L3 - Dyspepsia Flashcards
Location of myenteric plexus
between longitudinal and circular muscle
Location of submucousal plexus
lumenal side of circular muscle
Sympathetic fibres will terminate in…
- Meyenteric and submucousal plexus
- will inhibit ACH secretion.
Neuron’s within the myenteric and submucousal plexus constitute the enteric nervous system which involves what chemicals
- ACH
- Noradrenaline
- 5-Hydroxytrytamine (G-coupled receptor)
Chief cells release
Prorenin
Pepsingogen
Oxyntic cells (parietal cells) release
HCl
Intrinsic factor
Role of prostaglandins
e. g. PGE2 & I2
- cytoprotective role
- Increased bicarb secretion (act on EP1/2 receptor)
- Increase mucin secretion (EP4 receptor)
- Decrease H+ (EP2/3 on ECL)
- Prevents vasoconstriction, dilating BV
What is the process of acid output from parietal cell
- Cl- Actively transported into canaliculi in the cells which communicate with the lumen of the gastric gland.
- Accompanied by K+ secretion
- K+ exchanged for H+ within the cell via proton pump K+H+ATPase
- Carbonic anhydrase - carbonic acid - dissociation
- Bicarbonate exchanged from across basal membrane of parietal cell for Cl-
Gastrin binds to which receptors
CCK2 receptors on ECL.
ECL then releases histamine.
HIstamine binds to H2 receptor on parietal cell.
Parietal cell releases HCl
Gastrin produced?
- G cells in gastric antrum.
- Secreted into portal blood.
- Acts on gastrin / CCk receptors.
- Stimulates H+ secretion
- Stimulates histamine synthesis
ACH stimulates what receptor
- M3 receptor on parietal cells.
- Increases intracellular Ca2+
- stimulates H+ secretion.
- Inhibits somatostatin release from D-cells
Zollinger Ellison syndrome
Rare hypersecretory condition caused by gastrin producing tumour.
If untreated
- dysplasia of oesophagus epithelium which may progress to a pre-cancerous maybe dangerous Barret Oesophagus
How might NSAIDS contribute to GI problems?
May cause gastric bleeding, erosion.
- Inhibiting cyclooxygenase I which is key in the synthesis of protective prostaglandins.
Give an example of a cyclo-oxygenase II inhibitor causing less stomach damage
Celecoxib
Describe use and example of Histamine H2 receptor antagonists
- Inhibits histamine action at all H2 receptors
- Inhibits gastric acid secretion
Example
- Ranitidine
Use and example of PPI
- Peptic ulcer, reflux oesophagitis, ZE syndrome, part of therapy for H.Pylori
Example
- Omeprazole
- Lansoprazole
Antacids
Magnesium Trisilicate
Aluminium hydroxide
- used in dyspepsia
Bismuth Chelate use + unwanted effects
- Component of therapy for H. Pylori
- helps protect mucosa
- toxic to bacillus
Unwanted effects
- nausea, vomitting, blackening of tongue and faeces, raised plasma concentration of BC can lead to encephalopathy
Use of Cimetidine + side effects
- H2 receptor antagonist
- ONLY ONE WHICH inhibits cytochrome p450 hence slowing down metabolism of drug
- hence action of drugs increased
Side effects
- modest affinity for androgen receptor hence may cause gynecomastia in men
How do PPI’s work
e.g. Omeprazole
- irreversibly inhibits H+K+ATPase, hence basal and stimulated gastric H+ secretion decreases
Omeprazole must be converted to chiral form first before it can react with and inactivate ATPase
Why is in important to have a good balance of magnesium and aluminium salts in antacids
- Magnesium salts cause diarrhoea.
- Aluminium salts cause constipation.
Combination of both needed to help preserve normal bowel function.
Treatment of H.Bacter pylori infection
If test is positive then..
1-2 week regime of triple therapy
- PP1
- Antibiotic - Amoxicillin
- Metronidazole or clarithromycin
State examples of drugs protecting mucosa
- Bismuth Chelate
- Sucralfate
- Misoprostol
Describe mechanism of action of Sucralfate `
- Complex of Aluminium hyroxide and sulfates sucrose
- Strong negative charge
- Binds to cationic groups in proteins, glycoproteins
- Forms complex gel with mucus
- limiting diffusion H+
- limiting degradation by pepsin - Requires H+ environment for activation
- Reduces absorption of some fluroquinolone antibiotics such as theophylline and tetracycline
Mechanism of action by misoprostol
- Stable analogue of prostaglandin E1
- Used to promote ulcer healing
- Prevents gastric damage from chronic NSAID use
- Acts on ECL, inhibits basal gastric acid secretion
- Increased muscosal blood flow
- Increased mucus and bicarb secretion
Why should misoprostol not be given in pregnancy?
Can cause uterine contractions.
UNLESS to deliberately abort fetus.
Define Barret Oesophagus
Change from squamous to columnar epithelium lined oesophgus.
Intestinal metaplasia within the oesophageal squamous mucuosa.
Percursor lesion to cancer
- Red velvety mucosa
- can only be identified via endoscopy and biopsy
Patient with Zollinger-Ellison syndrome may present with
Duodenal ulcer, diarrhoea
Doubling of oxyntic mucosal thickness due to five fold increase in parietal cells.
Treatment for ZE syndrome
- Blockage of acid hypersecretion.
2. Proton pump inhibitors.
Gastritis vs Gastropathy
Gastritis
- inflammation with mucosal injury
Gastropathy
- epithelial cell damage and regeneration without inflammation
Describe infection by H. Pylori
- Colonizes mucous layer of gastric antrum
- adheres to gastric epithelial cell
- protected from H+ secreion by juxtamucosal mucus layer which traps HCO3- secreted by antral cells
How does H Pylori damage gastric epithelial cells
- Release of enzymes.
- Induction of apoptosis
- through binding to class II major histocompatibility MHC molecules.
Define peptic ulcer
- Break in superficial eptihelial cells penetrating down to muscularis mucosa of either stomach or duodenum.
How might you diagnose H.Pylori
- Serological test: detect IgG (wont detect current infection)
- 13C urea breath test : measure CO2 in breath after ingestion. Requires mass spectrometer
- Stool antigen test
- Biopsy urease test : H.Pylori have urease enzyme that will split urea forming ammonia. Ammonia will increase pH, colour change from Yellow to red.
Describe the Biopsy UREASE test
- Gastric biopsy + susbtrate containing urea and phenol red
- H.Pylori have urease enzyme that will split urea forming ammonia. Ammonia will increase pH, colour change from Yellow to red.
Dyspepsia
Epigastric pain or discomfort for atleast 3 months in patient who does not report predominant heart burn / regurgitation
GORD
Gastro-oesophageal reflux disease.
Most likely symptoms of heart burn if regurgitation dominates.
Odynophagia
Painful swallowing
How might you investigate a patient with dyspepsia?
Oesophagoduodenogastroscropy
- reserved for older patients with alarm symptoms
Alarm symptoms
- Chronic GI bleeding
- weight loss
- difficulty swallowing: dysphagia
- persistent vomitting
- iron deficiency anaemia
- palpable epigastric mass
Symptoms of GORD
- Heartburn
- Excessive saliva production (waterbrash)
- Regurgitation
- Odynophagia (painful swallowing)
Describe Nissen Fundoplication surgery
- Hiatus repaired
- Fundus wrapped around oesophagus
- artifical bowel produced
- prevents refluxing
Treatment for peptic ulceration
- Vagotomy and pylorplasty
- Pylorplasty because in vagus cut then pyloris wont relax, hence needs to be opened.
