Dyspepsia & Peptic Ulcers Flashcards
What stimulates gastric acid secretion?
How may this occur directly and indirectly?
Acetylcholine and gastrin
Occurs directly by binding to receptors on parietal cells
Occurs indirectly by stimulation of histamine release from ECL cells
How is gastric acid secretion inhibited?
Through somatostatin and prostaglandin PGE2
How does prostaglandin PGE2 work?
It binds to a receptor on parietal cells to activate an inhibitory G protein
This inhibits activation of adenyl cyclase
This decreases gastric acid production
What are the 5 types of cells found in the crypts of gastric mucosa?
What do they secrete?
- goblet cells - mucus
- parietal cells - gastric acid
- Chief cells - pepsinogen
- D cells - somatostatin
- G cells - gastrin
What are ECL cells and what do they secrete?
enterochromaffin-like cells
They produce histamine, which promotes acid secretion
What does stimulation of parietal cells lead to?
Stimulation of parietal cells stimulates a proton pump which secretes both H+ and Cl- ions
How does the action of G cells affect acid secretion?
G cells secrete gastrin
gastrin affects the ECL cells, increasing histamine production
This causes parietal cells to produce more HCl
How does the nervous system influence parietal cells?
Enteric neurones secrete acetylcholine
This causes parietal cells to secrete more gastric acid
What are the 3 interventions to prevent acid secretion by parietal cells?
- anti-histamines
- vagotomy
- proton pump inhibitors (PPIs)
How do anti-histamines work?
They are H2 blockers
They prevent histamine secretion, which reduces secretion of HCl
What is a vagotomy?
How does this reduce gastric acid secretion?
It involves selectively cutting the nerves which supply the parietal cells through the vagus nerve
This reduces stimulation of the parietal cells through ACh
How do PPIs work to reduce gastric acid secretion?
They affect the ATPase that pushes the H+ and Cl- ions out of the cell
What is the actual mechanism which leads to gastric acid secretion by parietal cells?
- When the stimulatory hormone binds to the receptor, this activates adenylate cyclase
- this converts ATP to cAMP
- cAMP activates protein kinase A
- protein phosphorylation activates the H+/K+ ATPase
- this leads to the secretion of gastric acid
When does a peptic ulcer occur?
When there is a break in the epithelial cells of the stomach or duodenum
This penetrates to the muscularis mucosa in either the stomach or the duodenum
How common is duodenal and gastric ulceration?
It is extremely common
It affects more than 10% of the population at some time in their lives
What is encompassed by the term peptic ulceration?
What is the problem with identifying symptoms?
Peptic ulceration is a broad term that encompasses ulceration of the oesophagus, duodenum and stomach
The site of the ulcer influences the type of pain and signs associated with it
What are typical symptoms of peptic ulceration?
- belching, bloating, distention
- heartburn
- chest discomfort
- unexpected weight loss and anorexia
- nausea and vomiting
- feeling full easily
- dark stools
- epigastric pain
What are the 3 potential complications arising from peptic ulceration?
- haemorrhage
- perforation of the stomach lining
- gastric outlet obstruction
What are the 2 main causes of peptic ulceration?
- infection with Helicobacter pylori
- use of non-steroidal anti-inflammatory drugs
e. g. aspirin, ibuprofen
These risk factors are independent and additive
What are less common causes of peptic ulceration?
- Zollinger-Ellison syndrome
2. crohn’s disease
What is Zollinger-Ellison syndrome?
A tumour arises in the islet cells of the pancreas
It secretes gastrin, which increases gastric acid secretion
What is H. Pylori and where is it found?
It is a slow-growing gram-negative bacterium which colonises the mucus layer in the stomach (and can be found in the duodenum)
What does H. pylori adhere to and what damage does it cause?
It adheres to gastric mucosal cells and causes gastritis and damage to the gastric epithelium
When is H. pylori infection usually acquired?
Childhood
But in developed countries, infection is more common in older people
What is H. pylori infection generally linked to?
Poor levels of hygiene
It is more common in lower income groups, where housing conditions are poorer
What enzyme is expressed by H. pylori?
Why is this significant?
Urease which converts urea into water and ammonia
Ammonia is alkaline so helps to neutralise the stomach acid
Which toxins are expressed by some strains of H. pylori?
What are these strains associated with?
CagA and VacA
These strains are associated with higher levels of inflammation and cause more gastric ulceration
How does H. pylori cause gastric ulceration?
It expresses the toxins CagA and VacA which inflame the stomach lining
It causes infection which damages the gastric mucosa and leads to increased gastrin and gastric acid secretion
In what other ways can H. pylori affect the stomach?
it can lead to stomach cancer
It is also associated with stomach pain, bloating and nausea
What 4 tests can be used to diagnose H. pylori infection?
- blood antibody test
- urea breath test
- stool antigen test
- stomach biopsy
How do the blood antibody, stool antigen and urea breath tests identify H. pylori?
- blood antibody test sees whether the body has made antibodies against H. pylori
- urea breath test can identify H. pylori in the stomach
- stool antigen test looks for blood and H. pylori antigens
Which patients should undergo endoscopy?
Older patients who express “alarm symptoms”
e.g. higher risk of stomach cancer
What is the basic treatment for H. pylori infection?
10 days - 2 weeks of antibiotics
Such as amoxicillin
What are the antibiotics combined with for treatment of H. pylori?
