GI Physiology 2 Flashcards
Why is oral drug delivery favoured
Ease of administration
Compliance is higher
What does pepsin do and what affect does it have on insulin
Pepsin digests enzymes. As insulin is a protein, it cannot be given orally as it would be digested
What impact does the presence of HCl have on drugs
It can render some inactive due to the very low pH values found in the stomach
Give 2 examples of drugs which can become inactivated due to the stomachs low pH. How do we prevent this
Penicillin G and erythromycin
We prevent inactivation by using enteric coatings
Where does the majority of drug absorption occur. Where else can it occur
In the small intestine. Some drugs may also be absorbed in the stomach
Which types of drugs can be absorbed from the stomach
Lipid soluble, weakly acidic drugs can be absorbed in the stomach (as they are unionised at pH1-2).
Examples include: Aspirin, paracetamol, warfarin
Give the equation for the relationship between ph and ionisation
pH = pKa + log [A-] / [AH] -
Why don’t human stomaches digest itself
The protease is released in an inactive form - pepsinogen. This means that no active protease is found at the sight of release
Which 3 ways does the gastric tissue prevent itself from coming into contact with highly corrosive HCl and protease
Tight junctions, high cell turnover and mucus
How do tight junctions prevent the gastric tissue being damaged by HCl and protease
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
How does mucus prevent the gastric tissue being damaged by HCl and protease
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
How does a high cell turn over prevent the gastric tissue being damaged by HCl and protease
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
What happens when there is a breakdown in mucus barrier function?
The epithelial cells are exposed to HCl/pepsin
This can result in the formation of Gastric (in the stomach)/duodenal ulcer
What can damage to the gastric tissue result in
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
What happens if there is complete erosion through the tract wall
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
What does H.pylori have to do with GI physiology
H. pylori can infect gastric mucosa
This decreases barrier efficacy resulting in ulcer formation
How does H. pylori infect the GI tract
It has a helical shape - evolved to help penetrate the mucus lining
It then binds to epithelial cells and establishes an infection.
Why isnt h.pylori not shed along with the rest of the epithelia cells every 2-3 days
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
How do we treat H pylori.
2 x antibiotics + PPI
Clarithromycin + amoxycillin + omeprazole
Clarithromycin + metronidazole + omeprazole
What is the major site of nutrient and drug absorption
Small intestine – major site of nutrient and drug absorption
What is peristalsis
Peristalsis – a wave of muscular contraction which propels contents along the GI tract
Which muscles are involved in peristalsis (in order)
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
How can altering peristalsis have an impact on water aborption
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
Which area of the brain regulates contraction of the longitudinal muscles
Neurones within the myenteric plexus (MP)
How does loperamide work to reduce diarrhoea
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
What is the pancreas
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
How does the body synthesise bile acids
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
What is the biosynthetic pathway for turning acetyl coenzyme A into bile acids
Acetyl CoA MHG-CoA Mevalonate Cholesterol Bile acids
Where are bile acids stored
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
What can high levels of cholesterol lead to
Atheroscerosis
How can statins reduce levels of excess cholesterol
By blocking an eznyme in the biosynthetic pathway hence reducing the synthesis of cholesterol
