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COMPLEX CHARACTERISTICS OF ETIOLOGY AND PATHOGENESIS OF
NEONATAL HYPERBILIRUBINEMIA STATES
Samiyeva Shakhnoza Utkurovna
Resident Physician of the Neonatology Department, Children's Multidisciplinary
Medical Center of Samarkand Region
Olimjonova Fotima
First-year student of the Medical Faculty
Samarkand State Medical University
Olimjonova Zukhra
First-year student of the Medical Faculty
Samarkand State Medical University
https://doi.org/10.5281/zenodo.15401268
Annotatsiya:
Pathological hyperbilirubinemia develops due to exacerbation of
physiological mechanisms or addition of pathogenetic factors, including: 1) hemolytic
conditions (immune conflicts, erythrocyte membranopathies and enzymopathies); 2)
polymorphism of genes encoding bilirubin metabolism enzymes; 3) obstructive processes in
the biliary system; 4) metabolic and endocrine disorders; 5) infectious and inflammatory
diseases with liver damage.
Keywords.
Neonatal jaundice, hyperbilirubinemia, bilirubin metabolism, UDP-
glucuronosyltransferase, hemolysis, liver transport proteins, enterohepatic circulation,
genetic polymorphism, bilirubin encephalopathy.
Research objective.
To study the molecular and cellular foundations of jaundice
syndrome development in the neonatal period.
Introduction.
Jaundice syndrome in the neonatal period represents a unique clinical
and biochemical phenomenon, reflecting a complex set of molecular and cellular processes
characteristic of postnatal adaptation of the newborn infant. The prevalence of this condition
reaches 60-80% among full-term and 80-90% among premature newborns, which determines
the high medical and social significance of in-depth study of its formation mechanisms at
subcellular and molecular levels.
Modern achievements in molecular biology, proteomics, and genomics have significantly
expanded our understanding of the fundamental principles of bilirubin metabolism and its
regulation in the perinatal period.
It has been established that the development of jaundice syndrome in newborns is
determined by a cascade of interrelated molecular events, including processes of formation,
transport, metabolic transformation, and excretion of bilirubin, each of which is characterized
by pronounced age-specific features.
Hemoglobin catabolism in the neonatal period has a number of fundamental differences,
caused by both accelerated destruction of fetal hemoglobin and peculiarities of the heme
oxygenase system functioning. It has been established that the activity of heme oxygenase-1
(HO-1) in monocytes and macrophages of newborns significantly exceeds that in adults,
which, combined with increased erythrocyte mass (on average 34% more per kilogram of
div weight), contributes to bilirubin production in the volume of 8-10 mg/kg/day compared
to 3-4 mg/kg/day in adults.
At the molecular level, the transport of unconjugated bilirubin into hepatocytes occurs
through several mechanisms, including both passive diffusion and active transport involving
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OATP (Organic Anion Transporting Polypeptides) carrier proteins, the expression of which in
the perinatal period is characterized by ontogenetic regulation. Molecular genetic studies
have shown that polymorphism of the SLCO1B1 and SLCO1B3 genes encoding the OATP1B1
and OATP1B3 transporters is associated with an increased risk of developing severe
hyperbilirubinemia in newborns.
The excretion of conjugated bilirubin into bile canaliculi occurs with the participation of
ATP-dependent transporters MRP2 (Multidrug Resistance-associated Protein 2) and BSEP
(Bile Salt Export Pump), the expression of which also has pronounced age-specific features.
Molecular studies have shown that in the perinatal period, there is a switch from
transcriptional regulation phenomena to post-translational mechanisms of canalicular
transport control, mediated by phosphorylation processes and changes in the subcellular
localization of transporter proteins.
The molecular and cellular mechanisms of the neurotoxic effect of unconjugated
bilirubin deserve special attention. It has been established that the damaging effect of
bilirubin on nervous system cells is based on processes of mitochondrial respiration
disruption, induction of oxidative stress, dysregulation of calcium homeostasis, and activation
of pro-apoptotic signaling pathways. Molecular genetic studies have identified a number of
candidate genes whose polymorphism may modify the susceptibility of neurons to the toxic
effects of bilirubin, including genes for antioxidant enzymes, neurotrophic factors, and ABC
family transporters.
Despite significant progress in understanding the molecular and cellular fundamentals
of neonatal jaundice development, a number of fundamental questions remain insufficiently
studied. In particular, epigenetic mechanisms regulating the expression of key proteins in
bilirubin metabolism, molecular foundations of individual variability in blood-brain barrier
permeability to bilirubin, as well as signaling cascades determining the selective vulnerability
of certain neuron populations to bilirubin-induced damage require in-depth research.
Conclusions:
Thus, a comprehensive study of the molecular and cellular foundations of
jaundice syndrome development in the neonatal period represents an actual direction of
modern neonatology and molecular medicine, capable of providing a fundamental basis for
developing personalized approaches to the prevention and treatment of pathological
hyperbilirubinemia in newborn infants.
References:
Используемая литература:
Foydalanilgan adabiyotlar:
1.
Watchko JF, Tiribelli C. Bilirubin-induced neurologic damage - mechanisms and
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2.
Bhutani VK, Wong RJ. Bilirubin-induced neurologic dysfunction (BIND). Semin Fetal
Neonatal Med. 2022;28(2):101291.
3.
Maisels MJ, McDonagh AF. Phototherapy for neonatal jaundice. N Engl J Med.
2022;358(9):920-928.
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Kaplan M, Bromiker R, Hammerman C. Hyperbilirubinemia, hemolysis, and increased
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