Jaundice Bilirubin

Type of jaundice Bilirubin Pigment I Pigment II Conjugated bilirubin... 

In cases of obstructive jaundice, bilirubin enters the lymphatic vessels, so that the lymphatic fluid is already icteric when it enters the thoracic duct. Exudates and transudates are always yellow-coloured in a certain correlation to the serum bilirubin values, although they contain less bilirubin (in accordance with their lower protein content) than the serum itself. Due to their larger protein content, exudates are more icteric in colour than transudates. Icteric colouring is hardly or not at all evident on paralyzed parts of the body. It would appear that bilirubin concentration also depends on normal nerve function. As a rule, jaundice is not detected in the region of an oedema (J. Meakins, 1927 J.H. Page, 1929). 

IU/1. Serology and autoimmune screens were negative, as were liver ultrasonography and computerized tomography. Cholangiopancreatography was normal. Irbesartan was replaced by amlodipine and metoprolol, and 2 months later she remained jaundiced (bilirubin 324 pmol/l). Liver biopsy showed portal tract expansion, minimal inflammation, ectatic ductules, and cholestatic rosettes. Within 16 weeks she fully recovered and continued to be anicteric more than 1 year later. 

Twenty percent of all human newborns accumulate enough bilirubin to stain their skin, resulting in jaundice. Bilirubin binds to cellular and mitochondrial membranes, causing cell death in a variety of tissues clinically, bilirubin toxicity may lead to mental retardation, cerebral palsy, deafness, seizures, or death. 

In jaundice, bilirubin may appear in the urine. Two factors seem to govern the renal excretion of bilirubin the solubility of bilirubin and the renal clearance of bilirubin. Unconjugated bilirubin is not normally excreted by the kidney only the more soluble conjugated bilirubin is found in the urine. The clearance for the diglucuronide is greater than that for the monoglucuronide. It is not known which part of the nephron excretes bilirubin. Some have postulated that bilirubin is excreted by glomerular filtration, and... 

In simple obstructive jaundice bilirubin appears, accompanied later by the bile salts. In the other forms of biliuria, pigments are present unaccompanied by bile salts. 

Older adults are particularly susceptible to a potentially fatal hepatitis when taking isoniazd, especially if they consume alcohol on a regular basis. Two other antitubercular drugs rifampin and pyrazinamide, can cause liver dysfunction in the older adult. Careful observation and monitoring for signs of liver impairment are necessary (eg, increased serum aspartate transaminase, increased serum alanine transferase, increased serum bilirubin, and jaundice). 

Hyjjerbilirubinaemia is an abnormality observed mainly in neonates in whom the liver is insufficiently developed to be able to detoxify the bile pigment bilirubin. This situation is known as neonatal jaundice and can sometimes become a serious disease causing neurotoxic symptoms. Bilirubin is produced by the degradation of heme [the Fe(II) complex of protoporphyrin IX] by heme oxygenase to give biliverdin, which is reduced by biliverdin reductase to... 

Knowledge of the biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins (see below) in the body. The porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of the various porphyrins. Although porphyrias are not very prevalent, physicians must be aware of them. A much more prevalent clinical condition is jaundice, due to elevation of bilirubin in the plasma. This elevation is due to overproduction of bilirubin or to failure of its excretion and is seen in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas. 

Figure 32-15. Diagrammatic representation of the three major processes (uptake, conjugation, and secretion) involved in the transfer of bilirubin from blood to bile. Certain proteins of hepatocytes, such as ligandin (a family of glutathione S-transferase) and Y protein, bind intracellular bilirubin and may prevent its efflux into the blood stream. The process affected in a number of conditions causing jaundice is also shown.

Type I Crigler-Najjar syndrome is a rare autosomal recessive disorder. It is characterized by severe congenital jaundice (serum bilirubin usually exceeds 20 mg/dL) due to mutations in the gene encoding bilirubin-UGT activity in hepatic tissues. The disease is often fatal within the first 15 months of life. Children with this condition have been treated with phototherapy, resulting in some reduction in plasma bilirubin levels. Phenobarbital has no effect on the formation of bilirubin glucuronides in patients with type I Crigler-Najjar syndrome. A liver transplant may be curative. 

Conjugated hyperbilirubinemia commonly results from blockage of the hepatic or common bile ducts, most often due to a gallstone or to cancer of the head of the pancreas. Because of the obstruction, bilirubin diglu-curonide cannot be excreted. It thus regurgitates into the hepatic veins and lymphatics, and conjugated bilirubin appears in the blood and urine (choluric jaundice). 

