Liver Function Tests (LFTs) — Notes OmpathStudy

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 absen