06-02-23 - Treatment of Peptic Ulceration and Inflammatory Bowel Disease Flashcards
Learning outcomes
- Describe the physiology of gastric acid production
- Describe the pathogenesis and clinical features of Helicobacter infection
- Describe the therapeutic approach to managing dyspepsia, GORD and peptic ulceration
- List the main drugs used to treat peptic ulceration
- Describe inflammatory bowel disease
- List the main drugs used to treat inflammatory bowel disease
What 3 processes are gastric secretions needed for?
- 3 processes gastric secretions are needed for:
1) Digestion of food
2) Iron absorption
3) Killing pathogens
What are 2 protective mechanisms against gastric secretions?
What are 3 functions of each?
What 2 things can occur if there is a disturbance in protective layer / secretions and acid?
What drugs can disturb these protective functions?
How do they do this?
- 2 protective mechanisms against gastric secretions:
1) Mucous secreting cells
* Trap bicarbonate ions (alkaline)
* Creates gel like barrier
* Important protective layer
2) Prostaglandins locally produced
* Stimulates secretion of mucus and bicarbonate
* Dilate mucosal blood vessels
* Cytoprotective (cell protection)
- If there is a disturbance in the protective layer / secretions and acid, this increases the risk of GORD and or ulcers
- GORD Is gastric oesophageal reflux disease
- Many NSAIDs disturb these protective functions (inhibit cyclo-oxygenase-1; enzyme responsible for synthesis of prostaglandins) i.e. increase this risk
What are the 4 different cell types in gastric glands?
What volume of gastric secretions are produced every day?
- 4 different cell types in gastric glands:
1) Surface epithelium
2) Mucous neck cells
3) Oxyntic (parietal) cells
* Produces Hydrochloric acid (HCl) and Intrinsic factor (needed to absorb B12)
4) Peptic (aka chief) cells
* Produces Proenzymes e.g. prorenin and pepsinogen (proenzyme for pepsin)
- 2.5L of gastric juice are produced a day
Where is HCl produced in Oxyntic (parietal) cells?
- HCl is produced in Villus like projections
- Secretions then go from the Villus like projections to the canaliculi, then into the stomach contents
What pump is involved in the formation of HCl in the gastric parietal cell?
Describe the 3 steps in HCl formation in the gastric parietal cell
- HCl formation in the gastric parietal cell involves a proton pump (K+H+ATPase)
- 3 Steps in HCl formation in the gastric parietal cell:
1) K+ is actively pumped into the cell from the interstitial fluid and exchanged for H+ using a proton pump (K+H+ATPase)
2) The breakdown of water and CO2 forms bicarbonate, which is exchanged for Cl- using an antiporter
3) The H+ and Cl- combine to form HCl outside of the parietal cell
What is a secretagogue?
What are 3 gastric secretagogues?
Where are they released from?
What effect do they have on other structures?
- A secretagogue is an agent that promotes the secretion of hormones, neurohormones, chemical neurotransmitters, enzymes, or other molecules synthesized and secreted by cell
- 3 gastric secretagogues:
1) Gastrin (polypeptide hormone)
* Gastrin is secreted by gastrin cells; G cells located in the gastric antrum and duodenum
* Proteins in food have a strong effect on the gastrin cells
* Gastrin is released into the blood and stimulates secretion of acid by parietal cells (through the proton pump)
* Also increases pepsinogen secretion – stimulates blood flow and increases gastric motility
2) Acetylcholine (neurotransmitter)
* Released from neurons
* Stimulates muscarinic receptors on surface of parietal cells and histamine containing cells
3) Histamine
* Histamine release increased by gastrin and acetylcholine
* Acts on parietal cell H2 receptors
What is Helicobacter Pylori (H.pylori)?
How is it thought to cause infection?
What % of the world’s population is infected with H. pylori?
Does it always cause disease?
