Bile + Enterohepatic Circulation Flashcards
In the hepatocyte, list 3 important features of the basolateral membrane
- fenestrated epithelium
- import/export of large molecules
- space of disse
In the hepatocyte, list 2 important features of the apical membrane
- Canaliculus
2. secretion of bile constituents
2 important cells found in the Space of Disse. What are their functions?
- stellate cell (Ito) – store lipids
2. kupffner cell-resident macrophages
In the synthesis of primary bile acids, what is the rate limiting step? What is the enzyme called?
The rate limiting step is the first step that converts cholesterol to 7-hydroxycholesterol
The enzyme is CYP7A1 also called 7alpha-hydroxylase.
Under negative feedback control
What are the two primary bile acids? What is their normal ratio?
Cholic acid and Chenodoxycholic acid
CA:CDCA normally 3:1
What produce secondary bile acids and where?
Bacterial enzymes; distal small intestine and colon
All bile acids are conjugated in the ____. They are conjugated into _____ or ______
liver. glycine or taurine
Conjugation of bile acids has 3 main effects
- increased solubility at luminal pH
- resistant to precipitation by Ca and H+ (because more soluble)
- prevents passive reabsorption
Alkaline phosphates is located in the (apical/basolateral) membrane only.
Apical (elevated in cholestatic disease–condition where bile from liver is slowed)
Conjugation of bile acids make bile acids more less (hydrophilic/hydrophobic)
less hydrophobic
What happens when cholesterol gets too high or bile salts get too low?
You get precipitated cholesterol –> gallstones form in the galbladder
What are the 3 components that form the mixed micelle? What do you need critical concentration of?
Bile salts, cholesterol, phosphatidylcholine.
Need critical [bile acid]
What cells surround the bile ductule? What cells line the bile ductule?
hepatocytes surround, cholangiocytes line
Role of bile ductules
transport and modification of bile
In the cholangiocytes, what gets secreted? Why? What drives this secretion? List the molecules and transport channel involved.
Bicarbonate secretion (and fluid). Helps alkalanize/neutralize the acidic environment in the dudodenum.
Driven by HCO3/Cl- exchange coupled to CFTR. Cl enters the cell and gets resecreted via CFTR back into lumen of bile duct.
What molecule gets reabsorbed in bile ductules?
Glucose
Are cholangocytes permeable to water?
Yes, use tight junctions and AQP
What follows paracellularly down electrical gradient in cholangiocytes?
Na
What regulates bile ductules. What secretes it? Location? What regulates it?
secretin (with Ach potentiation)
S cells located in dudodenum
regulated by pH
What is a marker of chonagiocyte injury?
GGT transporter that converts glutathione to amino acids
increases during injury
What gets reabsorbed in the gall bladder epithelium?
Na and Cl, water follows
Two main functions of the gallbladder
- concentration of bile acids
- maintenance of isotonicity, since micelle represents only one osmotic particle
____ stimulates gall bladder contraction directly and stimulates vagal afferents
CCK
Vagal efferents stimulate (relaxation/contraction) via what receptors?
Contraction, M3
ACh and CCK cause smooth muscle (Relaxation/Contraction) how long after starting a meal?
contraction, within 20 minutes
Regarding the sphincter of Oddi (located at junction of bile duct and duodenum):
____ stimulates vagal afferents. Presynaptic vagal efferents stimulate post synaptic neurons that release ____ and ____, causing (Relaxation/Contraction) of sphincter of oddi
CCk
NO and VIP
relaxation
Cholelithiasis
Gallstones
Absoprtion of FA occurs mostly in what part of the small intestines
terminal ileum
What breaks dietary triglycerides into FAs (in presence of bile salts)
pancreatic lipase
Once you get to colon, bacteria starts to mess with bile salts. What can bacterial enzymes do to it? What is the effect
-deconjugate them (lop off glycine or taurine) and/or get dehydroxylated
If get deconjugated, they can get reabsorbed and have on last chance to get reacclaimed before getting dumped forever!
Conjugated bile acids dont reabsorb passively, so they need ___ to get across the ileocyte luminal membrane
transport proteins
How does CYP7A1 get regulated
Bile acts like a hormone: binds to nuclear receptor FXR, upregulates FGF-19 (in ileal enterocyte). FGF19 acts on FGF-R in hepatocytes to downregulate bile salt synthesis by decreasing CYP7A1.
The gallbladder contains secondary bile as well as primary bile acids. This occurs because secondary bile acids are:
produced in the intestine (distal small intestine, primarily in colon) by bacteria and recirculated
Two precursors to form bilirubin
heme –> bilverdin –> bilirubin
In the blood stream, bilirubin is transported bound to
albumin (since bilirubin is insoluble in bloodstream)
Regarding bilirubin metabolism in the liver, unconjugated bilirubin bound to albumin enters the _____
space of disse
UDP glucaronyl transferase (UGT) role in hepatocyte
conjugates bilirubin to glucoronic acid
Conjugated or direct bilirubin has more/less aqueous solubility. What happens to it in the liver?
more aqueous solubility. Secreted into the bile canaliculus for excretion
What type of bilirubin is reabsorbed in the intestines?
Deconjugated (urobilinogen/UroB)
conjugated bilirubin is NOT reabsorbed
Some deconjugated bilirubin (UroB) is reabsorbed an processed by liver or excreted in the urine, producing what color?
yellow color
the remainder of unconjugated bilirubin (urobilinogen) in the gut is converted to urobilins and stercobilins and extreted in stool showing up as what color?
Brown color
Jaundice
yellowish discoloration of tissue due to bilirubin deposition
