GI Physiology 2

Question 1

Why is oral drug delivery favoured

Answer 1

Ease of administration

Compliance is higher

Question 2

What does pepsin do and what affect does it have on insulin

Answer 2

Pepsin digests enzymes. As insulin is a protein, it cannot be given orally as it would be digested

Question 3

What impact does the presence of HCl have on drugs

Answer 3

It can render some inactive due to the very low pH values found in the stomach

Question 4

Give 2 examples of drugs which can become inactivated due to the stomachs low pH. How do we prevent this

Answer 4

Penicillin G and erythromycin

We prevent inactivation by using enteric coatings

Question 5

Where does the majority of drug absorption occur. Where else can it occur

Answer 5

In the small intestine. Some drugs may also be absorbed in the stomach

Question 6

Which types of drugs can be absorbed from the stomach

Answer 6

Lipid soluble, weakly acidic drugs can be absorbed in the stomach (as they are unionised at pH1-2).

Examples include: Aspirin, paracetamol, warfarin

Question 7

Give the equation for the relationship between ph and ionisation

Answer 7

pH = pKa + log [A-] / [AH] -

Question 8

Why don’t human stomaches digest itself

Answer 8

The protease is released in an inactive form - pepsinogen. This means that no active protease is found at the sight of release

Question 9

Which 3 ways does the gastric tissue prevent itself from coming into contact with highly corrosive HCl and protease

Answer 9

Tight junctions, high cell turnover and mucus

Question 10

How do tight junctions prevent the gastric tissue being damaged by HCl and protease

Answer 10

Tight junctions:
Protein complexes lock epithelial cells together
This restricts movement of HCl and proteases across the epithelial cells which means the acid cant reach the underlying tissue

Question 11

How does mucus prevent the gastric tissue being damaged by HCl and protease

Answer 11

There is mucus – the foveolar cells produce mucus which covers the surface of the stomach forming a barrier
This barrier is alkaline and so neutralises HCl if it comes into contact with the stomach lumen

Question 12

How does a high cell turn over prevent the gastric tissue being damaged by HCl and protease

Answer 12

Damaged cells may allow HCl/protease to reach gastric tissue
Cells migrate from gastric pits
Every 2-3 days so any damaged cells can be replaced and the barrier is maintained

Question 13

What happens when there is a breakdown in mucus barrier function?

Answer 13

The epithelial cells are exposed to HCl/pepsin

This can result in the formation of Gastric (in the stomach)/duodenal ulcer

Question 14

What can damage to the gastric tissue result in

Answer 14

Damage may extend deep into wall of GI tract
Damage of blood vessels
Haemorrhage into the GI tract

In severe cases: there can be complete erosion through tract wall resulting in a
perforated ulcer

Question 15

What happens if there is complete erosion through the tract wall

Answer 15

Food, secretions & bacteria from within the GI tract enter the peritoneal cavity

This results in peritonitis – hospitalisation

It can lead to sepsis

In extreme cases: Multiple organ failure, death

Question 16

What does H.pylori have to do with GI physiology

Answer 16

H. pylori can infect gastric mucosa

This decreases barrier efficacy resulting in ulcer formation

Question 17

How does H. pylori infect the GI tract

Answer 17

It has a helical shape - evolved to help penetrate the mucus lining

It then binds to epithelial cells and establishes an infection.

Question 18

Why isnt h.pylori not shed along with the rest of the epithelia cells every 2-3 days

Answer 18

H. pyloribinds to the cells via the BabA protein

This protein is pH sensitive

As infected cells migrate upwards towards the gastric lumen, the reduction in pH disrupts BabA binding

This means H. pylori detaches from old cells

In then free to infect newer cells further down

Question 19

How do we treat H pylori.

Answer 19

2 x antibiotics + PPI
Clarithromycin + amoxycillin + omeprazole
Clarithromycin + metronidazole + omeprazole

Question 20

What is the major site of nutrient and drug absorption

Answer 20

Small intestine – major site of nutrient and drug absorption

Question 21

What is peristalsis

Answer 21

Peristalsis – a wave of muscular contraction which propels contents along the GI tract

Question 22

Which muscles are involved in peristalsis (in order)

Answer 22

Circular muscles - prevents backwards movement of material

Longitudinal
muscles - squeezes on the contents and pushes it forwards

Circular muscles - further along the gi tract contract meaning the process starts again

Question 23

How can altering peristalsis have an impact on water aborption

Answer 23

In peristalsis: contraction longitudinal smooth muscle moves material. If we can reduce the activity of these musles we can retain the contents. This leads to an increase in water absorption

Question 24

Which area of the brain regulates contraction of the longitudinal muscles

Answer 24

Neurones within the myenteric plexus (MP)

Question 25

How does loperamide work to reduce diarrhoea

Answer 25

It acts on the μ Opioid receptors of myenteric plexus.
This decreases muscle contraction hence reducing the transit of stomach contents meaning more water can be reabsorbed.
Side effects of opioid pain relief is constipation

Question 26

What is the pancreas

Answer 26

Pancreas – an accessory structure which secretes
Amylase – aids starch digestion
Lipase – aids lipid digestion
Proteases – trypsin, chymotrypsin (initially produced as zymogens)

It also secrets HCO3- - neutralises gastric acid within the duodenum

Question 27

How does the body synthesise bile acids

Answer 27

In the liver – accessory structure
Synthesises bile acids (e.g. taurocholic acid)
These are important in lipid emulsification, which aids absorption

Vitamins A,D,E,K dissolve in fat and are then absorbed

Question 28

What is the biosynthetic pathway for turning acetyl coenzyme A into bile acids

Answer 28

Acetyl CoA
MHG-CoA
Mevalonate
Cholesterol
Bile acids

Question 29

Where are bile acids stored

Answer 29

In the gall bladder and released into the bile duct and then into the duodenum.

They can be reabsorbed from the illeum into the liver and can be recycled several times a day

Question 30

What can high levels of cholesterol lead to

Answer 30

Atheroscerosis

Question 31

How can statins reduce levels of excess cholesterol

Answer 31

By blocking an eznyme in the biosynthetic pathway hence reducing the synthesis of cholesterol