Peptic Ulcer Disease
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The term ‘peptic ulcer’ refers to ulcer found in the lower oesophagus, stomach and duodenum. Rarely, they can occur in the jejunum and ileum (usually after surgery).
They are caused by infection with Helicobacter Pylori. It is thought that H. Pylori is transmitted through close social contact with an infected individual, and infections are associated with poor levels of sanitation. In some parts of the world, H. Pylori is endemic.
Peptic ulcers are more common than men in women, and duodenal ulcers are 2-3x more common than gastric ulcers.
They can present with upper abdominal pain and vomiting, and occasionally with iron deficiency anaemia. Up to half of cases are asymptomatic.
The diagnosis depends on the detection of H. pylori. This can be done by either a urea breath test, blood test for IgG against H. pylori and a stool test for H. Pylori. The breath test is the most accurate, but also the least convenient to perform and requires the longest period off PPI therapy.
Uncomplicated cases can be easily treated with triple therapy – a combination of proton pump inhibitors (PPIs) and antibiotics. Perforation is a serious complication that carries a 25% mortality, and results from an ulcer that erodes all the way through the stomach or duodenum.


DU’s are 2-3x more common than GU’s. Their prevalence is decreasing in young populations and increasing in older populations, particularly in older women. They are more common in Scotland and northern England than in the rest of the country.
Both types of ulcer are more common in men than women, DU’s; 2-5:1 (depending on geographical location), GU’s; 2:1.
Some books divide gastric ulcers into type I and type II. Type I are found in the body of the stomach, and type II are in the pylorus and the antrum.
Type I are the ones that often lead to gastric bleeding, and these are more likely to cause pain upon eating (rather than when hungry).
Prevalence and incidence increases with age. Peak incidence is 25-50 years, except for type I gastric ulcers, which are 50+.
10-15% of population
3-5% of population
Mostly anterior of first part of duodenum (the duodenal cap)
Mostly on lesser curve and antrum
Action of pepsin and / or acid on a normal abrasion in the duodenum, with abnormal healing. Increased acid and pepsin as a result of H. Pylori causing a depletion of Somatostatin reserves and a loss of natural feedback of acid production. Decreased bicarbonate secretion in duodenum ; possibly an effect of nitrates produced by of H. Pylori.
H. Pylori induced pangastritis, resulting in reduced effectiveness of gastric mucosal repair mechanisms.


This will usually present with:
  • Abdominal pain in the epigastric region. For DU’s, the pain is when you are hungry, and GU’s the pain is when you eat. This is because when you are hungry, you produce acid in anticipation of food (the cephalic phase), which is then washed straight into the duodenum and isn’t buffered. When you eat, the food buffers the acid, and so the pain is reduced. In GU, the pain is greater when you eat due to the physical pressure of food on the ulcer. DU pain is present at night as well as in the day.
  • Nausea may accompany the pain, and although vomiting is infrequent, it will often relieve the pain.
  • Weight loss may be present, particularly in gastric ulcers.
  • Left untreated, the symptoms of DU follow a spontaneous relapse and remission course
  • Examination is not always that helpful, as there is nearly always general tenderness in all dyspepsia’s.
  • History of NSAID’s / alcohol / steroids


  • Urea breath test to test for presence of H. Pylori
    • Patients will swallow urea that is labelled with an uncommon isotope – i.e. carbon 13 or 14. Usually Carbon 113 is used as it is non-radioactive. Then 10-30 minutes later, a breath sample is taken to measure the amounts of exhaled carbon dioxide containing the labelling isotope. The sample is measured using a mass-spectrometer, which is expensive, but is highly sensitive (97%) and specific (96%). This indicates that the urea has been split up and the carbon absorbed by the body. The urea is split by the enzyme urease which is present in H. Pylori, and thus this indicates the presence of H. Pylori.
    • Often a baseline sample of carbon dioxide is taken before the labelling isotope is given and then the two results compared.
    • There are also urea splitting bacteria in the colon that will cause the labelled carbon to be present in exhaled air about 5 hours after ingesting the urea.
  • Serological tests for IgG. These are useful for confirming the presence of H. Pylori, but not as accurate as the breath test. It is about 90% specific. It can take over a year for IgG levels to fall below 50% of their original value even after H. Pylori eradication, so this is not a useful test to see if the infection has been eradicated. Antibodies can also be found in the saliva, but these are nowhere near as accurate as serology.
  • Stool test. This is a highly sensitive (96%) and specific (97%) immunoassay that will detect the presence of H Pylori, and can also be used to see if H Pylori has been eradicated. PPI’s must be stopped one week before the test for eradication. This is now often the first line test.


