric liver diseases
biliary trauma
congenital anomalies of the biliary tract
gallstones
acute hepatitis
cystic fibrosis
intrahepatic cholestasis of pregnancy (obstetric cholestasis)
primary biliary cirrhosis, an autoimmune disorder
primary sclerosing cholangitis, associated with inflammatory bowel disease
some drugs (e.g. flucloxacillin and erythromycin)

Drugs such as gold salts, nitrofurantoin, anabolic steroids, chlorpromazine, prochlorperazine, sulindac, cimetidine, erythromycin, estrogen, and statins can cause cholestasis and may result in damage to the liver.

Mechanism

Bile is secreted by the liver to aid in the digestion of fats. Bile formation 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 the 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, or 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.

Diagnosis

Cholestasis can be suspected when there is an elevation of both 5'-nucleotidase and ALP enzymes. With a few exceptions, the optimal test for cholestasis would be elevations of serum bile acid levels. However, this is not normally available in most clinical settings. The gamma-glutamyl transferase (GGT) enzyme was previously thought to be helpful in confirming a hepatic source of ALP; however, GGT elevations are markedly sensitive and lack the necessary specificity to be a useful confirmatory test for ALP. Normally GGT and ALP are anchored to membranes of hepatocytes and are released in small amounts in hepatocellular damage. In cholestasis, synthesis of these enzymes is induced and they are made soluble. GGT is elevated because it leaks out from the bile duct cells due to pressure from inside bile ducts.

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

External links

Drug-induced cholestasis - medlineplus.org
FAQ from Obstetric Cholestasis Support

Diseases of the digestive system (primarily K20–K93, 530–579)

Upper GI tract

Esophagus	Esophagitis Candidal Eosinophilic Herpetiform Rupture Boerhaave syndrome Mallory-Weiss syndrome UES Zenker's diverticulum LES Barrett's esophagus Esophageal motility disorder Nutcracker esophagus Achalasia Diffuse esophageal spasm Gastroesophageal reflux disease (GERD) Laryngopharyngeal reflux (LPR) Esophageal stricture Megaesophagus

Stomach	Gastritis Atrophic Ménétrier's disease Gastroenteritis Peptic (gastric) ulcer Cushing ulcer Dieulafoy's lesion Dyspepsia Pyloric stenosis Achlorhydria Gastroparesis Gastroptosis Portal hypertensive gastropathy Gastric antral vascular ectasia Gastric dumping syndrome Gastric volvulus

Lower GI tract:
Intestinal/
Enteropathy

Small intestine (Duodenum/Jejunum/Ileum)	Enteritis Duodenitis Jejunitis Ileitis Peptic (duodenal) ulcer Curling's ulcer Malabsorption: Coeliac Tropical sprue Blind loop syndrome Small bowel bacterial overgrowth syndrome Whipple's Short bowel syndrome Steatorrhea Milroy disease bile acid malabsorption

Large intestine (Appendix/Colon)	Appendicitis Colitis Pseudomembranous Ulcerative Ischemic Microscopic Collagenous Lymphocytic Functional colonic disease IBS Intestinal pseudoobstruction / Ogilvie syndrome Megacolon / Toxic megacolon Diverticulitis/Diverticulosis

Large and/or small	Enterocolitis Necrotizing Gastroenterocolitis IBD Crohn's disease Vascular: Abdominal angina Mesenteric ischemia Angiodysplasia Bowel obstruction: Ileus Intussusception Volvulus Fecal impaction Constipation Diarrhea Infectious Intestinal adhesions

Rectum	Proctitis Radiation proctitis Proctalgia fugax Rectal prolapse Anismus

Anal canal	Anal fissure/Anal fistula Anal abscess Anal dysplasia Pruritus ani

GI bleeding/BIS

Accessory

Liver	Hepatitis Viral hepatitis Autoimmune hepatitis Alcoholic hepatitis Cirrhosis PBC Fatty liver NASH Vascular Budd-Chiari syndrome Hepatic veno-occlusive disease Portal hypertension Nutmeg liver Alcoholic liver disease Liver failure Hepatic encephalopathy Acute liver failure Liver abscess Pyogenic Amoebic Hepatorenal syndrome Peliosis hepatis Metabolic disorders Wilson's Disease Hemochromatosis

Gallbladder	Cholecystitis Gallstones/Cholecystolithiasis Cholesterolosis Rokitansky-Aschoff sinuses Postcholecystectomy syndrome Porcelain gallbladder

Bile duct/ Other biliary tree	Cholangitis Primary sclerosing cholangitis Secondary sclerosing cholangitis Ascending Cholestasis/Mirizzi's syndrome Biliary fistula Haemobilia Gallstones/Cholelithiasis Common bile duct Choledocholithiasis Biliary dyskinesia Sphincter of Oddi dysfunction

Pancreatic	Pancreatitis Acute Chronic Hereditary Pancreatic abscess Pancreatic pseudocyst Exocrine pancreatic insufficiency Pancreatic fistula

Abdominopelvic

Hernia	Diaphragmatic Congenital Hiatus Inguinal Indirect Direct Umbilical Femoral Obturator Spigelian Lumbar Petit's Grynfeltt-Lesshaft Undefined location Incisional Internal hernia

Peritoneal	Peritonitis Spontaneous bacterial peritonitis Hemoperitoneum Pneumoperitoneum

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