Urobilinogen

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Urobilinogen
Structure of urobilinogen.png
Identifiers
ECHA InfoCard 100.131.280 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
Properties
C33H44N4O6
Molar mass 592.726 (g/mol)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Urobilinogen is a yellow by-product of bilirubin reduction. It is formed in the intestines by the bacterial enzyme bilirubin reductase. [1] 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.

Contents

Increased amounts of bilirubin are formed in hemolysis, which generates increased urobilinogen in the gut. In liver disease (such as hepatitis), the intrahepatic urobilinogen cycle is inhibited also increasing urobilinogen levels. Urobilinogen is converted to the yellow pigmented urobilin apparent in urine.

The urobilinogen in the intestine is directly reduced to brownish colour stercobilin, which gives the feces their characteristic color. It can also be reduced to stercobilinogen, which can then be further oxidized to stercobilin.

In biliary obstruction, below-normal amounts of conjugated bilirubin reach the intestine for conversion to urobilinogen. With limited urobilinogen available for reabsorption and excretion, the amount of urobilin found in the urine is low. High amounts of the soluble conjugated bilirubin enter the circulation where they are excreted via the kidneys. These mechanisms are responsible for the dark urine and pale stools observed in biliary obstruction.

Low urine urobilinogen may result from complete obstructive jaundice or treatment with broad-spectrum antibiotics, which destroy the intestinal bacterial flora (obstruction of bilirubin passage into the gut or failure of urobilinogen production in the gut).

Low urine urobilinogen levels may result from congenital enzymatic jaundice (hyperbilirubinemia syndromes) or from treatment with drugs that acidify urine, such as ammonium chloride or ascorbic acid.

Elevated levels may indicate hemolytic anaemia (excessive breakdown of red blood cells RBC), overburdening of the liver, increased urobilinogen production, re-absorption – a large hematoma, restricted liver function, hepatic infection, poisoning or liver cirrhosis. [2] [3]

Nomenclature

Urobilinogen (a.k.a. D-urobilinogen) is closely related to two other compounds: mesobilirubinogen (a.k.a. I-urobilinogen) and stercobilinogen (a.k.a. L-urobilinogen). [4] Specifically, urobilinogen can be reduced to form mesobilirubinogen, and mesobilirubinogen can be further reduced to form stercobilinogen. [4] Confusingly, however, all three of these compounds are frequently collectively referred to as "urobilinogens". [5]

Measurement

Urobilinogen content is determined by a reaction with Ehrlich's reagent, which contains para-dimethylaminobenzaldehyde and may be measured in Ehrlich units. Ehrlich's reagent reacts with urobilinogen to give a pink-red color. One Ehrlich unit is equal to one milligram of urobilinogen per deciliter of sample (1 mg/dL). [6]

See also

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">Bilirubin</span> Red pigment of the bile

Bilirubin (BR) 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. 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. 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.

<span class="mw-page-title-main">Bile duct</span> Type of organ

A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. The bile duct is separated into three main parts: the fundus (superior), the body (middle), and the neck (inferior).

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">Urinalysis</span> Array of tests performed on urine

Urinalysis, a portmanteau of the words urine and analysis, is a panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and microscopic examination. Macroscopic examination targets parameters such as color, clarity, odor, and specific gravity; urine test strips measure chemical properties such as pH, glucose concentration, and protein levels; and microscopy is performed to identify elements such as cells, urinary casts, crystals, and organisms.

<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">Glucuronic acid</span> Sugar acid

Glucuronic acid is a uronic acid that was first isolated from urine. It is found in many gums such as gum arabic, xanthan, and kombucha tea and is important for the metabolism of microorganisms, plants and animals.

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

Indican is a colourless organic compound, soluble in water, naturally occurring in Indigofera plants. It is a precursor of indigo dye.

<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">Bilirubinuria</span> Medical condition

In medicine, bilirubinuria is an abnormality in which conjugated bilirubin is detected in the urine.

<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. Hall, Brantley; Levy, Sophia; Dufault-Thompson, Keith; Arp, Gabriela; Zhong, Aoshu; Ndjite, Glory Minabou; Weiss, Ashley; Braccia, Domenick; Jenkins, Conor; Grant, Maggie R.; Abeysinghe, Stephenie; Yang, Yiyan; Jermain, Madison D.; Wu, Chih Hao; Ma, Bing (2024-01-03). "BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen". Nature Microbiology. 9 (1): 173–184. doi:10.1038/s41564-023-01549-x. ISSN   2058-5276. PMC   10769871 . PMID   38172624.
  2. "Urobilinogen". Family Health Information. Retrieved 2008-03-30.
  3. "Urobilinogen in urine". Home test kist. Retrieved 2008-03-30.
  4. 1 2 "Biochemical Pathways Map No. L5 L6". ExPASy Bioinformatics Resource Portal. Retrieved 12 December 2011.
  5. Henry's clinical diagnosis and management by laboratory methods (PDF) (22nd ed.). Philadelphia, PA: Elsevier/Saunders. 2011. p. 543. ISBN   978-1-4377-0974-2.
  6. Urobilinogenfrom Information and Courses MediaLab, Inc. Retrieved on Jan 8, 2009