bilirubin /bilirubin/ (-roobin) a bile pigment produced by breakdown of heme and reduction of biliverdin; it normally circulates in plasma and

is taken up by liver cells and conjugated to form bilirubin diglucuronide, the water-soluble pigment excreted in bile. High concentrations of bilirubin may result in jaundice. conjugated bilirubin , direct bilirubin bilirubin that has been taken up by the liver cells and conjugated to form the water-soluble bilirubin diglucuronide. indirect bilirubin , unconjugated bilirubin the lipid-soluble form of bilirubin that circulates in loose association with the plasma proteins.

Bilirubin consists of an open chain of four pyrrole-like rings (tetrapyrrole). In heme, by contrast, these four rings are connected into a larger ring, called a porphyrin ring. 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, some of the double-bonds in bilirubin isomerize when exposed to light. This is used in the phototherapy of jaundiced newborns: the E,Z-isomers of bilirubin formed upon light exposure are more soluble than the unilluminated Z,Z-isomer, as the possibility of intramolecular hydrogen bonding is removed.[2] This allows the excretion of unconjugated bilirubin in bile. Some textbooks and research articles show the incorrect geometric isomer of bilirubin.[3] The naturally occurring isomer is the Z,Z-isomer.

[edit] Function
Bilirubin is created by the activity of biliverdin reductase on biliverdin, a green tetrapyrrolic bile pigment that is also a product of heme catabolism. Bilirubin, when oxidized, reverts to become biliverdin once again. This cycle, in addition to the demonstration of the potent antioxidant activity of bilirubin,[4] has led to the hypothesis that bilirubin's main physiologic role is as a cellular antioxidant.[5][6]

[edit] Metabolism
[edit] Unconjugated (indirect)
Erythrocytes (red blood cells) generated in the bone marrow are disposed of in the spleen when they get old or damaged. This releases hemoglobin, which is broken down to heme as the globin parts are turned into amino acids. The heme is then turned into unconjugated bilirubin in the reticuloendothelial cells of the spleen. This unconjugated bilirubin is not soluble in water, due to intramolecular hydrogen bonding. It is then bound to albumin and sent to the liver.

[edit] Conjugated (direct)

In the liver it is conjugated with glucuronic acid by the enzyme glucuronyltransferase, making it soluble in water. Much of it goes into the bile and thus out into the small intestine. However 95% of the secreted bile is reabsorbed by the small intestine. This bile is then resecreted by the liver into the small intestine. This process in known as enterohepatic circulation. About half of the conjugated bilirubin remaining in the large intestine(about 5% of what was originally secreted) is metabolised by colonic bacteria to urobilinogen, which can be further metabolized to stercobilinogen, and finally oxidised to stercobilin. Stercobilin gives feces its brown color. However, just like bile, some of the urobilinogen is reabsorbed, and 95% of what is reabsorbed is resecreted in the bile which is also part of enterohepatic circulation. A small amount of the reabsorbed urobilinogen(about 5%) is excreted in the urine where it is converted to an oxidized form, urobilin, which gives urine its characteristic yellow color. This whole process results in only 1-20% of secreted bile being lost in the feces. The amount lost depends on the secretion rate of bile. Although the terms direct and indirect bilirubin are used equivalently with conjugated and unconjugated bilirubin, this is not quantitatively correct, because the direct fraction includes both conjugated bilirubin and bilirubin (bilirubin covalently bound to albumin, which appears in serum when hepatic excretion of conjugated bilirubin is impaired in patients with hepatobiliary disease).[7]

[edit] Urine
Under normal circumstances, a tiny amount of urobilinogen, if any, is excreted in the urine. 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. However, in disorders involving hemolytic anemia, an increased number of red blood cells are broken down, causing an increase in the amount of unconjugated bilirubin in the blood. Because the unconjugated bilirubin is not water-soluble, 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.

[edit] Toxicity
Unconjugated hyperbilirubinaemia in a neonate can lead to accumulation of bilirubin in certain brain regions (particularly the basal ganglia) with consequent irreversible damage to these areas manifesting as various neurological deficits, seizures, abnormal reflexes and eye movements. This type of neurological injury is known as kernicterus. The neurotoxicity of neonatal hyperbilirubinemia manifests because the blood-brain barrier has yet to develop fully, and bilirubin can freely pass into the brain interstitium, whereas more developed individuals with increased bilirubin in the blood are protected. Aside from specific chronic medical conditions that may lead to hyperbilirubinaemia, neonates in general are at increased risk since they lack the intestinal bacteria that facilitate the breakdown and excretion of conjugated bilirubin in the feces (this is largely why the feces of a neonate are paler than those of an adult). Instead the

conjugated bilirubin is converted back into the unconjugated form by the enzyme glucuronidase and a large proportion is reabsorbed through the enterohepatic circulation.

