8. Pathophysiology of Gastric Disease Flashcards
Define dyspepsia.
Term used to describe a complex of upper gastrointestinal tract symptoms which are typically present for four or more weeks, including upper abdominal pain or discomfort, heartburn, acid reflux, nausea and/or vomiting
What are 5 common gastric disorders?
- Gord
- Gastritis
- Peptic ulcer disease
- zollinger-ellison disease
- cancer of the stomach
What is GORD?
gastro-oesophageal reflux disease
What are the symptoms of GORD?
Chest pain, acid taste in mouth, cough
What can trigger GORD (risk factors)? (5)
- Obesity
- Pregnancy
- Hiatus hernia
- LOS dysfunction
- Delayed Gastric emptying
What are the possible consequences of GORD?
- May not have consequences.
- Oesophagitis
- ulceration
- haemorrhage
- Strictures - due to scar tissue
- Barrett’s oesophagus
what is GORD caused by?
ineffective LOS
What does the lower oesophageal sphincter consist of?
- Muscular element
- Right crus of diaphragm - closes off oesophagus when high pressures
- Angle of entry of oesophagus into stomach
what does the muscular element of the LOS consist of ?
intrinsic smooth muscle and diaphragm
Is the LOS contracted or relaxed at rest?
Contracted
When are pressure of the LOS highest and lowest?
- Lowest after meals
* Highest at night
What are the different treatment options for GORD?
◦ Lifestyle modifications
◦ Pharmacological
◦ Surgery (rare) (fundoplication)
What pharmacological interventions are available for GORD?
Antacids, H2 antagonists, PPIs
What are some lifestyle changes for treatment of GORD?
- eat slower (stomach empties at a certain rate, prevents build of high pressures in stomach)
- Have smaller meals
- not eating before bed (lying down doesn’t help)
- losing weight (exercise, diet)
- stop smoking
- reduce alcohol and caffeine
What are hiatal hernias?
herniation of the stomach and LOS into the thorax through the oesophageal hiatus in the diaphragm
What does moving the LOS into the thorax do to its basal tone?
Reduces:
• basal tone
• The normal increase in LOS tone when straining
What are the changes to the LOS in hiatus hernias?
- weakened and shortened muscular LOS
- Loss of diaphragmatic support
- Loss of oblique entry of oesophagus into stomach
what is Barrett’s oesophagus?
the reversible (metaplastic) change of stratified squamous epithelia in the lower oesophagus into simple columnar epithelia due to repeated exposure to gastric contents
what is the risk with Barrett;s oesophagus?
increased risk of dysplasia into adenocarcinoma
What is gastritis?
inflammation of the gastric mucosa
What symptoms are present in gastritis?
Pain, nausea, vomiting, bleeding
What causes acute gastritis?
◦ Heavy use of NSAIDS
◦ Lots of alcohol
◦ Chemotherapy
◦ Bile reflux (irritant to the stomach)
What happens to gastric mucosa in exposure to chemical injury (HCL)?
Results in damaged epithelial cells and a reduction in mucus production
Which cells are seen in the gastric mucosa in response to acute gastritis?
Inflammatory cells, mainly neutrophils
what are the pathological changes of acute gastritis?
◦ epithelial damage
◦ some epithelial hyperplasia
◦ vasodilation
◦ neutrophil response
What is the treatment for acute gastritis?
Removal of irritant (NSAIDs, alcohol etc)
What are the 2 main causes of chronic gastritis?
◦ Bacterial - H. pylori
◦ Autoimmune (antibodies to parietal cells)
◦ (Chronic alcohol, NSAIDs etc. can also cause this)
what are the pathological changes seen in chronic gastritis?
◦ lymphocyte response
◦ glandular atrophy
◦ fibrotic changes
◦ metaplastic changes
how does autoimmune causes lead to gastritis?
◦ antibodies to parietal cells ◦ lose parietal cells ◦reduced acid production and intrinsic factor ◦ atrophy of stomach ◦ gastritis
What can chronic gastritis due to autoimmune disease also lead to?
Pernicious anaemia (Loss of intrinsic factor needed for B12 absorption) - also iron deficiency anaemia, iron uptake requires acidic environment
What are the symptoms of chronic gastritis due to autoimmune?
- Symptoms of anaemia
- Glossitis
- Anorexia
- Neurological symptoms
What are the symptoms of chronic gastritis due to H. pylori?
Asymptomatic or similar to acute gastritis
Symptoms may develop due to complications
What are some complications of H. pylori?
Peptic ulcers, adenocarcinoma, MALT lymphoma
What type of organism is H. pylori?
Helix shaped/gram negative/microaerophilic - stomach has correct O2
How does H.pylori spread?
• Oral to oral/faecal to oral
What are 5 virulence factors of H. pylori?
- Urease - converts urea to ammonia, increases it local pH
- Flagella - good motility to reach optimum environment
- Adhesins - resist peristalsis
- Cytotoxins
- chemotaxis - find areas with less acid
Where in the stomach do H. pylori live?
in mucus layer/adheres to gastric epithelia
How does H. pylori damage the stomach?
- releases cytotoxins, cause direct epithelial injury
- Urease, ammonia is toxic to epithelia and increases pH
- mucinase - damage mucus layer
- possibly degrades mucus layer
- promotes inflammatory response (self injury)
What are the effects of H. pylori if present in the antrum?