  • Endoscopy. (OGD) This will confirm the presence of an ulcer by sight, but a sample of gastric mucosa may also be taken. This can be tested in three ways:
    • Put in a urea solution containing Phenol red. If H. Pylori is present, then the urea will be rapidly split to release ammonia, and the solution will increase in pH and change colour. This is known as the rapid urease test.
    • Cultured and tests against various antibiotics
    • Looked at histologically.
  • FBC – to check for anaemia
  • U+E – rarely shows up Zollinger-Ellison syndrome
  • Faecal occult blood
  • Barium meal test – sometimes used in patients who are unable to tolerate endoscopy.
In patients under 55, with typical symptoms, then a positive test for H. Pylori will allow the commencing of treatment for peptic ulcer.
In patients over 55, an endoscopy is required, and the non-invasive tests may be skipped in preference of endoscopy if the symptoms match up. The ulcer will then be biopsied.
In any patient with red flag symptoms, then an urgent endoscopy is required.
It is important to remember that H. pylori status should not affect your choice of diagnosis regarding gastric cancer – i.e. don’t let H pylori make you always think its an ulcer, there may also be co-existing malignancy.


Helicobacter Pylori
It is a spiral shaped Gram negative urease secreting bacteria.
10-15% of the UK population are infected. Infection rates increase with age, and it infects about 50% of the over 50’s. Infection in the developing world is much more common, with up to 90% of the general population infected. Its presence is associated with low socio-economic status. The majority of these infections are asymptomatic and do not cause any problems. About 15% of those (worldwide) who are infected with H. pylori will develop a peptic ulcer.
80-90% of duodenal ulcers (DU) and 70% of gastric ulcers are attributed to H. pylori.
The mode of transmission is unclear, but it is thought to be oral-oral or faecal-oral. It is thought that most infections are acquired during childhood – and thus the higher infection rates in the older population could be due to poor hygiene in the past.
The bacterium has lots of flagella at one end that allow it to burrow through the mucous layer and adhere to the epithelial surface. Here the pH is close to neutral, but the bacteria’s production of urease leads to the formation of ammonia which also helps to neutralise any other acid; either between its two membrane layers or around the bacterium.
H. pylori only colonises gastric type mucosa and will only be found in the duodenum in association with patches of gastric metaplasia.
It mostly affects the antrum of the stomach.
Note how the bacterium converts human urea to ammonia using its own enzyme urease, to neutralise the acid around itself.
The mucosa will appear reddened under endoscopy, and histologically there is epithelial damage. The main cytokines are IL-6 and IL-8. These will recruit inflammatory cells to the site.
The bacteria will cause chronic gastritis buy provoking an inflammatory response in the gastric epithelium. Host genetic factors are also important – e.g. those who produce more interleukin-1β as part of their inflammatory response are more likely to suffer from gastric atrophy and as a result gastric carcinoma and other pathologies are more likely.
H. Pylori releases a protein called vacA, which affects host cells by causing an efflux of micronutrients, and increasing cell permeability. It will also cause large vacuoles to form inside cells, and possibly lead to apoptosis.
In most people, H. Pylori infection will cause depletion of somatostatin from the D cells of the stomach. This is the chemical that is normally released when the pH is very low in the stomach to prevent further acid secretion. It reduces the amount of histamine and gastrin released. This occurs because the bacteria sits very close to the pH ‘sensors’ in the stomach, and the ammonia it produces raise the pH around the sensor, so the feedback mechanisms think that pH is higher than it actually isThus the normal feedback mechanism to reduce acid secretion is lost.
This causes hypergastrinaemia, and leads to excessive acid production by the stomach. In the majority of cases this will have no clinical consequences but in others (perhaps smokers) this effect is exaggerated, and ulceration of the duodenum may result. It is thought that smoking impairs gastric mucosal healing. Genetic factors are also thought to be important – for example, those of blood group O, and who do not secrete blood group substances in their saliva are more likely to get DU’s.
Bicarbonate secretion in the duodenums is reduced by H. Pylori infection
In gastric ulcers, H. Pylori infection will cases pangastritis –gastritis of the body and antrum of the stomach. In GU, acid production is often normal or low, and the ulcer will be caused by reduced resistance of the mucosa to acid and pepsin. Local epithelium is damaged by cytokines released by H. Pylori, and there is abnormal mucus production.
In about 1% of people, this pangastritis will lead to gastric atrophy and hypochlorhydria. This can allow H. Pylori to proliferate, and the subsequent production of mutagenic nitrates from normal dietary nitrates and this is a predisposing factor for gastric cancer.
Remember that pepsin only works in acidic conditions (works best about pH 3.5). Mucus normally protects the stomach from its action, and bicarbonates normally protect the duodenum. In H. pylori infection, both these factors are affected. Thus, when PPIs are given they reduce the acidity of the stomach, and thus reduce the action of pepsin, allowing the ulcer to heal.
H. Hpylori sits in the stomach under the mucous layer, right next to sensors of acid. So, these sensors actually don’t think the stomach is very acid due to the fact H. Pylori is constantly making a little alkaline cloud around itself, and so they send the instruction for more acid to be produced – thus causing the excess acid seen in 99% of cases of H. Pylori infection.


