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Cholestasis

 

 
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Cholestasis
 
 
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In medicine
Medicine

Medicine is the art and science of healing. It encompasses a range of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, cholestasis is a condition where bile
Bile

Bile or gall is a bitter yellow or green fluid secreted by hepatocytes from the liver of most vertebrates. In many species, bile is stored in the gallbladder between meals and upon eating is discharged into the duodenum where the bile aids the process of digestion of lipids....
 cannot flow from the liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
 to the duodenum
Duodenum

The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum....
. Bile formation is a secretory function of the liver. It begins in bile canaliculi that form between two adjacent surfaces of liver cells (hepatocyte
Hepatocyte

Hepatocytes make up 70-80% of the cytoplasmic mass of the liver.These cells are involved in protein synthesis, protein storage and transformation of carbohydrates, synthesis of cholesterol, bile salts and phospholipids, and detoxification, modification and excretion of exogenous and endogenous substances....
s) 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.






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In medicine
Medicine

Medicine is the art and science of healing. It encompasses a range of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, cholestasis is a condition where bile
Bile

Bile or gall is a bitter yellow or green fluid secreted by hepatocytes from the liver of most vertebrates. In many species, bile is stored in the gallbladder between meals and upon eating is discharged into the duodenum where the bile aids the process of digestion of lipids....
 cannot flow from the liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
 to the duodenum
Duodenum

The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum....
. Bile formation is a secretory function of the liver. It begins in bile canaliculi that form between two adjacent surfaces of liver cells (hepatocyte
Hepatocyte

Hepatocytes make up 70-80% of the cytoplasmic mass of the liver.These cells are involved in protein synthesis, protein storage and transformation of carbohydrates, synthesis of cholesterol, bile salts and phospholipids, and detoxification, modification and excretion of exogenous and endogenous substances....
s) 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 duct
Bile duct

A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine....
s 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
Common hepatic duct

The common hepatic duct is the duct formed by the convergence of the right hepatic duct and the left hepatic duct . The common hepatic duct then joins the cystic duct coming from the gallbladder to form the common bile duct....
, which in turn joins the cystic duct
Cystic duct

The cystic duct is the short duct that joins the gall bladder to the common bile duct. It usually lies next to the cystic artery. It is of variable length....
 from the gall bladder, to give the common bile duct
Common bile duct

Bile, which is synthesized in the liver, is carried via the right and left hepatic ducts, with both converging to form the common hepatic duct. The cystic duct opens at the lower end of the common hepatic duct forming 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
Gallstone

In medicine, gallstones are crystalline bodies formed within the body by accretion or concretion of normal or abnormal bile component.Gallstones can occur anywhere within the biliary tree, including the gallbladder and the common bile duct....
 or malignancy
Malignant

Malignant is a medical term used to describe a severe and progressively worsening disease. The term is most familiar as a description of cancer....
 and metabolic types of cholestasis which are disturbances in bile formation that can occur because of genetic defects
Genetic disorder

A genetic disorder is an illness caused by abnormalities in genes or chromosomes. While some diseases, such as cancer, are due in part to a genetic disorders, they can also be caused by Environment factors....
 or acquired as a side effect of many medications.

Etiology

  • abdominal mass
    Abdominal mass

    An abdominal mass is any localized enlargement or swelling in the human abdomen. Depending on its location, the abdominal mass may be caused by an enlarged liver , enlarged spleen , protruding kidney, a pancreatic mass, a retroperitoneal mass , an abdominal aortic aneurysm, or various tumours, such as those caused by abdominal carcinomatosis...
     (e.g. cancer
    Cancer

    Cancer is a class of diseases in which a group of cell display uncontrolled growth , invasion , and sometimes metastasis . These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize....
    )
  • biliary atresia
    Biliary atresia

    Biliary atresia is a rare disease in neonate in which the common bile duct between the liver and the small intestine is blocked or absent. If unrecognised, the condition leads to liver failure but not to kernicterus....
     and other pediatric liver diseases
  • biliary trauma
    Physical trauma

    Physical trauma refers to a body injury. A trauma patient is someone who has suffered serious and life-threatening physical injury with the potential for secondary complications such as Shock , respiratory failure and death....
  • congenital anomalies of the bilary tract
  • gallstone
    Gallstone

    In medicine, gallstones are crystalline bodies formed within the body by accretion or concretion of normal or abnormal bile component.Gallstones can occur anywhere within the biliary tree, including the gallbladder and the common bile duct....
    s
  • intrahepatic cholestasis of pregnancy (obstetric cholestasis)
    Intrahepatic Cholestasis of Pregnancy

    Intrahepatic Cholestasis of Pregnancy , also termed Obstetric Cholestasis in the United Kingdom, gives rise to troublesome itching during pregnancy but may lead to possibly serious complications for the mother and very serious outcomes for the fetus....
  • primary biliary cirrhosis
    Primary biliary cirrhosis

    Primary biliary cirrhosis is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver....
    , an autoimmune disorder
  • primary sclerosing cholangitis
    Primary sclerosing cholangitis

    Primary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis and liver failure....
    , associated with inflammatory bowel disease
    Inflammatory bowel disease

    In medicine, inflammatory bowel disease is a group of inflammation conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.....
  • some drugs, (e.g. flucloxacillin
    Flucloxacillin

    Flucloxacillin or floxacillin is a narrow-spectrum antibiotic beta-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible Gram-positive bacteria....
     and erythromycin
    Erythromycin

    Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins....
    )


Histopathology

Under a microscope
Microscope

A microscope is an Laboratory equipment for viewing objects that are too small to be seen by the naked or unaided eye. The science of investigating small objects using such an instrument is called microscopy....
, the individual hepatocytes will have a brownish-green stippled
Stippling