- Increased Gastrin secretion (or decreased D cell activity)
- Increased parietal cell acid secretion and increased acid chyme enters duodenum
- Duodenal epithelial metaplasia due to damage (from duodenal epithelia to gastric epithelia)
- Colonisation of duodenum
- Duodenal ulceration
What are the effects of H. pylori if present in the body?
- Atrophic effect - atrophy of parietal cells so reduced acid production
- Gastric ulcer
- Leads to intestinal metaplasia
- Dysplasia
- cancer
What are the effects of H. pylori if present in the antrum and body?
Asymptomatic - effects cancel each other§
How can H. pylori be tested for?
- Urea breath test
- Stool antigen test
- Serum antibodies test
- Upper GI endoscopy with biopsy (can be used for CLO test/rapid urease test)
How does the urea breath test work?
Urea with labelled carbon (C13) ingested, converted to ammonia and CO2 by H. pylori, labelled C13 detected in breath
What is the treatment for H. pylori?
Triple therapy (2 antibiotics + 1 PPI): Amoxicillin + (clarithromycin or metronidazole)
How is the success of the treatment checked?
urea breath test
Define peptic ulcer.
Defects in the gastric or duodenal mucosa that extend through the muscularis mucosa
Where do peptic ulcers commonly occur?
◦ Most common in first part of duodenum
◦ Commonly affects lesser curve/antrum of stomach
What percentage of gastric and duodenal ulcers are associated with H. pylori?
Gastric 70%, Duodenal 95-100%
What is the most important cause of peptic ulcers?
Breakdown of normal defences
- more important than excessive acid
normal defence mechanisms of stomach
◦ mucous ◦ bicarbonate ◦ adequate mucosal bloodflow ◦ can remove acid that diffuses through injured mucosa ◦ prostaglandins ◦ epithelial renewal
What mechanism have been implicated in duodenal ulcers?
Rapid gastric emptying/inadequate acid neutralisation (from bile/pancreas)
What are the causes of peptic ulcer?
- Caused by mucosal injury
◦ H-pylori
◦ NSAIDS
◦ Smoking (really only contributes to relapse of ulcer disease)
◦ massive physiological stress e.g. Burns
what is the effect of NSAIDs on stomach defences?
reduces prostaglandin synthesis
what is the effect of prostaglandin on stomach defences?
maintains mucosal blood flow needed for removal of H+ ions
what is the difference in acid levels in gastric and duodenal ulcers?
gastric - normal/low - atrophy
duodenal - normal/high - increased gastrin release
When do acute peptic ulcer develop?
•Develop as part of acute gastritis
Where do chronic ulcers develop?
- Occur most frequently at mucosal junctions
- Where antrum meets body (on lesser curve)
- In duodenum where antrum meets small intestine
What is the morphology of peptic ulcers?
•Generally less than 2cm diameter (but can be 10cm) •Base of ulcer is necrotic tissue/granulation tissue •Muscularis propria can be replaced by scar tissue
What are 5 clinical consequences of peptic ulcers?
- scar tissue shrinks, narrow stomach or cause pyloric stenosis
- perforation causing peritonitis
- erosion into adjacent structure (liver, pancreas)
- haemorrhage from vessel in base of ulcer (gastro-duodenal artery if duodenal and splenic artery if gastric)
- malignancy (rare)
What are the symptoms of peptic ulcers/
• Epigastric pain (sometimes back pain)
- Burning/gnawing
- Follows meal times
• Often at night (especially DU)
Serious symptoms
• Haematemesis or malaena-Bleeding/anaemia
• Early satiety from repeated scarring
• Weight loss (reluctance to eat due to pain)
When does pain usually occur in peptic ulcers?
Following meal times, In duondenal ulcers can be 2-3 hrs after, after opening of the pyloric sphincter
What are the different management options of peptic ulcers?
- Lifestyle modification
- Stopping any exacerbating medications (e.g. NSAIDs)
- Testing for H-pylori (if present- eradicate)
- PPIs
- Endoscopy
what is the management of peptic ulcers if active bleeding?
endoscopic treatment
- adrenaline injected + cautery +/- clip application
What is functional dyspepsia?
Have symptoms of ulcer disease but no physical evidence of organic disease
Diagnosis of exclusion!
What are the different methods of diagnosis of gastric pathology?
Upper GI endoscopy - biopsies Urease breath test Erect CXR - perforation Blood test (FBC) - anaemia (bleeds, pernicious/iron def.)
What pharmacological interventions can reduce acid production?
H2 blockers (cimetidine, Ranitidine) PPi (omeprazole, (zoles))
What is Zollinger-Ellison syndrome?
Non beta islet cell gastrin secreting tumour of the pancreas
- large vol acid secretion
- severe stomach and small intestine ulceration
- abdominal pain, diarrhoea
What types of stress can cause mucosal damage?
Symptoms of gastritis/ulceration Following: • Severe burns • Raised intracranial pressure • Sepsis • Severe trauma • Multiple organ failure
What are the symptoms of stomach cancer?
- Dysphagia
- Loss of appetite
- Malaena
- Weight loss
- Nausea/vomiting/
- Virchow’s nodes
What are the risk factors for stomach cancer?
- Male
- H-pylori
- Dietary factors • Smoking
