Bilirubin in plasma

Decreased Delivery of Unconjugated Bilirubin (in Plasma) to Hepatocyte... 

Hepatic immaturity may be partly due to diversion in utero of blood from the liver by the ductus venosus. When this channel closes shortly after birth and normal hepatic blood flow is established, concentrations of a number of substances rise within the hepatocytes and may induce enzymes needed for their metabolism. Accumulation of bilirubin in plasma may play an important role in hastening the maturation. Although the liver normally matures within 1-2 weeks after birth, hypothyroidism can prolong this process for weeks or months. 

Derivative spectrophotometry was applied in different than pharmaceutical analysis areas of analysis. This method was utilised for the determination of amphothericin in various biological samples like plasma, serum, urine and brain tissue [40]. The combination of ratio spectra with their derivatisation allowed to remove spectral interferences caused by a presence of bilirubin in plasma [40]. 

Knowledge of the biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins (see below) in the body. The porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of the various porphyrins. Although porphyrias are not very prevalent, physicians must be aware of them. A much more prevalent clinical condition is jaundice, due to elevation of bilirubin in the plasma. This elevation is due to overproduction of bilirubin or to failure of its excretion and is seen in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas. 

Depending on the type of bilirubin present in plasma—ie, unconjugated or conjugated—hyperbihru-binemia may be classified as retention hyperbilirubinemia, due to overproduction, or regurgitation hyperbilirubinemia, due to reflux into the bloodstream because of bihary obstmction. 

Type I Crigler-Najjar syndrome is a rare autosomal recessive disorder. It is characterized by severe congenital jaundice (serum bilirubin usually exceeds 20 mg/dL) due to mutations in the gene encoding bilirubin-UGT activity in hepatic tissues. The disease is often fatal within the first 15 months of life. Children with this condition have been treated with phototherapy, resulting in some reduction in plasma bilirubin levels. Phenobarbital has no effect on the formation of bilirubin glucuronides in patients with type I Crigler-Najjar syndrome. A liver transplant may be curative. 

When levels of conjugated bilirubin remain high in plasma, a fraction can bind covalently to albumin (delta bilirubin). Because it is bound covalently to albumin, this fraction has a longer half-life in plasma than does conventional conjugated bilirubin. Thus, it remains elevated during the recovery phase of obstructive jaundice after the remainder of the conjugated bilirubin has declined to normal levels this explains why some patients continue to appear jaundiced after conjugated bilirubin levels have returned to normal. 

Bilirubin (normal plasma concentration < 20 iM) is able to scavenge singlet oxygen and peroxyl radicals. It has been proposed that bilirubin bound to human albumin contributes significantly to the non-enzymic antioxidant defences in human plasma (Stocker and Ames, 1987). 

This pattern of results is typical of hepatocellular damage (necrosis). The high activity of AST and ALT are due to leakage from damaged cells the normal albumin value indicates that this is an acute (recent) condition. The modest rise in bilirubin concentration in plasma is not itself diagnostic at this stage. 

Bilirubin derives largely from senescent erythrocyte hemoglobin [for reviews, see references (F9, G7, L6, S3, Wll)]. When transported in plasma the pigment is bound to albumin (B9, 04). Dissociation from albumin precedes rapid uptake by liver tissues (B4, Bll, B29). This uptake and the transfer of bilirubin to its sites of metabolism may be mediated by cytoplasmic binding proteins (G8, Gll, L8, M9). 

B14. Billing, B. H., Williams, R., and Richards, T. G., Defects in hepatic transport of bilirubin in congenital hyperbilirubinaemia an analysis of plasma bilirubin disappearance curves. Clin. Sci. 27, 245-257 (1964). 

LDL becomes oxidized in vivo. There is evidence that LDL is protected against oxidation in plasma by water-soluble antioxidative substances, such as ascorbic acid, uric acid, or bilirubin. Thus, it is likely that the majority of oxidative modification of LDL occurs in the artery wall, where LDL is largely isolated from the plasmatic antioxidants. Recent evidence suggests that metal ions (copper or iron) and the enzymes myeloperoxidase and lipoxygenase play major parts in the modification of LDL [161]. 

Pattern of serum alanine aminotransferase (ALT) and bilirubin in the plasma, following poisoning with the toxic mushroom Amanita phalloides. 

Z Uptake of bilirubin by the liven Bilirubin is only slightly soluble in plasma and, therefore, is transported to the liver by binding non-covalently to albumin. [Note Certain anionic drugs, such as salicylates and sulfonamides,1 can displace bilirubin from abu-min, permitting bilirubin to enter the central nervous system (CNS). This causes the potential for neural damage in infants.] Bilirubin dissociates from the carrier albumin molecule and enters a hepatocyte, where it binds to intracellular proteins, particularly the protein ligandin. 

It is relevant to ask how often the routine measurement procedures currently used in laboratory medicine provide results that are traceable to high-level calibrators and reference measurement procedures (Lequin personal communication). It turns out that primary reference measurement procedures and primary calibrators are only available for about 30 types of quantity such as blood plasma concentration of bilirubins, cholesterols and sodium ion. International reference measurement procedures from the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and corresponding certified reference material from BCR are available for the catalytic activity concentration of a few enzymes such as alkaline phosphatase and creatine kinase in plasma. For another 25 types of quantity, such... 

In complementary experiments Billing and Weinbren (cited in BIO) infused bilirubin in amounts sufficient to saturate the capacity of the liver to excrete the pigment and noted that, in addition to bilirubin, pigment I but no pigment II accumulated in the plasma. The liver poisons ethionine and icterogenin also cause an accumulation of pigment I but not of pigment II in the blood of experimental animals (B13). 

The efficiency of steroid therapy in causing a dramatic fall in plasma bile pigment concentration in hepatitis is well known the mode of action of these drugs has not, however, been established. It appears unlikely that they have a chloretic effect (C4, Sll), and the report of Katz et al. (K1) that treatment results in a decreased excretion of fecal urobilinogen suggests that there is either a decrease in the rate of hemoglobin breakdown or that another pathway of catabolism is employed which does not involve bilirubin. 

So-called physiological jaundice in infants is attributable to a rise in plasma bilirubin, the conjugated bile pigments being absent. Billing et al. (Bll) found that the maximum increase in bilirubin concentration... 

---