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Raised bilirubin

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Raised bilirubin

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Bilirubin ( BR ) is an orange-yellow pigment derived from senescent RBCs. It is extracted and biotransformed mainly in the liver and excreted in bile and urine 80 % from breakdown of Hb and prematurely destroyed erythroid cells in the bone marrow Rest -turnover of various heme-containing proteins found on other tissues 
( mainly liver and muscles )

Approximately 4 mg/ kg body weight of bilirubin ( BR ) produced /D
that roughly equates to 250-400 mg BR is insoluble in water Present in three forms in the plasma

In normal circumstances plasma BR is mostly unconjugated ( 80 % ) Once BR released into plasma it is bound to albumin which serves as its transport throughout the body BR is transported to liver ( bound to albumin ) then via a complex mechanism rendered water soluble in liver by conjugation with glucoronic acid mainly to diglucuronide which is excreted in the bile

Small amounts are abosrbed back from the gut and re-excreted 
( enterohepatic circulation )
 Only conjugated BR is excreted in urine when its plasma level ↑↑ es beyond a certain level – it is not present in the urine of normally and is not eliminated in the urine in cases of unconjugated hyerbilirubinemia

Beneficial effects of BR are not fully understood may have antioxidant , 
anti inflammatory and immune modulatory properties

Bilirubin is toxic to tissues ( hence transported bound to albumin ) as intracellular organelles and physiological processes Jaundice is defined as the elevation in the plasma BR levels above the normal range of 18-24 m/mol/l which is associated with yellow discoloration of the sclera and skin Clinically evident hyperbilirubinemia may no manifest until the level exceeds 50-51 mmol/L When plasma levels of unconjugated BR accumulates in circulation – it might result in harmful effects ( particularly for infants ) particularly neurotoxicity ( infants – blood brain barrier isn’t fully developed ) In cases of inherited or acquired deficiencies of bilirubin storage or excretion both UC and conjugated BR will accumulated in the plasma

BR can be checked in serum or plasma . its detection in urine is also informative Presence of conjugated BR in the plasma always indicates a pathological process Urine will turn dark – when excess conjugated BR is excreted ie detection of bilirubinemia also indicates a pathological process The excess BR in hepatibiliary disorders is typically totally or mainly conjugated In total biliary obstruction renal excretion becomes the major pathway of biliary excretion

Gilberts syndrome-Due to a very mild glucuronyl tranferase deficiency Frequent inherited disorder ( 5-7 % of general population ) Causes intermittent isolated raised unconjugated BR levels Liver morphologically normal and other LFTs are normal Intermittent jaundice may be precipitated by heavy physical exertion , fasting or an inter-current illness

References

 Disorders of Bilirubin Metabolism Tietz Textbook of Clinical Chemistry and Molecular Diagnostics Bilirubin Metabolism Namita Roy-Chowdhury , Yang Lu and Jayanta Roy-Chowdhury Bilirubin (serum plasma ) William Marshall Association of Clinical Biochemistry Physiology , Bilirubin Aditya Kalakonda :; Savio John SUNY Upstate Medical university December 2017 Evaluating Elevated Bilirubin Levels in Asymptomatic Adults Lisa b VanWagner et al JAMA Diagnostic Test Interpretation GP Referral Pathway Abnormal Liver Functions Tests-Non Jaundiced Patient-Swansea Locality Bilirubinuria patient UK via https://patient.info/doctor/bilirubinuria CKS NHS Gilbert’s syndrome and Jaundice

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