Gastric Acid Secretion, H. pylori and Ulceration Flashcards
Why is it necessary for gastric secretions to be acidic?
- Acid necessary for:
- Digestion of food
- Iron absorption
- Killing pathogens
What are the protective gastric secretions?
What are the consequences of disruption of this protective layer?
-
Mucous secreting cells:
- Trap bicarbonate ions (alkaline)
- Creates gel-like barrier
- Important protective layer
-
Prostaglandins locally produced:
- Stimulates secretion of mucous and bicarbonate
- Dilate mucosal blood vessels
- Cytoprotective
- If disturbance in protective layer or secretions PLUS acid - risk of GORD and peptic ulcers.
- Many NSAIDs disturb these protective functions (inhibit COX1 - enzyme responsible for synthesis of prostaglandins) therefore increase risk.
Which cells secrete HCl and intrinsic factor?
Parietal / oxyntic cells
Which cells secrete proenzymes e.g. prorenin and pepsinogen?
Chief / peptic cells
How much gastric juice is secreted per day?
2.5L
What are the 3 gastric endogenous secretagogues?
- Gastrin
- Acetylcholine
- Histamine
Describe the secretion and action of gastrin.
- Gastrin is a polypeptide hormone.
- Gastrin is secreted by gastrin cells (G cells).
- Located in the gastric antrum and duodenum.
- Proteins in food have astrong effect on the gastrin cells.
- Gastrin is released into the blood.
- Stimulates secretion of acid by parietal cells (through the proton pump).
- Also increases pepsinogen secretion - stimulates blood flow and increases gastric motility.
Describe the secretion and action of gastrin.
- Released from neurons.
- Stimulates muscarinic receptors on surface of parietal cells and histamine containing cells.
Describe the secretion and action of histamine in the stomach.
- Mast cells lying close to parietal cells release histamine.
- Histamine released increased by gastrin and acetylcholine.
- Acts on parietal cell H2 receptors.
What is Helicobacter pylori?
What diseases is it associated with?
- ~50% of the world population is infected with H. pylori.
- Causative factor in gastric and duodenal ulcers.
- Risk factor for gastric cancer (adenocarcinoma).
- Strong link with MALT lymphoma.
- Additional associations:
- Dyspepsia
- Atrophic gastritis
- Iron deficiency anaemia
- Idiopathic thrombocytopaenic purpura
By what mechanism can H. pylori colonise the gastric mucosa?
- Urease produced by the organism raises the gastric pH, allowing it to colonise.
Describe acute infection with H. pylori.
- Can cause acute infection with symptoms that include nausea, dyspepsia, malaisa and halitosis.
- Acute infection tends to last ~2 weeks.
- Gastric mucosa is inflamed with neutrophils and inflammatory cells with marked persistent lymphocyte penetration.
Describe chronic infection with H. pylori.
- Local inflammation and gastritis.
- Outcome depends on:
- Pattern of inflammation
- Host response
- Bacterial virulence
- Environmental factors
- Patient age
Define dyspepsia.
Pain or discomfort centred in upper abdomen, exacerbated by food.
Define GORD.
Reflux of gastric contents into oesophagus, heartburn, regurgitation, odynophagia, cough, associated water-brash.
What advice would you offer a patient with dyspepsia or GORD?
- Offer simple lifestyle advice:
- Healthy eating
- Weight reduction
- Smoking cesation
- Avoid known precipitants:
- Alcohol
- Coffee
- Chocolate
- Fatty foods
- Raising the head of the bed and not eating directly before going to bed can also help.
What medications can be considered when dealing with dyspepsia and GORD?
- STOP NSAIDs where appropriate / applicable.
- Consider over the counter remedies:
-
Antacids - directly neutralise acid and inhibit activity of peptic enzymes.
- Salts of magnesium and aluminium
- E.g. Maalox, Mucogel
-
Alginates - taken in combo with antacid (varying amounts), increases viscosity and adherence of mucus to oesophageal mucosa; some form a raft.
- E.g. Gaviscon
-
Simeticone - antifoaming agent (helps bloating, flatulence).
- E.g. Infacol
-
Antacids - directly neutralise acid and inhibit activity of peptic enzymes.
- Consider H. pylori testing
What are the common tests for diagnosis of H. pylori infection?
- Proton pump inhibitors should be stopped 2 weeks, and ABx 4 weeks, before diagnostic tests are conducted.
