1. MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Alterations in Liver Function

2. Jaundice/Icterus Yellow discoloration of the skin, eyes and mucous membranes Due to the presence of bilirubin Onset seen at bilirubin levels > 3.0 mg/dL Kernicterus – Yellow staining of the meninges of the brain due to bilirubin – Found in newborns – Causes brain damage

3. Classification of Jaundice Prehepatic Hepatic Posthepatic

4. Classifications of Jaundice Prehepatic – Abnormality is outside the liver – Liver function is normal – Cause: too much bilirubin presented to liver – Result Increase in unconjugated bilirubin Total bilirubin: increased or normal Increase in serum iron – Examples: acute /chronic hemolytic anemias

5. Classifications of Jaundice Hepatic – Intrinsic liver disease or defect – Caused by Disorders of bilirubin conjugation Disorders of bilirubin transport Hepatocellular injury or destruction – Cirrhosis – Tumors – Infection – Toxins – Intrahepatic obstructions

6. Inherited Hyperbilirubinemias Gilbert Syndrome  Reduction in the activity of UDP-glucoronyl transferase Crigler-Najjar syndrome  Defective UDPG-transferase Dublin-Johnson disease  Post-conjugation failure Liver

7. Acquired Hyperbilirubinemias Neonatal jaundice – Deficiency of glucuronyl transferase – Causes an increase in unconjugated bilirubin – Leads to kernicterus – Treat by exposure to UV light or exchange transfusion

8. Classifications of Jaundice Posthepatic – Abnormality is outside the liver – Liver function is normal – Biliary obstruction due to gallstones, tumors, edema – Stool turns clay-colored due to lack of bile – Results: Increased: Conjugated bilirubin, urinary bilirubin, ALP, GGT, total bilirubin, unconjugated bilirubin Decreased: Urine and fecal urobilinogen

9. Other Liver Dysfunctions Reye’s Syndrome Cirrhosis Drug & Alcohol Disorders Hepatitis

10. Reye Syndrome Group of disorders caused by infectious, metabolic, toxic or drug-induced disease found mostly in children Often preceded by viral syndrome Related to aspirin consumption during the viral syndrome Symptoms – Profuse vomiting – Neurological impairment

11. Cirrhosis Scar tissue replaces normal healthy liver tissue As time moves forward, function deteriorates and signs appear – Fatigue, nausea, weight loss, jaundice, etc Common causes – Chronic alcoholism – Hepatitis Results: – Increased: unconjugated and conjugated bilirubin, ALP, GGT,AST, ALT – Decreased: cholesterol, albumin

12. Drug and Alcohol Disorders Accounts for 1/3 to ½ of acute liver failure since the liver plays a major role in drug metabolism Drugs cause an immune mediated injury to the hepatocytes, resulting in disease Ethanol is the most significant Acetaminophen also common Several stages of classification based on disease severity

13. Alcoholic Liver Disease (ALD) Breakdown of alcohol leads to toxin formation Risk factors for ALD include: – History and magnitude of alcohol consumption – Hepatitis B or C infection – Gender – Genetic factors – Nutritional status

14. Alcoholic Injury Stages – Alcoholic Fatty Liver Mildest form Elevations of AST, ALT, GGT Complete recovery possible if drug removed – Alcoholic hepatitis Moderate elevations of AST, ALT, GGT Bilirubin, ALP also elevated Albumin decreased PT prolonged – Alcoholic cirrhosis Elevated AST, ALT, GGT, ALP, total bilirubin Albumin decreased PT prolonged

15. Hepatitis Inflammation of the liver Viral, bacterial, radiation, drugs, chemicals and others can cause inflammation Viral infections account for the majority of cases in the clinical lab Includes subtypes A, B,C, D, and E Clinical Symptoms – Jaundice, dark urine, fatigue, nausea, abdominal pain

16. Hepatitis Viruses VirusIncubation Period Mode of transmission VaccineChronic Infection Hepatitis A2-6 weeksFecal-oralYesNO Hepatitis B8-26 weeksParenteral, sexual Yes Hepatitis C2-15 weeksParenteral, sexual NoYes Hepatitis D21-90 daysParenteral, sexual Yes Hepatitis E3-6 weeksFecal-oralNo?

17. References Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins. http://kidshealth.org/parent/pregnancy_center/newborn_car e/jaundice.html http://kidshealth.org/parent/pregnancy_center/newborn_car e/jaundice.html Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson.