26. Bilirubin Metabolism

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Sudan International University Sudan International University Omaima Ali Mohamed Omaima Ali Mohamed

Msc Msc. Clinical Chemistry . Clinical Chemistry


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Bilirubin is the potentially toxic catabolicproduct of heme metabolism. It is thepigment that gives bile its characteristicbright greenish yellow color.

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80% of the daily bilirubin production isderived from hemoglobin, the remaining20% being contributed by the otherhemoproteins (as myoglobin; cytochromes;catalase; and peroxidase). In normal adultsa daily load of 25 0-300 mg of bilirubin is

produced.



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H emoglobin is found in red blood cells, thebreakdown of old blood cells (at the end ofthe life span 12 0 days) takes place in the

reticuloendothelial system, predominantlyin the spleen. H emoglobin is broken downto heme and globins.



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T he globins part is stored as amino acidfor reutilizing. T he heme part whichconsists of a ring of four pyrroles

(tetrapyrrole) and iron atom. is thendegraded by the enzyme He me oxygenase (HO), to form biliver din , while the iron isatom is released for reutilization.

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Biliverdin is reduced by the enzymeBiliv erd in red uct ase into thehy drop h obic compound bili rubin .Bilirubin is boun d to albu min andtransported in plasma from thereticuloendothelial system to the liver, asunc onjugat ed bi li rubi n.

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In the liver it is taken up by hepatocytesa process involving carrier proteins, thenbilirubin is conjugated principally withglucu orn ic ac i d to form bi li rubi n diglu cu ron i de (conjugat ed bi li rubi n),catalyzed by the enzyme u r i dyl

di ph osph at e glu cu ronylt ransferase .



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Conjugated bilirubin is then secreted bythe hepatocytes into the bi li ary canal i cu li ,ending up in the gut, particularly in theduodenum.In the gut, the intestinal flora hydrolysesand reduces conjugated bilirubin to formu robi li nogen, which is colorless and watersoluble.



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T hree things can happen to Urobilinogen:i. Most of it is oxi dized by gut bacteria

to form the dark pigment st erco bi li n,which is then excreted in the faeces,giving it its characteristic colour .



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ii. Some urobilinogen is rea bsor bedunchanged from the gut via the portalsystem and then recycled by the liver.

iii.T he remainder is rea bsor bed from thegut via the portal system, but insteadof being recycled by the liver it isexcre t ed in the urine.



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T he breakdown product of

Hgb from RB

Cs andother h eme containing proteins.

Produced by re ti cu loendoth eli al sys t emReleased to plasma bou nd t o albu mi nHepa t ocyt es conjugat e it and excrete throughbile channels into small intestine.T hen transferred to UrobilinogenUrobilinogen is then

Oxidized Reabsorbed & Recycled Reabsorbed & Excreted



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1 . U nconjugat ed Bi li rubi n:Unconjugated bilirubin is water

insoluble in and lipophilic, therefore itwill not be filtered by the glomeruli andobviously does not appear in the urine.It is also called I ndi rec t Bi li rubi n.



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2. C onjugat ed bi li rubi nT he conjugated bilirubin is water

soluble and is excreted in urine .It is also called D i rec t Bi li rubi n.



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T otal bilirubin: 0 .3 1.0 mg/dLConjugated bilirubin: 0 .10 .3 mg/dL



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T he bilirubin levels found in the bodyreflects the balance between productionand excretion.An increased plasma concentration ofbilirubin occurs when there is animbalance between its production andexcretion that could be due to:



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i. Increased production;ii. Decreased conjugation;

iii.Decreased secretion by the liver, orblockage of the bile ducts.



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An elevated serum bilirubin level isrecognized clinically as jau ndi ce . Itoccurs when there is a fault in the abovesequence of events leading to a buildupof bilirubin in the blood .



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J aundice is a yellow discoloration ofsclera, skin, and mucous membranes , dueto the increase circulation of the bilirubinin the blood stream resulting in depositionof bile pigment. It is clinically detectedwith serum bilirubin 2.5 3 .0 mg/dL or

more.



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J aundice is classified depending uponwhether the bilirubin is free orconjugated to glucuronic acid into twotypes:i. Unconjugated hyperbilirubinaemia.ii. Conjugated hyperbilirubinaemia.



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1 . Van den Ber gh : Originally the Van denBergh reaction was used for a qualitativeestimate of bilirubin, where the red - violetcompound formed by the condensation ofdiazotized sulfanilic acid with bilirubin.

Bilirubin + Diazotized Sulfanilic ( Diazo reagent ) Red - blue chromogen



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2. Ev elyn-Malloy Reac ti on: T he Red - violetcompound formed by the azo - couplingreaction but accelera t ed by 50% methanol solution.

Bilirubin + Diazo + 50% Methanol Red - blue chromogen



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3 . J endrass ik and Grof : th e proced u re u sed Caffeine - Benzoate - Acetate as anaccelerator for the azo - coupling reaction.

Bilirubin + Diazo +Caffeine - Benzoate - Acetate Red - blue chromogen



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Bilirubin concentration may be measured inplasma, or serum.

Specimen should be protected from light,where bilirubin is light sensitive.H amolysis should be avoided, where it

causes false increased bilirubin.


26. Bilirubin Metabolism

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