Bilirubin

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Bilirubin
Bilirubin (CAS 635-65-4).svg
Bilirubin-from-xtal-1978-3D-balls.png
Names
IUPAC name
3,3′-(2,17-Diethenyl-3,7,13,18-tetramethyl-1,19-dioxo-10,19,21,22,23,24-hexahydro-1H-biline-8,12-diyl)dipropanoic acid
Systematic IUPAC name
3,3′-([12(2)Z,6(72)Z]-13,74-Diethenyl-14,33,54,73-tetramethyl-15,75-dioxo-11,15,71,75-tetrahydro-31H,51H-1,7(2),3,5(2,5)-tetrapyrrolaheptaphane-12(2),6(72)-diene-34,53-diyl)dipropanoic acid
Other names
Bilirubin IXα
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.010.218 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C33H36N4O6/c1-7-20-19(6)32(42)37-27(20)14-25-18(5)23(10-12-31(40)41)29(35-25)15-28-22(9-11-30(38)39)17(4)24(34-28)13-26-16(3)21(8-2)33(43)36-26/h7-8,13-14,34-35H,1-2,9-12,15H2,3-6H3,(H,36,43)(H,37,42)(H,38,39)(H,40,41)/b26-13-,27-14- Yes check.svgY
    Key: BPYKTIZUTYGOLE-IFADSCNNSA-N Yes check.svgY
  • Key: BPYKTIZUTYGOLE-IFADSCNNBS
  • CC1=C(/C=C2C(C)=C(C=C)C(N/2)=O)NC(CC3=C(CCC(O)=O)C(C)=C(/C=C4C(C=C)=C(C)C(N/4)=O)N3)=C1CCC(O)=O
  • Cc1c(c([nH]c1/C=C\2/C(=C(C(=O)N2)C=C)C)Cc3c(c(c([nH]3)/C=C\4/C(=C(C(=O)N4)C)C=C)C)CCC(=O)O)CCC(=O)O
Properties
C33H36N4O6
Molar mass 584.673 g·mol−1
Density 1.31 g·cm-3 [1]
Melting point 235°C [2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Bilirubin (BR) (from the Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the destruction of aged or abnormal red blood cells. [3] In the first step of bilirubin synthesis, the heme molecule is stripped from the hemoglobin molecule. Heme then passes through various processes of porphyrin catabolism, which varies according to the region of the body in which the breakdown occurs. For example, the molecules excreted in the urine differ from those in the feces. [4] The production of biliverdin from heme is the first major step in the catabolic pathway, after which the enzyme biliverdin reductase performs the second step, producing bilirubin from biliverdin. [5] [6]

Ultimately, bilirubin is broken down within the body, and its metabolites excreted through bile and urine; elevated levels may indicate certain diseases. [7] It is responsible for the yellow color of healing bruises and the yellow discoloration in jaundice. The bacterial enzyme bilirubin reductase is responsible for the breakdown of bilirubin in the gut. [8] One breakdown product, urobilin, is the main component of the straw-yellow color in urine. [9] Another breakdown product, stercobilin, causes the brown color of feces.

Although bilirubin is usually found in animals rather than plants, at least one plant species, Strelitzia nicolai , is known to contain the pigment. [10]

Structure

Bilirubin consists of an open-chain tetrapyrrole. It is formed by oxidative cleavage of a porphyrin in heme, which affords biliverdin. Biliverdin is reduced to bilirubin. After conjugation with glucuronic acid, bilirubin is water-soluble and can be excreted. [11]

Bilirubin is structurally 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.[ citation needed ]

Like these other pigments, some of the double-bonds in bilirubin isomerize when exposed to light. This isomerization is relevant to 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. [12] Increased solubility allows the excretion of unconjugated bilirubin in bile.

Some textbooks and research articles show the incorrect geometric isomer of bilirubin. [13] The naturally occurring isomer is the Z,Z-isomer.

