Cc2

• Jaundice is the yellowish discoloration of the skin, mucous membrane, and sclera of the eyes
• Jaundice is a visible indication of hyperbilirubinemia
• Jaundice is clinically evident when bilirubin levels exceed 3.0 to 5.0 mg/dL
• Classification of Jaundice:

  • Pre-hepatic jaundice
  • Hepatic jaundice
  • Post-hepatic jaundice
• Pre-hepatic jaundice is caused by an increase in red blood cell destruction, leading to increased circulating bilirubin concentrations
• Hepatic jaundice occurs due to intrinsic liver defects or diseases resulting in hepatocellular injury or destruction
• Post-hepatic jaundice is caused by obstruction in the bile ducts, preventing the flow of conjugated bilirubin into the bile canaliculi
• Congenital Hyperbilirubinemia:

  • Gilbert syndrome is characterized by a bilirubin transport deficit
  • Crigler-Najjar Syndrome has two types: Type 1 with complete deficiency of enzyme UDPGT and Type 2 with partial deficiency
  • Dubin-Johnson syndrome results in defective excretion of bilirubin with liver pigmentation
  • Rotor syndrome is a milder form of Dubin-Johnson syndrome without liver pigmentation
  • Lucey-Driscoll syndrome is caused by a circulating inhibitor to bilirubin conjugation
• Kernicterus is severe unconjugated hyperbilirubinemia characterized by bilirubin deposition in the brain, leading to motor dysfunction and possibly death
• Carotenemia is characterized by yellowish skin discoloration due to increased ingestion of carotenoids
• Liver diseases:

  • Biliary obstruction is commonly caused by choledocholithiasis
  • Cirrhosis is characterized by scar tissue replacing healthy liver tissue and can be caused by chronic alcoholism or other factors
  • Tumors in the liver can be primary or metastatic, with hepatocellular carcinoma being the most common malignant tumor
  • Reye's syndrome is associated with ingestion of aspirin during a viral syndrome and leads to liver damage
• Drug and alcohol-related disorders can cause liver diseases, with ethanol and acetaminophen being common culprits
• Biliary atresia is a condition where the bile ducts fail to develop properly, leading to bile accumulation in the liver
• Liver is the chief metabolic organ
• 80% of the liver must be destroyed to diminish liver function
• Functions of the liver include:

  • Synthetic Function: involving plasma proteins, carbohydrates, lipids, clotting factors, and enzymes
  • Conjugation Function: related to bilirubin conjugation, detoxification, and drug metabolism
  • Excretory and Secretory Function: such as bile excretion and pigment secretion
  • Storage Function: for vitamins and glycogen
• Specimen collection and storage:

  • Liver function tests are performed on serum
  • A fasting sample is preferred to avoid lipemia affecting measured bilirubin concentration
  • Hemolyzed samples may decrease the reaction of bilirubin with diazo reagent
  • Bilirubin values may reduce by 30% to 50% per hour if left unprotected from light
  • Stable for 2 days at room temperature, 1 week at 4⁰C, and indefinitely at -20⁰C
• Assessment of Liver Function includes tests that evaluate hepatic synthetic function, conjugation and excretion function, and detoxification function
• Test that evaluate hepatic synthetic function include:

  • Total protein determination (TP)
  • Albumin tests
  • Albumin/ Globulin ratio (A/G ratio)
  • Prothrombin time (PT)
• Total protein determination:

  • Reference value: 6-8 g/dL
  • Increased in malignancy, multiple myeloma, and Waldenstrom macroglobulinemia
  • Decreased in hepatic cirrhosis, glomerulonephritis, and nephrotic syndrome
• Laboratory methodologies for protein determination include Kjeldahl method, Biuret method, Folin-ciocalteau method, Ultraviolet absorption method, Salt fractionation, Refractometry, Tubidimetric and Nephelometric Methods, and Serum Protein Electrophoresis
• Albumin determination:

  • Synthesized in the liver
  • Normal synthesis at about 120 mg/kg/day
  • Dye-binding methods are used for measurement
  • Increased in severe dehydration and decreased in liver disease, nephrotic syndrome, and malabsorption syndrome
• Albumin/Globulin Ratio:

  • Measured to determine if globulin is higher than albumin in serum
  • Reference value: 1.3 - 3:1
  • Increased in chronic inflammation, multiple myeloma, and Waldenstrom macroglobulinemia
• Reference values:

  • Albumin: 3.5 - 5 g/dL
  • Alpha1-globulin: 0.1 - 0.3 g/dL
  • Alpha2-globulin: 0.6 - 1.0 g/dL
  • Beta-globulin: 0.7 - 1.1 g/dL
  • Gamma globulin: 0.8 - 1.6 g/dL
• Must to know:

  • Analbuminemia: hereditary absence of albumin
  • Bisalbuminemia: albumin with unusual molecular characteristics
• Prothrombin Time Test/Vitamin K Response Test:

  • Differentiates intrahepatic from extrahepatic causes of coagulopathy
• Presence of albumin bands instead of a single band in electrophoresis is associated with the presence of therapeutic drugs in serum (e.g., penicillin)
• Prothrombin Time Test/Vitamin K Response Test differentiates intrahepatic disorders from extrahepatic obstructive liver disease
• The liver is responsible for the synthesis of Vitamin K-dependent clotting factors
• Vitamin K is administered intramuscularly, 10mg daily for 1-3 days
• If Prothrombin Time (PT) is prolonged, it indicates an intrahepatic disorder; if PT is normal, it indicates an extrahepatic disorder
• Serum albumin and Vitamin K-dependent clotting factors provide the most useful indices for assessing the severity of liver disease
• Bilirubin is the end product of hemoglobin metabolism and the principal pigment in bile
• Bilirubin is formed from the destruction of heme-containing products such as myoglobin, cytochrome oxidase, and catalase
• Unconjugated bilirubin reacts slowly, so accelerants like caffeine or methanol are used to measure both direct and indirect bilirubin
• Conjugated bilirubin is the fraction that produces a color in aqueous solution, while unconjugated bilirubin produces a color only after the addition of alcohol
• Obstruction in the biliary tract can cause elevated total cholesterol due to a block in the normal excretion of cholesterol in the bile
• Delta bilirubin is conjugated bilirubin tightly bound to albumin and is elevated in Delta Bilirubin
• Measurement of Bilirubin B2 is a sensitive and specific marker for hepatic and post-hepatic jaundice
• Reference ranges for bilirubin levels: Direct <0.3 mg/dL, Indirect 0.1-1 mg/dL, Total bilirubin 0.1-1.2 mg/dL