Bile & Bile Salts Flashcards
What is produced when heme oxygenase acts on hemoglobin?
Iron, CO, and biliverdin.
What is the primary source of bilirubin in the body?
Senescent RBCs (80%).
Where is heme oxygenase most plentiful?
Reticuloendothelial cells in the spleen.
How is bilirubin conjugated?
Once transported into the hepatocyte, UDP glucoronosyltransferase conjugates two glucoronides in the ER.
What are the organic components of bile, in order?
(1) bile salts
(2) phospholipids
(3) cholesterol
(4) protein
(5) bilirubin
How is bilirubin typically seen in the blood?
Unconjugated and bound to albumin by weak hydrogen bonds.
What are protective mechanisms against unconjugated bilirubin, a neurotoxic lipid?
(1) binding to albumin
(2) blood-brain barrier
(3) conjugation
(4) excretion in bile
What is delta bilirubin?
Conjugated bilirubin that is covalently bound to albumin. It is large, preventing passage into urine.
What does the presence of delta bilirubin indicate?
The protracted presence of conjugated bilirubin in the serum.
Describe what happens when bacteria in the gut encounter bilirubin.
(1) The bilirubin is converted to urobilinogen, a colorless, water-soluble substance.
(2) Some urobilinogen is absorbed (and can be excreted in urine).
(3) Alternatively, bacteria can further act on urobilinogen to produce pyrroles, which give stool its color.
What’s another term for jaundice?
Icterus.
How high must bilirubin levels be in the serum so that jaundice is seen?
At least twice normal.
Match:
Conjugated and Unconjugated:
Direct and Indirect.
Conjugated = Direct Unconjugated = Indirect
Which type of hyperbilirubinemia produces tea-colored urine?
Direct or conjugated.
Simply, what are the possible causes of unconjugated hyperbilirubinemia?
(1) overproduction of bilirubin
(2) reduced uptake of bilirubin by liver
(3) defects in bilirubin conjugation
What are causes of reduced hepatic uptake of bilirubin?
(1) altered circulation (portal systemic shunting, right heart failure, etc.)
(2) drug effects (rifamycin)
What are causes of overproduction of bilirubin?
(1) hemolysis
(2) extravasation into tissue
(3) ineffective erythropoiesis
What are causes of defective conjugation of bilirubin?
(1) Gilbert’s syndrome
(2) Crigler-Najjar syndrome types I and II
(3) drug effects (testosterone, novobiocin)
(4) chronic hepatitis (Wilson disease)
(5) hyperthyroidism
Why is jaundice common in newborns?
(1) immature transport and conjugation of bilirubin
(2) increased hemolysis
How is jaundice treated in newborns?
Phototherapy.
Why is phototherapy effective in treating some cases of jaundice?
Light exposure breaks the internal hydrogen bonds in unconjugated bilirubin, exposing the propionic acid groups and making it more water-soluble.
What is Gilbert’s syndrome?
An autosomal recessive disorder in which there is a defect in the promoter gene for glucoronosyltransferase leading to decreased activity. Unconjugated bilirubin is slightly elevated (especially during fasting), but the disease is benign.
How is Gilbert’s syndrome diagnosed?
It is a diagnosis of exclusion: unconjugated hyperbilirubinemia with no other cause.
What are causes of conjugated hyperbilirubinemia?
(1) inherited secretory defects
(2) disease of hepatocytes (necrotizing hepatitis, chronic hepatitis, cholestasis)
(3) biliary obstruction
