Liver Function and Metabolism

Question 1

How are fat soluble drugs normally carried around the blood?

Answer 1

Albumin

Question 2

What is degree of drugs extraction dependent on?

Answer 2

Hepatic blood flow

Drug-metabolizing enzyme activity

Question 3

What does phase 1 of drug metabolism in the Microsomal Drug Oxidising System (MDOS) involve?

Answer 3

Converting Lipophilic Drug → Product of oxidation/reduction/hydrolysis

Question 4

What does phase 2 of drug metabolism in the Microsomal Drug Oxidation System (MDOS) involve?

Answer 4

Coagulation of the products of oxidation/reduction/hydrolysis → Water soluble metabolites

Glycine, Acetic Acid, Sulphuric Acid

Question 5

What is the name of the isoenzyme in the liver used for drug metabolism?

Answer 5

P450

Question 6

At low concentrations, how is alcohol dealt with?

Answer 6

First pass metabolism

Question 7

At high concentrations of alcohol, what type of metabolism occurs?

Answer 7

Microsomal Drug Oxidising System/Microsomal Ethanol Oxidising System

Question 8

What is the enzyme used for the first step of first pass metabolism? and where is it found?

Answer 8

Alcohol Dehydrogenase found in the cytoplasm

Question 9

What is the enzyme involved in the second part of first pass metabolism? and what does it convert?

Answer 9

Acetaldehyde Dehydrogenase converts acetaldehyde → acetate

Question 10

What is the function of acetaldehyde dehydrogenase dependent upon?

Answer 10

The conversion of NAD+ to NADH

Question 11

What is another name for the acetate? and what does it become if not used?

Answer 11

Acetyl CoA, core metabolite in CREB cycle, converted to fat if not used

Question 12

What are the consequences of alcohol metabolism?

Answer 12

1. Change in NADH:NAD+ ratio
2. Increase lactate production → decrease pyruvate for gluconeogenesis
3. Increased malate production → decrease oxaloacetate for gluconeogenesis

Ultimately hypoglycaemia → brain temperature control → hypothermia

Question 13

What are the contributing factors for fatty liver due to alcohol? (4 marks)

Answer 13

Increased FA release from adipose tissue

Increased lipid biosynthesis

Decreased FA oxidation due to metabolic load of alcohol

Decreased release of triacylglycerides from Liver

Question 14

How may fatty liver progress?

Answer 14

It is reversible, but may progress to hepatitis, fibrosis and eventually cirrhosis

Question 15

Which two enzymes are related to liver damage? and which one is more specific?

Answer 15

ALT and AST

AST can also be raised in heart and skeletal damage, so ALT is more specific

Question 16

What is gamma-glutamyl transferase associated with?

Answer 16

It is an enzyme associated with the clearance of alcohol. A high level is associated with high levels of alcohol consumption.

Question 17

If there are high levels of conjugated bilirubin, what is this suggestive of?

Answer 17

Bile duct blockage

Hepatitis, liver injury, long term alcohol abuse

Question 18

What is a high unconjugated bilirubin level suggestive of?

Answer 18

Excessive breakdown of red blood cells = Haemolytic Anaemia

Question 19

What does detection of the following mean?

anti-mitochondrial antibodies

smooth muscle antibodies

antinuclear cytoplasmic antibodies

Answer 19

Anti-mitochondrial antibodies - Primary Biliary Cirrhosis

Smooth muscle antibodies - Autoimmune hepatitis

Antinuclear cytoplasmic antibodies - Primary sclerosing cholangitis