Bilirubin
Encyclopedia
Bilirubin is the yellow breakdown product of normal heme
catabolism
. Heme is found in hemoglobin
, a principal component of red blood cell
s. Bilirubin is excreted in bile
and urine
, and elevated levels may indicate certain diseases. It is responsible for the yellow color of bruise
s, the yellow color of urine (via its reduced breakdown product, urobilin
), the brown color of faeces (via its conversion to stercobilin
), and the yellow discoloration in jaundice
.
It has also been found in plants.
-like rings (tetrapyrrole). In heme
, by contrast, these four rings are connected into a larger ring, called a porphyrin
ring.
Bilirubin is very similar to the pigment
phycobilin
used by certain algae to capture light energy, and to the pigment phytochrome
used by plants to sense light. All of these contain an open chain of four pyrrolic rings.
Like these other pigments, some of the double-bonds in bilirubin isomerize when exposed to light. This is used in the phototherapy of jaundiced newborns: the E,Z-isomers of bilirubin formed upon light exposure are more soluble than the unilluminated Z,Z-isomer, as the possibility of intramolecular hydrogen bonding is removed . This allows the excretion of unconjugated bilirubin in bile.
Some textbooks and research articles show the incorrect geometric isomer of bilirubin. The naturally occurring isomer is the Z,Z-isomer.
on biliverdin
, a green tetrapyrrolic bile pigment that is also a product of heme catabolism. Bilirubin, when oxidized, reverts to become biliverdin once again. This cycle, in addition to the demonstration of the potent antioxidant activity of bilirubin, has led to the hypothesis that bilirubin's main physiologic role is as a cellular antioxidant.
are disposed off in the spleen
when they get old or damaged. This releases hemoglobin
, which is broken down to heme
as the globin parts are turned into amino acids. The heme is then turned into unconjugated bilirubin in the reticuloendothelial cells of the spleen. This unconjugated bilirubin is not soluble in water, due to intramolecular hydrogen bonding. It is then bound to albumin
and sent to the liver
.
by the enzyme glucuronyltransferase, making it soluble in water. Much of it goes into the bile and thus out into the small intestine. Some of the conjugated bilirubin remains in the large intestine and is metabolised by colonic bacteria to urobilinogen
, which is further metabolized to stercobilinogen
, and finally oxidised to stercobilin
. This stercobilin gives feces its brown color. Some of the urobilinogen is reabsorbed and excreted in the urine along with an oxidized form, urobilin
. Although the terms direct and indirect bilirubin are used equivalently with conjugated and unconjugated bilirubin, this is not quantitatively correct, because the direct fraction includes both conjugated bilirubin and δ bilirubin (bilirubin covalently bound to albumin, which appears in serum when hepatic excretion of conjugated bilirubin is impaired in patients with hepatobiliary disease).
. If the liver's function is impaired or when biliary drainage is blocked, some of the conjugated bilirubin leaks out of the hepatocytes and appears in the urine, turning it dark amber. However, in disorders involving hemolytic anemia
, an increased number of red blood cells are broken down, causing an increase in the amount of unconjugated bilirubin in the blood. Because the unconjugated bilirubin is not water-soluble, one will not see an increase in bilirubin in the urine. Because there is no problem with the liver or bile systems, this excess unconjugated bilirubin will go through all of the normal processing mechanisms that occur (e.g., conjugation, excretion in bile, metabolism to urobilinogen, reabsorption) and will show up as an increase in urine urobilinogen. This difference between increased urine bilirubin and increased urine urobilinogen helps to distinguish between various disorders in those systems.
can lead to accumulation of bilirubin in certain brain regions with consequent irreversible damage to these areas manifesting as various neurological deficits, seizure
s, abnormal reflexes and eye movements. This type of neurological injury is known as kernicterus
. The neurotoxicity of neonatal hyperbilirubinemia manifests because the blood-brain barrier
has yet to develop fully, and bilirubin can freely pass into the brain interstitium, whereas more developed individuals with increased bilirubin in the blood are protected. Aside from specific chronic medical conditions that may lead to hyperbilirubinaemia, neonates in general are at increased risk since they lack the intestinal bacteria that facilitate the breakdown and excretion of conjugated bilirubin in the feces (this is largely why the feces of a neonate are paler than those of an adult). Instead the conjugated bilirubin is converted back into the unconjugated form by the enzyme β-glucuronidase
and a large proportion is reabsorbed through the enterohepatic circulation
.
