Bilirubin Excretion

The sinusoids transport both portal and arterial blood to the hepatocytes. The systemic blood delivered to the liver contains nutrients, drugs, and ingested toxins. The liver processes the nutrients (carbohydrates, proteins, lipids, vitamins, and minerals) for either immediate use or for storage, while the drugs and toxins are metabolized through a variety of processes known as first-pass metabolism. The liver also processes metabolic waste products for excretion. In cirrhosis, bilirubin (from the enzymatic breakdown of heme) can accumulate this causes jaundice (yellowing of the skin), scleral icterus (yellowing of the sclera), and tea-colored urine (urinary bilirubin excretion). 

As yet it cannot be excluded that the observed latency is a preparation artifact resulting, e.g., from vesiclization (E2, Dl). If so, artificial activation would yield values closer to the native situation. Support for this hypothesis is found in the observation that maximum bilirubin excretion rates correlated well with the UDP-glucuronyltransferase activity of fully activated liver homogenate (H2, HIO). 

B2. Bakken, A. F., Bilirubin excretion in newborn human infants. I. Unconjugated bilirubin as a possible trigger for bilirubin conjugation. Acta Paediat. Scand. 59, 148-152 (1970). 

Fig. 7. Bilirubin excretion in the bile of a jaundiced rat after intravenous injections of bilirubin and bilirubin glucuronide (S10).

The findings of this study suggest that women who are already jaundiced at the initiation of HRT are most at risk of increased bilirubin levels and cholestasis. In view of this it would seem sensible that, as well as assessing bilirubin levels prior to treatment, women who want to take HRT should also be assessed for any history (including family history) of jaundice. This will include specific defects in bilirubin excretion, such as intrahepatic cholestasis of pregnancy or familial conjugated hyper-bilirubinaemia, which may worsen cholestasis. 

C-17oc-substituted steroids impair bilirubin excretion into the hepatic canaliculi the block is biochemical not mechcinical. These include synthetic anabolic steroids and oestrogens used in oral contraceptives jaundice due to the latter is rare with the low dose formulations now preferred. 

Fusidic acid interferes with hepatic bilirubin excretion to cause conjugated hyperbilirubinaemia, particularly in patients with sepsis. 

Hyperbilirubinaemia relates to functional disorders in the hepatocellular metabolism of bilirubin - with and without cholestasis (W. Siede, 1957). This means either dysfunctions regarding bilirubin conjugation (= conjugation jaundice) or bilirubin excretion (= excretion jaundice). 

Conjugated hyperbilirubinaemia derives from a congenital disorder which causes decreased bilirubin excretion in the canaliculi. This is why serum bilirubin, which reacts directly, is drastically elevated during an icteric episode. More than 40% (-85%) of the total bilirubin in the serum produces a direct diazo reaction. Unconjugated bilirubin is also found in the blood. Bilirubin is covalently bound to albumin. Bilirubinuria and urobilinogenuria are in evidence. (59) (s. tab. 12.4)... 

Genetically induced disorders of bilirubin metabolism affect (i.) bilirubin conjugation or (2.) bilirubin excretion through the canalicular membrane. This results in functional hyperbilirubinaemia. (s. tabs. 12.1, 12.4) see chapter 12)... 

Periportal zone/Zone 1 Glucose release Oxidative energy metabolism Amino acid utilization Protection against oxidants Bile acid uptake and excretion Bilirubin excretion... 

Gronwall, R., Engelking, L.R. Noonan, N. (1980) Direct measurement of biliary bilirubin excretion in ponies during fasting. American Journal of Veterinary Research, 41, 125-126. 

In adults, virtually all bilirubin excreted in bile is in the form of glycosidic conjugates glucuronides account for 95% of them and glucosides and xylosides constitute the remainder. Of the glucuronides, diglucuronide is the major fraction ( 90%) and monoglucuronide the minor fraction (-10%). 

McDonagh AF, Palma LA, Lightner DA. Blue light and bilirubin excretion. Science 1980 208 145-51. 

An inspiring, and likely the first, example for the therapeutic application of enzyme induction to affect the metabolic fate of an endogenous substance has recently been reported by Yaffe and his associates (71) phenobarbital treatment has been used to prevent hyperbilirubinemia by inducing the glucuronyl transferase, enhanced glucuronide formation enabled increased bilirubin excretion and resulted in decreased serum bilirubin concentration. 

Ibufenac reduces hepatic clearance of both indocyanine green and bilirubin (H5). This drug also inhibits glucuronyl transferase (H5) and S-aryl glutathione transferase (B38). In vivo, phenylbutazone depresses bilirubin excretion, but not that of BSP in vitro, the enzymes conjugating bilirubin and BSP, respectively, are both inhibited. There is no effect on the clearance of indocyanine green (H5). 

Metastatic breast carcinoma is the most likely diagnosis in this case. The liver function tests indicate that there is little hepatocellular damage present and that bilirubin excretion is normal. These findings, however, do not exclude the possibility of hepatic metastasis, giving rise to localized areas of intrahepatic obstruction. 

Hemoglobin Breakdown and Bilirubin Formation 385 Bilirubin Transport 385 Bilirubin Excretion 387 Urobilinogens 388 Jaundice 389 Neonatal Jaundice... 

Bilirubin is not used as such but is excreted by the liver cell. Bilirubin excretion starts with the conversion of bilirubin to bilirubin glucuronide, which was discovered rather recently. It was first observed that bile bilirubin hydrolysis yields two molecules of glucuronic acid per molecule of bilirubin. Bilirubin glucuronide was found in blood serum and was demonstrated to be the compound responsible for the classical van den Bergh reaction. 

Because the bile pigments may be further degraded in the intestinal tract quantitative estimations can only be made on the basis of bilirubin excreted in the bile. Eppinger reported the excretion of 300-370 mg of bilirubin per day in two patients with complete external biliary fistulas (343). 

In the body, the oxidation of the heme, derived from hemoglobin takes place at the a-methene link, this specific oxidation being brought about by some steric or enzymic factors as yet unknown. This may be inferred from the fact that the heme destroyed can be almost quantitatively accounted for in the bilirubin excreted. No chemical reason is evident for this biological attack at the a-methene carbon atom. 

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