A PPI (antacid)
These inhibit the H+ ATPase enzyme
What lifestyle advice is given to someone with H. pylori infection?
Avoid stress, alcohol, spicy food and smoking
What are NSAIDs?
What are they most commonly used for?
Non-steroidal anti-inflammatory drugs
They are used as minor painkillers and for the relief of inflammation
When else may NSAIDs be used?
- chronic inflammatory conditions, such as arthritis
- treatment of blood clotting disorders
- prevention of MI and stroke
What is the main side effect of NSAIDs?
Gastrointestinal bleeding
10-25% of patients on long term NSAID therapy will suffer from GI problems
What is the mechanism behind how NSAIDs work?
They inhibit cyclo-oxygenase (COX) enzymes
What is the role of cyclo-oxygenase enzymes?
They are responsible for the conversion of arachidonic acid into:
- prostaglandins
- thromboxane
- prostacyclin
What is the role of thromboxane?
It is involved in platelet aggregation (blood clotting)
What is the role of prostaglandins?
They are paracrine hormones which promote:
- inflammation
- vasodilation
- smooth muscle contraction
What is expression of COX 1 like?
It is expressed constitutively (all the time) in a range of tissues
e.g. gastric mucosa, kidney, platelets and vascular endothelial cells
What is expression of COX 2 like?
COX 2 expression is induced in monocytes and macrophages in response to inflammation
Why would a COX 2 specific NSAID be preferable to ibuprofen for long-term use?
Ibuprofen acts on COX 1 and COX 2
A COX 2 specific NSAID will target inflammation, but will not target the gut
What is the main problem with using aspirin as an NSAID?
Aspirin is more inclined to promote haemorrhage from peptic ulcers
Why is aspirin more inclined to promote haemorrhage?
Blocking thromboxane production reduces the amount of blood clotting that can occur
What are examples of H2 antagonists?
What are they used for?
Ranitidine (Zantac) and Famotidine (Pepcid)
They are available over-the-counter for common indigestion symptoms
How do H2 antagonists work?
They bind to and block the histamine H2 receptor
This suppresses acid secretion
What are examples of proton pump inhibitors?
- lansoprazole
- omeprazole
- pantoprazole
How do PPIs work?
They directly inhibit the H+/K+ ATPase which pumps H+ ions into the stomach
Why are dark stools a symptom of a peptic ulcer?
They result from bleeding from the ulcer in the upper part of the digestive system
The blood mixes with digestive fluids
Why do patients with a gastric ulcer become breathless?
What can this lead to?
Ulcers can cause hidden bleeding
This leads to symptoms of anaemia, such as fatigue and abdominal pain
What would blood tests of someone with a peptic ulcer show?
Low Hb levels due to anaemia
Raised urea due to blood proteins being digested to produce urea
Why may a kidney function test be performed on someone with a peptic ulcer?
If someone has been on long-term NSAID therapy, the kidneys may be damaged
What are the 4 types of dyspepsia?
- dyspepsia with alarm symptoms
- uncomplicated (or simple) dyspepsia
- un-investigated dyspepsia
- functional (“non-ulcer”) dyspepsia
What defines each type of dyspepsia?
Uncomplicated dyspepsia is dyspepsia without the “red-flag” features
Un-investigated dyspepsia is presenting to a physician for the first time
Functional dyspepsia has no structural cause for the symptoms at upper GI endoscopy
What are the alarm symptoms of dyspepsia?
- weight loss
- dysphagia or odynophagia
- persistent vomiting
- haematemesis or melaena
- palpable epigastric mass
- family history of gastric cancer
- dyspepsia onset over the age of 45-55 years
What is odynophagia?
Painful swallowing
What is haematemesis and melaena?
Haematemesis is vomiting blood
Melaena is dark, sticky stools containing partly digested blood
What are the main causes of dyspepsia?
- gastro-oesophageal reflux disease
- peptic ulcers
- gastric cancer
What % of people with dyspepsia have a normal endoscopy result?
80%
This is an example of functional dyspepsia
What is the prevalence and prognosis of dyspepsia?
Prevalence is 20 - 40%
40% of people experience long-term symptoms
60% of people experience resolution of symptoms
What is the treatment for dyspepsia with alarm symptoms?
Alarm symptoms warrant an urgent endoscopy
What are the 2 options for treatment of uncomplicated (simple) dyspepsia?
- test individuals for H. pylori, with eradication therapy for those who test positive
- give all patients PPIs to reduce acid secretion
Which of the 2 options for treating uncomplicated dyspepsia is preferred?
Method 1 is preferred when prevalence of H.pylori is greater than 10% of the population
If not, method 2 is preferred
What actually causes peptic ulcers?
They are not caused by a single factor
They are caused by a breakdown in the balance between the protective and defensive mechanisms
What are the 3 complications of peptic ulcers?
- perforation leads to gas under the diaphragm and leaking into the peritoneal cavity
- peptic ulcer may bleed
- pyloric stenosis
What is pyloric stenosis?
Gastric outlet obstruction leads to the pylorus/antrum being scarred with ulcers
What does pyloric stenosis lead to?
The stomach is unable to empty properly
This leads to a massively distended stomach with fluid and food debris
What usually treats perforation and pyloric stenosis?
Surgery
What usually treats bleeding?
Surgery or medication
Injection of adrenaline causes vasoconstriction
Heat can be applied to cause coagulation of the vessel
