Absorbed Conjugated bilirubin
Stercobilin Intestinal Contents
Urine diseases and various types of liver diseases. Therefore, while referring to Figure 70-2, let us explain this.
Briefly, when the red blood cells have lived out their life span (on average, 120 days) and have become too fragile to exist in the circulatory system, their cell membranes rupture, and the released hemoglobin is phagocytized by tissue macrophages (also called the reticuloendothelial system) throughout the body. The hemoglobin is first split into globin and heme, and the heme ring is opened to give (1) free iron, which is transported in the blood by transferrin, and (2) a straight chain of four pyrrole nuclei, which is the substrate from which bilirubin will eventually be formed. The first substance formed is biliverdin, but this is rapidly reduced to free bilirubin, which is gradually released from the macrophages into the plasma. The free bilirubin immediately combines strongly with plasma albumin and is transported in this combination throughout the blood and interstitial fluids. Even when bound with plasma protein, this bilirubin is still called "free bilirubin" to distinguish it from "conjugated bilirubin," which is discussed later.
Within hours, the free bilirubin is absorbed through the hepatic cell membrane. In passing to the inside of the liver cells, it is released from the plasma albumin and soon thereafter conjugated about 80 per cent with glu-curonic acid to form bilirubin glucuronide, about 10 per cent with sulfate to form bilirubin sulfate, and about 10 per cent with a multitude of other substances. In these forms, the bilirubin is excreted from the hepatocytes by an active transport process into the bile canaliculi and then into the intestines.
Formation and Fate of Urobilinogen. Once in the intestine, about half of the "conjugated" bilirubin is converted by bacterial action into the substance urobilinogen, which is highly soluble. Some of the urobilinogen is reabsorbed through the intestinal mucosa back into the blood. Most of this is re-excreted by the liver back into the gut, but about 5 per cent is excreted by the kidneys into the urine.After exposure to air in the urine, the uro-bilinogen becomes oxidized to urobilin; alternatively, in the feces, it becomes altered and oxidized to form ster-cobilin. These interrelations of bilirubin and the other bilirubin products are shown in Figure 70-2.
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 concentration of bilirubin, which is almost entirely the free form, averages 0.5 mg/dl of plasma. In certain abnormal conditions, 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 gastrointestinal tract. These two types of jaundice are called, respectively, hemolytic jaundice and obstructive jaundice. They differ from each other in the following ways.
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 urobilinogen in the intestine is greatly increased, and much of 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 by obstruction 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, but the 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 conjugated 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 the conjugated type rather than the free type.
Diagnostic Differences Between Hemolytic and Obstructive Jaundice. Chemical laboratory tests can be used to differentiate 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 den Bergh reaction can be used to differentiate between the two.
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 conjugated 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 observing 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 determine the severity of the disease.
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