Function

Bilirubin is created by the activity of biliverdin reductase 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, [14] has led to the hypothesis that bilirubin's main physiologic role is as a cellular antioxidant. [15] [16] Consistent with this, animal studies suggest that eliminating bilirubin results in endogenous oxidative stress. [17] Bilirubin's antioxidant activity may be particularly important in the brain, where it prevents excitotoxicity and neuronal death by scavenging superoxide during N-methyl-D-aspartic acid neurotransmission. [18]

Metabolism

Heme metabolism Heme Breakdown.png
Heme metabolism
Heme and bilirubin metabolism Bilirubin metabolism diagram.png
Heme and bilirubin metabolism

Bilirubin in plasma is mostly produced by the destruction of erythrocytes. Heme is metabolized into biliverdin (via heme oxygenase) and then into bilirubin (via biliverdin reductase) inside the macrophages. [11]

Bilirubin is then released into the plasma and transported to the liver bound by albumin, since it is insoluble in water in this state. In this state, bilirubin is called unconjugated (despite being bound by albumin). [11]

In the liver, unconjugated bilirubin is up-taken by the hepatocytes and subsequently conjugated with glucuronic acid (via the enzyme uridine diphosphate–glucuronyl transferase). In this state, bilirubin is soluble in water and it is called conjugated bilirubin. [11]

Conjugated bilirubin is excreted into the bile ducts and enters the duodenum. During its transport to the colon, it is converted into urobilinogen by the bacterial enzyme bilirubin reductase. [8] Most of the urobilinogen is further reduced into stercobilinogen and is excreted through feces (air oxidizes stercobilinogen to stercobilin, which gives feces their characteristic brown color). [11]

A lesser amount of urobilinogen is re-absorbed into portal circulation and transferred to the liver. For the most part, this urobilinogen is recycled to conjugated bilirubin and this process closes the enterohepatic circle. There is also an amount of urobilinogen which is not recycled, but rather enters the systemic circulation and subsequently the kidneys, where it is excreted. Air oxidizes urobilinogen into urobilin, which gives urine its characteristic color. [11] [19]

In parallel, a small amount of conjugated billirubin can also enter the systemic circulation and get excreted through urine. This is exaggerated in various pathological situations. [19]

Toxicity

Hyperbilirubinemia

Hyperbilirubinemia is a higher-than-normal level of bilirubin in the blood. Hyperbilirubinemia may refer to increased levels of conjugated, unconjugated or both conjugated and unconjugated bilirubin. The causes of hyperbilirubinemia can also be classified into prehepatic, intrahepatic, and posthepatic. [20]

Prehepatic causes are associated mostly with an increase of unconjugated (indirect) bilirubin. [20] They include:

Intrahepatic causes can be associated with elevated levels of conjugated bilirubin, unconjugated bilirubin or both. [20] They include: [20]

Post-hepatic causes are associated with elevated levels of conjugated bilirubin. [20] These include: [20]

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.).

Jaundice

Hemoglobin acts to transport oxygen which the body receives to all body tissue via blood vessels. Over time, when red blood cells need to be replenished, the hemoglobin is broken down in the spleen; it breaks down into two parts: heme group consisting of iron and bile and protein fraction. While protein and iron are utilized to renew red blood cells, pigments that make up the red color in blood are deposited into the bile to form bilirubin. [23] Jaundice leads to raised bilirubin levels that in turn negatively remove elastin-rich tissues. [24] Jaundice may be noticeable in the sclera of the eyes at levels of about 2 to 3 mg/dl (34 to 51 μmol/L), [25] and in the skin at higher levels. [note 1]

Jaundice is classified, depending upon whether the bilirubin is free or conjugated to glucuronic acid, into conjugated jaundice or unconjugated jaundice.[ citation needed ]

