Hepatic Secretions Flashcards
Hepatocyte border
sinusoids (blood), space of Disse (lymph), and bile cancliculi (bile)
Discontinuous capillaries
allows passage of proteins into blood
Tight junctions
prevent mixing of bile, blood, lymph
Bile allows secretion of
organic, high MW, and hydrophobic molecules that annot be excreted in urine
Bile is composed of
bile acids, phospholipids, cholesterol, HCO, bilirubin, water
Bile acids function
ampipathic, formation of micelle for digestion of fat (phospholipids, choleterol, long chain FFA)
Liver synthesizes primary bile acids
cholic acid and chenodeoxycholic acid from cholesterol
cholesterol 7alpha-hydroxylase
synthesize cholic acid
oxysterol 7alpha-hydroxylase
synthesizes chenodeoxycholic acid
Enterohepatic circulation
circulation of bile acids from liver, gall bladder, duodenum, colon, to liver via portal vein
During fasting, bile acids in portal venous blood is ______ so rate of syntehesis is
Low, synthesis high
During a meal, bile acids in portal venous blood is ______ so rate of syntehesis is
High, synthesis low
Passive absorption of bile acids occurs in
colon and proximal small intestine
Carrier mediated absorption of bile acids occurs in
ileum and liver
Sodium-dependent bile acid transporter (ASBT)
mediated uptake of bile acid in enterocytes of ileum (MAJOR MECHANISM)
Sodium-dependent transport proteins (NTCP) and Sodium-independent organic anion transport
mediate uptake of bile acids in the liver
ATP-dependent bile salt export (BSEP)
liver secretes bile acid into canaliculi
Multi-drug resistant-associated protein 2 (MRP2)
secretion of sulfated or glucuronidated bile acids into canaliculi
Secondary bile acids are formed by
bacteria in the colon
defect in bile acid formation may be due to
increased bile acid excretion in feces, loss of bile acid flow, decreased cholesterol absorption,
defects in membrane transport of bile acid
mutation in transporter protein
Defects involving bacterial transformation
bacterial overgrowth depletes bile acids
Defects in bile acid circulation
obstruction, crohn’s, celiac
Bilirubin
RBC death and binding of unconjugated bilirubin to albumin
UGT1A1
liver enzyme that conjugates bilirubin to two glucuronic acids
Excretion of liver
conjugated bilirubin is excreted into the bile (RATE-limiting step)
conjugated bilirubin in the colon is converted to
urobilinogen
Urobilinogen can be excreted in urine as ______ or feces as _______
urobilin; stercobilin
Jaundice
accumulation of bilirubin in the blood
Indirect bilirubin >80-85% of total indicated
unconjugated hyperbilirunemia; hemolysis of RBC, impaired conjugation, impaired hepatic uptake of bilirubin
Causes for indirect bilirubin
hemolysis, neonatal jaundice, Gilbert’s syndrome, prolonged fasting, sepsis
Direct bilirubin >50% of total
conjugated hyperbilirubinemia; defect in transfer from liver to canaliculi or transfer through ducts
Causes of direct bilirubin
hepatocellular disease, alcoholic liver, intra- or extraheptic obstruction
If there is bilirubin in urine, which type of bilirubinemia is indicated?
conjugated, since unconjugated is bound to albumin and cannot be filtered
Urobilinogen high in urine?
excessive hemolysis or hepatic uptake impaired
Urobilinogen low in urine?
obstruction
Bilirubin is a part of bile, but it is not
recirculated it is excreted
Water secretion into bile canaliculi is due to
solvent drag as bile acids are secreted into cancaliculi
Secretin causes
HCO3 secretion through bile duct epithelial cells
When the bile in the canaliculi increases, presure causes bile to flow down duct to either
gallbladder (if resistance to filling is low) or to duodenum (if Sphincter of Oddi resistance is low)
During fasting the bile flows to
gallbladder, (sphincter of oddi is resistant)
Concentration of Bile in gall bladder is achieved by
Na absorption from lumen into gallbladder epithelium and formation of micelles, BOTH are required for H2O flux from gall bladder
Factors that cause bile to flow from gall bladder to duodenum
vagal stimulation, food consumption, CCK release,
Cholesterol Gall Stones
- excessive bile cholesterol 2. Mucin: nucleation of cholesterol 3. abnormal gall bladder motor function
