Learn about Liver Function Tests (LFTs), including ALT, AST, bilirubin, and PT. Understand how LFTs assess liver health, detect damage, and diagnose jaundice &
Liver Function Tests (LFTs) – Summary Notes Introduction - The liver is the second largest organ, weighing about three pounds , located under the right rib cage . - Functions: Metabolizes nutrients, detoxifies blood, and synthesizes proteins . - Liver Function Tests (LFTs) assess liver health, detect damage, monitor disease, and evaluate treatment effectiveness . - 1. Common Liver Function Tests a) Liver Enzyme Tests - Alanine Transaminase (ALT): High levels indicate liver damage. - Aspartate Transaminase (AST): Found in the liver and muscles; elevated levels suggest liver or muscle damage. - Alkaline Phosphatase (ALP): Increased in liver or bile duct diseases. - Gamma-Glutamyl Transpeptidase (GGT): High in liver and bile duct damage. - b) Liver Protein Tests - Total Protein: Measures albumin and globulin. - Globulin: Supports immunity; low levels may indicate liver disease. - Albumin: Indicates liver’s protein synthesis function; low levels suggest liver failure. - Prothrombin Time (PT): Measures clotting ability; prolonged PT suggests impaired liver function. - c) Bilirubin Tests - Bilirubin: Breakdown product of red blood cells (RBCs); high levels cause jaundice . - Total Bilirubin: Includes both conjugated (direct) and unconjugated (indirect) bilirubin. - Conjugated Bilirubin: Water-soluble and excreted in bile; elevated levels suggest bile duct obstruction . - Unconjugated Bilirubin: Fat-soluble; high levels indicate excessive RBC breakdown or impaired liver processing. - 2. Bilirubin Formation and Detoxification - RBCs are broken down in the liver, spleen, and bone marrow (Reticuloendothelial System - RES). - Heme → Choleglobin → Biliverdin (green) → Bilirubin (yellow, water-insoluble) . - Bilirubin binds to albumin → enters the liver → conjugated with glucuronic acid → bilirubin diglucuronide (water-soluble) . - Excretion Pathway:Bile → Small intestine → Converted to stercobilinogen → Oxidized to stercobilin (brown pigment in feces). - Some stercobilinogen is reabsorbed → Liver → Excreted in urine as urobilinogen (oxidized to urobilin when exposed to air). - 3. Key Liver Function Test Analyses - Total Bilirubin Measurement: Includes conjugated and unconjugated bilirubin. - Specific Bilirubin Determination: Differentiates between direct (conjugated) and indirect (unconjugated) bilirubin . - 4. Factors Affecting Liver Function Tests - Large Liver Reserve Capacity: Liver can still function even with some damage. - Liver Regeneration: The liver can self-repair , but chronic damage (e.g., cirrhosis) is irreversible. - Diseases Related to Bilirubin Formation and Detoxification 1. Jaundice (Icterus) - Yellow discoloration of skin, mucous membranes, and plasma due to elevated bilirubin levels ( 100 mL/L). - Classified based on cause and location of bilirubin accumulation: - 2. Types of Jaundice A) Post-Hepatic Jaundice (Obstructive Jaundice) - Cause: Blockage in bile flow due to gallstones, tumors, or bile duct obstructions . - Accumulated Bilirubin: Conjugated bilirubin (bilirubin diglucuronide) . - Common Causes:Lumen obstruction: Gallstones, parasitic worms. - Wall obstruction: Bile duct cancer, strictures, atresia. - External compression: Pancreatic cancer, lymph node enlargement at porta hepatis. - - Symptoms:Severe jaundice, dark urine, pale stools . - High conjugated bilirubin in serum and urine . - Gallstones (Cholelithiasis) - Types:Cholesterol Stones (most common) – Risk factors: obesity, age, female sex, diabetes, hyperlipidemia. - Pigment Stones – Due to excessive bilirubin from hemolytic anemia. - - Presentation:Biliary colic: Severe upper right quadrant pain . - Intermittent jaundice, bilirubinuria . - Elevated ALP, GGT levels . - Prolonged painless obstructive jaundice . - B) Pre-Hepatic Jaundice (Hemolytic Jaundice) - Cause: Excess RBC breakdown → increased bilirubin load on the liver . - Accumulated Bilirubin: Unconjugated bilirubin . - Causes:Hemolytic Disorders: Sickle cell anemia. - Hereditary spherocytosis. - G6PD deficiency. - Autoimmune hemolytic anemia. - Blood group incompatibility (e.g., neonatal jaundice). - Bacterial toxins and malaria. - - Ineffective erythropoiesis: Megaloblastic anemia. - - Lab Findings:High unconjugated bilirubin (liver overwhelmed by RBC breakdown) . - Normal conjugated bilirubin (no bile duct obstruction). - No bilirubin in urine (unconjugated bilirubin is not water-soluble) . - Increased urine urobilinogen (increased bilirubin metabolism). - Hematological tests: High reticulocyte count, RBC morphology changes. - C) Intrahepatic Jaundice (Hepatocellular Jaundice) - Cause: Liver cell damage → impaired bilirubin metabolism and excretion . - Accumulated Bilirubin: Both unconjugated and conjugated bilirubin (due to liver dysfunction and canaliculi obstruction). - Causes:Liver diseases: Hepatitis, cirrhosis, drug toxicity, infections. - Inherited defects in bilirubin metabolism:Gilbert’s Syndrome: Decreased UDP-glucuronosyltransferase (UDPGT) activity due to a TA insertion mutation . - Mildly elevated unconjugated bilirubin , worsened by fasting or infections. - - Crigler-Najjar Syndrome:Type I: Complete absence of UDPGT enzyme → severe unconjugated bilirubin elevation . - Type II: Partial UDPGT deficiency → milder symptoms. - - Defective bilirubin excretion:Dubin-Johnson Syndrome & Rotor Syndrome:Benign inherited disorders causing increased conjugated bilirubin in blood and urine due to impaired excretion. - 3. Key Diagnostic Features of Jaundice Types These conditions highlight the importance of bilirubin metabolism in diagnosing liver function and systemic diseases . Classification of Jaundice by Type of Bilirubin 1. Unconjugated Hyperbilirubinemia - Physiological Jaundice Occurs on days 3-5 after birth (never on day 1). - Bilirubin levels may reach 150 μM/L (all unconjugated). - Managed with phototherapy . - - Blood Group Incompatibility (Hemolytic Disease of the Newborn) Develops on day 1 . - Caused by Rhesus or ABO incompatibility . - Maternal IgG antibodies attack fetal RBCs → hemolysis . - In severe cases, may cause hydrops fetalis (fetal anemia & heart failure). - - Inherited Hemolytic Disorders Similar to hemolytic diseases in adults. - Complications - Kernicterus : Risk increases when unconjugated bilirubin 200 μM/L . - Risk factors:Low albumin . - Drugs that displace bilirubin from albumin. - Acidosis, hypoxia, hypoglycemia, hypothermia, sepsis (increase bilirubin entry into the brain). - Heparin (releases free fatty acids that displace bilirubin). - Clinical Features - Lethargy - Hypotonia - Poor feeding - Spasticity → Can lead to death . - Treatment - Phototherapy Light at 440-470 nm converts bilirubin into water-soluble isomers excreted in urine. - - Exchange Transfusion Required if bilirubin 305 μM/L (term babies) or 200 μM/L (preterm babies). - 2. Conjugated Hyperbilirubinemia - Neonatal Hepatitis (Infectious Jaundice) Causes: Rubella, CMV, herpes simplex, toxoplasmosis . - Liver immaturity (especially in preterm infants) contributes to jaundice. - Shorter RBC lifespan & increased RBC mass contribute to higher bilirubin load. - - Biliary Atresia Cause unclear; may be due to toxic bile duct degeneration rather than congenital malformation. - - Metabolic Disorders Various inherited conditions can lead to impaired bilirubin metabolism . - Treatment - Treat the underlying cause (e.g., infection, metabolic disorder). - Determination of Bilirubin Levels: Van den Bergh Test - Detects conjugated and unconjugated bilirubin in circulation. - Reagents Used - Van den Bergh Reagent A – Sulfuric acid ( H₂SO₄ ) - Van den Bergh Reagent B – Dilute sodium nitrite ( NaNO₂ ) - Ehrlich’s Diazole Reagent – Formed by mixing Reagent A & B in a 5:0.15 ratio . - Procedure & Interpretation - Direct (Positive) Test – Immediate pink color (within 30 sec ) → High conjugated bilirubin . - Indirect (Negative) Test – No color change → Suggests:Presence of unconjugated bilirubin (water-insoluble). - No bilirubin at all .