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8/3/2019 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.
http://organs/HEART.asphttp://organs/HEART.asp


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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 states.

Malignancy.

Liver infiltration.

Inherited diseases.


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Total parenteral nutrition.

Post operative patient.

Following organ transplantation. Sickle cell disease.

Intrahepatic cholestasis of pregnancy.

End-stage liver disease.

Hepatocellular injury.


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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.


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CONCLUSION

Icterus may be the first or only sign of liverdisease; thus its evaluation is of critical

importance. High bilirubin levels in children or

adults, however, strongly suggest a medicalcondition that must be investigated and

treated.


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THANKS FOR LISTENING


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REFERENCEBerk 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. Hereditaryhyperbilirubinemias: a molecular and mechanisticapproach. Semin Liver Dis 1988; 8:168.

Roy, Chowdhury, J, Arias, IM. Disorders of bilirubinconjugation. 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
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