Bile and biliary system Flashcards
What happens to bile salts once they’ve aided in fat absorption?
- return to lumen of enterocyte + absorbed through small intestine passively + via active transport in distal ileum
- reabsorbed into blood circ - taken up by liver + goes back into bile salt pool
How can a deficit in bile salts be caused and how is this fixed?
- loss of bile slats in feaces
- resyn in liver but majority re-circ and reabsorbed in small intestine
– balance between loss and re-syn
What does the gall bladder contain?
- Stored bile salts
- bile conc up to 15x
What is the Sphincter of Oddi?
where pancreatic duct joins common bile duct into duodenum
What is the effect of CCK?
- gallbladder constriction - release bile into common bile duct which enters duodenum through sphincter
- Relaxation of sphincter of Oddi
What is effect of secretin?
- stim secretion of bile rich in HCO3- from liver
- stim HCO3- secretion from pancreas
What also causes weak contraction of gall bladder?
Vagal stim
How is bile prod stim in liver?
Para impulses along vagus nerve stim bile prod
How are bile salts conc in gall bladder?
- HCO3-/Cl- exchanger allowing Cl- gradient
- allows removal of water from lumen of gallbladder – conc bile salts
- Na/K pump maintains Na gradient
What is bilirubin?
Major component of bile
Where does bilirubin comes from?
85% from breakdown of RBCs
What are properties of bilirubin?
- fat sol
- toxic
- bound to albumin in blood
Where is bilirubin taken up?
By liver
How much and where is bilirubin absorbed per day?
15% reabsorbed from intestine by enterohepatic circ (between liver and intestine)
What is biliary disease caused by?
- abnormalities in bile composition, biliary anatomy, and function.
- liver determines chem comp of bile, + this may be mod later by gallbladder + biliary epi.
- Cholesterol, ordinarily insol in water, comes into solution by forming vesicles with phospholipids (principally lecithin)/mixed micelles with bile salts + phospholipids.
What is dev of jaundice in absence of abdominal pain suggestive of?
a malignant obstruction of the bile duct e.g. gall stone.
Describe onset and symptoms of painless jaundice
- normal plasma bilirubin: 3-10mg/ml, jaundice: 18mg/ml
- gradual
- may be associated with anorexia; weight loss; and soft/loose stools.
What Nonbiliary causes of painless jaundice should be considered?
- increased bilirubin production (e.g., from hemolysis, blood transfusions, or ineffective erythropoiesis)
- decreased bilirubin clearance due to hereditary defects
What happens to long chain FAs and other products of lipid digestion?
- converted back to TAGs, phospholip, + esters of chol in SER
What happens to lipids in SER?
- fat droplets form in cisternae
- apoproteins syn in RER transferred to SER + ass with newly syn TAGs
How are short chain FAs absorbed?
- pass directly through enterocyte and enter capillary
- efficient diffusion into enterocyte through unstirred layers as they’re H2O sol
- then transported directly to hepatic portal vein in liver
What happens to the apoproteins in GA?
- Chlymicrons + VLDL arrive
- apoproteins glycosylated
What is the function of bile salt micelles?
- form ring around long chain FAs in unstirred H2O layer
- transform multilamellar vesicles into unilamellar vesicles + then into mixed micelles which are composed of bile salts, mixed lipids, i.e. fatty acids, monoglycerides, lysophospholipids and cholesterol.
- mixed micelles create high [lipid] in unstirred H2O layer - diffusion into enterocytes
Why can Glycerol, short-chain and medium-chain fatty acids pass through enterocyte and enter
blood capillaries?
- have small size
- pass across fenestrations = high perm to small mol e.g. aa, glucose, water capillaries
How do micelles enter enterocyte?
- When fatty acid/bile salt mixed micelles reach surface of enterocyte, they encounter a low pH environment at the brush-border,
- fatty acids leave micelle to enter the enterocyte by nonionic diffusion or by collision and incorporation into lipid bilayer.
What happens to emulsion droplets arriving from stomach?
Pancreatic lipases and biliary bile salts, lecithin and cholesterol adsorb to the surface
Describe large chain FA absorption in enterocyte
enterocyte re-esterifies mixed lipids to TAGs, phospholipids + esters of chol in SER
- apoproteins syn in RER transferred to SER - ass with newly syn TAGs - become chylomicrons
- chylo in vesicles fuse with fuse with BL mem of enterocyte - as too large to enter fenestrated cap - enter the lymph through larger interendo channels of the lymphatic cap.
- Lymph flows to thoracic duct to enter blood circ via L subclavian
vein. - protein + lipid comp of both chylomicrons + VLDLs mod during passage through lymph + entry into blood.
What can be said about unstirred H2O layer?
- unstirred water layer at mucosal surface of intestine is ~40 um thick and does not constitute a major absorptive barrier.
What are chylomicrons?
- largest of 5 lipoprotein particles in blood (others are VLDL, IDL, LDL and HDL)
- emulsion-like particles
What happens to components of chylomicrons after leave gut?
Delivered to target organs
Describe transport of bile in liver
- Bilirubin + bile acids exocytosed into bile ductile
- Secretin + vagal stim activate HCO3-, secretion, H2O - help bile acids + bili flow thorugh bile canliculi
How is bilirubin removed from body?
- bili-rubin albumin complex in sys circ
- bili Enters hepatocytes + conjugated to bilirubin - mono + diglucuronides
- exocytosed as bilirubin - glucuronide + urobilinogen - gets conc in gall bladder by H2O removal
- enters small intestine - further breakdown
- excreted in faeces - brown colour
Describe digestion and absorption of fats
- enters stomach and broken down my lipase of tongue glands and pancreatic lipase
- emulsification by gastric contractions
- breakdown in stomach (10-30%)
pancreatic lipase and bile salts enter duodenum - breakdown + micelle formation in duodenum + jejunem (70-90%)
- absorption in small intestine
- excretion (5%)
What are causes of gallstones?
- too much absorption of H2O from bile,
- ” of bile acids from bile
- too much chol in bile
- inflammation of epi
What can gallstones cause?
- Could build up pressure in pancreatic duct
- obstruct release of micelles for fat absorption + cause back pressure in pancreatic duct – proenz enter parenchyma (tissue space) + ass with lysosomes + become activated + dissolve tissue
Describe Relationship between bile flow and liver blood flow and the role of oxygen delivery on bile flow and what this means
- when O2 limiting – linear relationship where as blood flow inc, bile flow inc
- but as get O2 delivery + super sat of O2 - bile flow indep of blood flow
- shows Hydrostatic/liver sinusoidal blood pressure not mech that drives bile secretion
- Secretion of bile is active process requiring energy expenditure - occurs against a pressure gradient from bile ductules to vasculature e.g. if pressure in bile duct above that in liver circ
- secreting bile not consequence of raising hydrostatic from blood to bile duct
What stim secretin secretion?
Acidic chyme entering duodenum stim secretin stim into blood
How is bile conc in the gall bladder?
- HCO3-/Cl- exchanger on lum mem of epi cell - gens Cl- gradient into cell + out into ISF - H2O follows
- removal of H2O from lumen of gallbladder into ISF - conc bile salts inside
- Na+/K+ pump on BL mem maintains Na+ gradient out of cell so H2O follows
Why is bili removal by liver important?
- don’t get jaundice