Kernicterus

Unbound bilirubin (Bf) levels can be used to predict the risk of neurodevelopmental handicaps within infants. [26] Unconjugated hyperbilirubinemia in a newborn can lead to accumulation of bilirubin in certain brain regions (particularly the basal nuclei) with consequent irreversible damage to these areas manifesting as various neurological deficits, seizures, abnormal reflexes and eye movements. This type of neurological injury is known as kernicterus. The spectrum of clinical effect is called bilirubin encephalopathy. The neurotoxicity of neonatal hyperbilirubinemia manifests because the blood–brain barrier has yet to develop fully,[ dubious – discuss ] 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 hyperbilirubinemia, 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 (in the gut, this enzyme is located in the brush border of the lining intestinal cells) and a large proportion is reabsorbed through the enterohepatic circulation. In addition, recent studies point towards high total bilirubin levels as a cause for gallstones regardless of gender or age. [27]

Health benefits

In the absence of liver disease, high levels of total bilirubin confers various health benefits. [28] Studies have also revealed that levels of serum bilirubin (SBR) [29] are inversely related to risk of certain heart diseases. [30] [31] While the poor solubility and potential toxicity of bilirubin limit its potential medicinal applications, current research is being done on whether bilirubin encapsulated silk fibrin nanoparticles can alleviate symptoms of disorders such as acute pancreatitis. [32] In addition to this, there has been recent discoveries linking bilirubin and its ε-polylysine-bilirubin conjugate (PLL-BR), to more efficient insulin medication. It seems that bilirubin exhibits protective properties during the islet transplantation process when drugs are delivered throughout the bloodstream. [33]

Blood tests

Bilirubin is degraded by light. Blood collection tubes containing blood or (especially) serum to be used in bilirubin assays should be protected from illumination. [34] For adults, blood is typically collected by needle from a vein in the arm. [35] In newborns, blood is often collected from a heel stick, a technique that uses a small, sharp blade to cut the skin on the infant's heel and collect a few drops of blood into a small tube. Non-invasive technology is available in some health care facilities that will measure bilirubin by using an bilirubinometer which shines light onto the skin and calculates the amount of bilirubin by analysing how the light is absorbed or reflects. [36] This device is also known as a transcutaneous bilirubin meter. [37]

Bilirubin (in blood) is found in two forms:

Abb.Name(s)Water-solubleReaction
"BC""Conjugated bilirubin"Yes (bound to glucuronic acid)Reacts quickly when dyes (diazo reagent) are added to the blood specimen to produce azobilirubin "Direct bilirubin"
"BU""Unconjugated bilirubin"NoReacts more slowly, still produces azobilirubin, Ethanol makes all bilirubin react promptly, then: indirect bilirubin = total bilirubin – direct bilirubin

Note: Conjugated bilirubin is often incorrectly called "direct bilirubin" and unconjugated bilirubin is incorrectly called "indirect bilirubin". Direct and indirect refer solely to how compounds are measured or detected in solution. Direct bilirubin is any form of bilirubin which is water-soluble and is available in solution to react with assay reagents; direct bilirubin is often made up largely of conjugated bilirubin, but some unconjugated bilirubin (up to 25%) can still be part of the "direct" bilirubin fraction. Likewise, not all conjugated bilirubin is readily available in solution for reaction or detection (for example, if it is hydrogen bonding with itself) and therefore would not be included in the direct bilirubin fraction.[ citation needed ]

Total bilirubin (TBIL) measures both BU and BC. Total bilirubin assays work by using surfactants and accelerators (like caffeine) to bring all of the different bilirubin forms into solution where they can react with assay reagents. 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. [38]

Total bilirubin

Total bilirubin = direct bilirubin + indirect bilirubin [39]

Elevation of both alanine aminotransferase (ALT) and bilirubin is more indicative of serious liver injury than is elevation in ALT alone, as postulated in Hy's law that elucidates the relation between the lab test results and drug-induced liver injury [40]

Indirect (unconjugated)

