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
What are the notable inherited defects of bilirubin secretion?
(1) Dubin-Johnson syndrome
(2) Rotor syndrome
LFTs are normal as is secretion of bile salts. In Dubin-Johnson, the liver may have black pigmentation.
What are symptoms of cholestasis?
(1) jaundice
(2) pruritus
(3) vitamin deficiencies
(4) hypercholesterolemia
What are signs of vitamin A malabsorption?
Night blindness.
What are signs of vitamin D malabsorption?
Osteomalacia.
What are signs of vitamin K malabsorption?
Impaired prothrombin synthesis.
What are signs of vitamin E malabsorption?
Cerebellar and peripheral nerve disorder.
What is a xanthelasma?
Deposits of cholesterol in tissue, particularly around the orbit.
What are extrahepatic causes of cholestasis?
(1) gallstones
(2) strictures
(3) pancreatitis
(4) cancer of the pancreas, bile duct or gallbladder
What are 3 predisposing factors for gallstones?
(1) supersaturation
(2) stasis
(3) nucleation factors
How do gallstones form?
When cholesterol or bilirubin precipitate out in bile.
How are gallstones detected?
Primarily by ultrasound.
What can the color of a gallstone indicate?
Pale: primarily cholesterol
Black: primarily unconjugated bilirubin, formed in gallbladder
Brown: primarily unconjugated bilirubin, formed in bile ducts
What profile is at increased risk of gallstones?
An obese female over thirty that doesn’t exercise, eats a Western diet, and has multiple children.
Rapid weight loss, estrogen, somatostatin, and TPN can also contribute.
What is needed for a gallstone to be visible on X-ray?
Higher concentration of calcium salts.
What is a precursor “lesion” for gallstones?
Sludge.
What can be used to dissolve cholesterol gallstones?
(1) ursodeoxycholic acid
(2) chenodeoxycholic acid
Not effective for pigment stones.
What type of gallstone is most easily seen on X-ray?
Black pigment stones (and calcium-rich cholesterol stones).
What additional contents are seen in brown pigment stones?
Bacteria and fatty acids.
