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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 (metabolic) 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

UpToDate Contents

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1. 肝酵素および肝機能検査値の異常が認められた患者に対するアプローチ approach to the patient with abnormal liver biochemical and function tests
2. 妊娠性肝内胆汁うっ滞 intrahepatic cholestasis of pregnancy
3. 胆汁うっ滞関連そう痒症 pruritus associated with cholestasis
4. 新生児胆汁うっ滞の原因 causes of neonatal cholestasis
5. 新生児胆汁うっ滞に対するアプローチ approach to neonatal cholestasis

English Journal

Endothelin-1 and -3 induce choleresis in the rat through ETB receptors coupled to nitric oxide and vagovagal reflexes.

Rodriguez MR, Soria LR, Ventimiglia MS, Najenson AC, Di María A, Dabas P, Fellet A, Marinelli RA, Vatta MS, Bianciotti LG.SourceCátedras de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Clinical science (London, England : 1979).Clin Sci (Lond).2013 Dec;125(11):521-32. doi: 10.1042/CS20120633.
We have reported previously that centrally applied ET (endothelin)-1 and ET-3 induce either choleresis or cholestasis depending on the dose. In the present study, we sought to establish the role of these endothelins in the short-term peripheral regulation of bile secretion in the rat. Intravenously
PMID 23642207

Interpretation and management of hepatic abnormalities in pregnancy.

Kia L, Rinella ME.SourceDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.Clin Gastroenterol Hepatol.2013 Nov;11(11):1392-8. doi: 10.1016/j.cgh.2013.05.016. Epub 2013 May 23.
The spectrum of liver disease in pregnancy includes liver disease unrelated to pregnancy, liver diseases that occur with increased frequency or severity in pregnancy, and liver disease specific to pregnancy. Diseases of the liver unique to pregnancy reliably occur at specific points in the gestation
PMID 23707777

Chemotherapy-induced hepatotoxicity.

Thatishetty AV, Agresti N, O'Brien CB.SourceDepartment of Medicine, Memorial Health, University Medical Center, 4700 Waters Avenue, Savannah, GA 31403, USA.
Clinics in liver disease.Clin Liver Dis.2013 Nov;17(4):671-86. doi: 10.1016/j.cld.2013.07.010. Epub 2013 Aug 22.
Most hepatotoxicity secondary to chemotherapy is idiosyncratic and, therefore, neither dose dependent nor predictable. Some chemotherapy is cleared by the liver and requires dose adjustment in the face of significant liver dysfunction. In addition, preexisting abnormal liver function has been shown
PMID 24099024

Japanese Journal

胆汁酸排出トランスポーターBSEPと肝内胆汁うっ滞 (特集脂質代謝とトランスポーター)

林久允
膜 = Membrane 39(2), 80-84, 2014-03
NAID 40020035725

Early Amino Acid and Lipid Administration for Preterm Infants Weighing Less than 400 Grams Improved Growth but Needed Care for Cholestasis

Hokuto Isamu,Yamamoto Hitoshi
Journal of St. Marianna University 4(2), 99-105, 2013-12
NAID 40019942572

Emulsification Using Highly Hydrophilic Surfactants Improves the Absorption of Orally Administered Coenzyme Q10

Sato Yuki,Mutoh Hanami,Suzuki Mika,Takekuma Yoh,Iseki Ken,Sugawara Mitsuru
Biological & pharmaceutical bulletin 36(12), 2012-2017, 2013-12
… Attention must be given to CoQ10 supplementation for patients whose bile is not excreted to the intestine such as patients with cholestasis. …
NAID 120005372273

Related Pictures

Cholestasis - Wikipedia 8 Natural Treatments for Cholestasis | Get Collagen Supplements South Africa Drug-induced cholestasis. Causes, symptoms, treatment Drug-induced cholestasis cholestasis - Humpath.com - Human pathology Neonatal Cholestasis Intrahepatic cholestasis of pregnancy - Genetics Home Reference - NIH Cholestasis; Biliary Stasis; Bile Duct Obstruction

★リンクテーブル★

リンク元	「bile duct obstruction」「bile stasis」
拡張検索	「intrahepatic cholestasis」

「bile duct obstruction」

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
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