Jaundice-Excess Bilirubin in the Extracellular Fluid
Jaundice refers to a yellowish tint to the body tissues,including a yellowness of the skin as well as the deep tissues. The usual cause of jaundice is large quantities of bilirubin in the extracellular fluids, either free bilirubin or conjugated bilirubin. The normal plasma concentra-tion of bilirubin, which is almost entirely the free form, averages 0.5 mg/dl of plasma. In certain abnormal con-ditions, this can rise to as high as 40 mg/dl, and much of it can become the conjugated type. The skin usually begins to appear jaundiced when the concentration rises to about three times normal—that is, above 1.5 mg/dl.
The common causes of jaundice are (1) increased destruction of red blood cells, with rapid release of bilirubin into the blood, and (2) obstruction of the bile ducts or damage to the liver cells so that even the usual amounts of bilirubin cannot be excreted into the gas-trointestinal tract. These two types of jaundice are called, respectively, hemolytic jaundice and obstructivejaundice. They differ from each other in the followingways.
Hemolytic Jaundice Is Caused by Hemolysis of Red Blood Cells.
In hemolytic jaundice, the excretory function of the liver is not impaired, but red blood cells are hemolyzed so rapidly that the hepatic cells simply cannot excrete the bilirubin as quickly as it is formed. Therefore, the plasma concentration of free bilirubin rises to above-normal levels. Likewise, the rate of formation of uro-bilinogen in the intestine is greatly increased, and muchof this is absorbed into the blood and later excreted in the urine.
Obstructive Jaundice Is Caused by Obstruction of Bile Ducts or Liver Disease. In obstructive jaundice, caused either byobstruction of the bile ducts (which most often occurs when a gallstone or cancer blocks the common bile duct) or by damage to the hepatic cells (which occurs in hepatitis), the rate of bilirubin formation is normal, butthe bilirubin formed cannot pass from the blood into the intestines. The free bilirubin still enters the liver cells and becomes conjugated in the usual way. This conju-gated bilirubin is then returned to the blood, probably by rupture of the congested bile canaliculi and direct emptying of the bile into the lymph leaving the liver. Thus, most of the bilirubin in the plasma becomes theconjugated type rather than the free type.
DiagnosticDifferencesBetweenHemolyticandObstructive Jaundice. Chemical laboratory tests can be used to dif-ferentiate between free and conjugated bilirubin in the plasma. In hemolytic jaundice, almost all the bilirubin is in the “free” form; in obstructive jaundice, it is mainly in the “conjugated” form. A test called the van denBergh reaction can be used to differentiate between thetwo.
When there is total obstruction of bile flow, no biliru-bin can reach the intestines to be converted into uro-bilinogen by bacteria. Therefore, no urobilinogen is reabsorbed into the blood, and none can be excreted by the kidneys into the urine. Consequently, in total obstructive jaundice, tests for urobilinogen in the urine are completely negative. Also, the stools become clay colored owing to a lack of stercobilin and other bile pigments.
Another major difference between free and conju-gated bilirubin is that the kidneys can excrete small quantities of the highly soluble conjugated bilirubin but not the albumin-bound free bilirubin. Therefore, in severe obstructive jaundice, significant quantities of conjugated bilirubin appear in the urine. This can be demonstrated simply by shaking the urine and observ-ing the foam, which turns an intense yellow. Thus, by understanding the physiology of bilirubin excretion by the liver and by the use of a few simple tests, it is often possible to differentiate among multiple types of hemolytic diseases and liver diseases, as well as to deter-mine the severity of the disease.
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