1 CLINICAL CHEMISTRY-2 (MLT 302) LIVER FUNCTION AND THE BILIARY TRACT LECTURE FOUR Dr. Essam H. Aljiffri

2 JAUNDICE Neonatal Jaundice The major enzyme which conjugates bilirubin in the liver (UDP glucuronyl transferase) is not fully mature at birth; - unconjugated hyperbilirubinaemia and jaundice are common. This is usually physiological causes of neonatal jaundice.

3 Neonatal Jaundice Physiological jaundice is maximal within 2-5 days of delivery; it is more severe in premature infants. Unconjugated bilirubin is toxic to the nervous system Jaundice has no effect on the central nervous system in adults, since bilirubin does not cross the blood brain barrier.

4 Neonatal Jaundice The blood brain barrier is immature in neonates and unconjugated bilirubin can enter brain tissue. One of the methods of treating physiological jaundice include: phototherapy.

5 Congenital Defects in Bilirubin Transport Gilbert's Disease Gilbert's disease is a common congenital disorder of bilirubin transport - affecting approximately 2% of the population, - males more than females.

6 Gilbert's Disease The activity of UDP­glucuronyl transferase is reduced and defects in the uptake of bilirubin by hepatocytes also occur. Gilbert's disease characteristically causes mild jaundice, serum bilirubin concentrations usually being µmol/L.

7 Other Congenital Transport Syndromes A severe congenital deficiency in UDP­glucuronyl transferase occurs in Crigler-Najjar syndrome, Most patients dying in infancy from high unconjugated bilirubin which is toxic to the nervous system.

8 It is possible to investigate many of the functions of the liver in detail. ASSESSMENT OF HEPATIC FUNCTIONS

9 ASSESSMENT OF LIVER FUNCTIONS Hepatic carbohydrate metabolism can be assessed by measuring blood galactose removal following injection, and glucose output can be quantified. The assessment of liver function in daily clinical practice is usually performed by measuring serum levels of bilirubin, hepatic enzymes and proteins.

10 ASSESSMENT OF LIVER FUNCTION Serum enzymes in liver disease Small amounts of enzymes leak from their intracellular location into serum and cellular dysfunction often causes increased leakage. The measurement of enzyme activity in serum may be useful in the investigation of organ dysfunction to differentiate patterns of disease.

11 Serum enzymes in liver disease Abnormal mainly in hepatocellular disease Alanine aminotransferase (transaminase) (ALT) Aspartate aminotransferase (transaminase) (AST) Lactate dehydrogenase (LDH) Abnormal mainly in cholestasis Alkaline phosphatase (ALP) y-Glutamyl transferase (transpeptiase) (GGT)

12 Aminotransferases Aminotransferases are involved in amino acid metabolism. Aspartate aminotransfer­ase (AST) occurs in both the cytosol and mitochondria of cells Alanine aminotransferase (ALT) is a cytosolic enzyme. Increased amounts of both transaminases leak from: - inflamed or damaged hepatocytes

13 Aminotransferases Measurement of one of these enzymes is included in liver function tests. ALT is more specific for liver disease than AST, AST is more sensitive because the liver contains larger amounts.

14 Lactate Dehydrogenase Lactate dehydrogenase (LDH) is often raised in hepatocellular dysfunction It is rarely measured for this purpose since it lacks specificity because of wide distribution of LDH in the body.

15 Alkaline Phosphatase Levels of alkaline phosphatase increase in cholestasis, mainly because of increased synthesis of the enzyme.

16 Gama-glutamyl Transferase Increased serum activities of GGT are found in both: - hepatocellular and - cholestatic disease. Higher activities are found in cholestasis, when levels greater than 50 times the upper limit of normal. Increased synthesis of GGT is induced by excessive ethanol intake.

17 KEY POINTS Transaminase (ALT and AST) levels are raised mainly in hepatocellular disease Alkaline phosphatase levels is raised mainly in obstructive disease Increased in serum GGT levels are modest in hepatocellular and marked in obstructive disease

18 Proteins measured in the investigation of disease

19 Plasma Proteins in Liver Disease Albumin has a half-life in serum of about 20 days and levels fall slowly if no synthesis occurs. Serum albumin is usually normal/decrease in hepatic failure and chronic liver diseases such as cirrhosis, impaired synthesis may lead to low serum levels.

20 Plasma Proteins in Liver Disease Serum globulins are often increased in cirrhosis alpha1-Antitrypsin deficiency: - neonatal jaundice and - cirrhosis in children and young adults.

21 Plasma Proteins in Liver Disease Alpha-fetoprotein: - modest levels are found, e.g; during acute viral hepatitis, - very high values occur in hepatocellular carcinoma.

22 Investigation of Liver Disease Biochemical liver function tests are an essential part of assessment of liver disease. Tests must be interpreted with knowledge of:  the clinical details of the patient, and  the results of other investigations.

23 Investigation of Liver Disease These often include:  ultrasound examination,  radiological procedures, and  liver biopsy.