IHL I - Bilirubin Metabolism and Excretion Flashcards
senescent RBC
after 120 days, picked up by the phagocytes in the spleen
spleen = graveyard for RBCs
what are the components of bile?
bilirubin, bile acids/salts, cholesterol
what happens to majority of bile salts?
reabsorbed by the liver (95%)
what are the breakdown products of RBCs?
globin and heme
globin is catabolized
heme is broken to bilirubin
iron binds to transferrin
bilirubin
produced by biliverdin reductase from biliverdin
(biliverdin formed from heme by heme oxygenase)
bilirubin is water-insoluble, unconjugated
what happens to bilirubin after it is synthesized in the macrophage?
travels in blood (bound to albumin) to the liver
UDP-GT
combines bilirubin with 2x UDP-glucuronic acid to form bilirubin di-glucuronide
glucuronic acid
combined with bilirubin by UDP-GT to form bilirubin diglucuronide
what is the fate of bilirubin diglucuronide
secreted into the bile through canaliculus and goes to small intestine
hyperbilirubinemia
aka jaundice or icterus
high levels of bilirubin in extracellular fluid
stercobilinogen
always in the large intestine
excretion form is stercobilin
urobilinogen
from stercobilinogen that leaks
goes to liver or kidney
in kidney - converted to urobilin - excreted
heme oxygenase
converts heme to biliverdin
release of CO (only place where this happens) > in spleen
kupffer cells
macrophage in the liver
biliverdin reductase
biliverdin converted to bilirubin
requires NADPH
where is bilirubin formed?
in the spleen (NOT liver)
it is water insoluble - transported by albumin to hepatocytes**
what is bile color from?
bilirubin
UDG-glucuronyl Transferase
converts bilirubin to bilirubin diglucuronide (conjugated or direct)
in the liver
**know this enzyme
indirect
unconjugated bilirubin (water insoluble)
direct
conjugated bilirubin (water soluble)
**bc can react directly
clay colored stool
liver damage or bile duct obstruction
what color stool if bilirubin metabolism pathway defective?
clay colored
what color is stercobilinogen
colorless!
stercobilin is dark brown
normal blood level of unconjugated, conjugated, and total bilirubin
unconjugated: < 1 mg/dL
conjugated: < 0.2 mg/dL
total: < 1.2 mg/dL
jaundice bilirubin level?
> 2 mg/dL
icterus bilirubin level?
> 2.5 mg/dL
cholestasis
impaired bile flow
increased concentration of bilirubin, bile acids, and cholesterol in blood
kernicterus
high concentration (15-20mg/dL) bilirubin unconjugated
what will hemolytic diseases cause
increased indirect bilirubin
- liver cannot handle all of it and you can't break it down - ex/ G6PD deficiency, pyruvate kinase deficiency, Vit K toxicity
pyruvate kinase deficiency?
cannot produce ATP in RBCs
-results in hemolytic anemia
crigler-najjar syndrome
gene for glucuronyl transferase is defective
-cannot conjugate bilirubin
high indirect bilirubin**
bilirubin levels 30-50 mg/dL
gilbert syndrome
gene for glucuronyl transferase has point mutation
medical student : jaundice that goes away **
indirect bilirubin slightly elevated
under stress causes jaundice
Kernicterus
in newborn
massive destruction of RBCs
-at birth the glucuronyl transferase is induced
increase in indirect bilirubin
Hb F does not respond to 2,3 BPG
increase in direct bilirubin due to?
intra or extrahepatic bile duct, gallstone/tumor, defective canalicular transport
increase direct and indirect bilirubin
liver malfunction or damage cirrhosis alcoholic cirrhosis hepatitis Wilson's disease - Cu problem
dubin johnson syndrome
black coloration of liver **
increased direct bilirubin
chronic benign
defective canalicular transport
rotor syndrome
high levels of direct bilirubin
problem with storage of bilirubin in liver cells
-leakage of bilirubin into the blood
multiple defects in hepatocellular uptake and excretion of bilirubin
jaundice, but normal life
type I vs. type II crigler-najjar syndrome
type I has highest level of unconjugated bilirubin (>20mg/dL)
type I can lead to kernicterus in infancy
what disorder results in a glossy black liver?
dubin-johnson syndrome
high levels of conjugated bilirubin
hereditary disorders of bilirubin metabolism?
all recessive
what are the two disorders with high unconjugated bilirubin
crigler-najjar and gilberts
treatment of bilirubin metabolism disorders?
no real treatment, but important to be aware
phototherapy in infants
what causes prehepatic jaundice?
hemolytic processes
what causes hepatic jaundice?
abnormal liver function
-cannot deal with load of iron
-gilberts, crigler-najjar, dubin-johnson
posthepatic jaundice
problem with excretion of bilirubin
mechanical obstruction of bile to the intestines
-gallstone or tumor
decreased levels of stercobilin in stool (clay-colored)
why do newborns have jaundice?
massive destruction Hg F after birth
all this goes to liver, can’t handle it
lots of unconjugated bilirubin
phototherapy given to newborns
where does conjugation occur?
liver by UDP-GT
makes it water soluble for secretion
