The accessory organs: Pancreas, liver and gallbladder
Paul Ong, Rachel Skittrall in Gastrointestinal Nursing, 2017
Hyperbilirubinaemia is the excessive accumulation of bilirubin in the body. Although the neonate liver is immature it can perform the same functions as an adult liver albeit less effectively. This means the neonate liver is at risk of hyperbilirubinaemia. Bilirubin is generated from the breakdown of haemoglobin (Figure 6.14). The process begins with macrophages breaking down heme (blood pigment) to biliverdin. This is then broken down to bilirubin. Unconjugated or indirect bilirubin is insoluble and cannot therefore be excreted so it binds to plasma albumin and is transported to the liver hepatocytes where it is metabolised into conjugated or direct bilirubin which is soluble. Conjugated bilirubin is soluble so when it is in this form it can be excreted into bile and transported to the duodenum. Once in the small intestine the conjugated bilirubin is then metabolised by the bacterial flora to produce urobilin and stercobilin. It is stercobilin that gives stool its distinctive colour.
Liver Diseases
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
Mild hyperbilirubinemia is present and the urine is often dark containing conjugated bilirubin excreted by the kidney. The extracting ability of the liver to remove further bilirubin metabolites is impaired and thus urobilin appears in the urine. In 10% of viral hepatitis patients cholestasis develops. Due to cholestasis, bilirubin and bile acid excretion in the stool is decreased and fat elimination is increased. Steatorrhea is present in about half of the hepatitis cases. The duration of the biliary stasis varies from a few days to 4 weeks or longer. When urobilinogen reappears in the urine, it indicates the beginning of the recovery followed by the reversal of bilirubin elimination via the urine. Serum bilirubin levels also return to normal.
Answers
John D Firth, Professor Ian Gilmore in MRCP Part 2 Self-Assessment, 2018
When haemoglobin is broken down the porphyrin ring is converted into biliverdin and thence to bilirubin. Unconjugated bilirubin is relatively insoluble and is transported in the blood as a complex with albumin: it is not excreted in the urine. Hepatocytes take up unconjugated bilirubin and conjugate it to form the soluble diglucuronide, which is excreted into the bile. Further metabolism by gut bacteria forms the soluble colourless compound urobilinogen. Some of this enters the blood stream and is excreted in the urine. Urobilinogen remaining in the gut is converted to the brown pigment, urobilin, and is excreted. If a patient with jaundice has no urobilinogen in their urine, then they must have complete obstruction to bile flow.
Balance of saccharolysis and proteolysis underpins improvements in stool quality induced by adding a fiber bundle containing bound polyphenols to either hydrolyzed meat or grain-rich foods
Published in Gut Microbes, 2019
Matthew I. Jackson, Dennis E. Jewell
Heme is catabolized to biliverdin before enzymatic reduction to bilirubin and excretion in bile. Urobilins are microbial metabolites of bilirubin, and fecal levels are higher in human subjects with irritable bowel syndrome who respond to low fermentable substrate foods, implying that urobilins are markers for specific microbial activity associated with bowel pathophysiology.42 Indeed, bile pigment deconjugation and enterohepatic recirculation has been shown to be mediated most strongly by only a few bacterial commensals,43 and levels of urobilins are decreased in human Crohn’s-type inflammatory bowel disease.44 In this study, levels of urobilins were more strongly impacted when fiber was added to GR food than to HM food. On balance, urobilinoids were decreased by inclusion of fiber into either food; 2 of 3 detected urobilinoids were decreased on either HM or GR foods. Biliverdin was not changed on either HM Fiber or GR Fiber, whereas bilirubins themselves were decreased by inclusion of fiber into GR but not HM food. The decreased bile pigment effects appear to be microbiome mediated, as fiber per se would be expected to entrap and promote excretion of luminal bile pigments, increasing fecal levels. There may be instances where modulation of microbiome urobilin postbiotic production has physiological utility, and dietary fiber from natural sources could be a safe dietary way to effect this change.
Fumarate hydratase as a therapeutic target in renal cancer
Published in Expert Opinion on Therapeutic Targets, 2020
Priyanka Kancherla, Michael Daneshvar, Rebecca A. Sager, Mehdi Mollapour, Gennady Bratslavsky
In an effort to identify metabolic biomarkers, Zheng et al. aimed to develop a metabolic signature of FH-deficient renal cell carcinoma using an FH-deficient mouse model [78]. The authors identified the urinary metabolites most characteristic of FH loss to be fumarate, urobilin, a product of heme degradation, and 2-SC, as expected based on the known metabolic derangements associated with FH loss presented in this review. Additionally, argininosuccinate, a urea cycle metabolite, was also identified. This metabolic signature was replicated in the spent culture media of UOK262 cells compared to UOK262 cells with re-constituted FH expression. The authors suggest that the generation of argininosuccinate serves as a means by which FH-deficient cells excrete accumulated fumarate. Reversal of the urea cycle enzyme argininosuccinate lyase generates argininosuccinate from arginine and excess fumarate, causing cells to become dependent on exogenous arginine. The authors aim to exploit this weakness for therapeutic benefit. They demonstrated that arginine deprivation using pegylated arginine deiminase inhibited cellular proliferation in FH-deficient cells. Their findings suggest a role for argininosuccinate and arginine deprivation in the diagnosis and treatment of HLRCC [78].
Related Knowledge Centers
- Biliverdin
- Heme
- Jaundice
- Porphyrin
- Urine
- Urobilinogen
- Bilirubin
- Feces
- Tetrapyrrole
- Stercobilin