Causes of Jaundice Flashcards
Causes of Jaundice (7)
- Extravascular hemolysis or ineffective erythropoiesis
- Physiologic jaundice of newborn
- Gilbert syndrome
- Crigler-Najjar Syndrome
- Dubin-Johnson Syndrome
- Biliary tract obstruction (obstructive jaundice)
- Viral hepatitis
Extravascular hemolysis or Ineffective erythropoiesis
Etiology
Lab Findings
Clinical Features (2)
Extravascular hemolysis: excessive destruction of RBCs by RES
Ineffective erythropoiesis: death of defected RBC
Etiology:
- High levels of UCB overwhlem conjugating ability of liver
Lab Findings:
- Inc. UCB
Clinical Features:
- Dark urine due to inc. urine urobilinogen (UCB is NOT water soluble, therefore is absent from urine)
- Inc. risk for pigmented bilirubin gallstones due to inc. CB
Physiologic jaundice of the newborn
Etiology
Lab Findings
Main Clinical Feature
Treatment
Etiology:
- Newborn liver has transiently low UGT (conjugating) activity
Lab Findings:
- Inc. UCB
Clinical Features:
-
Kernicterus (UCB is fat soluble and can deposit in basal ganglia)
- Occurs after first 24 hrs of life and usually resolves without treatment in 1-2 weeks
- Can lead to neurological deficits –> death
Treatment:
- Phototherapy (does not conjugate bilirubin but does make UCB water soluble)
Gilbert Syndrome vs. Crigler-Najjar Syndrome
Etiology
Lab Findings
Clinical Features (2)
Etiology:
- GS: Mildly low UGT activity; autosomal recessive
- CN, Type I: Absence of UGT
Lab Findings:
- GS: Inc. UCB
- CN, Type I: Very inc. UCB
Clinical Features:
- GS: Jaundice during stress (e.g., severe infection); otherwise, not clinically significant
- CN, Type I: Kernicterus; usually fatal
*** These two syndromes = opposite extremes of a similar problem!!!
Dubin-Johnson Syndrome vs. Rotor Syndrome
Etiology
Lab Findings
Clinical Feature
Etiology:
- DJS: Deficiency of bilirubin canalicular transport protein (ABCC2); AR
- Rotor: Deficiency of bilirubin sinusoidal transport protein (OATP1B1/B3); AR
Lab Findings:
- Inc. CB
Clinical Features:
- DJS: Liver is DARK due to impaired excretion of epinephrine metabolites; otherwise, not clinically significant
- Rotor syndrome is similar to DJS but LACKS liver discoloration
- Can differentiate on biopsy (dark granular pigments for DJS)
A 22-year-old motorcycle accident victim with unknown past medical history is brought into the ED with severe head injuries. He is stabilized and brought to the surgical ICU where he is deemed to be brain dead by both the intensivist and neurosurgery staff. The organ transplant team is contacted and determine that he is an eligible kidney donor. However, he is not eligible for liver donation. Upon entering the abdomen during harvest, the team notices that his liver is black.
Dubin-Johnson Syndrome
Biliary tract obstruction (obstructive jaundice)
Etiology
Lab Findings (3)
Clinical Features (5)
Etiology:
- Associated with:
- Gallstones
- Pancreatic carcinoma
- Cholangiocarcinoma
- Parasites
- Liver fluke (Clonorchis sinensis)
Lab FIndings:
- Inc. CB
- Dec. urobilinogen
- Inc. alkaline phosphatase
Clinical Features:
- Dark urine (due to bilirubinuria)
- Pale stool (feces is not mixing with bilirubin which is trapped in common bile duct)
- Pruritis due to inc. plasma bile acids (deposits in skin)
- Hypercholesterolemia with xanthomas
- Steatorrhea with malabsorption of fat-soluble vitamins
Viral hepatitis
Etiology
Lab Findings (2)
Clinical Features
Etiology:
- Inflammation disrupts hepatocytes and small bile ductules
Lab Findings:
- Inc. CB (b/c damaging hepatocytes)
- Inc. UCB (b/c damaging small bile ductules)
Clinical Features:
- Dark urine due to inc. urine bilirubin (CB is water soluble –> will leak into urine)
- Urine urobilinogen is normal or decreased (due to hepatocyte damage so CB not entering duodenum)
An infant is brought to the pediatrician by his parents because they are concerned about the yellow color of his skin and general behavior changes. They report that he has seemed more tired and weak with his arms just flopping down by his side instead of him reaching for his toys. The parents are known to be first cousins.
Crigler-Najjar syndrome
Normal bilirubin metabolism
- RBCs consumed by macrophages of reticuloendothelial system (spleen)
- Protoporphyrin (from heme) converted –> UCB
- Albumin in serum carries UCB –> liver
- Uridine glucuronyl transferase (UGT) in hepatocytes conjugates bilirubin
- CB transferred to bile canaliculi to form bile (stored in gallbladder)
Bile is released into duodenum to add in digestion.
Intestinal flora convert CB –> urobilinogen –> oxidized to stercobilin (makes stool brown) and urobilin (partially reabsorbed into blood and filtered by kidney, making urine yellow)
Unconjugated (indirect) hyperbilirubinemia
- Hemolytic
- Physiologic (newborns)
- Crigler-Najjar
- Gilbert
Conjugated (direct) hyperbilirubinemia
- Biliary tract obstruction: gallstones, cholangiocarcinoma, pancreatic/liver cancer, liver fluke
- Biliary tract disease:
- Primary sclerosing cholangitis
- Primary biliary cirrhosis
- Excretion defect:
- Dubin-Johnson
- Rotor
Mixed (direct and indirect) hyperbilirubinemia
Hepatitis
Cirrhosis
