Heme Degradation Flashcards
Pre-hepatic steps of heme degradation
- Heme oxygenase from reticuloendothelial cells in presence of O2 and NADPH add hydroxyl group to menthenyl btw 2 pyrrole rings in heme
- 2nd oxygenation by same enzyme system and another NADPH causes ferric and CO to release changing heme to biliverdin
- Biliverdin is reduced forming bilirubin
Color of biliverdin
Green
Color of bilirubin
Red-orange
What transports bilirubin in blood?
Albumin binds non-covalently
Effect of anionic drugs (sulfonamidea and salicylate) on bilirubin
Displaces from albumin
Bilirubin may enter CNS w/ potential neural damage
Protein bilirubin binds to in liver
Ligandin
Steps in hepatocyte in heme degradation
- Bilirubin becomes conjugated by adding 2 glucuronic acid molecules from UDP-glucuronic acid via glucuronate donor
- Bilirubin diglucuronide (conjugated) transported into bile canaliculi then into bile
Steps in heme degradation in small intestine
. Conjugated bilirubin hydrolyzed and reduced by bacteria in gut to form urobilinogen (colorless)
. Some urobilinogen reabsorbed into portal blood and transported to kidney
. Most urobilinogen oxidized by intestinal bacteria to stercobilin
Step in heme degradation in kidney
Urobilinogen that comes to kidney is converted to urobilin (yellow) and excreted in urine
Jaundice
. Also called icterus
. Yellow color of skin and sclera caused by bilirubin deposition from inc. bilirubin in blood
. Sign, not disease itself
Major forms of jaundice
Hemolytic/pre-hepatic, obstructive/post-hepatic, and hepatocellular
Hemolytic Jaundice
. Massive lysis of rbcs
. Greater than normal bilirubin so more unconjugated in blood
. Greater than normal amount is bilirubin is conjugated causing elevated levels of bilirubin excreted in bile through normal route
. Inc. urobilinogen enter circulation causing increased urobilin and urobilinogen in urine because not all can be converted
Obstructive jaundice (Post-hepatic)
. Obstruction in bile duct blocks passage of bilirubin to intestine
. Less bilirubin in intestine causes less urobiliogen and stercobilin
. Bile can back up into liver causing liver to regurgitate conjugated bilirubin in blood
. Conjugated bilirubin excreted into urine causing it to be dark red-orange
. Prolonged obstruction can cause liver damage and impair ability to conjugate (rise of unconjugated bilirubin in blood in this case)
Hepatocellular jaundice
. From damage to liver cells (cirrhosis, hepatitis)
. Elevation in serum AST, ALT, at early stages in response to hepatocyte necrosis
. Initial stages of damage release conjugated bilirubin into blood
. Urine dark (red-orange) due to conjugated bilirubin in blood
. Later liver disease stages (after necrosis ends) ability to take up and conjugate bilirubin impaired causing high serum unconjugated bilirubin
Jaundice in newborns
. Newborns accumulate bilirubin because activity of hepatic bilirubin glucuronyl transferase is low
. Adults levels achieved at 2 weeks old
. Inc. bilirubin in excess of albumin binding capacity can cause toxic encephalopathy
. Treated w/ blue fluorescent light that converts bilirubin into water-soluble form
