CLINICAL SIGNIFICANCE OF BILIRUBIN IN LIVER FUNCTION TESTS

A SEMINAR PRESENTED BY ABDULSALAM JUMAI O

INTRODUCTION
Liver Function Tests are a group of Clinical Biochemistry laboratory assays designed to give information about the state of a patients liver. The parameters includes; PT/INR, APTT, Albumin, Bilirubin (Indirect and Direct),Alkaline phosphatase,5 Nucleotidase, Lactate dehydrogenase, serum glucose, liver transaminases (AST/ALT),GGT.

THE LIVER
The liver is the largest glandular organ of the body. It weighs about 3 lb (1.36 kg). It is reddish brown in color and is divided into four lobes of unequal size and shape. The liver lies on the right side of the abdominal cavity beneath the diaphragm. Blood is carried to the liver via two large vessels called the hepatic artery and the portal vein. The heptic artery carries oxygen-rich blood from the aorta (a major vessel in the heart). The portal vein carries blood containing digested food from the small intestine. These blood vessels subdivide in the liver repeatedly, terminating in very small capillaries. Each capillary leads to a lobule. Liver tissue is composed of thousands of lobules, and each lobule is made up of hepatic cells, the basic metabolic cells of the liver.

FUNCTIONS OF THE LIVER

The liver has many functions, Some of these functions are; 1. To produce substances that break down fats. 2. Convert glucose to glycogen. 3. Produce urea (the main substance of urine). 4. Make certain amino acids (the building blocks of proteins). 5. Filter harmful substances from the blood (such as alcohol). 6. Storage of vitamins and minerals (vitamins A, D, K and B12). 7. Maintain a proper level of glucose in the blood.

FUNCTIONS OF THE LIVER

8. The liver is also responsible for producing cholesterol. It produces about 80% of the cholesterol in your body. 9. The liver's main job is to filter the blood coming from the digestive tract, before passing it to the rest of the body. 10. The liver also detoxifies chemicals and metabolizes drugs. As it does so, the liver secretes bile that ends up back in the intestines.

APPLICATION OF LIVER FUNCTION TESTS

They provide a non invasive method to screen for the presence of liver disease. The serum aminotransferases for example are part of the panel of tests used to screen all blood donors in the united states for the presence of transmissible viruses. They can be used to measure the efficacy of treatments for liver disease (such as immunosuppressant agents for autoimmune hepatitis). To monitor the progression of a disease such as viral/alcoholic hepatitis. They can reflect the severity of liver disease, particularly in patients who have cirrhosis.

APPLICATION OF LIVER FUNCTION TESTS

To detect the presence of liver disease. To distinguish among different types of liver disorders. To guage the extent of known liver damage. They are carried out on those individuals taking certain medicationsanticonvulsants are a notable example, in order to ensure that the medications are not damaging the persons liver.

BILIRUBIN
Bilirubin is an orange pigment derived from the degradation of the heme moiety of hemoproteins, particularly the hemoglobin of mature circulating erythrocytes. Bilirubin is a potentially toxic waste product that is normally rendered harmless by binding to serum albumin, conjugation in the liver, and efficient excretion into bile by the liver. Bilirubin is an antioxidant, and a protective role of bilirubin against oxidant damage has been suggested. On the other hand, patients with profound unconjugated hyperbilirubinemia are at risk for bilirubin encephalopathy (kernicterus). Accumulation of bilirubin in plasma and tissues results in jaundice.

Bilirubin is the yellow-colored pigment that the liver produces when it recycles wornout red blood cells. Normal bilirubin levels are less than 1 mg/dl (milligram per deciliter). When levels become elevated, eyes and skin may turn yellow (jaundice), urine may appear a dark-tea color, and stools may look like light colored clay. Elevated bilirubin, while not the most common abnormality in blood tests pertaining to the liver, is quite obvious on a physical exam, and it is the liver-related abnormality most familiar to the general.

METABOLISM OF BILIRUBIN

ESTIMATION OF BILIRUBIN
Bilirubin is estimated using the colorimetric method based on that described by Jendrasik and Groft (1938). PRINCIPLE Direct (conjugate): Bilirubin reacts with diazotized sulphanilic acid in alkaline medium to form a blue coloured complex. Total Bilirubin : is determined in the presence of caffeine, which releases albumin bound bilirubin, by the reaction with diazotized sulphanilic acid.