Bilirubin (in blood) is in one of two forms:
Total bilirubin ("TBIL") measures both BU and BC. Total and direct bilirubin levels can be measured from the blood, but indirect bilirubin is calculated from the total and direct bilirubin.
Indirect bilirubin is fat-soluble and direct bilirubin is water-soluble.
was used for a qualitative estimate of bilirubin.
This test is performed routinely in most medical laboratories
and can be measured by a variety of methods.
Total bilirubin is now often measured by the 2,5-dichlorophenyldiazonium (DPD) method, and direct bilirubin is often measured by the method of Jendrassik and Grof.
s that are similar but not identical. Some examples for adults are provided below (different reference ranges are often used for newborns):
Mild rises in bilirubin may be caused by:
Moderate rise in bilirubin may be caused by:
Very high levels of bilirubin may be caused by:
Cirrhosis may cause normal, moderately high or high levels of bilirubin, depending on exact features of the cirrhosis
To further elucidate the causes of jaundice or increased bilirubin, it is usually simpler to look at other liver function tests
(especially the enzymes alanine transaminase
, aspartate transaminase
, gamma-glutamyl transpeptidase, alkaline phosphatase
), blood film
examination (hemolysis
, etc.) or evidence of infective hepatitis (e.g., hepatitis A, B, C, delta, E, etc.).
may be noticeable in the sclera
(white) of the eyes at levels of about 2 to 3 mg/dL (34 to 51 μmol/L), and in the skin at higher levels.
Jaundice is classified depending upon whether the bilirubin is free or conjugated to glucuronic acid
into conjugated jaundice or unconjugated jaundice.
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
catabolism
Catabolism
Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...
. Heme is found in hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
, a principal component of red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s. Bilirubin is excreted in 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...
and urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, and elevated levels may indicate certain diseases. It is responsible for the yellow color of bruise
Bruise
A bruise, also called a contusion, is a type of relatively minor hematoma of tissue in which capillaries and sometimes venules are damaged by trauma, allowing blood to seep into the surrounding interstitial tissues. Bruises can involve capillaries at the level of skin, subcutaneous tissue, muscle,...
s, the yellow color of urine (via its reduced breakdown product, urobilin
Urobilin
Urobilin is a yellow linear tetrapyrrole, resulting from the breakdown of heme, a cyclic tetrapyrrole.Urobilin is produced when Urobilinogen is oxidized by intestinal bacteria; it can also be...
), the brown color of faeces (via its conversion to stercobilin
Stercobilin
Stercobilin is a tetrapyrrolic bile pigment and is one end-product of heme catabolism. It is the chemical responsible for the brown color of human fecal material and was originally isolated from feces in 1932...
), and the yellow discoloration in 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...
.
It has also been found in plants.
Chemistry
Bilirubin consists of an open chain of four pyrrolePyrrole
Pyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4H4NH. It is a colourless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C4H4NCH3...
-like rings (tetrapyrrole). In heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
, by contrast, these four rings are connected into a larger ring, called a porphyrin
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
ring.
