Liver Function Tests (LFTs)

### **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 ce