1. Liver Biochemistry

Question 1

With regards to hepatic circulation what does it mean to say there is one way out but two ways in

Answer 1

• Blood flows out through three veins into the Inferior Vena Cava (OUT)
• Oxygen rich blood flows into liver through hepatic artery (IN 25%)
• Nutrient rich blood flows into liver through portal vein (IN 75%)

Question 2

When looking at liver cell types what do endothelial cells and hepatocytes do

Answer 2

Hepatocytes- 80% of liver cells, carry out metabolic function
Endothelial Cells- allow exchange of material

Question 3

When looking at liver cell types what do Kupffer and Hepatic Stellate cells do

Answer 3

Kupffer- macrophages that protect the liver, have well developed ENDOCYTIC and PHAGOCYTIC functions (lots of lysosomes)
Hepatic Stellate- serve as storage for vit A and other lipids

Question 4

When looking at liver cell types what do Pit cells (lymphocytes) and Cholangiocytes do

Answer 4

Pit cells- natural killer cells protect liver against viruses and tumor cells
Cholangiocytes- line bile ducts and control bile flow rate and bile pH

Question 5

Generally what is the function of the liver

Answer 5

Works as the primary receiving, distribution and recycling center

Question 6

What does the liver due with carbohydrate metabolism

Answer 6

• liver plays a central role in glucose metabolism, specifically in maintaining optimal levels of circulating glucose
• Glucostasis (glycogen synthesis, glycogenolysis, gluconeogenesis)
• Under starvation, liver makes ketone bodies for use as energy source

Question 7

What does the liver do with regards to removal of nitrogen and synthesis of blood proteins

Answer 7

• Removal of nitrogen generated by amino acid metabolism via the urea cycle
• Synthesis of blood proteins such as albumin, igGs, prothrombin, blood coagulation factors

Question 8

What does the liver do with regards to waste management

Answer 8

Liver is responsible for inactivation, detoxification and biotransformation of metabolites and xenobiotics

Question 9

What is unique about the liver’s circulation

Answer 9

• Receives blood from Enteric Circulation (portal vein) and from periphery (hepatic artery)
• Low blood pressure

Question 10

What allows greater access and increased contact between liver and blood

Answer 10

• lack of basement membrane
• gaps between endothelial cells
• fenestrations (pores)

Question 11

From what are bile acids and bile salts synthesized

Answer 11

hepatic cholesterol

Question 12

Whats the difference between a bile acid and bile salt

Answer 12

Acid- protonated form

Salt- deprotonated form

Question 13

What enzyme is present at the commited step of the synthesis of bile acids

Answer 13

7alpha-hydroxylase (present in ER of hepatocytes)

Question 14

When are bile acids conjugated and why

Answer 14

prior to secretion because the lower the pKa the better the detergent effect

Question 15

What are the two given examples of secondary bile acids

Answer 15

Deoxycholic acid (derived from cholic acid)

Litocholic acid (derived fom chenodeoxycholic acid)

Question 16

How is rate of bile acid synthesis increased

Answer 16

Induction of 7alpha-hydroxylase

Question 17

What is cholestyramine and what does it do

Answer 17

Non-absorbale bile-acid binding resin

Causes large increase in excretion of bile acids

Question 18

What are gall stones (crystals) made of

Answer 18

Bile supersaturated with CHOLESTEROL

Question 19

What is the difference between metabolites and xenobiotics

Answer 19

Metabolites- made in body

Xenobiotics- ingested from outside

Question 20

What are the two phases in the inactivation and detoxification of xenobiotics

Answer 20

Phase 1- polarity is increased
Phase 2- functional groups are conjugated for safe excretion

Phase 1 catalyzed by Cytochrome P450 (CYP)

Question 21

What three forms of CYP are responsible for most of the phase 1 drug metabolism

Answer 21

CYP1
CYP2
CYP3

(operate via an electron transfer system)

CYPR is rate limiting due to 4:1 ratio of CYP to CYPR

Question 22

Agents that inhibit or stimulate CYP will do what

Answer 22

• Agents that INHIBIT CYP will cause INCREASE in drug levels in plasma
• Agents that STIMULATE CYP will cause DECREASE in drug levels in plasma

Question 23

What are exmaples of CYP inducers and inhibitors

Answer 23

Inhibitors- Citrus juices, Grapefruit juice (itraconozole, clarithromycin, cyclosporine)

Stimulators- St John’s Wort (rifampcin, carbamazepine)

Question 24

How can we use CYPs to personalize medicine

Answer 24

Genotyping CYPs to identify gene-relevant polymorphisms may become common in order to personalize an individual’s response to a particular drug

Question 25

What do diseases of the liver do

Answer 25

-Impair the free exchange of material between hepatocytes and blood
(loss of fenestrations and space between endothelial cells)
(leaky basement membrane replaced by fibrillar collagen)
(portal hypertension)

Question 26

What increases in liver disease and is released from damaged hepatocytes

Answer 26

Serum activity of ALT and AST (increases)