Jaundice and Hyperbilirubinemia Overview

Jaundice

• Caused by bilirubin metabolism abnormalities.
• Bilirubin, a hemoglobin breakdown product, is produced in several steps:
  • Aged or damaged RBCs are phagocytosed in the liver and spleen.
  • Hemoglobin is degraded in Kupffer cells and the spleen.
  • Iron is removed from heme, resulting in bilirubin.
  • Bilirubin is released into the blood and binds to albumin.
  • Unconjugated, non-water-soluble bilirubin is conjugated in the liver.
  • Water-soluble, conjugated bilirubin becomes part of bile, aiding in fat digestion.
  • Excess bilirubin is reabsorbed in the intestines and recycled to the liver.
  • Bilirubin is also excreted in urine. This process is called enterohepatic circulation.

Hyperbilirubinemia

• Occurs when bilirubin levels are elevated.
• Normal level is 0.3-1 mg/dl.
• Classified biochemically:
  • Conjugated
  • Unconjugated
  • Mixed conjugated & unconjugated
• Jaundice, the yellow coloration of the skin and sclera, occurs when:
  • Bilirubin levels exceed 3 mg/dl.
  • It is an observable clinical marker for liver dysfunction.
• Types of jaundice:
  • Prehepatic (hemolytic) jaundice: unconjugated hyperbilirubinemia.
  • Hepatic jaundice: mixed, conjugated & unconjugated hyperbilirubinemia.
  • Posthepatic (obstructive) jaundice: conjugated hyperbilirubinemia.

Prehepatic (hemolytic) Jaundice

• Excessive bilirubin formation due to erythrocyte lysis (hemolysis).
• Etiology:
  • Abnormal hemoglobins (sickle cell, thalassemia).
  • Immune-mediated blood mismatches.
  • Drug-induced hemolysis.
  • Hypersplenism.
  • Resolution of large bruises (especially in newborns).
  • Genetic lack of conjugating enzymes (Gilbert's Syndrome):
    • Autosomal dominant defect in bilirubin uptake.
    • Mild jaundice, not clinically significant.
• Hemolysis overwhelms the liver's capacity to conjugate and excrete bilirubin.
• Tissue bilirubin deposition leads to jaundice.

Hepatocellular Jaundice

• Most common type of jaundice seen clinically.
• Failure of the liver to take up, conjugate, or excrete bilirubin.
• Hyperbilirubinemia can be predominantly unconjugated or conjugated depending on the pathology.
• Etiology:
  • Damage to liver cells by infection, tumors, drugs or chemicals.
    • Viral hepatitis is the most common cause.
    • Other causes include drugs, alcoholic cirrhosis, and metabolic diseases.
  • Neonatal jaundice in newborns:
    • Due to liver immaturity and increased bilirubin load.
    • Predominantly unconjugated.

Post-hepatic (obstructive) Jaundice

• Obstruction of the bile duct system.
• Disturbance in the excretion of conjugated bile.
• Bile flow to the duodenum is reduced or blocked (cholestasis).
• Bilirubin and bile salts accumulate in the liver and spill into the blood.
• Etiology:
  • Intrahepatic causes:
    • Infections, drugs, and swelling causing compression of intrahepatic ducts.
    • Congenital biliary atresia: deficient quantity of bile ducts.
  • Extrahepatic causes:
    • Obstruction of the common bile duct.

Hepatitis B Virus Carrier State

• Some patients are unable to eliminate HBV particles due to inadequate immune response.
• Infection persists, with minimal liver dysfunction or no abnormality.
• Carriers are asymptomatic but still infectious and capable of spreading the virus for prolonged periods.
• Identifying carriers can be difficult as some may have had undiagnosed mild infections.
• Does not exist for hepatitis A, but exists for hepatitis B & C.
• High among homosexuals and intravenous drug users.

Hepatitis C

• First NANB virus identified.
• Etiology:
  • Responsible for most post-transfusion hepatitis before screening for HCV.
  • Sporadic epidemics.
  • Sexual transmission possible.
• Pathology and prognosis:
  • Initial illness milder than HBV but progresses to chronic hepatitis in 50% of infected individuals.
  • Risk factors:
    • Development of cirrhosis.
    • Higher incidence of hepatocellular carcinoma.

Hepatitis D

• Cannot infect alone, only in concert with HBV.
• HDV is a viroid, an incomplete RNA virus that requires HBV for infection.
• Infection occurs simultaneously with HBV (co-infection) or superimposed on established HBV (superinfection).

Hepatitis E

• Not common in the US.

Gallbladder Carcinoma

• Common in older patients, mostly female.
• Risk factor: gallstones.
• Grows into the liver, extrahepatic ducts, and duodenum.
• Few symptoms until late disease, with early metastases.
• Poor prognosis.

Pancreas

• Two main diseases: inflammation (pancreatitis) and neoplasia (pancreatic cancer).
• Problems uncommon but significant.

Anatomy and Physiology of the Pancreas

• Head: in the curve of the duodenum.
• Tail: against the hilum of the spleen.
• Body: centrally located.
• Predominately exocrine tissue: secretes 20 digestive enzymes.
• Duct system:
  • Pancreatic duct joins the common bile duct, both entering the duodenum at the Ampulla of Vater.
  • Entry is controlled by the sphincter of Oddi.
• Pancreatic juices contain:
  • Bicarbonate: neutralizes gastric acid.
  • Pro-enzymes: inactive forms of enzymes.

Pancreatitis

• Can be acute (life-threatening) or chronic (recurring acute episodes).

Acute Pancreatitis

• Etiology and pathogenesis:
  • Potent proteolytic and lipolytic enzymes are normally inactive.
  • Digestion of pancreatic tissue and blood vessels by these enzymes causes necrosis and hemorrhage.
  • Commonly seen in patients with alcohol abuse.
• Histology: moderately differentiated with prominent fibrosis.

Pancreatic Cancer

• Bulk of pancreas is in the head, containing most of the ducts.
• Body – 10%.
• Tail - 5%.
• Diffuse – 25%.
• Histology: most are moderately differentiated with prominent fibrosis.
• Clinical picture:
  • Early metastases, widely spread at diagnosis.
  • Location of pancreas makes metastasis easy.
  • Main routes:
    • Local: obstructive jaundice.
    • Lymphatic: regional lymph nodes.
    • Hematogenous: liver first.
• Clinical presentation syndromes:
  • Weight loss, anorexia, chronic epigastric pain radiating to the back.
  • Obstructive jaundice with painless gallbladder enlargement (Courvoisier's sign).
  • Migratory thrombophlebitis in the legs.
• Other symptoms: ascites, splenomegaly, intestinal obstruction.
• Prognosis: very poor due to aggressive growth and early metastases.
• 5-year survival rate is 5%, compared to 50% for colorectal and 70% for Hodgkin's.
• Most die within 6-12 months of diagnosis.