case 5- secretion and excretion in the liver

Question 1

what are particulates phagocytosed by

Answer 1

Kupffer cells

Question 2

what is the blood supply to the liver

Answer 2

75% from portal vein
Rich in absorbed nutrients
Recycled bile acids/salts

25% from hepatic artery
Regular systemic arterial blood

Question 3

where do both of these feed into

Answer 3

both feed into hepatic sinusoids
Single venous drainage pathway - central vein with feeds into hepatic vein and back to heart via the vena cava

Question 4

what is zone one of the liver

Answer 4

Zone 1:
periportal
Amino acid catabolism
Glycogenesis
Cholesterol synthesis

Question 5

what is zone three of the liver

Answer 5

Zone 3:
Pericentral
Lipid synthesis
Ketogenesis
Glutamine synthesis
Drug metabolism
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Question 6

what is zone three

Answer 6

a mixture of both

Question 7

where do you first see fibrosis occur

Answer 7

around the central veins

Question 8

what are hepatocytes

Answer 8

polarised epithelial cells

Question 9

what does fenestrated mean

Answer 9

Fenestrated means there are holes in the cells and these around found in the sinusoid (blood)

Question 10

what does the bile canaliculi have

Answer 10

mitochondrion
Bile canaliculus
Junctional complex

Question 11

what are the functions of bile

Answer 11

secretion of bile acids or salts to aid intestinal lipid digestion and absorption
Secretion of water and electrolytes
Excretion of waste products (those that are not easily excreted by the kidney)
Excretion of hormones
Excretion of drugs and other xenobiotics

Question 12

what is the composition of bile

Answer 12

around 1000ml per day to the -1 secreted by the liver
Around 500ml per day to the -1 reaches the duodenum

bile salts/acids and phospholipids and cholesterol
Bilirubin (conjugated)
Metabolites of hormones and drugs
Heavy metal ions
Electrolytes (HC03- neutralise acid) and water (as a vehicle)

Question 13

what are some features of primary bile acids

Answer 13

primary bile acids (synthesised in the liver) are weakly ionised, hence ‘bile acids’. (Bile acid plus hydrogen=undissociated)

Question 14

what are bile acids produced from

Answer 14

cholesterol

Question 15

what are bile acids conjugated with

Answer 15

Conjugation with taurine, glycine, sulphate, glucuronate, makes them more water soluble and charged, hence ‘bile salts’ (BA-X-)

Question 16

what is secondary

Answer 16

Secondary = bacterial modification in terminal ileum and colon

Question 17

what are unconjugated and conjugated bile salts secreted via

Answer 17

un-conjugated (BA-) and conjugated bile salts (BA-Z and BA-Y) secreted via:
Bile salt export pump (BSEP)
Multidrug resistance - associated protein 2 (MRP2)
Z = taurine and glycine
Y = sulphate and glucuronate

Question 18

what are both of these

Answer 18

both are ABC transporters with wide substrate speceificities

Question 19

what is the cholesterol transporter

Answer 19

ABCA1

Question 20

what is MDR1

Answer 20

p-glycoprotein

Question 21

what is the bile salt export pump

Answer 21

BSEP

Question 22

what is ABCG2

Answer 22

sulphated steroids

Question 23

what is ABCG5/8

Answer 23

cholesterol

Question 24

where is active uptake of conjugated bile salts

Answer 24

Active uptake of conjugated bile salts in terminal ileum via Na+ bile salt co transporter (ASBT) and organic solute transporter (OST)

Question 25

what is the co transport mechanism of bile salts in the liver

Answer 25

Co transport with Na+ via Na+-taurocholate co transporting peptide (NTCP)

Question 26

how are organic anions secreted

Answer 26

basolateral uptake by exchange with Cl- via OATP (large family)
Conjugation with glucuronate or sulphate (Y)
Apical secretion via MRP2
Sulphated sex steroids (St-Y) via another ABC transporter ABCG2
NB transporter diversity - also seen in kidney and BBB

Question 27

how are organic cations and lipids excreted

Answer 27

cytotoxic drugs, local anaesthesia and antibiotics
Small cations = facilitated diffusion via organic cation transporters (OCT1/3) ad then by exchange with H+ (MATE1)
Bulky molecules via OATP and the multi drug resistance transporter 1 (MDR1)

cholesterol via ABCG5/8
Phospholipids via a flippase (MDR3)

Question 28

describe the excretion of bilirubin

Answer 28

breakdown of haem to bilirubin following phagocytosis
The intermediate step is biliverdin
Carried by albumin to liver and taken up via OATP and ??
Conjugation with glucuronate (Y) in ER and secretion via MRP2

conjugated and actively secreted by the liver
Eventually move to the small intestine towards the ileum
The bacteria deconjugate some of the bilirubin and convert it to urobilinogen (colourless)
Most then converted to stercobilin (Brown) in colon
Some urobilinogen is reabsorbed and excreted as urobilin (yellow) via the kidney

Question 29

describe jaundice

Answer 29

unconjugated = haemolysis or failure of liver too conjugate. Normal urine and neurotoxicity (kernicterus)

Conjugated = chloleostasis (blockage in biliary system). Dark urine

Mixture = acute liver disease e.g hepatitis

Question 30

what happens if NH3 crosses the BBB

Answer 30

neurotoxicity

confusion-cognition changes-coma

Question 31

what is the biliary system

Answer 31

ductal secretion

Question 32

what is the fluid secretion carried out by

Answer 32

Fluid secretion by cholangiocytes

Question 33

what is 30-50% of hepatic bile secreted by

Answer 33

30-50% of hepatic bile is secreted by epithelial cells (cholangiocytes) lining the bile ducts

Question 34

what is the mechanism for HCO3- rich isotonic fluid

Answer 34

HCO3- rich, isotonic fluid, mechanism similar to pancreatic duct:
Secondary active transport of Cl- and HCO3-
Paracellular Na+ transport with isosmotic water flow

Question 35

what is it stimulated by

Answer 35

stimulated by secretin, VIP, glucagon

Question 36

Na+ is reabsorbed via what

Answer 36

Na+ reabsorbed via apical NHE and basolateral Na+,K+ -ATPase

Question 37

chloride is reabsorbed in exchange for what

Answer 37

Some Cl- reabsorbed in exchange for HCO3- but net H+ secretion