Jaundice - classification, etiology, pathogenesis, and clinical manifestations.
Definition
Jaundice is yellowish discoloration of skin, mucous membranes, and sclera caused by hyperbilirubinemia (serum bilirubin >2–2.5 mg/ dL).
Classification
By mechanism
Etiology
Pre- hepatic jaundice
- Hemolytic anemias (e.g., hereditary spherocytosis, sickle cell disease, malaria).
- Ineffective erythropoiesis (e.g., thalassemia).
Hepatic jaundice
- Viral hepatitis (HAV, HBV, HCV).
- Alcoholic liver disease.
- Drug- induced liver injury (e.g., acetaminophen overdose).
- Cirrhosis.
- Genetic disorders (e.g., Gilbert syndrome, Crigler- Najjar syndrome).
Post- hepatic jaundice
- Gallstones (choledocholithiasis).
- Tumors (pancreatic head carcinoma, cholangiocarcinoma).
- Biliary strictures.
Pathogenesis
Normal bilirubin metabolism
- Hemoglobin breakdown → unconjugated (indirect) bilirubin.
- Transported to liver bound to albumin.
- Hepatocytes conjugate bilirubin with glucuronic acid → conjugated (direct) bilirubin.
- Excreted into bile → intestine → converted to urobilinogen → excreted in feces (stercobilin gives brown color ).
Pre- hepatic jaundice
- Excessive hemolysis → increased unconjugated bilirubin → exceeds liver’s capacity to conjugate.
Hepatic jaundice
- Hepatocyte dysfunction → impaired uptake and/or conjugation → mixed increase of unconjugated and conjugated bilirubin.
- Impaired excretion of conjugated bilirubin.
Post-hepatic jaundice
- Obstructed bile flow → regurgitation of conjugated bilirubin into blood.
Clinical manifestations
General
- Yellow discoloration of skin and sclera (first seen in sclera due to high elastin affinity).
Pre-hepatic
- Predominantly unconjugated hyperbilirubinemia.
- No bilirubinuria (unconjugated bilirubin is not water-soluble).
- Dark stools (increased stercobilin).
- Possible splenomegaly (if hemolytic).
Hepatic
- Mixed hyperbilirubinemia.
- Dark urine (conjugated bilirubin present).
- Possible pale stools.
- Signs of liver dysfunction: fatigue, coagulopathy, hepatomegaly.
Post-hepatic
- Predominantly conjugated hyperbilirubinemia.
- Dark urine (water-soluble bilirubin excreted).
- Pale (acholic) stools (lack of stercobilin).
- Pruritus (bile salt deposition in skin).
- Possible right upper quadrant pain, weight loss (if tumor).