Liver and Biliary System

Question 1

3 key functions of the liver

Answer 1

1. contributions to whole body metabolism
2. detox
3. excretion of portein bound/lipid soluble waste products

Question 2

the hepatocyte is a 1 cell thick ….

Answer 2

epithelium

constitutes a functional barrier between two fluid compartments with different ionic concentrations

Question 3

stellate cells

Answer 3

in the space of Disse

storage site for retinoids and are source of growth factors for hepatocytes

during abnormal conditions these produce collagen - thereby liver dysfunction

Question 4

flow of bile

Answer 4

canaliculi –> biliary ducts –> large bile ducts –> right and left hepatic ducts –> common hepatic duct –>

either cystic duct to gallbladder

or common bile duct to duodenum

Question 5

cholangiocytes

Answer 5

simple columnar epithelial cells that line the biliary ducts

modify the concentration of bile

Question 6

between meals, the sphincter of Oddi is…

Answer 6

blocked by constriction –> bile redirected to the gall bladder

Question 7

bile (general)

Answer 7

micellar solution

major solutes = bile acids, phosphatidylcholine, and cholesterol (10:3:1)

secretion of these solutes drives the movement of water and electrolytes across the tight junctions

Question 8

transporters on bile lumen side of the biliary duct cell

Answer 8

Cl-/HCO3- ion exchanger (HCO3- excreted)…Cl- recycle back out with Cl- channels

aquaporin water channels

Question 9

transporters on ECF side of biliary duct cell

Answer 9

Na+/HCO3- cotransporter into cell

Na+/H+ exchanger (H+ out)

Na/K/2Cl cotransporter

K+ out channel

Question 10

gamma glutamyl transpeptidase

Answer 10

in apical surface of cholangiocytes

breakdown glutathione into amino acid constituents

Question 11

pH of bile at beginning of synthesis

Answer 11

slightly alkaline due to HCO3- secretion

Question 12

in general, what is the function of the gall bladder

Answer 12

store and concentrate the bile

Question 13

mechanism of bile concentration in gall bladder

Answer 13

1. tight junctions are very impermeable to bile acid anions (BA-)…so they stay trapped in the lumen
2. water passes freely through aquaporins, across both sides –> increases [Na+] left behind
3. NaCl reabsorbed via
   - N+/H+ (NHE) === more active therefore will be a net secretion of H + (so now bile is more acidic)
   - Cl-/HCO3- exchangers
   (fueled by Na/K pump on basolateral side)
   –> leads to isotonic fluid reabsorption
4. H+ that are excreted quickly are buffered by the HCO3- secreted –> CO2 and water –> CO2 diffuses out of lumen passively

Question 14

changes in bile composition during gallbladder storage

Answer 14

Cl- and HCO3- decrease in concentration

Na+ and BA- increase in concentration and becoming equal

bile changes from slightly basic –> slightly acidic

Question 15

bile and lipid digestion and absorption

Answer 15

emulsification

detergent action on particles of dietary fat –> fat globules –> droplets

increases surface area of fat

Question 16

bile and waste excretion

Answer 16

bilirubin and excess cholesterol are big examples

conjugated bile acids cannot passively cross epithelial lining in intestine

Question 17

other bile functions

Answer 17

inhibition of bacterial growth

neutralization of gastric acid in the SI

Question 18

cholesterol metabolism

Answer 18

end product = bile acids

Question 19

cholesterol 7alpha-hydroxylase

Answer 19

initial and RLS of cholesterol metabolism

Question 20

HMG-CoA reductase

Answer 20

target for statin drugs to lower cholesterol

RLS of cholesterol synthesis in liver

Question 21

primary bile acids

Answer 21

chenodeoxycholic and cholic acid

made by hepatocytes

Question 22

secondary bile acids

Answer 22

lithocholic, ursodeoxycholic, deoxycholic acid

primary acids metabolized by colonic lumen microbes

they are conjugated with glycine or taurine –> depress there pKa so they can be ionized in the SI….now cannot transverse the cell membranes

but are reabsorbed via apical Na+-dependent transporter

Question 23

what forms can cholesterol be excreted

Answer 23

native molecule form

after conversion to bile acids (1/3 despite enterohepato recycling)

Question 24

enterohepatic circulation

Answer 24

10% of bile acids are made in SER of hepatocytes

90% recirculated by reabsorption from intestinal cells and transported to hepatocyte from the blood to bile canaliculi

Question 25

CCK and bile acid secretion from gall bladder

Answer 25

relaxes sphincter of Oddi and contracts the SmM that encircles the gallbladder epithelium

Question 26

heme oxygenase

Answer 26

in Kupffer and spleen cells

liberates iron from the heme molecule and produces the green pigment biliverdin

this in turn can be reduced to yellow bilirubin

Question 27

jaundice

Answer 27

bilirubin (yellow) is insoluble in aqueous solution at neutral pH…it is transported through the blood bound to albumin

when this complex reaches the liver, it enters the space of Disse

where it is selectively taken up across the basolateral membrane via a OATP transport

then it is conjugated…if cannot = yellow jaundice look

Question 28

UDP glucuronyl transferase

Answer 28

conjugates bilirubin –> glucuronic acid