1. Liver Biochemistry Flashcards
With regards to hepatic circulation what does it mean to say there is one way out but two ways in
- 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%)
When looking at liver cell types what do endothelial cells and hepatocytes do
Hepatocytes- 80% of liver cells, carry out metabolic function
Endothelial Cells- allow exchange of material
When looking at liver cell types what do Kupffer and Hepatic Stellate cells do
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
When looking at liver cell types what do Pit cells (lymphocytes) and Cholangiocytes do
Pit cells- natural killer cells protect liver against viruses and tumor cells
Cholangiocytes- line bile ducts and control bile flow rate and bile pH
Generally what is the function of the liver
Works as the primary receiving, distribution and recycling center
What does the liver due with carbohydrate metabolism
- 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
What does the liver do with regards to removal of nitrogen and synthesis of blood proteins
- Removal of nitrogen generated by amino acid metabolism via the urea cycle
- Synthesis of blood proteins such as albumin, igGs, prothrombin, blood coagulation factors
What does the liver do with regards to waste management
Liver is responsible for inactivation, detoxification and biotransformation of metabolites and xenobiotics
What is unique about the liver’s circulation
- Receives blood from Enteric Circulation (portal vein) and from periphery (hepatic artery)
- Low blood pressure
What allows greater access and increased contact between liver and blood
- lack of basement membrane
- gaps between endothelial cells
- fenestrations (pores)
From what are bile acids and bile salts synthesized
hepatic cholesterol
Whats the difference between a bile acid and bile salt
Acid- protonated form
Salt- deprotonated form
What enzyme is present at the commited step of the synthesis of bile acids
7alpha-hydroxylase (present in ER of hepatocytes)
When are bile acids conjugated and why
prior to secretion because the lower the pKa the better the detergent effect
What are the two given examples of secondary bile acids
Deoxycholic acid (derived from cholic acid)
Litocholic acid (derived fom chenodeoxycholic acid)
How is rate of bile acid synthesis increased
Induction of 7alpha-hydroxylase
What is cholestyramine and what does it do
Non-absorbale bile-acid binding resin
Causes large increase in excretion of bile acids
What are gall stones (crystals) made of
Bile supersaturated with CHOLESTEROL
What is the difference between metabolites and xenobiotics
Metabolites- made in body
Xenobiotics- ingested from outside
What are the two phases in the inactivation and detoxification of xenobiotics
Phase 1- polarity is increased
Phase 2- functional groups are conjugated for safe excretion
Phase 1 catalyzed by Cytochrome P450 (CYP)
What three forms of CYP are responsible for most of the phase 1 drug metabolism
CYP1
CYP2
CYP3
(operate via an electron transfer system)
CYPR is rate limiting due to 4:1 ratio of CYP to CYPR
Agents that inhibit or stimulate CYP will do what
- Agents that INHIBIT CYP will cause INCREASE in drug levels in plasma
- Agents that STIMULATE CYP will cause DECREASE in drug levels in plasma
What are exmaples of CYP inducers and inhibitors
Inhibitors- Citrus juices, Grapefruit juice (itraconozole, clarithromycin, cyclosporine)
Stimulators- St John’s Wort (rifampcin, carbamazepine)
How can we use CYPs to personalize medicine
Genotyping CYPs to identify gene-relevant polymorphisms may become common in order to personalize an individual’s response to a particular drug
What do diseases of the liver do
-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)
What increases in liver disease and is released from damaged hepatocytes
Serum activity of ALT and AST (increases)