Elevation in TB causes jaundice and can signal a number of problems; 1) Prehepatic : Increased bilirubin production. This can be due to a number of causes, including hemolytic anaemias and internal hemorrhage. 2) Hepatic : Problems with the liver, which are reflected as deficiencies in bilirubin metabolism (e.g reduced hepatocyte uptake, impaired conjugation of bilirubin, reduced hepatocyte secretion of bilirubin). Some examples would be cirrhosis and viral hepatitis. 3) Posthepatic : Obstruction of the bile ducts, reflected as deficiencies in bilirubin excretion.(Obstruction can be located either within the liver or the bile duct)

TOTAL BILIRUBIN

DIRECT BILIRUBIN
It is also known as conjugated bilirubin. It ranges from 0.1 0.4 mg/dl. If DB is normal, then the problem is an excess of unconjugated bilirubin and the location is upstream of bilirubin secretion. Hemolysis, viral hepatitis can be suspected. If DB is elevated then the liver is conjugating bilirubin normally, but is not able to excrete it. Bile duct obstruction by gallstones or cancer should be suspected.

JAUNDICE
It is often used with hyperbilirubinemia. However, a careful clinical examination cannot detect jaundice until the serum bilirubin is greater than 2mg/dl, twice the normal upper limit. The yellow discolouration is best seen in the periphery of the ocular conjunctivae and in the oral mucous membranes (under the tongue, hard palate). It is also known as Icterus.

HYPERBILIRUBINEMIA
The cause of hyperbilirubinemia can be classified into three; Plasma elevation of predominantly unconjugated bilirubin due to the overproduction of bilirubin, impaired bilirubin uptake by the liver or abnormalities of bilirubin conjugation. Plasma elevation of both unconjugated and conjugated bilirubin due to hepatocellular disease, impaired canalicular excretion, and biliary obstruction. In some situations, both overproduction and reduced dispositions contributes to the accumulation of bilirubin in plasma.

Disorders associated with unconjugated hyperbilirubinemia

Overproduction of bilirubin Extravascular hemolysis. Extravasation. Intravascular hemolysis. Dyserythropoiesis. Serum bilirubin in concentration. Bilirubin overproduction with coexisting liver disease. Urobilinogen secretion. Gallstones. Impaired hepatic bilirubin uptake. Impaired bilirubin conjugation.

 Biliary obstruction. Intrahepatic causes. Viral hepatitis. Alcoholic hepatitis. Non alcoholic hepatitis. Primary biliary cirrhosis. Drugs and toxins. Sepsis and low perfusion states. Malignancy. Liver infiltration. Inherited diseases.

Disorders associated with conjugated hyperbilirubinemia

 Total parenteral nutrition. Post operative patient. Following organ transplantation. Sickle cell disease. Intrahepatic cholestasis of pregnancy. End-stage liver disease. Hepatocellular injury.

Excess bilirubin in newborns damages developing brain cells in infants and may cause mental retardation, physical abnormalities or blindness. It may result from the breakdown of Red Blood Cells due to Rhesus typing incompatibility.

CONCLUSION
Icterus may be the first or only sign of liver disease; thus its evaluation is of critical importance. High bilirubin levels in children or adults, however, strongly suggest a medical condition that must be investigated and treated.

THANKS FOR LISTENING

Berk PD, Howe RB, Bloomer JR, Berlin NI. Studies of bilirubin kinetics in normal adults. J Clin Invest 1969; 48:2176 http://dx.doi.org/10.1036/ommbid.154 Jansen PL, Oude Elferink RP. Hereditary hyperbilirubinemias: a molecular and mechanistic approach. Semin Liver Dis 1988; 8:168. Roy, Chowdhury, J, Arias, IM. Disorders of bilirubin conjugation. In: Bile Pigments and Jaundice, Ostrow, JD (Eds), Marcel Dekker, New York 1986. p.317. Shapiro SM, Bhutani VK, Johnson L. Hyperbilirubinemia and kernicterus. Clin Perinatol 2006; 33:387.

REFERENCE