9: Liver Biochem

Question 1

Why is the liver an impressive organ?

Answer 1

Largest solid organ in the body

Question 2

Two sources of blood supply to liver, what, and how much they contribute

Answer 2

1. Portal vein: nutrient rich blood from GI; 75%

2. Hepatic artery: O2 rich blood; 25%

Question 3

One way out of the liver for blood

Answer 3

Into the IVC

Question 4

Does liver have G6P? What is the point?

Answer 4

Yes, it permits release of free glucose into blood

Question 5

Name some blood proteins that are formed in the liver

Answer 5

albumin, Igs, apoproteins, fibrinogen, prothrombin, blood coagulation factors, APPs, CRP, bilirubin

Question 6

Why is it good that the liver gets first access to enteric blood?

Answer 6

Can utilize ingested material and turn it into useful forms + harmful products can be converted safely and excreted

Question 7

Two major functions of bile acids and salts

Answer 7

1. Emulsification/digestion/absorption of fats + fat-soluble vitamins
2. Elimination of cholesterol, prevention of cholesterol precipitation

Question 8

How are bile salts considered detergents?

Answer 8

Theyre amphipathic

Question 9

Purpose of bile acids being detergents

Answer 9

Help form micelles to increase surface area of lipids for digestion by lipases

Question 10

PKa of taurocholic and glycocolic acids and why this matters

Answer 10

Taurocholic acid: pKA 2
Glycocolic acid: pKa 4
Duodenum has a pKa of 6, so these two acids are good for emulsification

Question 11

Bile acid binding resins

Answer 11

Drugs that lower cholesterol

Question 12

How do bile acid binding resins work? Four steps

Answer 12

1. Bile acid binding resins cause large increase in bile acid excretion
2. Increase bile acid synthesis
3. Depletion of liver cholesterol pool
4. Increased hepatic uptake of LDL from circulation

Question 13

How much bile acid is reabsorbed vs excreted daily

Answer 13

95% reabsorbed, 5% excreted

Question 14

Gallstone composition

Answer 14

Bile supersaturated with cholesterol

Question 15

Two ways gallstones can form

Answer 15

1. Insufficient secretion of bile salts/phospholipids

2. Excess cholesterol secretion into bile

Question 16

Side effects of chronic disturbance in bile salt metabolism

Answer 16

Steatorrhea, deficiency in fat soluble vitamins

Question 17

Xenobiotics

Answer 17

Compounds ingested from outside with no nutritional value (pharmacological agents, recreational drugs, food additives, etc.)

Question 18

Metabolites

Answer 18

Compounds made in the body

Question 19

Goal of hepatic metabolism of metabolites and xenobiotics

Answer 19

Increase hydrophilicity for easier excretion

Question 20

How do agents that inhibit CYP work?

Answer 20

Drug forms a stable complex with CYP -> inhibits metabolism of other drugs that are substrates of that CYP

Question 21

Four examples of agents that inhibit CYPs

Answer 21

Itraconozole, clarithromycin, cyclosporine, grapefruit juice

Question 22

Three examples of agents that stimulate CYPs

Answer 22

St. John’s Wort, rifampicin, carbamezepine

Question 23

Personal medicine and CYPs

Answer 23

Allelic variation of CYPs exist - genotyping CYPs can allow for understanding of an individual’s response to a particular drug

Question 24

Liver cirrhosis

Answer 24

Result of chronic hepatitis characterized by fibrosis of liver lobes

Question 25

Mechanism in liver cirrhosis

Answer 25

Stellate cells increase ECM synthesis -> infiltrates liver -> interferes with hepatocyte function

Question 26

Major mechanism for liver diseases

Answer 26

Normally leaky basement membrane between endothelial cells and hepatocytes replaced by high density membrane containing fibrillar collagen + spaces between endothelial cells and fenestrations in plasma membrane are lost, causing impairment of free exchange of material between hepatocytes and blood

Question 27

Liver function panel: values to look for

Answer 27

1. Transaminases: ALT, AST
2. Albumin, alkaline phosphatase, PT, bilirubin, urea (BUN), glucose, triacyglycerol
3. Cholesterol: total, VLDL, LDL, HDL