Bilirubin is very similar to the pigment phycobilin used by certain algae to capture light energy, and to the pigment phytochrome used by plants to sense light. All of these contain an open chain of four pyrrolic rings.
Like these other pigments, bilirubin changes its conformation when exposed to light. This is used in the phototherapy of jaundiced newborns: the isomer of bilirubin formed upon light exposure is more soluble than the unilluminated isomer.
Several textbooks and research articles show incorrect chemical structures for the two isoforms of bilirubin.
In the liver it is conjugated with glucuronic acid, making it soluble in water. Much of it goes into the bile and thus out into the small intestine. Some of the conjugated bilirubin remains in the large intestine and is metabolised by colonic bacteria to urobilinogen, which is further metabolized to stercobilinogen, and finally oxidised to stercobilin. This stercobilin gives feces its brown color. Some of the urobilinogen is reabsorbed and excreted in the urine along with an oxidized form, urobilin.
Normally, a tiny amount of bilirubin is excreted in the urine, accounting for the light yellow colour. If the liver’s function is impaired or when biliary drainage is blocked, some of the conjugated bilirubin leaks out of the hepatocytes and appears in the urine, turning it dark amber. The presence of this conjugated bilirubin in the urine can be clinically analyzed, and is reported as an increase in urine bilirubin. However, in the disorder hemolytic anemia, an increased number of red blood cells are broken down, causing an increase in the amount of unconjugated bilirubin in the blood. As stated above, the unconjugated bilirubin is not water soluble, and thus one will not see an increase in bilirubin in the urine. Because there is no problem with the liver or bile systems, this excess unconjugated bilirubin will go through all of the normal processing mechanisms that occur (e.g., conjugation, excretion in bile, metabolism to urobilinogen, reabsorption) and will show up as an increase in urine urobilinogen. This difference between increased urine bilirubin and increased urine urobilinogen helps to distinguish between various disorders in those systems.
|"BC"||conjugated||Yes (bound to glucuronic acid)||Reacts quickly when dyes are added to the blood specimen. Product is Azobilirubin "Direct bilirubin"|
|"BU"||unconjugated||No||Reacts more slowly. Still produces Azobilirubin. Ethanol makes all bilirubin react promptly. Indirect bilirubin = Total bilirubin - Direct bilirubin|
Total bilirubin measures both BU and BC. Total and direct bilirubin levels can be measured from the blood, but indirect bilirubin is calculated from the total and direct bilirubin.
To further elucidate the causes of jaundice or increased bilirubin, it is usually simpler to look at other liver function tests (especially the enzymes ALT, AST, GGT, Alk Phos), blood film examination (hemolysis, etc.) or evidence of infective hepatitis (e.g., Hepatitis A, B, C, delta, E, etc).
Bilirubin is an excretion product, and the body does not control levels. Bilirubin levels reflect the balance between production and excretion. Thus, there is no "normal" level of bilirubin.
Bilirubin is broken down by light, and therefore blood collection tubes (especially serum tubes) should be protected from such exposure.
|total bilirubin||5.1–17.0||0.2-1.9, 0.3–1.0, 0.1-1.2|
|direct bilirubin||1.0–5.1||0-0.3, 0.1–0.3, 0.1-0.4|
Mild rises in bilirubin may be caused by
Moderate rise in bilirubin may be caused by
Very high levels of bilirubin may be caused by
Cirrhosis may cause normal, moderately high or high levels of bilirubin, depending on exact features of the cirrhosis
Indirect bilirubin is fat soluble and direct bilirubin is water soluble.
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