Liver Diseases
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
The development of kernicterus is due to the presence of high amounts of unbound bilirubin crossing the blood-brain barrier. Consequently, the amount of pigment transferred into the brain is related to the amount of free and not to the total bilirubin. In the mechanism of action of free bilirubin on the brain cells, the inhibition of mitochondrial function is probably essential. Mitochondria accumulate bilirubin and the highly pigmented area contains decreased adenosine triphosphate. Bilirubin causes mitochondrial swelling and interferes with the oxidative phosphorylation.128,150,426,492 These developments can be prevented by the infusion of albumin; thus reducing the amount of free bilirubin in the serum by binding and protecting cellular respiration from interference by bilirubin. Conversely, in the presence of some compounds such as salicylate, oleate, the free bilirubin concentration is increased. These compounds bind competitively to albumin, release bilirubin into the medium, and increase the amount of bilirubin passing into the brain. Some drugs, such as sulfisoxazole, decrease serum bilirubin, but enhance the incidence of kernicterus. This action is probably associated with competition for albumin binding sites, and thus more bilirubin can cross the blood-brain barrier.
Metabolic diseases, brain malformations, and central nervous system infections
Lena Hellström-Westas, Linda S. de Vries, Ingmar Rosén in Atlas of AMPLITUDE-INTEGRATED EEGs in the NEWBORN, 2008
This chapter describes examples of aEEG with corresponding EEG traces from newborn infants with various causes of cerebral dysfunction. Infections and hypoglycemia are common in newborn infants, while metabolic diseases and cerebral malformations are rare. Most EEG changes in these conditions are non-specific and include acute stage background abnormalities such as electrocortical background depression and seizures.15 High bilirubin levels may affect the EEG, mainly with increased slow activity.156 EEG changes during blood exchange transfusion have also been described.157 Bilirubin encephalopathy with kernicterus is rare, but can be accompanied by seizures and electrocortical background changes. However, there are no examples including very high bilirubin levels in this Atlas. Specific EEG changes have only been described in a few conditions (see below). The aEEG examples cannot cover all rare conditions but show how the aEEG can be used to give continuous information on brain function and its development during the clinical course in these infants.
Fetal and neonatal medicine
Jagdish M. Gupta, John Beveridge in MCQs in Paediatrics, 2020
4.29. Which of the following statements is/are true of physiological jaundice?It rarely (<5%) presents before the age of 24 h.It is due mainly to temporarily impaired hepatic clearance of bilirubin.In premature infants it may persist for 3-4 weeks.Direct bilirubin levels may be as high as indirect bilirubin levels,It may cause kernicterus.
Deep brain stimulation for childhood dystonia: current evidence and emerging practice
Published in Expert Review of Neurotherapeutics, 2018
Lior M. Elkaim, Phillippe De Vloo, Suneil K. Kalia, Andres M. Lozano, George M. Ibrahim
Up to 85% of newborns are exposed to neonatal unconjugated hyperbilirubinemia and subsequent clinical jaundice [82]. If left untreated, hyperbilirubinemia may lead to bilirubin-induced neurological dysfunction (BIND), also called kernicterus. Neurological manifestations of BIND include intellectual disability, auditory and oculomotor dysfunction. Movement disorders, including choreoathetosis, spasticity, and dystonia, also occur [83]. Underlying mechanisms of bilirubin neurotoxicity are not well understood; however, increased sensitivity to bilirubin in certain brain areas, like the basal ganglia and cerebellum [82], may partially explain the presence of dystonic symptoms. The most appropriate therapeutic approach consists of preventing severe hyperbilirubinemia and thus development of BIND.
Thiol-Disulfide Homeostasis, Serum Ferroxidase Activity, and Serum Ischemia Modified Albumin Levels in Neonatal Jaundice
Published in Fetal and Pediatric Pathology, 2019
Ismail Topal, Cuma Mertoglu, Ilknur Surucu Kara, Gulsah Siranli, Gamze Gok, Özcan Erel
Neonatal jaundice is a common clinical problem both in term and preterm infants [1]. It is still one of the most common causes of hospitalization of the neonates in their first month of life affecting approximately 15–20% [2]. Although it is usually a self-limiting condition and the disease improves without treatment, very high levels of bilirubin are known to cause kernicterus and permanent brain damage [3,4]. Principally, un-conjugated hyperbilirubinemia occurs as a result of excessive bilirubin formation mainly due to the rapid breakdown of red blood cells and inadequate clearance of bilirubin by the immature liver [5,6]. The association of hyperbilirubinemia with augmented oxidative stress parameters in infants has previously been reported [7,8]. There are also some studies reporting that neonatal hyperbilirubinemia is associated with decreased oxidative stress [9].
Advances in understanding disease mechanisms and potential treatments for Crigler–Najjar syndrome
Published in Expert Opinion on Orphan Drugs, 2018
Giulia Bortolussi, Andrés Fernando Muro
Crigler and Najjar were the first to characterize the syndrome in 1952, as severe congenital familiar non-hemolytic jaundice [22]. The CNS is a recessively inherited metabolic disorder of the liver with an estimated frequency of 1 in a million live births and is equally distributed in both genders [23,24]. It has been reported that CNS is relatively more frequent in specific populations such as the Amish and Mennonite communities, and in the sub-Mediterranean region (Tunis) [25,26]. Two distinct forms of the disease have been characterized according to the severity of the outcome: type I (CNS-I) and type II (CNS-II). Untreated CNS-I patients have total serum bilirubin levels exceeding 20 mg/dl (340 µM) and can increase up to 50 mg/dl (850 µM). This is the most severe form of the disease since patients completely lack UGT1A1 enzyme activity. Bile acid test in these patients showed that bile is almost completely composed by UCB with only traces of mono-glucuronide bilirubin [27]. If not promptly treated, these patients develop severe neurological damage and are at constant risk of kernicterus. Genetic mutations in CNS-I patients are well distributed along all the exons and are point missense or nonsense mutations, single base deletions, insertions or in few cases promoter polymorphisms (see [13] for a detailed description).
Related Knowledge Centers
- Central Nervous System
- Jaundice
- Bilirubin
- Blood
- Brain
- Neurotoxicity
- Grey Matter
- Neurology
- Brain Damage
- Liver Failure