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GIGU > Liver Biochemistry > Flashcards

Liver Biochemistry Flashcards

(72 cards)

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1
Q

Largest solid organ in the body?

A

Liver

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2
Q

What is the blood supply to the liver and percentage of each supply?

A 
75% = portal vein
25% = hepatic artery
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3
Q

What does the portal vein bring to the liver?

A

Nutrient rich blood

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4
Q

What does the hepatic artery bring to the liver?

A

Oxygen rich blood

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5
Q

The portal vein and hepatic artery mix in sinusoids. How does the blood leave the liver?

A

Inferior vena cava

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6
Q

How does bile leave the liver?

A

Flows out through the bile duct

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7
Q

6 liver cell types

A 
Hepatocytes
Endothelial cells
Kupffer cells
Stellate cells
Pit cells
Cholangiocytes
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8
Q

Job of hepatocytes?

A

Carry out most metabolic functions = main cell

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9
Q

Where will you find endothelial cells?

A

Lining the sinusoids

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10
Q

Describe endothelial cells that line sinusoids in the liver

A

Have fenestrations (pores) to allow for material exchange between hepatocytes and blood

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11
Q

Where will you find Kupffer cells?

A

Lining the sinusoids

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12
Q

Job of Kupffer cells?

A

They are macrophages that protect the liver from toxins via phagocytosis and remove dead RBCs
- contain lots of lysosomes

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13
Q

Job of Stellate (Ito) cells?

A

Storage of vitamin A and regulates contractility of sinusoids

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14
Q

During liver cirrhosis, what cell type can negatively impact liver function by producing fibril-producing collagen?

A

Stellate cells

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15
Q

Job of Pit cells?

A

Natural killer cells in the liver that defend against toxins

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16
Q

Where will you find cholangiocytes?

A

Lining the bile ducts in the liver

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17
Q

Job of cholangiocytes?

A

Control the bile flow rate and pH

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18
Q

Overall function of the liver?

A

Primary receiving, distributing and recycling center

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19
Q

The liver is important in many functions of metabolism. List some

A

Carbohydrate (glucose) metabolism
Lipid metabolism (creates TAGs, bile acids, bile salts and ketones)
Synthesis of blood proteins

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20
Q

How does liver manage waste?

A

Inactivation, detoxification and transformation of metabolites

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21
Q

What allows for greater access and increased contact between the liver cells and the blood?

A

Fenestrations and lack of tight junctions in the sinusoidal epithelium

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22
Q

3 main things that bile is made up of?

A

Cholesterol
Bile acids
Bile salts

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23
Q

What are bile acids and bile salts synthesized from?

A

Hepatic cholesterol

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24
Q

Pathway for bile?