Normal erosions occur in the stomach and duodenum all the time. These just affect the superficial epithelium. An ulcer will affect as far down as the muscularis mucosae and it will have a fibrous base. They will be an exceptionally large amount of inflammatory cells.
Only very occasionally are ulcers seen without the presence of H. Pylori – one example being in the case of Zollinger-Ellison syndrome. This is a rare condition caused by tumours in the head of the pancreas or in the duodenum. The tumours are called gastrinomas, and will release large amounts of gastrin. This makes the stomach produce large amounts of acid, leading to profound ulceration. Ulcers are found in 95% of patient’s with Zollinger-Ellison.
In about 50-66% of patients the tumours will be malignant. In these patients there will usually be many ulcers of the stomach and duodenum. If these ulcers do not respond to treatment, then you may suspect Zollinger-Ellison, although usually they will have presented previously with symptoms such as; sever abdominal pain, diarrhoea, and haematemesis.
  • These are usually held responsible for the ulcers where H pylori infection is absent (about 25%). They inhibit cyclo-oxygenases (COX), which are enzymes that enable the production of prostanoids (prostaglandins and thromboxanes). There are 3 variants of COX, 1,,& 3. COX-1 is involved with protection of the gastric mucosa, and it is sometimes called the ‘housekeeping’ enzyme, due to its role in every day wear and tear repair.
  • Ultimately, NSAID’s inhibit prostaglandin formation and so reduce the ability of the stomach to heal itself. Small abrasions to the lining of the stomach that occur all the time, and would normally heal are now less likely to heal. Pepsin may also act on these abrasions, and ulceration may possibly occur.
  • The major repair pathways that prostaglandins affect are:
    • Bicarbonate secretion into the mucous layer
    • Tight junction maintenance between gastric cells to prevent lumen contents getting between the cells
    • Gastric bloodflow – delivering lots of bicarbonate ions to buffer to acid to the gastric cells.
  • Taking long term aspirin makes you 3x as more likely to get an ulcer, and other NSAID’s have a similar effect. Take them both together and your risk is 10x greater!
You need more than one factor to cause ulceration. NSAID’s on their own are unlikely to cause ulceration, but combined with increased acid production and pepsin activity (probably as a result of H. Pylori) an ulcer may form. Pepsin will potentiate, but not initiate ulcer formation.
Affects mucosal repair mechanisms, thus increases the likelyhood of ulcer formation.
Decreases prostaglandin synthesis.


