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MLAB 2401: Clinical Chemistry Keri Brophy-Martinez. Alterations in Liver Function. 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
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MLAB 2401: Clinical ChemistryKeri Brophy-Martinez Alterations in Liver Function
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
Classification of Jaundice • Prehepatic • Hepatic • Posthepatic
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
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
Inherited Hyperbilirubinemias Liver • Gilbert Syndrome • Reduction in the activity of UDP-glucoronyltransferase • Crigler-Najjar syndrome • Defective UDPG-transferase • Dublin-Johnson disease • Post-conjugation failure
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
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
Other Liver Dysfunctions • Reye’s Syndrome • Cirrhosis • Drug & Alcohol Disorders • Hepatitis
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
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
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
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
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
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
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_care/jaundice.html • Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .