clinical significance of bilirubin in liver function tests

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    CLINICAL SIGNIFICANCE OF

    BILIRUBIN IN LIVER FUNCTION

    TESTS

    A SEMINAR PRESENTED

    BY

    ABDULSALAM JUMAI O

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    INTRODUCTION

    Liver Function Tests are a group of ClinicalBiochemistry 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, livertransaminases (AST/ALT),GGT.

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    THE LIVERThe liver is the largest glandular organ of the body. It

    weighs about 3 lb (1.36 kg). It is reddish brown in colorand is divided into four lobes of unequal size andshape. The liver lies on the right side of the abdominalcavity beneath the diaphragm. Blood is carried to theliver via two large vessels called the hepatic artery andthe portal vein. The heptic artery carries oxygen-richblood from the aorta (a major vessel in the heart). Theportal vein carries blood containing digested food fromthe small intestine. These blood vessels subdivide in

    the liver repeatedly, terminating in very smallcapillaries. Each capillary leads to a lobule. Liver tissueis composed of thousands of lobules, and each lobuleis made up of hepatic cells, the basic metabolic cells of

    the liver.

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    FUNCTIONS OF THE LIVERThe 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.

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    FUNCTIONS OF THE LIVER

    8. The liver is also responsible for producing

    cholesterol. It produces about 80% of thecholesterol in your body.

    9. The liver's main job is to filter the blood

    coming from the digestive tract, beforepassing it to the rest of the body.

    10. The liver also detoxifies chemicals and

    metabolizes drugs. As it does so, the liversecretes bile that ends up back in the

    intestines.

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    APPLICATION OF LIVER FUNCTION

    TESTS

    They provide a non invasive method to screen for thepresence of liver disease. The serum aminotransferasesfor example are part of the panel of tests used toscreen all blood donors in the united states for thepresence of transmissible viruses.

    They can be used to measure the efficacy oftreatments for liver disease (such asimmunosuppressant agents for autoimmune hepatitis).

    To monitor the progression of a disease such asviral/alcoholic hepatitis.

    They can reflect the severity of liver disease,particularly in patients who have cirrhosis.

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    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 thatthe medications are not damaging the

    persons liver.

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    BILIRUBINBilirubin is an orange pigment derived from

    the degradation of the heme moiety ofhemoproteins, particularly the hemoglobin ofmature circulating erythrocytes. Bilirubin is apotentially toxic waste product that is normally

    rendered harmless by binding to serum albumin,conjugation in the liver, and efficient excretioninto 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 unconjugatedhyperbilirubinemia are at risk for bilirubinencephalopathy (kernicterus). Accumulation of

    bilirubin in plasma and tissues results in jaundice.

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    Bilirubin is the yellow-colored pigmentthat the liver produces when it recycles worn-

    out red blood cells. Normal bilirubin levels areless than 1 mg/dl (milligram per deciliter).When levels become elevated, eyes and skinmay turn yellow (jaundice), urine may appeara dark-tea color, and stools may look like lightcolored clay. Elevated bilirubin, while not themost common abnormality in blood tests

    pertaining to the liver, is quite obvious on aphysical exam, and it is the liver-relatedabnormality most familiar to the general.

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    METABOLISM OF BILIRUBIN

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    ESTIMATION OF BILIRUBIN

    Bilirubin is estimated using the

    colorimetric method based on that describedby Jendrasik and Groft (1938).

    PRINCIPLE

    Direct (conjugate): Bilirubin reacts withdiazotized sulphanilic acid in alkaline mediumto form a blue coloured complex.

    Total Bilirubin : is determined in the

    presence of caffeine, which releases albuminbound bilirubin, by the reaction withdiazotized sulphanilic acid.

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    TOTAL BILIRUBINElevation in TB causes jaundice and can signal anumber of problems;

    1) Prehepatic : Increased bilirubin production. Thiscan be due to a number of causes, includinghemolytic anaemias and internal hemorrhage.

    2) Hepatic : Problems with the liver, which arereflected as deficiencies in bilirubin metabolism(e.g reduced hepatocyte uptake, impairedconjugation of bilirubin, reduced hepatocytesecretion of bilirubin). Some examples would be

    cirrhosis and viral hepatitis.3) Posthepatic : Obstruction of the bile ducts,

    reflected as deficiencies in bilirubinexcretion.(Obstruction can be located either

    within the liver or the bile duct)

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    DIRECT BILIRUBINIt 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.

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    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 inthe periphery of the ocular conjunctivae and

    in the oral mucous membranes (under the

    tongue, hard palate). It is also known asIcterus.

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    HYPERBILIRUBINEMIAThe cause of hyperbilirubinemia can be

    classified into three;

    Plasma elevation of predominantly unconjugatedbilirubin due to the overproduction of bilirubin,impaired bilirubin uptake by the liver orabnormalities of bilirubin conjugation.

    Plasma elevation of both unconjugated andconjugated bilirubin due to hepatocellulardisease, impaired canalicular excretion, andbiliary obstruction.

    In some situations, both overproduction andreduced dispositions contributes to theaccumulation of bilirubin in plasma.

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    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.

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    Disorders associated with conjugated

    hyperbilirubinemia

    Biliary obstruction. Intrahepatic causes.

    Viral hepatitis.

    Alcoholic hepatitis.

    Non alcoholic hepatitis.

    Primary biliary cirrhosis.

    Drugs and toxins.

    Sepsis and low perfusion s

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