The liver produces and secretes 250 to 1,500 ml of bile per day. The major constituents of bile are bile pigment (bilirubin), bile salts, phospholipids (mainly lecithin), cholesterol, and inorganic ions.
Bile pigment, or bilirubin, is produced in the spleen, liver, and bone marrow as a derivative of the heme groups (minus the iron) from hemoglobin (fig. 18.23). The free bilirubin is not very water-soluble, and thus most is carried in the blood attached to albumin proteins. This protein-bound bilirubin can neither be filtered by the kidneys into the urine nor directly excreted by the liver into the bile.
The liver can take some of the free bilirubin out of the blood and conjugate (combine) it with glucuronic acid. This conjugated bilirubin is water-soluble and can be secreted into the bile. Once in the bile, the conjugated bilirubin can enter the intestine where it is converted by bacteria into another pigment—urobilinogen. Derivatives of urobilinogen impart a brown color to the feces. About 30% to 50% of the urobilinogen, however, is absorbed by the intestine and enters the hepatic portal vein. Of the urobilinogen that enters the liver sinusoids, some is secreted into the bile and is thus returned to the intestine in an enterohepatic circulation; the rest enters the general circulation (fig. 18.24). The urobilinogen in plasma, unlike free bilirubin, is not attached to albumin. Urobilinogen is therefore easily filtered by the kidneys into the urine, where its derivatives produce an amber color.
Jaundice is a yellow staining of the tissues produced by high blood concentrations of either free or conjugated bilirubin. Jaundice associated with high blood levels of conjugated bilirubin in adults may occur when bile excretion is blocked by gallstones. Since free bilirubin is derived from heme, jaundice associated with high blood levels of free bilirubin is usually caused by an excessively high rate of red blood cell destruction. This is the cause of jaundice in infants who suffer from hemolytic disease of the newborn, or erythroblastosis fetalis. Physiological jaundice of the newborn is due to high levels of free bilirubin in otherwise healthy neonates. This type of jaundice may be caused by the rapid fall in blood hemoglobin concentrations that normally occurs at birth. In premature infants, it may be caused by inadequate amounts of hepatic enzymes that are needed to conjugate bilirubin so that it can be excreted in the bile.
Newborn infants with jaundice are usually treated by exposing them to blue light in the wavelength range of 400 to 500 nm. This light is absorbed by bilirubin in cutaneous vessels and results in the conversion of the bilirubin into a more polar form that can be dissolved in plasma without having to be conjugated with glucuronic acid. This more water-soluble photoisomer of bilirubin can then be excreted in the bile and urine.
Clinical Investigation Clues
Remember that Alan had high blood levels of conjugated bilirubin and had yellowing of his sclera.
■ What does the yellowing of the sclera indicate, and what is its cause?
■ What could cause his elevated blood levels of conjugated bilirubin?
© The McGraw-Hill Companies, 2003
■ Figure 18.23 Simplified pathway for the metabolism of heme and bilirubin. Heme can be formed from the hemoglobin in red blood cells. The iron from the heme group is recycled back to the bone marrow when the heme is converted into biliverdin. Notice that carbon monoxide is produced in this processes and, since it is toxic, must be eliminated from the body.
Hemolysis in spleen, liver, bone marrow
Hemolysis in spleen, liver, bone marrow
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