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Peptic Ulcer Disease

Introduction

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.

Epidemiology

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+.
Duodenal
Gastric
Prevalence
10-15% of population
3-5% of population
Location
Mostly anterior of first part of duodenum (the duodenal cap)
Mostly on lesser curve and antrum
Cause
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.
 
 
 

Presentation

This will usually present with:

Investigations

Non-Invasive

Invasive

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.

Causes

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.

Pathology

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.
NSAID’s
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.
Alcohol
Affects mucosal repair mechanisms, thus increases the likelyhood of ulcer formation.
 
Smoking
Decreases prostaglandin synthesis.

Treatment

Tell the patient to stop smoking! This is a major factor in inhibiting gastric mucosal healing.
Eradication therapy
This should be commenced if:
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.
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.

Complications

Perforation

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:

Investigations

Management

Complications (of surgery)

Immediate
Early
Late

Flashcard

References

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