What should be done following treatment of H. pylori if eradication has been successful?
And if eradication has been unsuccessful?
What is the first-line treatment for H. pylori?
- Offer patients who test positive for H. pylori a 7-day, twice-daily course of treatment with:
- PPI
- Amoxicillin
- Either clarithromycin or metronidazole
- Offer patients who are allergic to penicillin a 7-day, twice-daily course of treatment with:
- PPI
- Clarithromycin and metronidazole
- Offer people who are allergic to penecillin and who have had previous exposure to Clarithromycin a 7-day, twice-daily course of treatment with:
- PPI
- Bismuth
- Metronidazole
- Tetracycline
What are PPIs used to treat?
- Peptic ulcer disease
- Reflux oesophagitis
- One component of H pylori eradication and Zollinger-Ellison syndrome
Describe the action of a PPI.
- Block K+H+ATPase (proton pump) of gastric parietal cells, reducing gastric acid secretion.
- The first was Omeprazole - inhibits K+H+ATPase irreversibly.
- Drug is weak base and accumulated in acid environment of the canaliculi of the stimulated parietal cell.
- Usually oral administration.
What are the adverse effects of PPIs?
In which conditions is PPI use cautioned?
- Relatively uncommon:
- Headache
- Diarrhoea
- Rashes
- Dizziness
- Somnolence
- Confusion
- Abdominal pain
- Constipation
- Dry mouth
- GI disorder
- Gynaecomastia
- Caution in liver disease, severe renal insufficiency, pregnancy, breast feeding, risk of osteoporosis.
- May mask the symptoms of gastric cancer, may increase risk of GI infections.
What is depicted in this endoscopy photograph?
Ulcer of the mucosa on / adjacent to acid environment. Most common in stomach or proximal duodenum.
How are peptic ulcers formed?
- Can be associated with infection of gastric mucosa with H. pylori.
- Imbalance between mucosal-damaging and mucosal-protecting factors:
- Acid
- Pepsin
- Mucus
- Bicarbonate
- Prostaglandins
- Nitric oxide
What are the symptoms of peptic ulcer disease?
- Burning epigastric pain
- May be partially relieved by antacids and related to meal times
- DU pain - worse at night and when hungry
- Nausea
- Heartburn
- Flatulence
- Perforation / haemorrhage / bleeding
Describe the appropriate management of peptic ulcer disease in adults.
What is the initial treatment for peptic ulcer disease?
-
H. pylori positive
- Offer H. pylori eradication if peptic ulcer disease and H. pylori positive.
-
NSAID-associated ulcers
- Stop the use of NSAIDs where possible.
- Offer full-dose PPI or H2RA therapy for 8 weeks and, if H. pylori is present, subsequently offer eradication therapy.
-
H. pylori negative; no NSAID use
- Offer full dose PPI or H2RA therapy for 4-8 weeks.
What are Histamine H2 receptor antagonists used to treat?
State their mechanism of action.
- Clinically used for peptic ulcers and reflux oesophagitis.
- Competitively inhibit histamine actions at all H2 receptors.
- Inhibit histamine-, gastrin- and acetylcholine- stimulated acid production.
- Pepsin secretion also falls with reduction in volume of gastric juice.
Give examples of H2 receptor antagonists.
- Ranitidine (approximately 50% bioavailability, half life 2-2.5 hours, renal excretion).
- Cimetidine (>60% bioavailablilty, half life 2 hours, renal excretion).
- Usually given orally
- Low dose available over the counter
What are the adverse effects of H2RA?
More specifically, of Cimetidine?
-
Side effects are rare
- Diarrhoea
- Constipation
- Dizziness
- Muscle pains
- Alopecia
- Transient rashes
- Hypergastrinaemia
- Ranitidine is the better tolerated of the two
-
Cimetidine
-
Can interact with androgen receptors
- Gynaecomastia in men
- Decreased sexual function
- Inhibits cytochrome P450
- Slows the metabolism (and potentiates action) of range of drugs e.g. oral anticoagulants and tricyclics
- Confusion in the elderly
-
Can interact with androgen receptors
What should you do with a patient who has undergone treatment but still has an unhealed peptic ulcer?
- Exclude non-adherence, malignancy, failure to detect H. pylori, inadvertent NSAID use, other ulcer-inducing medication and rare causes such as Zollinger-Ellison syndrome or Crohn’s disease.