Bilirubin is very similar to the pigment
Pigment
A pigment is a material that changes the color of reflected or transmitted light as the result of wavelength-selective absorption. This physical process differs from fluorescence, phosphorescence, and other forms of luminescence, in which a material emits light.Many materials selectively absorb...
phycobilin
Phycobilin
Phycobilins are chromophores found in cyanobacteria and in the chloroplasts of red algae, glaucophytes and some cryptomonads...
used by certain algae to capture light energy, and to the pigment phytochrome
Phytochrome
Phytochrome is a photoreceptor, a pigment that plants use to detect light. It is sensitive to light in the red and far-red region of the visible spectrum. Many flowering plants use it to regulate the time of flowering based on the length of day and night and to set circadian rhythms...
used by plants to sense light. All of these contain an open chain of four pyrrolic rings.
Like these other pigments, some of the double-bonds in bilirubin isomerize when exposed to light. This is used in the phototherapy of jaundiced newborns: the E,Z-isomers of bilirubin formed upon light exposure are more soluble than the unilluminated Z,Z-isomer, as the possibility of intramolecular hydrogen bonding is removed . This allows the excretion of unconjugated bilirubin in bile.
Some textbooks and research articles show the incorrect geometric isomer of bilirubin. The naturally occurring isomer is the Z,Z-isomer.
Function
Bilirubin is created by the activity of biliverdin reductaseBiliverdin reductase
Biliverdin reductase is an enzyme found in the liver that facilitates the conversion of biliverdin to bilirubin. It accomplishes this through the reduction of a double-bond between the second and third pyrrole ring into a single-bond....
on biliverdin
Biliverdin
Biliverdin is a green tetrapyrrolic bile pigment, and is a product of heme catabolism. It is the pigment responsible for a greenish color sometimes seen in bruises.- Metabolism :...
, a green tetrapyrrolic bile pigment that is also a product of heme catabolism. Bilirubin, when oxidized, reverts to become biliverdin once again. This cycle, in addition to the demonstration of the potent antioxidant activity of bilirubin, has led to the hypothesis that bilirubin's main physiologic role is as a cellular antioxidant.
Unconjugated (indirect)
Erythrocytes (red blood cells) generated in the bone marrowBone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
are disposed off in the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
when they get old or damaged. This releases hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
, which is broken down to heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
as the globin parts are turned into amino acids. The heme is then turned into unconjugated bilirubin in the reticuloendothelial cells of the spleen. This unconjugated bilirubin is not soluble in water, due to intramolecular hydrogen bonding. It is then bound to albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
and sent to 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...
.
Conjugated (direct)
In the liver it is conjugated with glucuronic acidGlucuronic acid
Glucuronic acid is a carboxylic acid. Its structure is similar to that of glucose. However, glucuronic acid's sixth carbon is oxidized to a carboxylic acid...
by the enzyme glucuronyltransferase, making it soluble in water. Much of it goes into the bile and thus out into the small intestine. Some of the conjugated bilirubin remains in the large intestine and is metabolised by colonic bacteria to urobilinogen
Urobilinogen
Urobilinogen is a colourless product of bilirubin reduction. It is formed in the intestines by bacterial action. Some urobilinogen is reabsorbed, taken up into the circulation and excreted by the kidney. This constitutes the normal "enterohepatic urobilinogen cycle".Increased amounts of bilirubin...
, which is further metabolized to stercobilinogen
Stercobilinogen
Stercobilinogen is a chemical created by bacteria in the gut. It is made of broken-down hemoglobin. It is further processed to become the chemical that gives feces its brown color....
, and finally oxidised to stercobilin
Stercobilin
Stercobilin is a tetrapyrrolic bile pigment and is one end-product of heme catabolism. It is the chemical responsible for the brown color of human fecal material and was originally isolated from feces in 1932...
. This stercobilin gives feces its brown color. Some of the urobilinogen is reabsorbed and excreted in the urine along with an oxidized form, urobilin
Urobilin
Urobilin is a yellow linear tetrapyrrole, resulting from the breakdown of heme, a cyclic tetrapyrrole.Urobilin is produced when Urobilinogen is oxidized by intestinal bacteria; it can also be...
