peptic ulcers Flashcards
What are the two types of peptic ulcer
A peptic ulcer = an area of damage to the inner lining of the stomach (gastric ulcer) or the upper part of the duodenum (duodenal ulcer).
Compare the time course between the onset of symptoms in gastric and duodenal ulcers
o These ulcers can be distinguished based on timing of symptoms:
Gastric ulcer – pain at mealtimes when the acid is secreted.
Duodenal ulcer – pain relieved by a meal as the pyloric sphincter closes (pain starts after 2-3 hours).
o Duodenal: Gastric ulcers = 4: 1.
What is a typical presentation of peptic ulcers
Epigastric pain, burning sensation that occurs after meals
Outline the investigations that you would perform to diagnose H.Pylori infection
Carbon-urea breath test – positive
Stool antigen test – positive
H Pylori positive peptic ulcer
Describe the basis of the carbon-urea breath test
Give a urate mixture that contains a distinctive isotope of carbon
H. pylori has enzymes that can break down the urate mixture and liberate the carbon isotope
This carbon isotope is then incorporated into carbon dioxide and is breathed out – this can then be detected to confirm high levels of H. pylori
Outline the pathophysiology of a H.Pylori infection
Helicobacter pylori (H pylori)
Dissolves mucus layer in the gastric antrum
Causes epithelial cell death (due to loss of mucus protective layer which makes them more exposed to the acidity of the stomach).
Increased acidity peptic ulcer
Stomach receives a large proportion of the cardiac output- thus there is a risk of severe G.I bleeding with severe stomach ulceration- this is a medical emergency.
What is important to remember about the extent of the damage caused by H.Pylori
Dissolves the mucus layer in ‘pockets’
The whole mucuc lining isn’t obliterated- just a small portion to cause an ulcer.
Summarise the treatment plan for a patient who is suspected of having a H.Pylori infection which is causing a peptic ulcer
Amoxicillin (penicillin) & Clarithromycin (macrolide)/Metronidazole (good gram negative antibiotic)– Antibiotics
Proton Pump Inhibitor (PPI) – reduces acid production (see later)
So two antibiotics + PPI- triple therapy
What are the risk factors for acquiring H.Pylori
Risk factors for acquiring H. pylori are unknown and the methods of transmission are uncertain but could be:
o Socioeconomic conditions.
o Contact with animals and contaminated faeces.
Describe the key features of H.Pylori
Gram negative, motile, microaerophilic bacterium
Resides in human GI tract – exclusively colonising gastric-type epithelium (present commensally in 70-80% of individuals)
The fact that it is motile is important- can move around the stomach and gut to cause more ulcers.
Describe how H.Pylori can result in ulcer formation
Increased gastric acid formation – gastrin or somatostatin
Gastric metaplasia – cell transformation due to excessive acid exposure
Downregulation of defence factors - epidermal growth factor & bicarbonate production
Describe the virulence of H.Pylori
Urease – catalyses urea into ammonium chloride & monochloramine damage epithelial cells
Urease – antigenic evokes immune response- inflammation
Hence urease can cause damage both directly and indirectly
Certain virulent strains produce CagA (antigenic) or VacA (cytotoxic) – more intense tissue inflammation
These are exotoxins
CagA- antigenic and so stimulates inflammatory immune response
VacA- cytotoxic- damages cells directly.
What is important to remember about the different strains of H.Pylori
Not all of them produce exotoxins,
Describe the epidemiology of H.Pylori infections
Aim is to eliminate H. pylori which infects a lot of people (50-80% are worldwide chronically infected).
o ~100% of duodenal ulcers and 80-90% of gastric ulcers are infected with H. pylori.
Describe two ways in which H.Pylori can cause epithelial cell death
Causes epithelial cell death: exotoxins & inflammation
Increased acidity peptic ulcer
Describe the second line therapy in chronic infections with H.pylori
quinolone and tetracycline Abx instead of penicillins, especially in chronic infections; bismuth therapy is a chelating agent that can be used (or sucralfate)
Also give a PPI (omeprazole)- 4-12 weeks
Describe the K+/H+ ATPase pump in the stomach
Expressed on secretory vesicles within parietal cells
[Ca2+]i — cAMP — translocation of secretory vesicles to parietal cell apical surface H+ secretion
What two things can increase the expression of K+/H+ ATPase pumps
Ca2+
cAMP (via Gs receptors) -will then stimulated protein kinases to bring about changes (i.e translocation for more proton pumps into apical membrane).
Describe the role of proton pumps in ulcer formation
Increased activity of proton pump – H+ secretion reduction gastric pH
Summarise the actions of bismuth and sucralfate
Create an acidic environment around the stomach- less access for bacteria- they also reduce inflammation around gastric epithelium.