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Breakdown of haemoglobin occurs in the spleen and reticuloendothelial system as RBCs are removed from the circulation. The iron is recycled, and the porphyrin ring is converted into biliverdin, and thence to bilirubin.
First step:
haem + O2 + NADPH --> biliverdin + NADP+ + Fe3+ + H2O + CO
Second step:
biliverdin + NADPH + H+ --> bilirubin + NADP+
Conjugated bilirubin does not enter the bloodstream unless there is liver damage, either obstructive or non-obstructive. If it does enter the bloodstream, conjugated bilirubin is excreted by the kidney, resulting in darkening of the urine. In complete biliary obstruction, no bilirubin reaches the gut, so urobilinogen and urobilin are not formed.
An understanding of the bilirubin metabolism pathway clarifies how a positive urine bilirubin assay reflects a buildup of conjugated bilirubin. Following hemoglobin breakdown, the majority (95%) of bilirubin is in the unconjugated form, which undergoes hepatic conjugation. Conjugated bilirubin then goes into the intestines, where it is predominantly deconjugated and recycled (enterohepatic circulation) to be reconjugated in the liver. Alternatively, some of its metabolism products are excreted in feces as urobilinogen, with ~1% of urobilinogen being renally excreted.
Unconjugated bilirubin (tightly bound to albumin) is highly insoluble, so it cannot be excreted in urine. Excess unconjugated bilirubin (eg, hemolysis) undergoes the regular conjugation pathway, and the resultant excess urobilinogen is primarily recycled; however, a higher than normal amount is excreted in feces or urine, leading to a positive urine urobilinogen assay. On the other hand, conjugated bilirubin (loosely bound to albumin) is water soluble, so it can be excreted in urine. However, as conjugated bilirubin is usually degraded in the intestines, no bilirubin is normally seen on urinalysis (negative urine bilirubin assay). When there is hepatic dysfunction, biliary obstruction, or a defect in hepatic bilirubin storage or uptake, there is buildup of conjugated bilirubin, which leaks into urine. This results in dark urine and a positive urine bilirubin assay.