The measurement of unconjugated bilirubin (UCB) is underestimated by measurement of indirect bilirubin, as unconjugated bilirubin (without/yet glucuronidation) reacts with diazosulfanilic acid to create azobilirubin which is measured as direct bilirubin. [41] [42]

Direct

Direct bilirubin = Conjugated bilirubin + delta bilirubin [39]

Conjugated

In the liver, bilirubin is conjugated with glucuronic acid by the enzyme glucuronyltransferase, first to bilirubin glucuronide and then to bilirubin diglucuronide, making it soluble in water: the conjugated version is the main form of bilirubin present in the "direct" bilirubin fraction. Much of it goes into the bile and thus out into the small intestine. Though most bile acid is reabsorbed in the terminal ileum to participate in enterohepatic circulation, conjugated bilirubin is not absorbed and instead passes into the colon. [43]

There, colonic bacteria deconjugate and metabolize the bilirubin into colorless urobilinogen, which can be oxidized to form urobilin and stercobilin. Urobilin is excreted by the kidneys to give urine its yellow color and stercobilin is excreted in the feces giving stool its characteristic brown color. A trace (~1%) of the urobilinogen is reabsorbed into the enterohepatic circulation to be re-excreted in the bile. [44]

Conjugated bilirubin's half-life is shorter than delta bilirubin. [45]

Delta bilirubin

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.[ citation needed ]

Delta bilirubin is albumin-bound conjugated bilirubin. [39] In the other words, delta bilirubin is the kind of bilirubin covalently bound to albumin, which appears in the serum when hepatic excretion of conjugated bilirubin is impaired in patients with hepatobiliary disease. [46] Furthermore, direct bilirubin tends to overestimate conjugated bilirubin levels due to unconjugated bilirubin that has reacted with diazosulfanilic acid, leading to increased azobilirubin levels (and increased direct bilirubin).

δ bilirubin = total bilirubin – (unconjugated bilirubin + conjugated bilirubin) [39]

Half-life

The half-life of delta bilirubin is equivalent to that of albumin since the former is bound to the latter, yields 2–3 weeks. [47] [41]

A free-of-bound bilirubin has a half-life of 2 to 4 hours. [47]

Measurement methods

Originally, the Van den Bergh reaction 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. [48]

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. [49]

Blood levels

The bilirubin level found in the body reflects the balance between production and excretion. Blood test results are advised to always be interpreted using the reference range provided by the laboratory that performed the test. The SI units are μmol/L. [50] Typical ranges for adults are: [51]

μmol/l = micromole/litremg/dl = milligram/ decilitre
total bilirubin<21 [52] <1.23
direct bilirubin1.0–5.1 [53] 0–0.3, [54]
0.1–0.3, [53]
0.1–0.4 [55]
Blood values sorted by mass and molar concentration.png
Reference ranges for blood tests, comparing blood content of bilirubin (shown in blue near horizontal center at around 3 mg/L and 3 μmol/L, scroll to the right to view) with other constituents [56]

Urine tests

Urine bilirubin may also be clinically significant. [57] Bilirubin is not normally detectable in the urine of healthy people. If the blood level of conjugated bilirubin becomes elevated, e.g. due to liver disease, excess conjugated bilirubin is excreted in the urine, indicating a pathological process. [58] Unconjugated bilirubin is not water-soluble and so is not excreted in the urine. Testing urine for both bilirubin and urobilinogen can help differentiate obstructive liver disease from other causes of jaundice. [59]

As with billirubin, under normal circumstances, only a very small amount of urobilinogen is excreted in the urine. 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 of urobilinogen in the urine. This difference between increased urine bilirubin and increased urine urobilinogen helps to distinguish between various disorders in those systems. [59]

History

In ancient history, Hippocrates discussed bile pigments in two of the four humours in the context of a relationship between yellow and black biles. [60] Hippocrates visited Democritus in Abdera who was regarded as the expert in melancholy "black bile". [60]

