Plasma conjugated bilirubin

Both conjugated bilirubin and unconjugated bilirubin may be present in plasma. Conjugated bilirubin is water. soluble. Unconjugated bilirubin is not water soluble and binds to albumin from which it may be transferred to other proteins such as those in cell membranes. It is neurotoxic, and if levels rise too high in neonates, permanent brain damage can occur. 

Bilirubin formed in peripheral tissues is transported to the hver by plasma albumin. The further metabolism of bihtubin occuts primarily in the hver. It can be divided into thtee processes (1) uptake of bilirubin by hver parenchymal cells, (2) conjugation of bilirubin with glucuronate in the endoplasmic reticulum, and (3) secretion of conjugated bilirubin into the bile. Each of these processes will be considered separately. 

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. 

It is generally accepted that in normal subjects, most, but not necessarily all, of the bilirubin formed results from the breakdown of hemoglobin in the reticuloendothelial system. The bilirubin is then conjugated in the liver and excreted into the bile as a water-soluble pigment. The capacity of the liver to conjugate bilirubin is limited (W6), so that in cases of overproduction (e.g., hemolytic jaundice) free bilirubin will appear in the plasma. A similar result will be obtained if the ability of the liver to conjugate bilirubin is diminished (e.g., in the newborn infant). On the other hand, if the excretion of the bile is for some reason... 

Electrophoretic studies (G2, M2) have shown that both types of bilirubin are bound to albumin and sometimes a-globulin. Klatskin and Bungards (K6) found that this binding occurs between pH 6 and pH 9 and that below pH 5 separation occurs almost completely with respect to bilirubin but only partially with the conjugated pigment. This suggests that bilirubin and conjugated bilirubin are attached in different ways to plasma proteins. 

In a small proportion of cases of hemolytic disease of the newborn (inspissated bile syndrome), large amounts of conjugated bilirubin as well as free bilirubin accumulate in the plasma due to obstruction (J3, L2, S16). Conjugated bilirubin is apparently nontoxic to the brain so that exchange transfusions in such infants are indicated only if the free bilirubin and not the total bile pigment concentration is rising above 20 mg/100 ml plasma. 

Chronic idiopathic jaundice, which is characterized by heavy black pigmentation of the parenchymal cells in the centrilobular zones of the liver, differs from other forms of familial jaundice so far described in that conjugated bilirubin as well as unconjugated bilirubin is present in the plasma and bilirubinuria occurs. The type of conjugated pigment in the plasma has not been characterized, and up to the present no adequate explanation for the jaundice has been put forward (D6). 

Increased plasma AST and ALT activities and decreased platelet levels correlated with increased cumulative CDD and CDF intake in 11-week-old infants. No effect on plasma GGT activity or plasma cholesterol, total and conjugated bilirubin, or leukocyte levels 8.7- 62.7 (mean of 28.1) cumulative intake 5.7- 123.7 ng TEQ (mean of 44.7) Pluim et al. 1994a... 

Rifampicin impairs hepatic uptake and excretion of bilirubin plasma xmconjugated and conjugated bilirubin may be elevated during the first 2-3 weeks of dosing. 

Doumas BT, Yein F, Perry B, Jendrzejczak B, Kessner A. Determination of the sum of bilirubin sugar conjugates in plasma by bilirubin oxidase. Clin Chem 1999 45 1255-60. 

When heme proteins are degraded in mammals, the polypeptides are hydrolyzed to amino acids while the heme groups are freed of their iron, which is salvaged, and are converted to bilirubin. After transport to the liver, bilirubin is coupled to glucuronic acid and the conjugated bilirubin is excreted into bile as the principal bile pigment. When increased production or decreased excretion of bilirubin causes its plasma concentration to exceed 0.1-1.0 mg/dL (2-17 /rmol/L), it diifuses into tissues and... 

The plasma of normal subjects contains 0.1-1 mg of bilirubin per deciliter (2-17 /zmol/L), mostly in the unconjugated form. Unconjugated bilirubin is known as indirect-reacting bilirubin and conjugated bilirubin as direct-reacting bilirubin (see Table 29-2). 

Jaundice occurs when plasma becomes supersaturated with bilirubin (>2-2.5 mg/dL) and the excess diffuses into the skin, sclera, and other tissues. The sclera is particularly affected because it is rich in elastin, which has a high affinity for bilirubin. Reddish yellow pigments, particularly carotene and lycopene, may give a yellowish tinge to the skin but they do not usually produce scleral coloration. Hyperbilirubinemia may result from elevation of unconjugated or conjugated bilirubin levels. 

Historically, the conjugated and unconjugated forms were known as direct and indirect bilirubin, respectively. The unconjugated bilirubin reacts more slowly in analytical methods and the plasma total bilirubin reflects the balance between production and excretion. In most laboratory animals, the plasma total bilirubin is lower... 

Although it is possible to measure both total and conjugated (direct) bilirubin, measurement of total bilirubin is usually sufficient because plasma total bilirubin levels are lower in laboratory animals compared to humans. If plasma total bilirubin is markedly elevated, it imparts a visible yellow color to the plasma. Plasma total bilirubin values in rats and dogs are near the limit of detection by common colorimetric methods, which rely on diazotization reactions with bilirubin concentrations in rats... 

Plasma bilirubin, bound to albumin, is taken up by the liver cells, and conjugated with glucuronic acid to form bilirubin glucuronide (Schmid et al., 1957). The enzyme which catalyses the first step in this reaction is glucuronyl transferase (Brown, 1957). Subsequently, the conjugated bilirubin is excreted by the liver into the biliary system, transported to the duodenum, where further metabolism occurs. 

When the amount of bilirubin produced is greater than the amount excreted, bilirubin accumulates in the blood and stains the tissue, leading to yellow discoloration called jaundice. The mechanism by which bilirubin stains tissue is not clear. It is assumed that bilirubin is transferred from plasma proteins to tissue proteins, and, as can be expected, some proteins have a greater affinity for bilirubin than others. For example, elastic tissue avidly picks up bilirubin. Direct bilirubin is more readily fixed by tissues than indirect bilirubin, except in brain of the newborn, where unconjugated bilirubin is more easily picked up by the brain than conjugated bilirubin. 

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