Physiology and Pharmacology of the Liver

Question 1

Functions of Liver?

Answer 1

• Carb metabolism
• Fat metabolism
• Protein metabolism
• Degradation fro insulin, steroid, glucagon & ADH
• Activation of Vit D to hydroxyvitamin D2
• Storage Vit A, B12, E, D + K, copper, iron, glycogen
• Coagulation
• Synthesis of plasma proteins
• Protective
• Detoxification

Question 2

Examples of carb etabolism?

Answer 2

Gluconeogenesis
Glycogenolysis
Glycogenesis
Glycolysis

Question 3

What is gluconeogenesis?

Answer 3

Producing glucose form amino acids

Question 4

What is glycogenolysis?

Answer 4

Release glucose as required

Question 5

Glycogenesis?

Answer 5

To store polymerised glucose as glycogen

Question 6

Glycolysis?

Answer 6

Form pyruvate, thence lactat or acetyl Co-A

Question 7

What is involved in fat metabolism?

Answer 7

• Processing of chlyomicron remenants
• Synthesis of lipoproteins & cholesterol
• Ketogenesis (starvation)

Question 8

What is involved in protein metabolism?

Answer 8

• Trans and de-amination of amino acids
• Convert ammonia to urea
• Synthesis of plasma proteins

Question 9

When is bile secreted?

Answer 9

Between meals

Question 10

Where is bile stored?

Answer 10

Stored and concentrated in gall-bladder

Question 11

What happens in regards to bile during a meal?

Answer 11

Chyme in duodenum stimulates the GB smooth muscle to contract via CCK

• Sphincter of Oddi opens
• Bile spurts into duodenum via cystic and common bile ducts

Question 12

What does bile consist of?

Answer 12

Cholic and chenodeoxycholic acids

Question 13

What is cholelthiasis?

Answer 13

Concentration of bile in gall bladder caused by resorption of water- producing a supersaturated solution that is unstable
Cholesterol may crystallise and over time produce gall stones

Question 14

What is the best treatment for symptomatic gall stones?

Answer 14

Laparoscopic cholecystectomy

Question 15

What is given to patients with impaired GB function with small-medium sized radiolucent stones? And the drugs adverse affect?

Answer 15

Ursodeoxycholic acid

Diarrhoea

Question 16

What does atropine or GTN relieve?

Answer 16

Biliary spasm

Question 17

Bile acid sequesterants?

Answer 17

Colesevalam
Colestipol
Colestyramine

Question 18

What do bile acid sequesterants do?

Answer 18

Bind to bile acids preventing reabsorption

Lower plasma cholesterol indirectly

Question 19

What are bile acid sequesterants used for? And what are their adverse affects/limitations?

Answer 19

Used in hyperlipidaemia, cholestatic jaundice and bile acid diarrhoea

-Unpalatable, Causes diarrhoea, reduced absorption of fat soluble vitamins

Question 20

Where does Phase 1 of drug metabolism occur?

Answer 20

Right Liver

Question 21

3 processes in phase 1 of drug metabolism?

Answer 21

Oxidation
Reduction
Hydrolysis

Question 22

What is the effect of drug metabolism phase 1?

Answer 22

Makes drug more polar

Adds chemically reactive group permitting conjugation

Question 23

Where does phase 2 of drug metabolism occur?

Answer 23

Left liver

Question 24

What happens in phase 2 of drug metabolism?

Answer 24

Conjugation
An endogenous compound is added increasing polarity
Then excreted (some drugs excreted unchanged and don't go through the phases)

Question 25

What does drug metabolism do?

Answer 25

Acts to convert patent drugs to more polar metabolites that are not readily reabsorbed by kidney facilitating excretion

Question 26

What is CYP450? What does it stand for? What does it do?

Answer 26

Cytochrome P450 Metabolizing enzyme in liver Paracetamol and other drugs mess this up so liver can't metabolise (do it's job)

Question 27

What does not occur in severe hepatic failure? | What condition is this known as?

Answer 27

Detoxification of NH3 to urea | Hepatic encephalopathy

Question 28

What effect does a lack of detoxification of NH3 to urea have?

Answer 28

Blood NH3 levels rise | Resulting in coma

Question 29

What do you use in hepatic encephalopathy?

Answer 29

Lactulose | Converts ammonia to ammonium which is not absorbed/digested in SI

Question 30

Examples of plasma protein secretions?

Answer 30

Albumin Alpha globulins Beta globulins

Question 31

What do alpha globulins do?

Answer 31

Transport lipoproteins, lipids, hormones and bilirubin

Question 32

What do beta globulins do?

Answer 32

Transferrin (transports Fe3+, store bound to ferritin) | Fibrinogen (inactive from of fibrin, clotting blood)

Question 33

What is albumin?

Answer 33

Most abundant plasma protein | Small, negatively charged, water soluble, liver synthesizes about 14g/day

Question 34

What do lipoproteins do?

Answer 34

Transport dietary fats + synthesized fats. Only liver can metabolise and excrete cholesterol

Question 35

What vitamins does the liver store and for how long?

Answer 35

Vitamin A- 10 months Vitamin D- 3 weeks Vit B12- Few years

Question 36

What does cholesterol synthesis require?

Answer 36

C atoms-Acetyl Co-A Reducing power-NADPH Energy- ATP

Question 37

What is the role of HMG-CoA reductase?

Answer 37

Catalyiss irreversible form of mevalonic acid Rate limiting enzyme Statins target this to lower cholesterol

Question 38

Products form cholesterol?

Answer 38

Vitamin D- Regulates calcium + phosphorous metabolism Steroid hormones- Corticosteroids, androgens, estrogens Bile salts-Main metabolic product of cholesterol