What are the differences between physiological reflux and pathological reflux?(GORD)
• Physiological reflux typically occurs post-prandially, short-lived, asymptomatic and rarely occur at night.
• GORD is associated with symptoms of mucosal injury and often occur at night.
What are the six factors that lead to pathological reflux?
1) Delayed gastric emptying.
2) Transient LES relaxation.
3) Decreased LES tone.
4) Decreased salivation.
5) Decreased tissue resistance (In oesophagus)
6) Impaired oesphageal clearance.
What are the two common symptoms of GORD?
1) Heartburn; most commonly occurred in post prandial period.
2) Acid regurgitation.
What is the red flag symptom of GORD? And what can it mean?
- Slowly progressive dysphagia can indicate an oesophageal stricture, Long term GORD can lead to adenocarcinoma.
Aside from heartburn, acid regurgitation and dysphagia, what are the other presenting symptoms of GORD?
Chest pain, Water brash (Excess salivating), odynophagia and nausea.
What factors are associated with GORD?
• Family History
• High BMI
What behavioural factors are associated with GORD?
• Alcohol consumption
• Prescription medication
What are the complications of GORD?
• Barrett's Oesophagus, Stricture, Cancer
• Extra-oesophageal problems (Laryngeal, respiratory problems)
What is the definition of dyspepsia?
• Pain or discomfort in the upper abdomen.
• Rome III classification -
What are the two patterns of helicobacter gastritis?
1) Pan gastritis; body and antrum associated with diminished acid output.
2) Antral gastritis; associated with increased acid output.
What is peptic ulcer disease?
A breach in the mucosal lining of the gut due to attack by acid and pepsin.
What are the symptoms of peptic ulcers?
They may be asymptomatic and not present until a complication such as a perforation has occurred.
However, symptoms may include;
- Dyspepsia, radiation to back may occur, anorexia, weight loss, fatty food intolerance.
What are the complications of peptic ulcers?
• Perforation leading to peritonitis.
• Haemorrhage, by erosion to vessel.
• Penetration of surounding organ.
What are the red flags associated with peptic ulcer disease?
• Weight loss
• Persistant vomiting
• Palpable mass or lymphadenopathy
• Unexplained iron deficient anaemia
• Family history of upper GI cancer
• Previous GI surgery
What are the five types of gastric ulcers and which two are associated with acid hypersecretion?
1) Primary gastric ulcer. Associated with diffuse antral gastritis.
2) Gastric ulcers with duodenal ulcers, most likely secondary to duodenal ulcers.
3) Prepyloric or channel ulcers.
4) Proximal stomach or gastric cardia.
5) Can occur throughout stomach. Associated with chronic NSAID use.
What are the red flag symptoms associated with dyspepsia?
Anaemia, Loss of apetite, Anorexia, Recent progressive symptoms, Malaena/hemetemesis.
• Family history
• Previous gastric surgery
What are the lifestyle changes used to treat dyspepsia?
• stop smoking, decrease alcohol, decrease caffeine, weight loss, balanced diet.
What two types of medication are used in the treatment of dyspepsia?
• Acid suppression - PPIs and H2 antagonists.
What are the symptoms of peptic ulcers?
• Weight loss, dyspepsia, anorexia, IBS
Can be asymptomatic and only present when a complication occurs (i.e. perforation)
What are the complications of peptic ulcers?
What are the symptoms of a duodenal ulcer?
• 2-5 hours after eating / empty stomach.
• Burning/hunger like pain.
• Radiation to back.
What is the presentation of a gastric ulcer?
Severe pain after meals and less frequently relieved by antacids than duodenal ulcers.
What are the causes of peptic ulcers?
• Male > Femal
• Helicobacter pylori
Why does the longterm use of NSAIDS increase the risk of peptic ulcers?
Reduces COX1 levels in mucosa which in turn reduces the levels of prostaglandins.
The risk is further increased if elderly/comorbities.
How does Helicobacter pylori increase the risk of peptic ulcers?
• Pan gastritis, decreases acid production leading to GU/cancer.
• Antral gastritis, increases acid production causing DU.
What drugs are used to treat peptic ulcers?
•PPIs - Inhibits the transport of H+ from the parietal cell.
- Promotes ulcer healing and reduces symptoms and chance of recurring.
• H pylori erradication-
- Buffer with antacids.
- Reduce H+ secretory stimuli; H2 antagonists, Anticholinergics, Gastrin antagonists.
Which four secretory cells are present in the body of the stomach and what do they secrete?
1) Parietal cells - Acid, intrinsic factor.
2) Chief cells - pepsinogens
- Initiate protein breakdown/break peptide bonds.
3) Mucous cells - In neck of gland, mucous.
4) Endocrine cells - Histamine.
What seceretory cells are present in the antrum of the stomach and what do they secrete?
1) Chief cells - Pepsinogens
2) Endocrine cells-
- G-cells - Gastrin
- D-Cells - Somatostatin
At what pH is optimal pepsin activity?
What are the four stages of gastric secretion?
1) Basal (Background always present)
What occurs during the cephalic stage of gastric secretion?
• Smell/Sight/Taste, stimulates the vagus nerve.
• The vagus nerve causes increased ACh secretion leading to;
- Parietal H+ release
- Histamine release
- Antral G cells release gastrin (Stimulated by GRP)
• The vagus nerve also inhibits the release of somatostatin from D-cells.
