Bile + Enterohepatic Circulation

Question 1

In the hepatocyte, list 3 important features of the basolateral membrane

Answer 1

1. fenestrated epithelium
2. import/export of large molecules
3. space of disse

Question 2

In the hepatocyte, list 2 important features of the apical membrane

Answer 2

1. Canaliculus

2. secretion of bile constituents

Question 3

2 important cells found in the Space of Disse. What are their functions?

Answer 3

1. stellate cell (Ito) – store lipids

2. kupffner cell-resident macrophages

Question 4

In the synthesis of primary bile acids, what is the rate limiting step? What is the enzyme called?

Answer 4

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

Question 5

What are the two primary bile acids? What is their normal ratio?

Answer 5

Cholic acid and Chenodoxycholic acid

CA:CDCA normally 3:1

Question 6

What produce secondary bile acids and where?

Answer 6

Bacterial enzymes; distal small intestine and colon

Question 7

All bile acids are conjugated in the ____. They are conjugated into _____ or ______

Answer 7

liver. glycine or taurine

Question 8

Conjugation of bile acids has 3 main effects

Answer 8

1. increased solubility at luminal pH
2. resistant to precipitation by Ca and H+ (because more soluble)
3. prevents passive reabsorption

Question 9

Alkaline phosphates is located in the (apical/basolateral) membrane only.

Answer 9

Apical (elevated in cholestatic disease–condition where bile from liver is slowed)

Question 10

Conjugation of bile acids make bile acids more less (hydrophilic/hydrophobic)

Answer 10

less hydrophobic

Question 11

What happens when cholesterol gets too high or bile salts get too low?

Answer 11

You get precipitated cholesterol –> gallstones form in the galbladder

Question 12

What are the 3 components that form the mixed micelle? What do you need critical concentration of?

Answer 12

Bile salts, cholesterol, phosphatidylcholine.

Need critical [bile acid]

Question 13

What cells surround the bile ductule? What cells line the bile ductule?

Answer 13

hepatocytes surround, cholangiocytes line

Question 14

Role of bile ductules

Answer 14

transport and modification of bile

Question 15

In the cholangiocytes, what gets secreted? Why? What drives this secretion? List the molecules and transport channel involved.

Answer 15

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.

Question 16

What molecule gets reabsorbed in bile ductules?

Answer 16

Glucose

Question 17

Are cholangocytes permeable to water?

Answer 17

Yes, use tight junctions and AQP

Question 18

What follows paracellularly down electrical gradient in cholangiocytes?

Answer 18

Na

Question 19

What regulates bile ductules. What secretes it? Location? What regulates it?

Answer 19

secretin (with Ach potentiation)

S cells located in dudodenum

regulated by pH

Question 20

What is a marker of chonagiocyte injury?

Answer 20

GGT transporter that converts glutathione to amino acids

increases during injury

Question 21

What gets reabsorbed in the gall bladder epithelium?

Answer 21

Na and Cl, water follows

Question 22

Two main functions of the gallbladder

Answer 22

• concentration of bile acids

- maintenance of isotonicity, since micelle represents only one osmotic particle

Question 23

____ stimulates gall bladder contraction directly and stimulates vagal afferents

Answer 23

CCK

Question 24

Vagal efferents stimulate (relaxation/contraction) via what receptors?

Answer 24

Contraction, M3

Question 25

ACh and CCK cause smooth muscle (Relaxation/Contraction) how long after starting a meal?

Answer 25

contraction, within 20 minutes

Question 26

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

Answer 26

CCk
NO and VIP
relaxation

Question 27

Cholelithiasis

Answer 27

Gallstones

Question 28

Absoprtion of FA occurs mostly in what part of the small intestines

Answer 28

terminal ileum

Question 29

What breaks dietary triglycerides into FAs (in presence of bile salts)

Answer 29

pancreatic lipase

Question 30

Once you get to colon, bacteria starts to mess with bile salts. What can bacterial enzymes do to it? What is the effect

Answer 30

-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!

Question 31

Conjugated bile acids dont reabsorb passively, so they need ___ to get across the ileocyte luminal membrane

Answer 31

transport proteins

Question 32

How does CYP7A1 get regulated

Answer 32

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.

Question 33

The gallbladder contains secondary bile as well as primary bile acids. This occurs because secondary bile acids are:

Answer 33

produced in the intestine (distal small intestine, primarily in colon) by bacteria and recirculated

Question 34

Two precursors to form bilirubin

Answer 34

heme –> bilverdin –> bilirubin

Question 35

In the blood stream, bilirubin is transported bound to

Answer 35

albumin (since bilirubin is insoluble in bloodstream)

Question 36

Regarding bilirubin metabolism in the liver, unconjugated bilirubin bound to albumin enters the _____

Answer 36

space of disse

Question 37

UDP glucaronyl transferase (UGT) role in hepatocyte

Answer 37

conjugates bilirubin to glucoronic acid

Question 38

Conjugated or direct bilirubin has more/less aqueous solubility. What happens to it in the liver?

Answer 38

more aqueous solubility. Secreted into the bile canaliculus for excretion

Question 39

What type of bilirubin is reabsorbed in the intestines?

Answer 39

Deconjugated (urobilinogen/UroB)

conjugated bilirubin is NOT reabsorbed

Question 40

Some deconjugated bilirubin (UroB) is reabsorbed an processed by liver or excreted in the urine, producing what color?

Answer 40

yellow color

Question 41

the remainder of unconjugated bilirubin (urobilinogen) in the gut is converted to urobilins and stercobilins and extreted in stool showing up as what color?

Answer 41

Brown color

Question 42

Jaundice

Answer 42

yellowish discoloration of tissue due to bilirubin deposition