Cholestasis - AbsoluteAstronomy.com

In medicine

Medicine

Medicine is the science and art of healing. It encompasses a variety 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-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...

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, including 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...

. 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

A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder, but may pass distally into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of...

or malignancy

Malignant

Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...

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, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....

or acquired as a side effect of many medications.

Normal bile formation

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

A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...

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.The...

s 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

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

The common bile duct is a tube-like anatomic structure in the human gastrointestinal tract. It is formed by the union of the common hepatic duct and the cystic duct . It is later joined by the pancreatic duct to form the ampulla of Vater...

. This duct then enters the duodenum at the ampulla of Vater.

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...

(e.g. cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

)
biliary atresia
Biliary atresia
Biliary atresia, also known as "extrahepatic ductopenia" and "progressive obliterative cholangiopathy" is a congenital or acquired disease of the liver and one of the principle forms of chronic rejection of a transplanted liver allograft. As a birth defect in newborn infants, it has an occurrence...

and other pediatric liver diseases
biliary trauma
Physical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
congenital anomalies of the biliary tract
gallstone
Gallstone
A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder, but may pass distally into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of...

s
intrahepatic cholestasis of pregnancy (obstetric cholestasis)
Intrahepatic Cholestasis of Pregnancy
Intrahepatic cholestasis of pregnancy in the United Kingdom, is a medical condition in which cholestasis occurs during pregnancy...
primary biliary cirrhosis
Primary biliary cirrhosis
Primary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring,...

, 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, liver failure and liver cancer...

, associated with inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
some drugs, (e.g. flucloxacillin
Flucloxacillin
Flucloxacillin or floxacillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible Gram-positive bacteria. Unlike other penicillins, flucloxacillin has activity against beta-lactamase-producing organisms such as Staphylococcus...

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. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...

)

Histopathology

Under a microscope

Microscope

A microscope is an instrument used to see objects that are too small for the naked 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 creation of a pattern simulating varying degrees of solidity or shading by using small dots. Such a pattern may occur in nature and these effects are frequently emulated by artists.-Art:...

appearance within the cytoplasm

Cytoplasm

The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained 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

Biological tissue

Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...

, causing hepatic necrosis

Necrosis

Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

. 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. The process of removing the phosphate group is called dephosphorylation...

enzymes. With a few exceptions, the optimal test for cholestasis would be elevations of serum bile acid

Bile acid

Bile acids are steroid acids found predominantly in the bile of mammals. Bile salts are bile acids compounded with a cation, usually sodium. In humans, the salts of taurocholic acid and glycocholic acid represent approximately eighty percent of all bile salts. The two major bile acids are cholic...

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 duct.

In a later stage of cholestasis AST

Aspartate transaminase

Aspartate transaminase , also called aspartate aminotransferase or serum glutamic oxaloacetic transaminase , is a pyridoxal phosphate -dependent transaminase enzyme . AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in...

, ALT

Alanine transaminase

Alanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....

and bilirubin

Bilirubin

Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate 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 is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...

. Jaundice is an uncommon occurrence in intrahepatic cholestasis, but is common in obstructive cholestasis.
pale stool. This symptom implies obstructive cholestasis.
dark urine

Bile

is secreted by the liver to aid in the digestion

Digestion

Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....

of fat

Fat

Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...

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 synonym for the gold compounds used in medicine...

, nitrofurantoin

Nitrofurantoin

Nitrofurantoin is an antibiotic which is marketed under the following brand names; Furadantin, Macrobid, Macrodantin, Nitrofur Mac, Nitro Macro, Nifty-SR, Martifur-MR, Martifur-100 , Urantoin, and Uvamin . It is usually used in treating urinary tract infection...

, anabolic steroids, chlorpromazine

Chlorpromazine

Chlorpromazine is a typical antipsychotic...

, prochlorperazine

Prochlorperazine

Prochlorperazine is a dopamine receptor antagonist that belongs to the phenothiazine class of antipsychotic agents that are used for the antiemetic treatment of nausea and vertigo. It is also a highly-potent typical antipsychotic, 10-20x more potent than chlorpromazine...

, 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 as Clinoril.-Uses:...

, cimetidine

Cimetidine

Cimetidine INN 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. It is marketed by GlaxoSmithKline under the trade name Tagamet...

, 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. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...

, and estrogen

Estrogen

Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

can cause cholestasis and may result in damage to the liver