[edit] Blood tests

Bilirubin is broken down by light. Tubes containing blood or (especially) serum to be used in bilirubin assays should be protected from illumination. Bilirubin (in blood) is in one of two forms:

Hemoglobin Catabolism and Bilirubin

Introduction: The catabolism of hemoglobin is outlined in the graphic on the left. Red blood cells are continuously undergoing a hemolysis (breaking apart) process. The average life-time of a red blood cell is 120 days. As the red blood cells disintegrate, the hemoglobin is degraded or broken into globin, the protein part, iron (conserved for latter use), and heme (see middle graphic). The heme initially breaks apart into biliverdin, a green pigment which is rapidly reduced to bilirubin, an orange-yellow pigment (see bottom graphic). These processes all occur in the reticuloendothelial cells of the liver, spleen, and bone marrow. The bilirubin is then transported to the liver where it reacts with a solubilizing sugar called glucuronic acid. This more soluble form of bilirubin (conjugated) is excreted into the bile. The bile goes through the gall bladder into the intestines where the bilirubin is changed into a variety of pigments. The most important ones are stercobilin, which is excreted in the feces, and urobilinogen, which is reabsorbed back into the blood. The blood transports the urobilinogen back to the liver where it is either re-excreted into the bile or into the blood for transport to the kidneys. Urobilinogen is finally excreted as a normal component of the urine.

Types of Jaundice: Various conditions of jaundice result from the accumulation of bilirubin in the blood. A jaundice condition is characterized by yellow colored skin due to the presence of bilirubin. Hemolytic Jaundice: Excessive hemolysis or breakdown of red blood cells causes the formation of higher than normal amounts of bilirubin. Bilirubin made in the liver goes into bile and then into the gall bladder and into the intestines where most is excreted. The liver works normally, but could eventually be damaged from overwork. Usually the liver can handle the excess and the bilirubin is excreted via intestines and does not usually spill over into the kidneys. Urobilinogen levels are likely to be elevated in the blood and urine. Hepatic Jaundice: Hepatic jaundice is caused by damage or disease in the liver. Heme enters the liver but it does not take out as much bilirubin as is normal. Bilirubin builds up in the blood and spills over into the kidneys which filter it out into the urine. The amount of urobilinogen in the urine will be either normal or low if not enough bilirubin is being removed by the liver into bile and the intestines. Biliary Obstruction: If bilirubin cannot reach the intestinal area because of a blockage in the bile duct, than bilirubin builds up in the blood because it cannot get out of the liver. Bilirubin is then removed by the

kidneys into the urine. Little if any, urobilinogen will be found in the urine since little or no bilirubin is reaching the intestines.

cholecystectomy [kole-sis-tekto-me] excision of the GALLBLADDER, usually done to relieve the symptoms of CHOLECYSTITIS associated with GALLSTONES. During the operation a dye may be injected directly into the biliary ducts and a CHOLANGIOGRAM done to determine whether there are any stones within the ducts. If stones are known or suspected to be in the common bile duct, a T-tube is inserted to bypass the calculi and allow drainage of bile. The end of the tube is brought to the outside through a stab wound in the upper right quadrant and attached to a drainage bag. In spite of the intraoperative cholangiography, some patients will retain stones in the common bile duct after the surgery. LAPAROSCOPY is commonly used, which allows most patients to go home on the same day as surgery and return to full activity within a week. PATIENT CARE. During the preoperative period the patient will be given a thorough physical examination as well as specific tests for liver function and either radiologic or endoscopic studies of the gallbladder and biliary drainage system. Because nausea and flatulence are common problems in these patients, a nasogastric tube usually is inserted and attached to a decompression apparatus prior to surgery. When the patient returns from surgery a careful check is made for drainage tubes inserted during the operation. Sometimes the drains are devised so that bile and serous fluid from the operative site drain directly onto the surgical dressings. Other drains or tubes such as a T-tube or Y-tube are attached to a drainage bag so that the amount of bile removed can be measured periodically. In either case, dressings over the wound are checked frequently for signs of bleeding or other abnormalities in the character and amount of drainage. When bile leakage is copious, as it sometimes is, the dressings will need to be reinforced and the outer layers changed as often as necessary to keep the patient dry and comfortable and to avoid irritation of the skin around the incision. The nursing care plan of a patient with either a T-tube or a Y-tube should take into account three major potential problems: infection, obstruction, and dislodgment of the tube. Monitoring for infection includes watching for elevation of body temperature above 100 F and inspection of the tube insertion site for redness, swelling, warmth, and purulent drainage. The patient also is watched for jaundice and complaints of pain in the right upper quadrant, drainage around the tube when it is clamped, nausea, vomiting, and very dark urine and clay-colored stools, all of which indicate obstruction of the common bile duct. The amount of drainage from the tube is measured and recorded at least once every eight hours. A marked decrease in amount could mean that the tube has become dislodged.

Biliary tract disease continues to occur in approximately 5 to 8 per cent of all postcholecystectomy patients. The symptoms can appear within weeks after surgery or may occur years later and are the result of residual stones not removed at the time of surgery, newly formed gallstones, or stricture of the common bile duct. Infections and malignancies also can produce the symptoms of postcholecystectomy syndrome (PCS). Because of hormonal influences, women in the 40- to 49-year-old age group account for almost 80 per cent of patients with PCS. Treatment of the condition varies, but might entail more extensive surgery to provide a means by which bile can drain into the intestines.

Placement of T-tube following cholecystectomy. From Monahan et al., 1994. Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved.