Hepatotoxicity

Question 1

What percentage of body weight is the liver?

Answer 1

2-5%

Question 2

What are important aspects of the blood supply received by the liver?

Answer 2

Dual blood supply

• 75% from portal vein - nutrient rich but oxygen deficient
• 25% from hepatic artery - oxygen rich
• hepatic vein drains most to the inferior vena cava

Question 3

What are the sections of the liver called?

Answer 3

lobules

Question 4

What are the characteristics of liver lobules?

Answer 4

• central vein is in the centre
• portal triad is at the periphery
• portal triad consists of bile ductules, hepatic arteriole, hepatic portal venule
• divided into 3 zones
• zone 1 - periportal - encircles portal tract, where oxygenated blood enters
• zone 2 - centrilobular - around the central veins, oxygen is poor (oxygen tension is ~4%)
• zone 3 - midzone - inbetween
• there is metabolic heterogeneity across lobules 0 gradient of uptake, storage, metabolism due to differential expression of enzymes and protein

Question 5

What proteins/enzymes are found in the periportal region?

Answer 5

• cadherin (involved in cell adhesion)

- ATP-citrate lyase (FA biosynthesis, formation of acetyl CoA)

Question 6

What proteins/enzymes are found in the centrilobular region?

Answer 6

• many enzymes involved in biotransformation of xenobiotics which detoxify or activate the chemicals (e.g. NQO1 and P450 reductase)
• glutamine synathas, which catalyses condensation of glutamate with ammonia to form glutamine

Question 7

What sort of cells are found in the periportal and centrilobular regions?

Answer 7

Mostly hepatocytes in both ~60%

Endothelials cells are larger and more porous in the centrilobular region

Kupffer cells are more prevalent in the periportal but have increase phagocytic activity in the centrilobular

Stellate/Ito cells are more prevalent in the centrilobular region