. Although the terms direct and indirect bilirubin are used equivalently with conjugated and unconjugated bilirubin, this is not quantitatively correct, because the direct fraction includes both conjugated bilirubin and δ bilirubin (bilirubin covalently bound to albumin, which appears in serum when hepatic excretion of conjugated bilirubin is impaired in patients with hepatobiliary disease).
Urine
Under normal circumstances, a tiny amount of bilirubin, if any, is excreted in the urineUrine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
. If the liver's function is impaired or when biliary drainage is blocked, some of the conjugated bilirubin leaks out of the hepatocytes and appears in the urine, turning it dark amber. However, in disorders involving hemolytic anemia
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
, an increased number of red blood cells are broken down, causing an increase in the amount of unconjugated bilirubin in the blood. Because the unconjugated bilirubin is not water-soluble, one will not see an increase in bilirubin in the urine. Because there is no problem with the liver or bile systems, this excess unconjugated bilirubin will go through all of the normal processing mechanisms that occur (e.g., conjugation, excretion in bile, metabolism to urobilinogen, reabsorption) and will show up as an increase in urine urobilinogen. This difference between increased urine bilirubin and increased urine urobilinogen helps to distinguish between various disorders in those systems.
Toxicity
Unconjugated hyperbilirubinaemia in a neonateInfant
A newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth...
can lead to accumulation of bilirubin in certain brain regions with consequent irreversible damage to these areas manifesting as various neurological deficits, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s, abnormal reflexes and eye movements. This type of neurological injury is known as kernicterus
Kernicterus
Kernicterus is damage to the brain centers of infants caused by increased levels of unconjugated bilirubin. This may be due to several underlying pathologic processes. Newborn babies are often polycythemic. When they break down the erythrocytes, one of the byproducts is bilirubin, which circulates...
. The neurotoxicity of neonatal hyperbilirubinemia manifests because the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
has yet to develop fully, and bilirubin can freely pass into the brain interstitium, whereas more developed individuals with increased bilirubin in the blood are protected. Aside from specific chronic medical conditions that may lead to hyperbilirubinaemia, neonates in general are at increased risk since they lack the intestinal bacteria that facilitate the breakdown and excretion of conjugated bilirubin in the feces (this is largely why the feces of a neonate are paler than those of an adult). Instead the conjugated bilirubin is converted back into the unconjugated form by the enzyme β-glucuronidase
Glucuronidase
Beta-glucuronidases are members of the glycosidase family of enzymes that catalyze breakdown of complex carbohydrates. Human β-glucuronidase is a type of glucuronidase that catalyzes hydrolysis of β-D-glucuronic acid residues from the non-reducing end of mucopolysaccharides such as heparan sulfate...
and a large proportion is reabsorbed through the enterohepatic circulation
Enterohepatic circulation
Enterohepatic circulation refers to the circulation of biliary acids from the liver, where they are produced and secreted in the bile, to the small intestine, where it aids in digestion of fats and other substances, back to the liver....
.
Blood tests
Bilirubin is broken down by light. Tubes containing blood or (especially) serum to be used in bilirubin assays should be protected from illumination.Bilirubin (in blood) is in one of two forms:
| Abb. | Name(s) | Water-soluble? | Reaction >- | "BC" |
"Conjugated" or "Direct bilirubin" |
Yes (bound to glucuronic acid Glucuronic acid Glucuronic acid is a carboxylic acid. Its structure is similar to that of glucose. However, glucuronic acid's sixth carbon is oxidized to a carboxylic acid... ) |
azobilirubin Azobilirubin Azobilirubin: The red-violet compound formed by the condensation of diazotized sulfanilic acid with bilirubin in the van den Bergh reaction.... "Direct bilirubin" >- | "BU" |
"Unconjugated" or "Indirect bilirubin" | No | Reacts more slowly. Still produces azobilirubin. Ethanol makes all bilirubin react promptly then calc: Indirect bilirubin = Total bilirubin - Direct bilirubin |
Total bilirubin ("TBIL") measures both BU and BC. Total and direct bilirubin levels can be measured from the blood, but indirect bilirubin is calculated from the total and direct bilirubin.