What occurs during the Intestinal phase of gastric secretion?
Protein digestion products stimulate intestinal G and Endocrine cells to release, Gastrin and 'Entero-oxyntin', respectively.
This stimulates the parietal cells to secrete H+.
What three layers make up the gastroduodenal mucosal defence?
1) Mucous HCO3 layer.
2) Surface epithelial cells.
3) Microvascular system within sub-mucosa.
How does the mucous HCO3 layer of the gut protect it?
• Physiochemical barrier.
• 95% water and glycoproteins/lipids.
• HCO3 secreted by epithelial cells.
• Results in pH 1-2 at luminal surface but 6-7 at epithelial surface.
How do the surface epithelial cells protect the gut?
• Mucous production
* Tight junctions
• Epithelial cells migrate to injury sites in order to repair damaged area.
How does the microvascular network in the submucosa help to protect the gut lining?
• Provide HCO3.
• Takes away toxic metabolites.
• Micronutrient and oxygen supply.
What role do prostaglandins play in the defence and repair of the gastric epithlium?
• Regulate release of HCO3 and mucous.
• Maintain mucosal blood flow.
• Cell restituion.
What is the production pathway of prostaglandins?
• Phospholipds are converted by phospholipidase A2 into Arachadonic acid.
• This is then converted by COX (cyclooxygenase) into prostaglandins.
How do NSAIDS inhbit the production of prostaglandins?
• They inhibit COX.
There are two forms of COX, what are they and where are they located?
1) COX1 - expressed in stomach, platelets, endothelium and kidneys.
2) COX2- inducible by inflammatory mediators.
What is Zollinger Elison syndrome?
• Gastrin secreting pancreatic adenoma.
- Leading to high gastric acid secretion
- Treated with PPI.
How Helicobacter Pylori cause PUD?
• Causes Antral inflammation.
- Antral D cells produce less somatostatin.
- Antral G cells produce more gastrin.
- Increased acid production.
There are two stages to oesophageal peristalsis, what are they and how are they initiated?
1) Primary - initiated by swallowing.
2) Secondary - initiated by distension of the oesophagus.
What are the epithelial changes that occur with Barrett's Oesophagus?
• Squamous epithelium of the oesophagus is replaced by specialised columnar intestinal epithelium.
What form of cancer is a complication of Barrett's Oesophagus?
Which three receptors on parietal cells are responsible for driving Proton pumps?
1) H2 receptor
2) M3 receptor
3) CCK2 receptor
There are five mechanisms that are targeted for the treatment of GORD/PUD, what are they and what are the drugs used?
1) Neutralise acid - Antacids
2) Reduce irritancy of acids - Alginates
3) Promote mucosal defence - Sucralfate, misoprostol
4) Gastric stimulants - Domperidone, Metoclopramide
5) Reduce acid secretion - PPIs, H2 antagonists
How do alginates work?
They increase the viscosity of the stomach contents, some produce a 'raft' which helps to reduce the symptoms of reflux.
What are some of the side-effects of alginates and antacids?
• Constipation (Aluminium)
• Diarrhoea (Magnesium)
• Interfere with medication (reducing absorption)
What are the indications for sucralfate?
• Treatment of gastric and duodenal ulceration.
• Prophylaxis of stress ulceration.
What is the mechanism of sucralfate?
• Protects damaged mucosa.
• Stimulate local production of prostaglandins and bicarbonate.
What are the side effects of sucralfate?
What is Misoprostol and what is it's mechanism of action?
• A prostaglandin analogue, binds to the prostaglandin receptors on the parietal cell to decrease H+ secretion.
What are the side-effects and contraidications of Misoprostol?
• Constipation and abdominal pain.
• Pregnant women or women of child-bearing age.
What is the mechanism of action of the gastric stimulant drugs and give two examples.
• Increases peristalsis in the duodenum and jejenum, thought to be due to the stimulation of muscarinic receptors in the GIT.
• Domperidone and metoclopramide.
What are the indications for use of a H2-receptor antagonist?
• GORD symptoms.
• Treatment of peptic ulcer disease.
• High-dose used in Zollinger-Ellison syndrome.
Give four examples of a H2 receptor antagonist.
What is the mechanism of action for H2-receptor antagonists?
Bind competively and reversibly to H2 receptors, supressing acid production.
They also interfere with gastrin and ACh mediated gastric secretion.
What are the side effects of H2 receptor antagonists?
• Diarrhoea, confusion, headaches, constipation, hallucinations.
What are the indications for the use of PPIs?
• GORD symptoms.
• Prevention and treatment of NSAID-induced ulceration.
• H.Pylori eradication (With ABx)
• Zollinger-Ellison Syndrome.
• Stress ulceration prevention, in critical care patients.
Give four examples of PPIs.
What are the side effects of PPIs?
• Rash, Headache, Nausea and Diarrhoea.
What is the typical dose of Omperazole for a patient woth GORD?
• 40mg od for four weeks, followed by a maintaince dose of 20mg od.
Give two treatment regimes for H.pylori erradication.
1) •Omeprazole 20mg bd
• Amoxicillin 1g bd
• Clarithromycin 500mg bd
2) • Omperazole 20mg bd.
• Clarithromycin 250mg bd.
• Metronidazole 500mg bd.
What are some of the long-term risks associated with PPIs?