Liver 2

Question 1

What does the parenchyme consist of and do?

Answer 1

Consists of Hepatocytes 80%

-Glucose, lipid and protein metabolism
-Bile synthesis
-Detoxification

Question 2

What are the most important non-parenchyme cells?

Answer 2

Stellate cell = fibroblast, produces scar tissue
Kupffer cells = Macrophages

Question 3

What is a sinusoid and what does it do?

Answer 3

a discontinuous capillary = blood vessel

• Enhance exchange of metabolites between blood and hepatocytes

Question 4

What does Bile contain?

Answer 4

• Contains bile salt, water, lipids and bilirubin

Question 5

How is bile made?

Answer 5

• Synthesized by hepatocytes

Question 6

What are bile salts?

Answer 6

• Bile salts are molecules essentrial for the uptake of fat and fat soluble vitamins

Question 7

What is the enterohepatic circulation of bile salts?

Answer 7

• bile enters the intestine via common bile duct
• Bile salts emulsify fats and fat soluble compounds for efficient absorption by micelle formations
• Waste products are excreted in feces
  BS cycle 5-7 times/day and are reabsorbed

Question 8

What is the circulation of bile?

Answer 8

Bile salts and water soluble compounds go to the liver via the portal vein
Log p>5, fat compounds go to lymphatic system and enter circulation
Lipidemic compounds avoid first-pass clearance

Question 9

Describe the enterohepatic circulation and bioavailability with and without charcoal?

Answer 9

With charcoal = plasma levels go down, because charcoal absorbs hormone
Without charcoal = plasma levels high, because the hormone keeps cycling

Question 10

What are bioactivation and bioinactivation?

Answer 10

Bio-activation = compound gets activated after metabolism
Bio-inactivation = compound gets inactivated after metabolism

Question 11

Where do phase 1 and 2 reactions happen?

Answer 11

In the hepatocytes.

Question 12

What is Cytochrome P450 en what does it do?

Answer 12

Superfamily of proteins, responsible for detoxification reactions
- heme containing enzymes
- responsible for 75% of drug metabolism
- mostly redoxreactions
- Oxidizes the compound with oxygen

Question 13

Where is Cytochrome P450 located?

Answer 13

• Located in the mitochondria and smooth ER

Question 14

What Factors affect activity of CP450?

Answer 14

Extrinsic factors like
- Medicine, smoke
- grapefruit juice: inhibit enzymes

Question 15

What happens during phase 1 reactions?

Answer 15

Phase 1: make compound more water soluble
- Reduction, oxidation, hydrolysis

Question 16

What happens during phase 2 reactions?

Answer 16

Phase 2: conjugation reaction, increases hydrophilicity and excretion

Question 17

Codeine:

Answer 17

• Prodrug
• Metabolised by CYP2D6 to become morphine
• Phase 2 reaction for codeine is Glucuronidation
• The metabolites are more active

Question 18

Acetaminophen:

Answer 18

• Paracetamol
• Can become toxic (NAPQI) if metabolised by CYP450 2E1
• By glutathione it can become non-toxic again

Question 19

Ethanol:

Answer 19

• Becomes acetaldehyde
• Detoxification
• If system is overloaded you get drunk

Question 20

What is the link between CYP450 2E1; alcohol and acetaminophen?

Answer 20

Door veel alcohol te drinken maakt je lichaam meer CYP450 2E1 aan. Hierdoor wordt acetaminophen gemetaboliseerd naar het toxische NAPQi

Question 21

What is the main difference between intrinsic and idiosyncratic drug reactions?

Answer 21

Intrinsic is predictable and dose related
Idiosyncratic is unpredictable and not always dose related