Tell the patient to stop smoking! This is a major factor in inhibiting gastric mucosal healing.
Eradication therapy
This should be commenced if:
  • The patient is under 55 and has tested positive for H. Pylori
  • The patient is over 55 and testes have confirmed a gastric ulcer is responsible for their symptoms.
  • The patient has no significant underlying pathologies (e.g. cancer) but H. Pylori is present. This is slightly controversial as it has been implicated in GORD, but it is still recommended.
If PPI’s are used alone to treat ulcers, then the ulcer will normally recur within a year.
Proper eradication therapy is effective in 90% of patients. In developed countries, recurrence is about 1%. In the developing world, it is >50% due to high resistance rate and poor compliance.
  • First line therapy – Triple therapy – patients will be treated with a proton pump inhibitor, and two antibiotics. An example would be:
  • Omeprazole 20mg + metronidazole 400mg + clarithromycin 400mg  All twice daily.
  • Omeprazole 20mg + metronidazole 400mg + amoxicillin 1g  All twice daily.
  • There is very high resistance for metronidazole (25%) and that is why another antibiotic is taken.  This regimen should be followed for 7 days, and then a PPI taken for a further 3-4 weeks.
Second line therapy – Sometimes Tripotassium dicitratobismuthate may be taken (bismuth chelate). This will bind to the base of the ulcer and stimulate prostaglandin secretion. It is often used in conjunction with two antibiotics, and it will blacken the tongue and stools. Ranitidine is the name of a bismuth containing compound.
PPI’s have generally superseded the use of H2 receptor agonists. The most commonly used PPI is omeprazole. Most of the PPI have similar efficacy, but omeprazole is by far the cheapest. Omeprazole should not be given with warfarin.
A treatment is judges ‘successful’ if the symptoms no longer persist. If they do, then a check for H. pylori eradication should be carried out. Patients with gastric ulcers should be re-endoscoped six weeks after successful therapy to check for gastric cancer.
If both the first and second line therapies fail, then the patient can either try again with a triple therapy, try a quadruple therapy (2 AB’s, bismuth and a PPI) or they can take long term acid therapy.
Patients with gastric ulcers should be re-endoscoped six weeks after successful therapy to check for gastric cancer.


  • Perforation
  • Haemorrhage – this is a result of an ulcer being in an ‘unlucky’ place, and as it gets deeper, it comes across a blood vessel. This can be quite serious if it is a relatively major vessel, and result in anaemia.
  • Penetration of adjacent organs
  • Anaemia
  • Malignancy


Duodenal ulcers are more likely to perforate than gastric ulcers, and it is usually ulcers on the anterior wall of the duodenum that perforate. Perforation is often the first sign of an ulcer – there may have been no previous symptoms.
Presentation – Perforated Peptic Ulcer
This will usually present with:
  • Sudden onset severe abdominal pain. At first pain may be localised to the upper abdomen, but it quickly spreads and becomes generalised.
  • If the pain radiates to the back, then it is likely to be a posterior duodenal ulcer.
  • Localised or generalised peritonitis. Very tender to the touch. You can tell if someone has peritonitis as opposed to a different cause of abdominal pain because if they have peritonitis they will want to lie very still, but with other causes of pain, they may ‘writhe’ around in pain.
  • Signs of SIRS (systemic inflammatory response syndrome).
  • Breathing will be shallow due to diaphragmatic pain and shock.
  • The abdomen will be immobile with board like rigidity.
  • Bowel sounds are absent, and the dullness over the liver may not be there due to the prescence of gas in the abdominal cavity
  • After a few hours, the initial symptoms may die down, but there will still be the rigidity. Over a longer period of time, the patien’s condition will deteriorate due to peritonitis.
  • Perforation has a mortality rate of 25% – this is dependent on the patient’s age and other factors.
  • The main problem with a perforated ulcer is that it will cause peritonitis.


  • X-ray may show gas under the diaphragm (in about 50% of cases)– pneumoperitoneum – shown below by the distinctive lines underneath the diaphragm. Don’t get this confused with air in the stomach, which is perfectly normal and most commonly seen after a recent meal. It is important when taking an x-ray like this that the patient has been sat upright for at least 10 minutes beforehand and is sat upright when the x-ray is taken Otherwise you will not be able to see any air! Sitting like this may be uncomfortable for the patient.


  • After resuscitation then the perforation will be treated surgically – it will be closed by being sewn up, and then part of the greater omentum may also be sewn over the affected area – the omentum is still attached to the rest of itself! If this is not possible, then a pyloroplasty may be made from the perforation.
  • A pyloroplasty is where the pyloric sphincter of the stomach is widened. It allows quicker emptying of the stomach in people at high risk of PUD and is sometimes performed before an ulcer has perforated. In this case it is performed because sealing up the perforation is too difficult, and it is a treatment that may have beneficial effects for the patient by reducing the risk of future ulcers.

Complications (of surgery)

  • Peritonitis
  • Chest infection from aspiration during intubation
  • Wound infection
  • Adhesions. These can occur years after surgery and will ofte4n cause obstruction of the bowel. They are much lea common with key hole surgery than with open surgery – probably due to the reduces physical moving of the bowel by this type of surgery.
  • Keyloid scarring – this is where a big thick scar develops over the site of the incision and is virtually impossible to get rid of. You can get rid of it by cutting it off, but it is very likely to grow back again just the same.



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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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