Relevant documentation emerged in 1827 when M. Louis Jacques Thénard examined the biliary tract of an elephant that had died at a Paris zoo. He observed dilated bile ducts were full of yellow magma, which he isolated and found to be insoluble in water. Treating the yellow pigment with hydrochloric acid produced a strong green color. Thenard suspected the green pigment was caused by impurities derived from mucus of bile. [60]

Leopold Gmelin experimented with nitric acid in 1826 to establish the redox behavior in change from bilirubin to biliverdin, although the nomenclature did not exist at the time. [60] The term biliverdin was coined by Jöns Jacob Berzelius in 1840, although he preferred "bilifulvin" (yellow/red) over "bilirubin" (red). The term "bilirubin" was thought to have become mainstream based on the works of Staedeler in 1864 who crystallized bilirubin from cattle gallstones. [60] [61]

Rudolf Virchow in 1847 recognized hematoidin to be identical to bilirubin. [62] It is not always distinguished from hematoidin, which one modern dictionary defines as synonymous with it [63] but another defines as "apparently chemically identical with bilirubin but with a different site of origin, formed locally in the tissues from hemoglobin, particularly under conditions of reduced oxygen tension." [64] [60] The synonymous identity of bilirubin and hematoidin was confirmed in 1923 by Fischer and Steinmetz using analytical crystallography. [60]

In the 1930s, significant advances in bilirubin isolation and synthesis were described by Hans Fischer, Plieninger, and others, [60] and pioneering work pertaining to endogenous formation of bilirubin from heme was likewise conducted in the same decade. [65] The suffix IXα is partially based on a system developed Fischer, which means the bilin's parent compound was protoporphyrin IX cleaved at the alpha-methine bridge (see protoporphyrin IX nomenclature). [66]

Origins pertaining to the physiological activity of bilirubin were described by Ernst Stadelmann in 1891, who may have observed the biotransformation of infused hemoglobin into bilirubin possibly inspired by Ivan Tarkhanov's 1874 works. [60] Georg Barkan suggested the source of endogenous bilirubin to be from hemoglobin in 1932. [67] Plieninger and Fischer demonstrated an enzymatic oxidative loss of the alpha-methine bridge of heme resulting in a bis-lactam structure in 1942. [60] It is widely accepted that Irving London was the first to demonstrate endogenous formation of bilirubin from hemoglobin in 1950, [68] and Sjostrand demonstrated hemoglobin catabolism produces carbon monoxide between 1949 and 1952. [65] 14C labeled protoporphyrin biotransformation to bilirubin evidence emerged in 1966 by Cecil Watson. [60] Rudi Schmid and Tenhunen discovered heme oxygenase, the enzyme responsible, in 1968. [65] Earlier in 1963, Nakajima described a soluble "heme alpha-methnyl oxygeanse" which what later determined to be a non-enzymatic pathway, such as formation of a 1,2-Dioxetane intermediate at the methine bridge resulting in carbon monoxide release and biliverdin formation. [66]

Notable people

See also

Notes

  1. ↑ For conversion, 1 mg/dl = 17.1 μmol/L.

Related Research Articles

<span class="mw-page-title-main">Jaundice</span> Abnormal pigmentation symptom for disease of the liver

Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metabolism, liver dysfunction, or biliary-tract obstruction. The prevalence of jaundice in adults is rare, while jaundice in babies is common, with an estimated 80% affected during their first week of life. The most commonly associated symptoms of jaundice are itchiness, pale feces, and dark urine.

<span class="mw-page-title-main">Heme</span> Chemical coordination complex of an iron ion chelated to a porphyrin

Heme, or haem, is a ring-shaped iron-containing molecular component of hemoglobin, which is necessary to bind oxygen in the bloodstream. It is composed of four pyrrole rings with 2 vinyl and 2 propionic acid side chains. Heme is biosynthesized in both the bone marrow and the liver.

