Medical Biochemistry Exam Study Guide — OmpathStudy

Continued from $1. SECTION C: ANSWER ANY TWO QUESTIONS (40 MARKS) Question 41: Jaundice A) Discuss the various forms and causative factors of jaundice. (10 Marks) Jaundice is a clinical condition characterized by yellowish discoloration of skin, sclera, and mucous membranes due to elevated bilirubin levels ( 2-3 mg/dL or 34-51 μmol/L). It results from disruption in normal bilirubin metabolism. 1. PRE-HEPATIC JAUNDICE (Hemolytic Jaundice) Pathophysiology: Excessive breakdown of red blood cells leading to overproduction of bilirubin The liver's capacity to conjugate bilirubin becomes overwhelmed Results in predominantly unconjugated (indirect) hyperbilirubinemia Causative Factors: Inherited Hemolytic Anemias : Sickle cell disease, thalassemia, hereditary spherocytosis Acquired Hemolytic Anemias : Autoimmune hemolytic anemia, drug-induced hemolysis Infections : Malaria, sepsis, Clostridium perfringens Mechanical Hemolysis : Prosthetic heart valves, march hemoglobinuria Transfusion Reactions : ABO incompatibility, delayed hemolytic reactions Genetic Enzyme Deficiencies : G6PD deficiency, pyruvate kinase deficiency 2. HEPATIC JAUNDICE (Hepatocellular Jaundice) Pathophysiology: Impaired hepatocyte function affecting bilirubin uptake, conjugation, or excretion Results in mixed hyperbilirubinemia (both conjugated and unconjugated) Associated with elevated liver enzymes (ALT, AST) Causative Factors: Viral Hepatitis : Hepatitis A, B, C, D, E, EBV, CMV Toxic Hepatitis : Alcohol, acetaminophen, halothane, mushroom poisoning Drug-Induced : Statins, antibiotics, antiepileptics, herbal supplements Genetic Disorders : Wilson's disease, α1-antitrypsin deficiency, hemochromatosis Autoimmune : Autoimmune hepatitis, primary biliary cholangitis Ischemic Hepatitis : Shock liver, right heart failure Infiltrative Diseases : Metastatic cancer, lymphoma, sarcoidosis 3. POST-HEPATIC JAUNDICE (Obstructive/Cholestatic Jaundice) Pathophysiology: Mechanical obstruction of bile flow from liver to duodenum Conjugated bilirubin backs up into hepatocytes and bloodstream Results in predominantly conjugated (direct) hyperbilirubinemia Associated with elevated alkaline phosphatase and GGT Causative Factors: Intrahepatic Cholestasis: Drug-Induced : Oral contraceptives, anabolic steroids, cyclosporine Pregnancy : Intrahepatic cholestasis of pregnancy Genetic : Progressive familial intrahepatic cholestasis (PFIC) Infiltrative : Primary sclerosing cholangitis, sarcoidosis Extrahepatic Obstruction: Gallstones : Choledocholithiasis (most common cause) Malignancies : Pancreatic cancer, cholangiocarcinoma, ampullary carcinoma Inflammatory : Chronic pancreatitis, autoimmune pancreatitis Strictures : Post-surgical, post-inflammatory, ischemic Parasitic : Ascaris lumbricoides, liver flukes Congenital : Biliary atresia, choledochal cysts B) Describe how each type of jaundice can be differentiated using the Van Den Bergh test. (10 Marks) The Van Den Bergh test is a biochemical assay that differentiates between conjugated (direct) and unconjugated (indirect) bilirubin, helping classify the type of jaundice. Principle: Based on the differential reaction of conjugated and unconjugated bilirubin with diazotized sulfanilic acid Conjugated bilirubin reacts directly and immediately (within 1 minute) Unconjugated bilirubin requires alcohol or caffeine as an accelerator and reacts slowly Test Procedure: Direct Reaction : Serum + diazotized sulfanilic acid → immediate color development Total Reaction : Serum + diazotized sulfanilic acid + alcohol → complete color development after 30 minutes Indirect Bilirubin : Calculated as Total - Direct bilirubin Normal Values: Total bilirubin: 0.2-1.2 mg/dL (3.4-20.5 μmol/L) Direct (conjugated): <0.3 mg/dL (<5.1 μmol/L) Indirect (unconjugated): 0.2-0.8 mg/dL (3.4-13.7 μmol/L) Differentiation of Jaundice Types: 1. Pre-hepatic (Hemolytic) Jaundice: Direct bilirubin : Normal or slightly elevated (<20% of total) Indirect bilirubin : Markedly elevated ( 80% of total) Pattern : Predominantly indirect hyperbilirubinemia Additional findings : Elevated LDH, decreased haptoglobin, reticulocytosis 2. Hepatic (Hepatocellular) Jaundice: Direct bilirubin : Moderately elevated (20-50% of total) Indirect bilirubin : Moderately elevated Pattern : Mixed hyperbilirubinemia Additional findings : Elevated ALT/AST ( 10x normal), prolonged PT/INR 3. Post-hepatic (Obstructive) Jaundice: Direct bilirubin : Markedly elevated ( 50% of total, often 80%) Indirect bilirubin : Normal or slightly elevated Pattern : Predominantly direct hyperbilirubinemia Additional findings : Elevated ALP/GGT ( 3x normal), elevated cholesterol Clinical Significance: Ratio 0.2 : Suggests hepatocellular or obstructive jaundice Ratio <0.2 : Suggests hemolytic jaundice Delta bilirubin : In chronic liver disease, bilirubin may be covalently bound to albumin, requiring special consideration --- Question 42: Muscle Contraction and LDH A) Describe the biochemical events during muscle