Hydrochloric Acid Production

HCl is produced by the parietal cells of the stomach. To begin with, water (H2O) and carbon dioxide (CO2) combine within the parietal cell cytoplasm to produce carbonic acid (H2CO3), which is catalysed by carbonic anhydrase. Carbonic acid then spontaneously dissociates into a hydrogen ion (H+) and a bicarbonate ion (HCO3–).

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The hydrogen ion that is formed is transported into the stomach lumen via the H+– K+ ATPase ion pump. This pump uses ATP as an energy source to exchange potassium ions into the parietal cells of the stomach with H+ ions.

The bicarbonate ion is transported out of the cell into the blood via a transporter protein called anion exchanger which transports the bicarbonate ion out the cell in exchange for a chloride ion (Cl–). This chloride ion is then transported into the stomach lumen via a chloride channel.

This results in both hydrogen and chloride ions being present within the stomach lumen. Their opposing charges leads to them associating with each other to form hydrochloric acid (HCl).

Control of Gastric Acid Production

At rest, the number of H+– K+ ATPases present within the parietal cell membrane is minimal. The rest are sequestered within tubulovesicles in the parietal cell. Upon stimulation the vesicles fuse with the cell membrane which leads to the increased insertion of H+– K+ ATPase into the membrane, hence allowing for the increased movement of hydrogen ions into the stomach thus increasing acid production.

Increasing Gastric Acid Production

There are three ways in which acid production is increased. The first of these is via ACh, which is released from the vagus nerve. This is released firstly during the cephalic phase of digestion, which is activated upon seeing or chewing food, leading to direct stimulation of parietal cells via the vagus nerve. It is also produced during the gastric phase of digestion when intrinsic nerves detect distension of the stomach, stimulating the production of ACh by the vagus nerve.

The main regulation pathway involves the hormone gastrin which is secreted from G cells in the stomach. G cells are activated by the vagus nerve, gastrin related peptide, and by peptides in the stomach lumen produced via protein digestion. Activation of the G cells leads to the production of gastrin which is released into the blood and travels through the blood until it reaches the parietal cells. Gastrin binds to CCK receptors on the parietal cells which also elevates calcium levels causing increased vesicular fusion.

Finally, enterochromaffin-like cells in the stomach secrete histamine which binds to H2 receptors on the parietal cells. These cells release histamine in response to the presence of gastrin and ACh. This leads to increased fusion however it is via the secondary messenger cAMP as opposed to calcium in the other methods.

Decreasing Gastric Acid Production

There are a number of ways in which acid production can be decreased.

The first of these is via accumulation of acid in the empty stomach between meals. This increase in acid leads to a lower pH within the stomach, which inhibits the secretion of gastrin, via the production of somatostatin from D cells. Once food has been broken down into chyme, it passes into the duodenum, triggering the enterogastric reflex. This reflex can be stimulated by distention of the small bowel, if there is excess acid in the upper intestine, the presence of protein breakdown products as well as excess irritation to the mucosa. Inhibitory signals are sent to the stomach via the enteric nervous system, as well as signals to the medulla – reducing vagal stimulation of the stomach. The enterogastric reflex is important in slowing down gastric emptying when the intestines are already filled.

The presence of chyme within the duodenum also stimulates entero-endocrine cells to release cholecystokinin and secretin, both of which play a variety of important roles in completing digestion, but also inhibit gastric acid secretion. Secretin is released by the S cells of the duodenum when there is excessive acid production in the stomach.

Other hormones including glucose-dependent insulinotropic peptide (GIP) and vasoactive intestinal polypeptide also work to decrease acid production in the stomach.

Clinical Relevance

Hypersecretion

Excessive secretion of stomach acid can lead to the formation of peptic ulcers. Potential complications of peptic ulcers include excessive bleeding due to erosion through a blood vessel. There are two main drugs used to prevent excessive acid formation. H2 antagonists such as ranitidine bind to the H2 receptors preventing the binding of histamine and thus reduce acid secretion.

It is important to note that the other two pathways for stomach acid secretion still operate, thus acid secretion is only reduced and not completely inhibited. Proton pump inhibitors (PPIs) such as omeprazole bind to the H+– K+ ATPase (proton pump), hence preventing the transportation of hydrogen ions into the stomach lumen. PPIs completely prevent stomach acid formation due to hydrogen ions not being able to react with chloride ions in the stomach.

Clinical Relevance

Achlorhydria

This is a state where there is a decrease in the volume of stomach acid produced. Achlorhydria can result in an increased risk of salmonella and cholera. There are a variety of causes and further tests must be undertaken to ascertain the cause to allow for a targeted treatment regime.

Common questions about omeprazole

How does omeprazole work?

Omeprazole is a type of medicine called a proton pump inhibitor (PPI).

Proton pumps are enzymes in the lining of your stomach that help it make acid to digest food.

Omeprazole prevents proton pumps working properly. This reduces the amount of acid the stomach makes.

When will I feel better?

You should start to feel better within 2 to 3 days, but it may take up to 4 weeks for omeprazole to work fully. You may still have some acid symptoms during this time.

If you treated yourself with omeprazole that you bought from a pharmacy and your symptoms are no better after 2 weeks, tell your doctor. They may want to do tests or put you on a different medicine.