A
  • Made in hepatocytes
  • Travel to bile canaliculi
  • Travel through bile ducts to gallbladder where they are stored
  • Released to duodenum in response to food
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25
Bile acids are?
Protonated form
26
Bile salts are?
Deprotonated form
27
Do bile acids or bile salts do the emulsification of fats?
Bile salts
28
Describe the process bile salts take for the emulsification of fats
Bile acid ionizes to conjugate bile salt - Hydrophobic surface associates with TAG - Multiple of these join to form a micelle (aggregate) - Hydrophilic surface faces outward to associate with pancreatic lipases - Pancreatic lipases digest fatty acids so they can be absorbed in intestinal mucosa
29
Bile acids are formed from cholesterol. What are the main structural features of cholesterol?
4 rings and an OH group on carbon 3
30
What is the first step and rate limiting step in bile acid synthesis?
7alpha-hydroxylase takes cholesterol to | 7alpha-hydroxycholesterol
31
What are the main structural features of | 7alpha-hydroxycholesterol?
4 rings, an OH group on carbon 3 AND 7
32
7alpha-hydroxycholesterol then creates what 2 primary bile acids?
Cholic acid | Chenodeoxycholic acid
33
What are the main structural features of cholic acid?
4 rings, an OH group on carbon 3, 7, 12 and a COOH
34
What are the main structural features of chenodeoxycholic acid?
4 rings, an OH group on carbon 3, 7 and a COOH
35
The primary bile acids are then conjugated before secretion. Why?
The lower the pKa, the stronger the detergent effect
36
What 2 groups may be added to either cholic acid or chenodeoxycholic acid to form the primary conjugated bile acids?
Glycine | Taurine
37
If you add glycine to cholic acid or to chenodeoxycholic acid, what will you get?
Glycine + cholic acid = glycocholic acid | Glycine + chenodeoxycholic acid = glycochenodeoxycholic acid
38
If you add taurine to cholic acid or to chenodeoxycholic acid, what will you get?
Taurine + cholic acid = taurocholic acid | Taurine + chenodeoxycholic acid = taurochenodeoxycholic acid
39
List the 4 primary conjugated bile acids
Glycocholic acid Taurocholic acid Glycochenodeoxycholic acid Taurochenodeoxycholic acid
40
List the 2 primary bile acids
Cholic acid | Chenodeoxycholic acid
41
Primary conjugated bile acids are then changed to what?
Primary bile salts for emulsification
42
What can deconjugate/dehydroxylate primary bile salts?
Bacteria
43
Bacteria deconjugates/dehydroxylates primary bile salts into what?
Primary and secondary bile acids
44
What absorbs the primary and secondary bile acids for recycled use in the liver?
Ileum
45
What are the secondary bile acids?
Deoxycholic acid | Lithocholic acid
46
What are cholesterol lowering drugs?
Bile acid - binding resins
47
What do bile acid - binding resins do?
Cause an increase in the excretion of bile acids
48
How do bile acid- binding resins can an increase in the excretion of bile acids?
They cause an increase in bile acid synthesis which then depletes the liver cholesterol pool and lowers the plasma cholesterol levels
49
Gallstones are made of?
Bile crystals with lots of cholesterol
50
Insufficient secretion of bile salts from the gallbladder OR excess cholesterol secretion into the bile
Cholelithiasis
51
Xenobiotic
Ingested compounds with no nutritional value
52
Metabolites
Compounds made in the body
53
Liver is the primary site for conversion/degradation of?
Xenobiotics and metabolites
54
What are the phases for inactivation of xenobiotics?
Phase 1 = increase polarity (add OH) | Phase 2 = add functional group to make safe for excretion
55
What catalyzes phase 1 reactions for inactivation of xenobiotics?
Cytochrome P450 = CYPs (enzymes)
56
What version of CYP metabolizes the greatest number of drugs?
CYP3A4
57
Agents that inhibit CYP will cause?
Increase in drug levels
58
Agents that stimulate CYP will cause?
Decrease in drug levels
59
Ex. of a CYP inhibitor on statin drugs
Grapefruit juices
60
Grapefruit juices will ____ statin levels
Increase
61
Ex. of a CYP stimulator on statin drugs
St. Johns wort
62
St. Johns wort will _____ statin levels
Decrease
63
Variations in responses to drugs and drug metabolism is based on?
CYP polymorphisms between people
64
CYP3A4 oxidizes ____ to NABQ1 that will damage hepatocytes
Excess Tylenol
65
Disease of the liver cause impairment of what?
Free exchange of material between blood and hepatocytes due to fibrillar collagen
66
Excess tylenol is converted to NABQ1 by CYP3A4. NABQ1 is normally detoxified by?
Glutathione
67
With a tylenol overdose, what is the antidote to destory NABQ1?
N-acetyl cystein
68
pKa of glycocholic acid
4
69
pKa of taurcholic acid
2
70
What is the stronger detergent, glycocholic acid or taurocholic acid?
Taurcholic acid because it has a lower pKa!
71
What is an example of a non-absorbable bile acid - binding resin that is used to treat high cholesterol?
Cholestyramine
72
What does cholestyramine do?
Binds bile acids to excrete them because it is non-absorbable; (most bile acids are reabsorbed); this causes an increase in bile acid synthesis and depletion of cholesterol levels!

GIGU (29 decks)

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