Diagnosis

Jaundice

Etiology

Cause [r4a]

1. Prehepatic unconjugated: increased bilirubin production

   • Hemolysis: blood group incompatibilities, RedBloodCell defects (Sickle-cell anemia, Spherocytosis, Thalassemia, G-6-PD-deficiency, Pyruvate kinase deficiency), Hemolytic–uremic syndrome, intracranial hemorrhage, polycythemia, sepsis

   • Gilbert syndrome

   • Crigler-Najjar syndrome

   • Neonatal jaundice (immature metabolism of bilirubin, clearance is compromised)

2. Hepatic conjungated/unconjungated: decreased bilirubin metabolism/clearance

   • Cirrhosis

   • Viral Hepatitis

   • Alcoholic liver disease

   • Cholestatic liver disease: Primary biliary cholangitis, Primary sclerosing cholangitis

   • Hepatotoxicity / Drug-induced liver injury: sulfa, ceftriaxone, penicillins, oral contraceptives, rifampin, probenecid, steroids, chlorpromazine, herbal medications, arsenic

   • Gilbert syndrome (prevalence ~5%)

   • Crigler–Najjar syndrome

   • Hypothyroidism and cretinism (congenital hypothyroidism)

   • Leptospirosis

   • Infiltrative diseases: Amyloidosis, lymphoma, sarcoidosis, tuberculosis

   • Total parenteral nutrition

   • Intestinal obstruction and pyloric stenosis

3. Posthepatic conjungated (elevated ALP): impaired/obstructed hepatobiliary flow

   • Gallstones: Choledocholithiasis, Mirizzi's syndrome

   • Cancer: Pancreatic cancer, Cholangiocarcinoma, Hepatocellular carcinoma

   • Cysts: Choledochal cysts, Pancreatic pseudocysts

   • Cholestasis of pregnancy

   • Pancreatitis

   • Infection: syphilis, toxoplasmosis, HIV, CMV, herpes virus, rubella, parasite (liver flukes)

   • Congenital: Biliary atresia, Alagille syndrome, alpha-1 anti-trypsin deficiency, galactosemia, fructosemia, Tyrosinemia type 1, cystic fibrosis, progressive familial intrahepatic cholestasis, Aagenaes syndrome, Dubin-Johnson syndrome, bile acid synthesis disorders, Rotor's syndrome

Pathophysiology [r4a]

1. Prehepatic phase --> Production of bilirubin:

   • Heme (released by senescent or defective RBCs) --> Biliverdin --> Bilirubin

2. Hepatic phase:

   • Unconjugated (non-soluble) bilirubin --> conjugation to glucuronic acid in the hepatocytes resulting in conjugated bilirubin, which is soluble in the bile

3. Posthepatic phase:

   • Conjugated bilirubin --> bile canaliculi --> bile ducts --> gallbladder --> ampulla of Vater --> colonic bacteria deconjugate: bilirubin --> urobilinogen

     • 80% excreted into the feces (stercobilin)

     • 10-20% into the enterohepatic circulation

     • ~5% renal excretion (the yellow pigment of urine)

Complication [r4a]

• Permanent neurologic injury (kernicterus)

Epidemiology

Incidence per 100.000 [kek][hge][wog]

Approach

• Blood test:

  • Liver function tests: bilirubin (conjugated/unconjugated) ASAT, ALAT, PT-INR, albumine, GGT, ALP

  • Blood type and Rh determination in mother and infant

  • Serelogy: hepatitis-serelogy, auto-antibodies, Direct antiglobulin test

  • Hemolysis: Reticulocyte count, Haptoglobine

  • Thyroid function tests

  • Blood gas

• Abdominal ultrasound

• Abdominal CT

• MRCP

• Biopsy

Treatment

Treatment of the underlying cause: [r4a]

1. Symptomatic:

   • Pruritus: warm baths, oatmeal baths, antihistamine, bile acid sequestrant

2. Physiologic jaundice: Phototherapy of the newborn

3. Autoimmune hemolysis: Intravenous immunoglobulin, exchange transfusion

4. Bile duct blockage:

   • Bile duct stent (ERCP, PTC)

   • Kasai

   • Resection of pancreas, liver or bile ducts

   • Liver transplantation

Differential diagnoses

Acute pancreatitis, Alcoholic liver disease, Autoimmune hepatitis, Biliary atresia, Cholangiocarcinoma, Choledochal cysts, Choledocholithiasis, Cholelithiasis, Cirrhosis, Crigler-Najjar syndrome, Cytomegalovirus, Drug-induced liver injury, Gilbert syndrome, Hemolysis, Hemolytic anemia, Hypothyroidism, Intestinal atresia, Neonatal hepatitis, Nonalcoholic fatty liver disease, Pancreatic cancer, Primary biliary cirrhosis, Pyloric stenosis, Toxoplasmosis, Viral hepatitis, Wilson's disease