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.
Heme Degradation and Bilirubin Formation
Karel P. M. Heirwegh, Stanley B. Brown in Bilirubin, 1982
Wise and Drabkin44–46 showed that a light mitochondrial fraction from the hemophagus organ of the dog (a marginal tissue band, with erythrophagocytic properties found in placenta) exhibited a heme cleaving activity. Presumably this organ was chosen because it sometimes contains a green pigment which is certainly a heme degradation product, probably biliverdin. This fraction catalyzed the formation of [14Clbiliverdin-IXα and 14CO when incubated with [14C]hemin or [14C]hemoglobin. A number of cofactors including NADP were required and the system was heat labile. Although it seems likely that this represents a true enzymic reaction, little further work appears to have been done on this system, possibly because it could not play a general role in mammalian heme catabolism.
Structure, Photochemistry, and Organic Chemistry of Bilirubin*
Karel P. M. Heirwegh, Stanley B. Brown in Bilirubin, 1982
In chloroform, a different set of bilirubin photooxygenation products is thought to arise. In one case, various monopyrrole and dipyrrole compounds have been detected by paper chromatography following exposure of a chloroform solution of bilirubin to air and diffuse daylight for up to 500 days (!) at room temperature.121 In that work and earlier work114,122 it was deduced that biliverdin is also a photooxidation product from bilirubin. Subsequently, Lightner et al.123 isolated biliverdin (as its dimethyl ester) in high yield, and Bonnett and Stewart124 detected biliverdin, its dimethyl ester and two other minor verdins by TLC. The yield of biliverdin appears to increase with increasing bilirubin concentration in methanolic ammonia or chloroform.
The brain heme oxygenase/biliverdin reductase system as a target in drug research and development
Published in Expert Opinion on Therapeutic Targets, 2022
Biliverdin is not the final product of heme metabolism in humans because it is rapidly converted into BR in almost all cell types. Whether endogenous BV per se has biological effects or not is still a matter of debate, because it is sometimes hard to distinguish its own basal outcomes from those attributable to BR. As far as the nervous system is concerned, it has been shown that BV (2 µg/ml) counteracts inflammation and apoptosis in rat hippocampal neurons exposed to oxygen glucose deprivation/reoxygenation and reduce the extent of cerebral infarction and apoptosis in a rat model of middle cerebral artery occlusion/reperfusion injury [77]. Recently, Zou et al. have reported that BV (35 mg/kg intraperitoneally) modulates microRNA (miRNA) and mRNA to improve neurobehavior in rats with cerebral ischemia reperfusion damage [78]. In addition, it has been suggested that BV (10 µM and 50 µM) regulates the LPS-mediated expression of complement receptor 5a (C5aR) via the mTOR pathway in mouse macrophages [79]. Ultimately, BV (50 mg/kg intraperitoneally) protects against ischemia/reperfusion injury in cardiac, renal, and liver transplanted rats [80,81].
A Neglected and Promising Predictor of Severe Hyperbilirubinemia Due to Hemolysis: Carboxyhemoglobin
Published in Fetal and Pediatric Pathology, 2020
Birol Karabulut, Baran Cengiz Arcagok
Hemolysis, the most common cause of increased bilirubin load, leads to an earlier and more severe increase in the bilirubin level. Accordingly, the early detection of hemolysis should prevent neurological sequelae by predicting excessive increases in bilirubin. Therefore, a number of studies on hemolysis have been carried out. Biliverdin (bilirubin), Fe+2, and CO are produced by the process of heme degradation [4]. Many studies have investigated the level of these products in attempts to measure the degree of hemolysis, differentiating hemolytic disease from hemolysis of elderly fetal erythrocytes in the pathophysiology of developmental jaundice. Laboratory methods used for detecting hemolysis include TSB, the direct antiglobulin test (DAT), elevated reticulocyte count, and erythrocyte morphologic abnormalities. As none of these parameters has sufficient sensitivity on its own, the correlations of these parameters with early detection of hemolysis and new diagnostic methods are being investigated. Regrettably, no clinical tests or point-of-care devices are currently available that can reliably detect ongoing hemolysis. However, given that 86% of CO in the body originates in the red blood cells, CO measurement methods have become important in the detection of hemolysis [5].
Spirulina extract improves age-induced vascular dysfunction
Published in Pharmaceutical Biology, 2022
Michal Majewski, Mercedes Klett-Mingo, Carlos M. Verdasco-Martín, Cristina Otero, Mercedes Ferrer
Under pathophysiological conditions associated with increased oxidative stress, different homeostatic mechanisms can be activated. Thus, nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the transcription of phase II antioxidant proteins responsible for the elimination of reactive oxygen species (ROS; Howden 2013) and hemeoxygenase-1 (HO-1). This process has been recognised as one of the most important factors protecting vascular tissue from a pro-oxidant environment (Kang et al. 2015; Drummond et al. 2019). This enzyme synthesises carbon monoxide (CO) from the degradation of haem to biliverdin/bilirubin. This gas mediator molecule is able to activate GC, increase cGMP levels and induce relaxation (Ryter et al. 2006). In addition, both NO (Félétou and Vanhoutte, 1996) and CO (Leffler et al. 2006) are able to activate potassium channels and induce membrane hyperpolarization in vascular smooth muscle cells. Thus, the participation of hyperpolarizing mechanisms through the activation of calcium- and ATP-dependent potassium channels (KCa or KATP, respectively), in conditions with decreased NO bioavailability, has been demonstrated in conductance and resistance vessels (Edwards et al. 2010; Dogan et al. 2019).
Related Knowledge Centers
- Biliverdin Reductase
- Heme
- Hemosiderin
- Bruise
- Catabolism
- Bile
- Hemoglobin
- Red Blood Cell
- Macrophage
- Senescence