Stippling is the technique of using small dots to simulate varying Grayscale or shading.In a drawing or painting, the dots are made of pigment of a single color, applied with a pen or brush; the denser the spacing of the dots, the darker the apparent shade?or lighter, if the pigment is lighter than the surface....
 appearance within the cytoplasm
Cytoplasm

The cytoplasm is the part of a Cell that is enclosed within the plasma membrane. In eukaryote cells the cytoplasm contains organelles, such as mitochondrion, that are filled with liquid kept separate from the rest of the cytoplasm by biological membranes....
, 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
Biological tissue

Tissue is a cellular organizational level intermediate between cells and a complete organism. Hence, a tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function....
, causing hepatic necrosis
Necrosis

Necrosis is the name given to premature death of cell s and living biological tissue. Necrosis is caused by external factors, such as infection, toxins, or trauma....
. These areas are known as bile lakes, and are typically seen only with extra-hepatic obstruction.

Biochemical pathology

Cholestasis can be suspected when there is an elevation of both 5'-nucleotidase and ALP
Alkaline phosphatase

Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids....
 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 GGT 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
GGT

GGT may refer to:*Gamma-glutamyltransferase, an enzyme that catalysis the reaction between a peptide and an amino acid*Gamma-glutamyl transpeptidase, a liver enzyme or liver function test of that enzyme...
 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 duct.

In a later stage of cholestasis AST
AST

AST is a three letter acronym that stands for a number of different things.In science and technology* Aspartate transaminase, an enzyme associated with liver parenchymal cells...
, ALT
Alt

ALT may stand for:*ALT , a group of musicians, the members of which are Andy White, Liam O'Maonlai and Tim Finn.*ALT Linux, a distribution of Linux computer software, or a team of developers that work on the software....
 and bilirubin
Bilirubin

Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is formed from hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile, and its levels are elevated in certain diseases....
 may be elevated due to liver damage as a secondary effect of cholestasis.

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 mixed opioid agonist/antagonist Naltrexone is used to treat pruritus due to cholestasis.
  • jaundice
    Jaundice

    Jaundice, also known as icterus , is a yellowish discoloration of the skin, the conjunctival membranes over the sclera , and other mucous membranes caused by hyperbilirubinemia ....
    . Jaundice is an uncommon occurrence in intrahepatic cholestasis, but is common in obstructive cholestasis.
  • pale stool. This symptom implies obstructive cholestasis.
  • dark urine


Bile
Bile

Bile or gall is a bitter yellow or green fluid secreted by hepatocytes from the liver of most vertebrates. In many species, bile is stored in the gallbladder between meals and upon eating is discharged into the duodenum where the bile aids the process of digestion of lipids....
 is secreted by the liver to aid in the digestion
Digestion

Digestion is the mechanical and chemical breaking down of food into smaller components, to a form that can be Absorption, for instance, by a blood stream....
 of fat
Fat

Fats consist of a wide group of compounds that are generally soluble in organic solvents and largely insoluble in water. Chemistry, fats are generally ester of glycerol and fatty acids....
s. Drugs such as gold salts
Gold salts

Gold salts describe ionic chemical compounds of gold. The term, which is a misnomer, has evolved into a euphemism for the gold compounds used in medicine....
,nitrofurantoin
Nitrofurantoin

Nitrofurantoin is an antibiotic. It is usually used in treating urinary tract infection. Like many other drugs, it is often used against E Coli....
, anabolic steroids, chlorpromazine
Chlorpromazine

Chlorpromazine is a phenothiazine antipsychotic, and the oldest in the antipsychotic family of drugs. It is a typical antipsychotic. It is principally used in the treatment of schizophrenia, though it has also been used to treat severe manic episodes in people with bipolar disorder....
, prochlorperazine
Prochlorperazine

Prochlorperazine is a drug that belongs to the phenothiazine class of antipsychotic agents that are used for the treatment of nausea and vertigo ....
, sulindac
Sulindac

Sulindac is a non-steroidal anti-inflammatory drug of the arylalkanoic acid class that is marketed in the UK & U.S. by Merck & Co. as Clinoril....
, cimetidine
Cimetidine

Cimetidine is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers....
, erythromycin
Erythromycin

Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins....
, estrogen
Estrogen

Estrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone....
 can cause cholestasis and may result in damage to the liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
.

See also

  • Jaundice
    Jaundice

    Jaundice, also known as icterus , is a yellowish discoloration of the skin, the conjunctival membranes over the sclera , and other mucous membranes caused by hyperbilirubinemia ....
  • Liver function tests
    Liver function tests

    Liver function tests , which include liver enzymes, are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver....
  • Lipoprotein-X
    Lipoprotein-X

    Lipoprotein-X is an abnormal low density lipoprotein found in cholestasis....
     - an abnormal low density lipoprotein
    Low density lipoprotein

    Low-density lipoprotein is a type of lipoprotein that transports cholesterol and triglycerides from the liver to peripheral tissues. LDL is one of the five major groups of lipoproteins; these groups include chylomicrons, very low-density lipoprotein , intermediate-density lipoprotein , low-density lipoprotein, and high-density lipoprotein ,...
     found in cholestasis
  • Intrahepatic cholestasis of pregnancy
    Intrahepatic Cholestasis of Pregnancy

    Intrahepatic Cholestasis of Pregnancy , also termed Obstetric Cholestasis in the United Kingdom, gives rise to troublesome itching during pregnancy but may lead to possibly serious complications for the mother and very serious outcomes for the fetus....
  • Progressive familial intrahepatic cholestasis
    Progressive familial intrahepatic cholestasis

    Progressive familial intrahepatic cholestasis refers to a group of familial cholestasis conditions caused by defects in bile epithelial transporters....


External links

  • - medlineplus.org
  • from Obstetric Cholestasis Support