Indirect bilirubin is fat-soluble and direct bilirubin is water-soluble.
Measurement methods
Originally the Van den Bergh reactionVan den Bergh reaction
Clark Van den Berghe reaction is a chemical reaction used to measure bilirubin levels in blood. More specifically, it determines the amount of conjugated bilirubin in the blood. The reaction produces azobilirubin....
was used for a qualitative estimate of bilirubin.
This test is performed routinely in most medical laboratories
Medical laboratory
A medical laboratory or clinical laboratory is a laboratory where tests are done on clinical specimens in order to get information about the health of a patient as pertaining to the diagnosis, treatment, and prevention of disease.-Departments:...
and can be measured by a variety of methods.
Total bilirubin is now often measured by the 2,5-dichlorophenyldiazonium (DPD) method, and direct bilirubin is often measured by the method of Jendrassik and Grof.
Blood levels
There are no normal levels of bilirubin as it is an excretion product, and levels found in the body reflects the balance between production and excretion. Different sources provide reference rangeReference ranges for common blood tests
Reference ranges for blood tests are sets of values used by a health professional to interpret a set of medical test results from blood samples....
s that are similar but not identical. Some examples for adults are provided below (different reference ranges are often used for newborns):
| umol/L | mg/dL >- | total bilirubin |
5.1–17.0 | 0.3–1.0, | 1.0–5.1 | 0-0.3, 0.1–0.3, 0.1-0.4 |
Hyperbilirubinemia
Hyperbilirubinemia results from a higher-than-normal level of bilirubin in the blood.Mild rises in bilirubin may be caused by:
- HemolysisHemolysisHemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
or increased breakdown of red blood cells - Gilbert's syndromeGilbert's syndromeGilbert's syndrome , often shortened to GS, also called Gilbert-Meulengracht syndrome, is the most common hereditary cause of increased bilirubin and is found in up to 5% of the population...
- a genetic disorder of bilirubin metabolism that can result in mild jaundice, found in about 5% of the population - Rotor syndromeRotor syndromeRotor syndrome, also called Rotor type hyperbilirubinemia, is a rare, relatively benign autosomal recessive bilirubin disorder of unknown origin...
: non-itching jaundice, with rise of bilirubin in the patient's serum, mainly of the conjugated type.
Moderate rise in bilirubin may be caused by:
- Pharmaceutical drugs (especially antipsychoticAntipsychoticAn antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
, some sex hormones, and a wide range of other drugs)
- SulfonamideSulfonamideSulfonamide or sulphonamide may refer to:*Sulfonamide – the sulfonamide functional group. *Sulfonamide – the group of sulfonamide antibacterial drugs....
s are contraindicated in infants less than 2 months old (exception when used with pyrimethaminePyrimethaminePyrimethamine is a medication used for protozoal infections. It is commonly used as an antimalarial drug , and is also used in the treatment of Toxoplasma gondii infections in immunocompromised patients, such as HIV-positive individuals.-Mechanism of action:Pyrimethamine interferes with...
in treating toxoplasmosisToxoplasmosisToxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself...
) as they increase unconjugated bilirubin leading to kernicterusKernicterusKernicterus is damage to the brain centers of infants caused by increased levels of unconjugated bilirubin. This may be due to several underlying pathologic processes. Newborn babies are often polycythemic. When they break down the erythrocytes, one of the byproducts is bilirubin, which circulates...
.- HepatitisHepatitisHepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
(levels may be moderate or high) - ChemotherapyChemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
- Biliary stricture (benign or malignant)
- Hepatitis
Very high levels of bilirubin may be caused by:
- Neonatal hyperbilirubinaemiaNeonatal jaundiceNeonatal jaundice or Neonatal hyperbilirubinemia is a yellowing of the skin and other tissues of a newborn infant. A bilirubin level of more than 85 umol/l manifests clinical jaundice in neonates whereas in adults a level of 34 umol/l would look icteric...
