Liver 2 Flashcards
What does the parenchyme consist of and do?
Consists of Hepatocytes 80%
-Glucose, lipid and protein metabolism
-Bile synthesis
-Detoxification
What are the most important non-parenchyme cells?
Stellate cell = fibroblast, produces scar tissue
Kupffer cells = Macrophages
What is a sinusoid and what does it do?
a discontinuous capillary = blood vessel
- Enhance exchange of metabolites between blood and hepatocytes
What does Bile contain?
- Contains bile salt, water, lipids and bilirubin
How is bile made?
- Synthesized by hepatocytes
What are bile salts?
- Bile salts are molecules essentrial for the uptake of fat and fat soluble vitamins
What is the enterohepatic circulation of bile salts?
- 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
What is the circulation of bile?
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
Describe the enterohepatic circulation and bioavailability with and without charcoal?
With charcoal = plasma levels go down, because charcoal absorbs hormone
Without charcoal = plasma levels high, because the hormone keeps cycling
What are bioactivation and bioinactivation?
Bio-activation = compound gets activated after metabolism
Bio-inactivation = compound gets inactivated after metabolism
Where do phase 1 and 2 reactions happen?
In the hepatocytes.
What is Cytochrome P450 en what does it do?
Superfamily of proteins, responsible for detoxification reactions
- heme containing enzymes
- responsible for 75% of drug metabolism
- mostly redoxreactions
- Oxidizes the compound with oxygen
Where is Cytochrome P450 located?
- Located in the mitochondria and smooth ER
What Factors affect activity of CP450?
Extrinsic factors like
- Medicine, smoke
- grapefruit juice: inhibit enzymes
What happens during phase 1 reactions?
Phase 1: make compound more water soluble
- Reduction, oxidation, hydrolysis
What happens during phase 2 reactions?
Phase 2: conjugation reaction, increases hydrophilicity and excretion
Codeine:
- Prodrug
- Metabolised by CYP2D6 to become morphine
- Phase 2 reaction for codeine is Glucuronidation
- The metabolites are more active
Acetaminophen:
- Paracetamol
- Can become toxic (NAPQI) if metabolised by CYP450 2E1
- By glutathione it can become non-toxic again
Ethanol:
- Becomes acetaldehyde
- Detoxification
- If system is overloaded you get drunk
What is the link between CYP450 2E1; alcohol and acetaminophen?
Door veel alcohol te drinken maakt je lichaam meer CYP450 2E1 aan. Hierdoor wordt acetaminophen gemetaboliseerd naar het toxische NAPQi
What is the main difference between intrinsic and idiosyncratic drug reactions?
Intrinsic is predictable and dose related
Idiosyncratic is unpredictable and not always dose related