When levels of conjugated bilirubin remain high in plasma, a fraction can bind covalently to albumin (delta bilirubin). Because it is bound covalently to albumin, this fraction has a longer half-life in plasma than does conventional conjugated bilirubin. Thus, it remains elevated during the recovery phase of obstructive jaundice after the remainder of the conjugated bilirubin has declined to normal levels this explains why some patients continue to appear jaundiced after conjugated bilirubin levels have returned to normal. 

The commonest causes of obstructive (posthepatic) jaundice are cancer of the head of the pancreas and a gallstone lodged in the common bile duct. The presence of bilirubin in the urine is sometimes referred to as choluria—therefore, hepatitis and obstruction of the common bile duct cause choluric Jaundice, whereas the Jaundice of hemolytic anemia is referred to as acholuric. The laboratory results in patients with hepatitis are variable, depending on the extent of damage to parenchymal cells and the extent of micro-obstruction to bile ductules. Serum levels of ALT and AST are usually markedly elevated in hepatitis, whereas serum levels of alkaline phosphatase are elevated in obstructive liver disease. 

In jaundice secondary to hemolysis, the increased production of bilirubin leads to increased production of urobilinogen, which appears in the urine in large amounts. Bilirubin is not usually found in the urine in hemolytic jaundice (because unconjugated bihmbin does not pass into the urine), so that the combination of increased urobilinogen and absence of bihmbin is suggestive of hemolytic jaundice. Increased blood destruction from any cause brings about an increase in urine urobilinogen. 

Chowdhury JR et al Hereditary jaundice and disorders of bilirubin metabolism. In The Metabolic and Molecular Bases oflnher itedDisease, 8th ed. Scriver CR et al (editors). McGraw-Hill, 2001. 

If the fluorometric procedure is used, with protein precipitation, then bilirubin will not interfere with the hexokinase procedure. Even if protein precipitation is not resorted to, the interference from bilirubin does not become significant until one is dealing with an infant in severe jaundice. This can be seen in Table III. 

The sinusoids transport both portal and arterial blood to the hepatocytes. The systemic blood delivered to the liver contains nutrients, drugs, and ingested toxins. The liver processes the nutrients (carbohydrates, proteins, lipids, vitamins, and minerals) for either immediate use or for storage, while the drugs and toxins are metabolized through a variety of processes known as first-pass metabolism. The liver also processes metabolic waste products for excretion. In cirrhosis, bilirubin (from the enzymatic breakdown of heme) can accumulate this causes jaundice (yellowing of the skin), scleral icterus (yellowing of the sclera), and tea-colored urine (urinary bilirubin excretion). 

Liver Fever, lethargy, change in color or quantity of bile in patients w/ biliary T-tube, graft tenderness and swelling, back pain, anorexia, ileus, tachycardia, jaundice, ascites, encephalopathy Abnormal LFTs, increased bilirubin, alkaline phosphatase, transaminases, biopsy positive for mononuclear cell infiltrate with evidence of tissue damage... 

A jaundiced one-day-old premature infant with an elevated free bilirubin is seen in the premature-baby nursery The mother received an antibiotic combination preparation containing sulfamethizole for a urinary tract infection (UTI) one week before deliver)1 You suspect that the infant s findings are caused by the sulfonamide because of the following mechanism ... 

The activity of glucuronidation is low in the newborn, especially in premature babies (6). This is evident in the jaundice observed in many newborns because the major clearance pathway for bilirubin is glucuronidation. This can also lead to increased toxicity of some drugs in the newborn such as the grey baby syndrome seen in newborns treated with chloramphenicol. 

Bilirubin is a product of the breakdown of haemoglobin in red blood cells. Neonatal jaundice occurs when bilirubin builds up faster than a newborn baby s liver is able to break it down. This results in the deposition of water-insoluble bilirubin in the skin (giving the skin a yellow colour) and untreated it can lead to damage of the central nervous system by deposition in brain cells. 

See also Chapter 6 for details of jaundice and bilirubin production. 

The over-production of bilirubin to the point at which the liver s capacity to metabolize is exceeded or if there is dysfunction of the liver itself due to damage or metabolic immaturity, can lead to a yellow discolouration of tissues called jaundice. The accumulation of unconjugated bilirubin in neonates, often as a result of antibody-mediated destruction of the baby s red cells is dangerous as serious and irreversible brain damage can occur. Acute or chronic damage to the adult liver (hepatitis) may cause jaundice but not brain damage. 

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