In healthy people, the total daily biliary
coproporphyrinogen (CPG) excretion (a by-product of the heme synthesis) is
about three times higher than urinary CPG excretion, and urinary CPG III
concentration is about three times higher than CPG I concentration. In DJS,
the total amount of urinary CPG is normal, but CPG isomer I accounts for
80% of total CPG. Hence, the diagnosis is based on increased levels of
CPG I in the urine, whereas the CPG III level is below normal. Furthermore,
the rise in the sulfobromophthalein sodium test is delayed, and the liver
appears macroscopically dark blue or even black. Histologically, the
cytoplasm of hepatocytes (especially in zone III) contains big lysosomes
packed with a lipochromic pigment, which is responsible for the brown-black
color. This pigment has many similarities to melanin but is not melanin. It
has been theorized that the pigment may be composed of polymers of
epinephrine metabolites. The amount of pigment is variable; for example, it
can disappear almost completely during an acute viral hepatitis but then
reappear slowly after recovery.