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gihep 21: bile + jaundice (i) (bilirubin (excreted into bile (rate…
gihep 21: bile + jaundice (i)
bile
500ml/day secreted by adult liver
stored in gallbladder
duodenum sense partially digested food - secretes CCK
liver makes bile
gallbladder contracts to release bile
composition varies with location...
more watery in liver
more bile pigments in gallbladder
detergent - emulsify fat
allows pancreatic lipase to work
formed by haem degradation
functions
1) excretory
for bile pigments/acids/salts,chol,drugs
removed from blood by Kupffer cells of liver
2) digestive
bicarb rich - neutralises chyme
emulsification
balt salts activate pancreatic hydrolase precursors
bile acid synthesis
1) in liver
chol -> primary bile acid (e.g. cholic acid, chenodeoxycholic acid)
primary bile acid -> conjugation with glycine/taurine -> conjugated bile acid
conjugated bile acid -> addition of Na+/K+ -> bile salt
2) in SI
primary bile acid -> secondary bile acid (e.g. deoxycholic acid, lithocholic acid)
catalysed by bacterial alpha-dehydrogenase (in gut flora)
bilirubin
degradation of RBC haem (75%)
old RBCs normally destroyed extravascularly
250-300 mg/day made
binds to albumin to be transported in blood to liver
conjugates with glucuronic acid to be H2O soluble
excreted into bile
rate-limiting
depends on active transport by multi drug resistant-like protein 3
but most oxidised to urobilinogens
excreted as urinary urobilin or faecal stercobilin
taken up by liver through high capacity binding
binds to cytoplasmic processes (e.g. protein Y)
mobilised, can't get back into blood
secreted into SI
deconjugated by glucoronidases in gut flora
some fat-soluble bilirubin reabsorbed
handling free (intravasc) haem
! toxic
haptoglobin
haemoglobin-haptoglobin complex metabolised in liver + spleen
forms iron-globin complex + bilirubin
prevents oron loss in urine
must prevent major iron losses
haemopexin
binds to free haem, then complex taken up by liver
iron stored as ferritin
methaemalbumin
oxidised haem-albumin complex
haem -> biliverdin
haem oxygenase (esp in spleen)
biliverdin -> bilirubin
biliverdin reductase