What if I do not get any better?

If you feel you are not getting any better, speak to your doctor. They may suggest trying another PPI, such as pantoprazole or rabeprazole.

Are there any long term side effects?

If you take omeprazole for more than 3 months, the levels of magnesium in your blood may fall.

Low magnesium can make you feel tired, confused, dizzy and cause muscle twitches, shakiness and an irregular heartbeat. If you get any of these symptoms, tell your doctor.

Taking omeprazole for more than a year may increase your chances of certain side effects, including:

• bone fractures
• gut infections
• vitamin B12 deficiency – symptoms include feeling very tired, a sore and red tongue, mouth ulcers and pins and needles

If you take omeprazole for longer than 1 year, your doctor will regularly check your health to see if you should carry on taking it.

It's not known if omeprazole works less well the longer you take it.

If you feel like omeprazole is not working any more, talk to your doctor.

Does taking omeprazole for a long time cause stomach cancer?

There is some research to suggest that taking medicines to reduce stomach acid, like PPIs and H2 blockers, may slightly increase the chance of developing stomach cancer. It also suggested that it could be more likely in people taking them for longer than 3 years. But studies involving more people need to be done to be sure that PPIs and H2 blockers cause stomach cancer, rather than something else causing it.

PPIs, like most medicines, have side effects so it's best to take them for the shortest time possible.

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It’s also important to speak to your doctor if you notice any of these symptoms which can be signs of stomach cancer:

• having problems swallowing (dysphagia)
• feeling or being sick
• feeling full very quickly when eating
• losing weight without trying

Speak to your doctor or pharmacist if you are concerned.

What will happen if I stop taking them?

Usually, you can stop taking omeprazole without reducing your dose first.

But if you've been taking omeprazole for a long time, speak to your doctor before you stop taking it.

Stopping suddenly could make your sto
mach produce a lot more acid, and make your symptoms come back.

Reducing the dose gradually before stopping completely will prevent this happening.

How does omeprazole compare with similar medicines?

There are 4 other medicines that are similar to omeprazole. They are:

• lansoprazole
• esomeprazole
• pantoprazole
• rabeprazole

Like omeprazole, these medicines are proton pump inhibitors (PPIs). They work in the same way as omeprazole by reducing acid in your stomach.

They generally work as well, and have similar side effects as omeprazole. But they may be given in different doses.

Sometimes, if omeprazole does not work or causes side effects, your doctor may suggest that you try taking another PPI.

Are there other indigestion medicines?

There are other prescription medicines and ones you can buy to treat indigestion and heartburn.

Antacids, like calcium carbonate (Tums), sodium bicarbonate, Maalox and Milk of Magnesia, relieve indigestion and heartburn by neutralising the acid in your stomach.

They give quick relief that lasts for a few hours. They're ideal for occasional stomach acid symptoms.

Some antacids, such as Gaviscon, have an extra ingredient called alginic acid.

They work by making a lining, so juices from your stomach do not splash up into your foodpipe. They're especially good for relieving acid reflux.

Antacids are available from pharmacies and supermarkets.

Histamine antagonists (commonly called H2 blockers) reduce the amount of acid made in your stomach, but they do this in a different way from PPIs.

They include cimetidine (Tagamet) and famotidine (Pepcid).

In general, PPIs like omeprazole are used first because they're better than H2 blockers at reducing stomach acid.

But if a PPI does not work or causes side effects, your doctor may prescribe an H2 blocker.

You can buy famotidine and nizatidine without prescription from pharmacies.

Can I take omeprazole with an antacid?

You can take omeprazole with an antacid (for example, Gaviscon) if you need to.

Is the omeprazole I buy the same as on prescription?

They're the same as omeprazole tablets you get on prescription, but only adults can take them, and they can only be taken for up to 14 days. If your symptoms are no better after 14 days, you should tell your doctor as they may want to do tests or put you on a different medicine.

Will it affect my contraception?

Omeprazole does not affect any type of regular contraception including the combined pill. But it may reduce the effectiveness of one type of emergency contraception called ellaOne (ulipristal), so a different form of emergency contraceptive may be recommended instead.

If using omeprazole makes you vomit or have severe diarrhoea for more than 24 hours, your contraceptive pills may not protect you from pregnancy. Check the pill packet to find out what to do.

Find out more:

• What to do if you're sick or have diarrhoea when taking the combined pill

Can I drink alcohol with it?

It’s best to avoid alcohol if possible. Although it does not affect the way omeprazole works, alcohol makes your stomach produce more acid than normal. This can irritate your stomach lining and make your symptoms worse.

Can lifestyle changes help stomach acid?

It may be possible to ease symptoms caused by too much stomach acid by making a few changes to your diet and lifestyle:

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• maintain a healthy weight by eating healthily
• do not eat foods that can make your symptoms worse, such as rich, spicy and fatty foods, and acidic foods like tomatoes, citrus fruits, salad dressings and fizzy drinks
• cut down on caffeinated drinks, such as tea, coffee and cola, as well as alcohol and smoking
• if you have symptoms at night, try not to eat for at least 3 hours before you go to bed
• prop your head and shoulders up when you go to bed – this can stop stomach acid coming up while you sleep