Unconjugated bilirubin

Serum ALP and total bilirubin (unconjugated and conjugated fractions) are traditionally used to monitor cholestatic injury. The ALP families of enzymes are zinc metalloproteases that are present in nearly all tissues. In the liver, ALP is immu-nolocalized to the microvili of the bile canaliculus [124]. Increased synthesis of ALP and its release into the circulation occurs within hours of cholestatic injury [129]. Serum assays of 5 -nucleotidase (5 -NT) or y-glutamyltransferase activity (GGT) are used to confirm the liver as the specific origin for the elevation of ALP. Increases in serum bilirubin or bile acids are usually the result of bile retention subsequent to impaired bile flow, increased production associated with accelerated erythrocyte destruction, or altered bilirubin metabolism [129]. 

Conjugated and unconjugated bilirubin concentrations in serum may be measured via the van den Bergh reaction. The conjugated bilirubin reacts directly with diazotized sulfanylic acid and is thus termed "direct bilirubin." Unconjugated (albumin-bound) bilirubin does not react with the reagent unless the serum is treated with alcohol, and its concentration is thus termed "indirect bilirubin." The determination of direct and indirect serum bilirubin, as well as... 

In jaundice, bilirubin may appear in the urine. Two factors seem to govern the renal excretion of bilirubin the solubility of bilirubin and the renal clearance of bilirubin. Unconjugated bilirubin is not normally excreted by the kidney only the more soluble conjugated bilirubin is found in the urine. The clearance for the diglucuronide is greater than that for the monoglucuronide. It is not known which part of the nephron excretes bilirubin. Some have postulated that bilirubin is excreted by glomerular filtration, and... 

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. 

Elevated Amounts of Unconjugated Bilirubin in Blood Occur in a Number of Conditions... 

In jaundice secondary to hemolysis, the increased production of bilirubin leads to increased production of urobilinogen, which appears in the urine in large amounts. Bilirubin is not usually found in the urine in hemolytic jaundice (because unconjugated bihmbin does not pass into the urine), so that the combination of increased urobilinogen and absence of bihmbin is suggestive of hemolytic jaundice. Increased blood destruction from any cause brings about an increase in urine urobilinogen. 

Progressive liver damage (shock liver) manifests as elevated serum hepatic transaminases and unconjugated bilirubin. Impaired synthesis of clotting factors may increase prothrombin time (PT), international normalized ratio, and activated partial thromboplastin time (aPTT). 

Because of its very low water solubility, bilirubin formed outside the liver must be transported through the circulation bound to albumin. This is called unconjugated bilirubin, indicating that it has not yet passed through the phase II reactions in the liver. 

Unconjugated bilirubin is taken into the hepatocytes by binding to membrane transport proteins and transported through the liver cells to the SER by proteins called ligandins. The SER is the location of a specific bilirubin-UDP-glucuronosyl transferase... 

The over-production of bilirubin to the point at which the liver s capacity to metabolize is exceeded or if there is dysfunction of the liver itself due to damage or metabolic immaturity, can lead to a yellow discolouration of tissues called jaundice. The accumulation of unconjugated bilirubin in neonates, often as a result of antibody-mediated destruction of the baby s red cells is dangerous as serious and irreversible brain damage can occur. Acute or chronic damage to the adult liver (hepatitis) may cause jaundice but not brain damage. 

Jaundice (yellow color of skin, whites of the eyes) may occur when blood levels of bilirubin exceed normal (icterus). Jaundice may be characterized by an increase in unconjugated (indirect) bilirubin, conjugated (direct) bilirubin, or both. Accumulation of bilirubin (usually unconjugiated) in the brain (kernicterus) may result in death. When conjugated bilirubin increases, it may be excreted, giving a deep yeUow-red color to the urine. Examples of conditions associated with increased bilirubin and jaundice include the following. 

With severe hemolysis, more bihrubin is released into the blood than can be transported on albumin and conjugated in the liver. Unconjugated and total bilirubin increase and may produce jaundice and kernicterus. Examples include ... 

B21. Bratlid, D., and Winsner, A., Determination of conjugated and unconjugated bilirubin by methods based on direct spectrophotometry and chloroform-extraction. A reappraisal. Scand, J. Clin. Ijoh. Invest. 28, 41-48 (1971). 

Partial or total deficiency, or inhibition of bilirubin UDP-glucuronyltransferase may cause unconjugated hyperbilirubinemia. Increased production (hemolysis, ineffective erythropoiesis) should be excluded by investigating hematologic parameters. Determination in vitro of bilirubin UDP-glycosyltransferase activities can contribute to a differential diagnosis. To minimize the effect of cytoplasmic carrier proteins, in in vitro... 

Bl. Bakken, A. F., Effects of unconjugated bilirubin on bilirubin-UDP-glucuronyl transferase activity in liver of newborn rats. Pediat. Res. 3, 205-209 (1969). 

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