Protection of the StomachJake Turner and David Gray

Why does the stomach need protection?•HCl•Digestive enzymes• Ingested bacteria and pathogens•Abrasive food / stomach contents•Consumed toxins

What might happen if the stomach loses its protection / its protection is overwhelmed?• Ulcer – Pain, GORD, Dysphagia, loss of appetite.• Perforation – Digestion of internal viscera, pain,

peritonitis, death.• Fistula – Pain, death, digestion of organ,

peritonitis.• Cancer – Due to GORD and Barrett’s oesophagus.• Malabsorption

Oesophageal cancer

What are the main methods of stomach protection?•Mucous barrier•Alkaline blood and mucous•Extremely good blood supply•Rapid healing ability (re-epithelialisation)

Stomach lumen (acid)

Mucous layer

Tight junctions

Epithelial cells

Gastric arteries (from the coeliac trunk)

Interstitial fluid (buffer zone)

What can make it all go wrong?• Helicobacter pylori• Choosing the wrong parents• NSAIDs• Alcohol• Excess acid (ZE)• Excessive antacid use• Trauma• Vascular disorder (think diabetes)• Crohns & other IBD’s

Summary of pathogenic mechanisms in peptic ulcer disease

How does the stomach get acidic?• The parietal cells secrete H+ into the stomach, which they generate

from CO2 and H2O. This reaction is catalysed by the carbonic anhydrase enzyme, and is shown below.

• CO2 + H2O = H2CO3 = HCO3- + H+

A couple of reminders • Barretts oesophagus is a premalignant lesion• Cancer in the lower 1/3 of the oesophagus is most likely to be an

adenocarcinoma.• NSAIDs will cause many systemic effects due to their inhibition of the

cyclooxygenase enzymes (COX1 and COX2). These produce prostaglandins (among many other things), which are important for many of the stomachs protection mechanisms.

• If there is ever an easy answer given to you, take it! And remember that they may give you the answer to one question in another one.

A couple of reminders continued…• There is a difference between the protective function of the stomach,

and the stomachs own protection, e.g. stomach acid will damage the stomach, but it is a protective function of the stomach because it helps to kill ingested pathogens.

• The one irreplaceable function of the stomach is the production of intrinsic factor, which is needed for vitamin B12 absorption.

• I have taken the next couple of slides from your lecture, and they are all nice and simple.

• It really is worth having a good grasp on how the stomach produces acid, but you don’t need to go into much more detail than what is on that slide!

• Focus your time on learning the basic bits, don’t worry about the really complicated mechanisms of stimulation and inhibition! If you know what stimulates something and what inhibits something then you can answer most questions about it.

Mechanism of Acid Secretion by the Parietal Cell

1. H+ and HCO3- are produced from

CO2 and H2O.

2. H+ is secreted into the lumen by a H+/K+-ATPase pump.

3. HCO3- moves out of the cell,

across the basolateral membrane via antiport with Cl-.

4. Cl- diffuses passively into the lumen via a Cl- channel.

• “Catch Up Biology” Chapter 9• Greater detail in Block 2

For more information on membrane transport:

Physiological Regulation of Gastric Acid Secretion

Stimulated by:• gastrin• acetylcholine• histamine

Inhibited by:• somatostatin• prostaglandins E2 and I2

• enteric hormones