Liver function tests, also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin time (aPTT), albumin, bilirubin, and others. The liver transaminases aspartate transaminase and alanine transaminase are useful biomarkers of liver injury in a patient with some degree of intact liver function.

<span class="mw-page-title-main">Stercobilin</span> Brown pigment of bile origin

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 feces and was originally isolated from feces in 1932. Stercobilin can be used as a marker for biochemical identification of fecal pollution levels in rivers.

<span class="mw-page-title-main">Kernicterus</span> Medical condition

Kernicterus is a bilirubin-induced brain dysfunction. The term was coined in 1904 by Christian Georg Schmorl. Bilirubin is a naturally occurring substance in the body of humans and many other animals, but it is neurotoxic when its concentration in the blood is too high, a condition known as hyperbilirubinemia. Hyperbilirubinemia may cause bilirubin to accumulate in the grey matter of the central nervous system, potentially causing irreversible neurological damage. Depending on the level of exposure, the effects range from clinically unnoticeable to severe brain damage and even death.

<span class="mw-page-title-main">Gilbert's syndrome</span> Medical condition

Gilbert syndrome (GS) is a syndrome in which the liver of affected individuals processes bilirubin more slowly than the majority. Many people never have symptoms. Occasionally jaundice may occur.

<span class="mw-page-title-main">Enterohepatic circulation</span> Circulation of substances in the human digestive system

Enterohepatic circulation is the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. Enterohepatic circulation is an especially important concept in the field of toxicology as many lipophilic xenobiotics undergo this process causing repeated liver damage.

<span class="mw-page-title-main">Neonatal jaundice</span> Medical condition

Neonatal jaundice is a yellowish discoloration of the white part of the eyes and skin in a newborn baby due to high bilirubin levels. Other symptoms may include excess sleepiness or poor feeding. Complications may include seizures, cerebral palsy, or kernicterus.

<span class="mw-page-title-main">Dubin–Johnson syndrome</span> Genetic liver disease

Dubin–Johnson syndrome is a rare, autosomal recessive, benign disorder that causes an isolated increase of conjugated bilirubin in the serum. Classically, the condition causes a black liver due to the deposition of a pigment similar to melanin. This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile, and is similar to Rotor syndrome. It is usually asymptomatic, but may be diagnosed in early infancy based on laboratory tests. No treatment is usually needed.

<span class="mw-page-title-main">Urobilinogen</span> Chemical compound

Urobilinogen is a yellow by-product of bilirubin reduction. It is formed in the intestines by the bacterial enzyme bilirubin reductase. About half of the urobilinogen formed is reabsorbed and taken up via the portal vein to the liver, enters circulation and is excreted by the kidney.

<span class="mw-page-title-main">Crigler–Najjar syndrome</span> Rare inherited disorder affecting the metabolism of bilirubin

Crigler–Najjar syndrome is a rare inherited disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of the heme in red blood cells. The disorder results in a form of nonhemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in infants. The disorder is inherited in an autosomal recessive manner. The annual incidence is estimated at 1 in 1,000,000.

<span class="mw-page-title-main">Urobilin</span> Yellow pigment in urine

Urobilin or urochrome is the chemical primarily responsible for the yellow color of urine. It is a linear tetrapyrrole compound that, along with the related colorless compound urobilinogen, are degradation products of the cyclic tetrapyrrole heme.

<span class="mw-page-title-main">Rotor syndrome</span> Medical condition

Rotor syndrome is a rare cause of mixed direct (conjugated) and indirect (unconjugated) hyperbilirubinemia, relatively benign, autosomal recessive bilirubin disorder characterized by non-hemolytic jaundice due to the chronic elevation of predominantly conjugated bilirubin.