, where the newborn's liver is not able to properly process the bilirubin causing jaundiceJaundiceJaundice 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... - Unusually large bile duct obstruction, e.g. stone in common bile duct, tumour obstructing common bile duct etc.
- Severe liver failure with cirrhosisCirrhosisCirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
(e.g. primary biliary cirrhosisPrimary biliary cirrhosisPrimary 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,...
) - Crigler-Najjar syndromeCrigler-Najjar syndromeCrigler-Najjar Syndrome or CNS is a rare disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of blood. The disorder results in an inherited form of non-hemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in...
- Dubin-Johnson syndromeDubin-Johnson syndromeDubin–Johnson syndrome is an autosomal recessive disorder that causes an increase of conjugated bilirubin in the serum without elevation of liver enzymes . This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile, and is similar to...
- Choledocholithiasis (chronic or acute)
Cirrhosis may cause normal, moderately high or high levels of bilirubin, depending on exact features of the cirrhosis
To further elucidate the causes of jaundice or increased bilirubin, it is usually simpler to look at other liver function tests
Liver function tests
Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...
(especially the enzymes alanine transaminase
Alanine transaminase
Alanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
, aspartate transaminase
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...
, gamma-glutamyl transpeptidase, alkaline phosphatase
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...
), blood film
Blood film
A blood film or peripheral blood smear is a thin layer of blood smeared on a microscope slide and then stained in such a way to allow the various blood cells to be examined microscopically...
examination (hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
, etc.) or evidence of infective hepatitis (e.g., hepatitis A, B, C, delta, E, etc.).
Jaundice
JaundiceJaundice
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...
may be noticeable in the sclera
Sclera
The sclera , also known as the white or white of the eye, is the opaque , fibrous, protective, outer layer of the eye containing collagen and elastic fiber. In the development of the embryo, the sclera is derived from the neural crest...
(white) of the eyes at levels of about 2 to 3 mg/dL (34 to 51 μmol/L), and in the skin at higher levels.
Jaundice is classified depending upon whether the bilirubin is free or conjugated to glucuronic acid
Glucuronic acid
Glucuronic acid is a carboxylic acid. Its structure is similar to that of glucose. However, glucuronic acid's sixth carbon is oxidized to a carboxylic acid...
into conjugated jaundice or unconjugated jaundice.
See also
- Biliary atresiaBiliary atresiaBiliary 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...
- Bilirubin diglucuronideBilirubin diglucuronideBilirubin diglucuronide is a conjugated form of bilirubin formed in bilirubin metabolism. The hydrophilic character of bilirubin diglucuronide enables it to be water-soluble. It is pumped across the hepatic canalicular membrane into the bile by the transporter MRP2....
- BiliverdinBiliverdinBiliverdin is a green tetrapyrrolic bile pigment, and is a product of heme catabolism. It is the pigment responsible for a greenish color sometimes seen in bruises.- Metabolism :...
- Crigler-Najjar syndromeCrigler-Najjar syndromeCrigler-Najjar Syndrome or CNS is a rare disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of blood. The disorder results in an inherited form of non-hemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in...
- Gilbert's syndromeGilbert's syndromeGilbert's syndrome , often shortened to GS, also called Gilbert-Meulengracht syndrome, is the most common hereditary cause of increased bilirubin and is found in up to 5% of the population...
, a genetic disorder of bilirubin metabolism that can result in mild jaundice, found in about 5% of the population. - Hy's LawHy's lawHy's law is a prognostic indicator that a pure drug-induced liver injury leading to jaundice, without a hepatic transplant, has a case fatality rate of 10% to 50%...
- Primary biliary cirrhosisPrimary biliary cirrhosisPrimary 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,...
- Primary sclerosing cholangitisPrimary sclerosing cholangitisPrimary 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...