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Measurement of total [[bilirubin]] includes both [[Unconjugated bilirubin|unconjugated]] (indirect) and conjugated (direct) bilirubin. Unconjugated bilirubin is a breakdown product of [[heme]] (a part of [[hemoglobin]] in red blood cells). The liver is responsible for clearing the blood of unconjugated bilirubin, by 'conjugating' it (modified to make it water-soluble) through an enzyme named [[UDP-glucuronyl-transferase]]. When the total bilirubin level exceeds 17 μmol/L, it indicates liver disease. When total bilirubin levels exceed 40 μmol/L, bilirubin deposition at the sclera, skin, and mucous membranes will give these areas a yellow colour, thus it is called [[jaundice]].<ref name="Shivaraj 2009">{{cite journal|display-authors=3|last1=Shivaraj|first1=Gowda|last2=Prakash|first2=B Desai|last3=Vinayak|first3=V Hull|last4=Avinash|first4=AK Math|last5=Sonal N|first5=Venekar|last6=Shruthi S|first6=Kulkarni|title=A review on laboratory liver function tests|journal=The Pan African Medical Journal|date=22 November 2009|volume=3|issue=17|pages=17|pmid=21532726|pmc=2984286}}</ref>
The increase in predominantly unconjugated bilirubin is due to overproduction, reduced hepatic uptake of the unconjugated bilirubin and reduced conjugation of bilirubin. Overproduction can be due to the reabsorption of a [[haematoma]] and ineffective [[erythropoiesis]] leading to increased red blood cell destruction. [[Gilbert's syndrome]] and [[Crigler–Najjar syndrome]] have defects in the [[UDP-glucuronyl-transferase]] enzyme, affecting bilirubin conjugation.<ref name="Shivaraj 2009"/>
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