- Helicobacter Pylori (H.pylori) is a gram-negative, microaerophilic, spiral bacterium usually found in the stomach.
- Its helical shape is thought to have evolved in order to penetrate the mucoid lining of the stomach and thereby establish infection
- About half of the world population is infected with H. pylori
- H. pylori infection is not always symptomatic/causing problems, and can become commensal
What are 8 H. pylori associations?
- 8 H. pylori associations:
1) Causative factor in gastric and duodenal ulcers
2) Risk factor for gastric cancer (adenocarcinoma)
3) Strong link with MALT (Mucosa Associated Lymphoid Tissue) Lymphoma
4) Gastro-oesophageal reflux disease (GORD)
5) Dyspepsia
* Indigestion – discomfort during and after eating e.g heartburn, bloating, nausea
6) Atrophic gastritis
* Known wearing and inflammation of the stomach
7) Iron deficiency anaemia
* Due to increased bleeds from damaged tissue
8) Idiopathic Thrombocytopenic Purpura
* Idiopathic – occurring without secondary cause
* Thrombocytopenic – low platelets
* Purpura – non-blanching rash
Why are acute H. pylori infections largely unrecognised?
How long does acute infection last for?
What are 4 symptoms of acute H. pylori infections?
How does it affect gastric mucosa?
- Acute H. pylori infections are largely unrecognised because many patients won’t have symptoms this early on
- Acute infections of H. Pylori last about 2 weeks
- 4 symptoms of acute H. pylori infections:
1) Nausea
2) Dyspepsia
3) Malaise
4) Halitosis - Gastric mucosa is inflamed with neutrophils and inflammatory cells with marked persistent lymphocyte penetration
What are 2 symptoms of chronic H.pylori infection?
What 5 factors does outcome of chronic H.pylori infection depend on?
- 2 symptoms of chronic H.pylori infection:
1) Local inflammation
2) Gastritis - 5 factors does outcome of chronic H.pylori infection depend on:
1) Pattern of inflammation
2) Host response
3) Bacterial virulence
4) Environmental factors e.g people who drink are at grater risk of stomach ulcers
5) Patient age
What are 2 non-invasive diagnostic tests for Helicobacter pylori?
What is a biopsy based diagnostic test for H.pylori?
What can each tests be used for?
Which medications should be stopped prior to certain tests?
Why can endoscopies be given when H.pylori is suspected?
- 2 non-invasive diagnostic tests for Helicobacter pylori:
1) Urea breath test
* Used for primary diagnosis and eradication control
* The Principal/Primary Diagnosis is the condition established after study to be chiefly responsible for causing the admission of the patient to the hospital for care
2) Stool antigen
* Used for primary diagnosis
* Stool antigen is not evidence based as a test for eradication
* This is because this test cant tell us if the H.pylori has been treated or gone away, meaning they will remain positive even if they aren’t currently infected with H.pylori
* Patients need to stop any proton pump inhibitor drugs 2 weeks before the test and any antibiotics 4 weeks before the test, as these could suppress H.pylori, which could result in it not being detected
- The rapid urease test (CLO test) is a biopsy based diagnostic test for H.pylori
- It is used as the gold standard
- It can be used for primary diagnosis if an endoscopy is required
- Like the stool antigen test, those specific medications should be stopped prior to the test
- Endoscopies can be given to investigate symptoms that may be caused by conditions such as a peptic ulcer or gastritis that may be due to H. pylori
Describe the 4 steps of the urease breath test (CLO test).
- 4 Steps of the urease breath test:
1) Carbon-13 marked urea is introduced to the patient
2) Urea is broken down by the urease enzyme, an enzyme not present in humans but is present in H.pylori
3) If H.pylori is present, the urease will be broken down to ammonia and the carbon marked CO2
4) We can then measure the CO2 in the exhaled breath and see if there is any marked carbon in it to confirm the presence of H.pylori
What are 2 types of drugs that reduce gastric acid secretions?