Neonatal cholestasis refers to elevated levels of conjugated bilirubin identified in newborn infants within the first few months of life. Conjugated hyperbilirubinemia is clinically defined as >20% of total serum bilirubin or conjugated bilirubin concentration greater than 1.0 mg/dL regardless of total serum bilirubin concentration. The differential diagnosis for neonatal cholestasis can vary extensively. However, the underlying disease pathology is caused by improper transport and/or defects in excretion of bile from hepatocytes leading to an accumulation of conjugated bilirubin in the body. Generally, symptoms associated with neonatal cholestasis can vary based on the underlying cause of the disease. However, most infants affected will present with jaundice, scleral icterus, failure to thrive, acholic or pale stools, and dark urine.

<span class="mw-page-title-main">Stercobilinogen</span> Chemical compound

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.

<span class="mw-page-title-main">Urine test strip</span> Diagnostic tool used in urinalysis

A urine test strip or dipstick is a basic diagnostic tool used to determine pathological changes in a patient's urine in standard urinalysis.

Cholestatic pruritus is the sensation of itch due to nearly any liver disease, but the most commonly associated entities are primary biliary cholangitis, primary sclerosing cholangitis, obstructive choledocholithiasis, carcinoma of the bile duct, cholestasis, and chronic hepatitis C viral infection and other forms of viral hepatitis.

<span class="mw-page-title-main">Bilirubin glucuronide</span> Chemical compound

Bilirubin glucuronide is a water-soluble reaction intermediate over the process of conjugation of indirect bilirubin. Bilirubin glucuronide itself belongs to the category of conjugated bilirubin along with bilirubin di-glucuronide. However, only the latter one is primarily excreted into the bile in the normal setting.

Hemolytic jaundice, also known as prehepatic jaundice, is a type of jaundice arising from hemolysis or excessive destruction of red blood cells, when the byproduct bilirubin is not excreted by the hepatic cells quickly enough. Unless the patient is concurrently affected by hepatic dysfunctions or is experiencing hepatocellular damage, the liver does not contribute to this type of jaundice.

Hyperbilirubinemia is a clinical condition describing an elevation of blood bilirubin level due to the inability to properly metabolise or excrete bilirubin, a product of erythrocytes breakdown. In severe cases, it is manifested as jaundice, the yellowing of tissues like skin and the sclera when excess bilirubin deposits in them. The US records 52,500 jaundice patients annually. By definition, bilirubin concentration of greater than 3 mg/ml is considered hyperbilirubinemia, following which jaundice progressively develops and becomes apparent when plasma levels reach 20 mg/ml. Rather than a disease itself, hyperbilirubinemia is indicative of multifactorial underlying disorders that trace back to deviations from regular bilirubin metabolism. Diagnosis of hyperbilirubinemia depends on physical examination, urinalysis, serum tests, medical history and imaging to identify the cause. Genetic diseases, alcohol, pregnancy and hepatitis viruses affect the likelihood of hyperbilirubinemia. Causes of hyperbilirubinemia mainly arise from the liver. These include haemolytic anaemias, enzymatic disorders, liver damage and gallstones. Hyperbilirubinemia itself is often benign. Only in extreme cases does kernicterus, a type of brain injury, occur. Therapy for adult hyperbilirubinemia targets the underlying diseases but patients with jaundice often have poor outcomes.

References

  1. ↑ Bonnett, Raymond; Davies, John E.; Hursthouse, Michael B. (July 1976). "Structure of bilirubin". Nature. 262 (5566): 326–328. Bibcode:1976Natur.262..326B. doi:10.1038/262326a0. PMID   958385. S2CID   4278361.
  2. ↑ Sturrock, E. D.; Bull, J. R.; Kirsch, R. E. (March 1994). "The synthesis of [10-13C]bilirubin IXα". Journal of Labelled Compounds and Radiopharmaceuticals. 34 (3): 263–274. doi:10.1002/jlcr.2580340309.
  3. ↑ Braunstein E (3 May 2019). "Overview of Hemolytic Anemia – Hematology and Oncology". Merck Manuals Professional Edition (in Latin). Retrieved 5 May 2019.
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