- 2 types of drugs that reduce gastric acid secretions:
1) Proton Pump Inhibitors (PPIs)
2) Histamine H2 Receptor Antagonists (histamine increase acid secretion)
What is the first line treatment for those who test positive for H.pylori?
- First line treatment for those who test positive for H.pylori:
- Offer people (non-penicillin allergic) a 7-day, twice-daily course of treatment with:
- a PPI (Lansoprazole and omeprazole more commonly used) and amoxicillin and either clarithromycin or metronidazole
What is the first PPI typically given?
What is the mechanism of action of Omeprazole?
What type of drug is Omeprazole?
Where does it accumulate?
How is omeprazole administered?
- The first PPI typically given is omeprazole
- MOA - Omeprazole inhibits K+H+ATPase irreversibly (the proton pump), which reduces basal and simulated gastric acid
- Omeprazole is a weak base and accumulates in acid environment of the canaliculi of the stimulated parietal cell
- Omeprazole is orally administered
What are considered peptic ulcers?
What can peptide ulcers be associated with?
What imbalance can cause peptic ulcers?
What are 2 mucosal damaging factors?
What are 4 mucosal protecting factors?
- Peptic ulcers are gastric or duodenal ulcers
- Peptic ulcers Can be associated with infection of gastric mucosa with H pylori (don’t need to be H.pylori infected to get peptic ulcers, but it increases the risk)
- Peptic ulcers can result from an imbalance between mucosal damage and mucosal protection
- Mucosal damaging:
1) Acid
2) Pepsin - Mucosal protecting:
1) Mucus
2) Bicarbonate
3) Prostaglandins
4) Nitric oxide
Describe the flow chart for managing peptic ulcer disease in adults (in picture)
How do we diagnose peptic ulcers?
- Flow chart for managing peptic ulcer disease in adults (in picture)
- Peptic ulcers are diagnosed using an endoscopy
When can Endoscopy and retesting for H. pylori occur during treatment for peptic ulcers?
How do we perform retesting for H. pylori?
Why is this needed?
- When can Endoscopy and retesting for H. pylori occur during treatment for peptic ulcers:
- Offer people with gastric ulcer and H. pylori repeat endoscopy 6 to 8 weeks after beginning treatment depending on the size of the lesion
- Offer people with peptic ulcer (gastric or duodenal) and H. pylori retesting for H. pylori 6 to 8 weeks after the beginning of treatment depending on the size of the lesion
- Perform re-testing for H. pylori using a carbon-13 urea breath test
- These tests may be needed as it is possible to have treatment failure or (less likely) re-infection
What is the protocol if the peptic ulcer is unhealed?
- In people with an unhealed ulcer, exclude:
1) Non-adherence
2) Malignancy
3) Failure to detect H. pylori
4) Inadvertent NSAID use
5) Other ulcer-inducing medication
6) Rare cases such as Zollinger-Ellison syndrome or Crohn’s disease
What lesions are seen in Crohn’s and Ulcerative colitis?
- In Crohn’s any part of the GIT can be affected
- The lesions seen are ‘skip’ lesions as they are not continuous
- They affect the full thickness of the GIT
- In ulcerative colitis, lesions start from the anus and work their way backwards in continuous fashion
- The lesions here don’t affect the full thickness of the GIT, but just the inner lining
What are 8 Complications of Inflammatory Bowel Disease?
- 8 Complications of Inflammatory Bowel Disease:
1) Stoma
* Due to surgery to remove part of bowel
2) Anaemia
* Due to bleeding risks
3) Perforation
* Due to inflammation and risk of full-thickness lesions from Crohn’s
4) Obstruction/stricture
* Due to scarring
5) Fistulae
6) Toxic megacolon
* Very large and inflamed colon
7) Malnutrition
* Due to absorption being affected by inflamed parts of bowel
8) Increased risk of bowel cancer
