Gastroenterology: Pathology - Oesophagus and stomach Flashcards
What is the most common cause of oesophagitis?
Reflux (GERD)
Describe the pathogenesis of reflux oesophagitis
Reflux of gastric juices results in mucosal injury
Conditions which decrease oesophageal tone or increase abdominal pressure contribute to GERD, e.g.:
- Alcohol and tobacco use
- Obesity
- CNS depressants
- Pregnancy
- Hiatus hernia
- Delayed gastric emptying
- Increased gastric volume
What is Barrett oesophagus?
Metaplastic change in distal oesophagus in response to prolonged injury (e.g. in chronic GERD)
Squamous epithelium is replaced by columnar intestinal epithelium
What are some of the risks associated with Barrett oesophagus?
- Ulceration
- Stricture
- Epithelial dysplasia
- Oesophageal adenocarcinoma (risk ~30x baseline)
What is the hallmark morphological feature of Barrett oesophagus?
Goblet cells present above the gastro-oesophageal junction
In what % of cirrhotic patients do varices occur?
90%
What are the two main causes of oesophageal varices?
Alcoholic liver disease
Hepatic schistosomiasis
Describe the pathogenesis of oesophageal varices
Severe portal HTN causes congestion at sites of shared portal and systemic circulation
Results in congestion of subepithelial and submucosal venous plexus in distal 1/3 oesophagus
Normally distal 1/3 of oesophagus drains via L gastric vein to portal circulation and via azygos vein to systemic circulation
What % of patients die during first variceal bleeding episode, and what is the usual cause of death?
Up to half
Death either due to shock, or hepatic coma triggered by hypovolaemia
Of those who survive an initial episode of variceal bleeding, in what % will additional instances of haemorrhage occur within the next 12 months?
> 50% will have another bleeding episode within the next 12 months
Mortality similar to first episode (up to half)
What % of deaths of patients with advanced cirrhosis are caused by variceal rupture?
> 50%
Which oesophageal cancer is more common: squamous cell or adenocarcinoma?
Squamous cell carcinoma (although rates of adenocarcinoma are increasing in developed world)
What causes oesophageal adenocarcinoma?
Typically due to Barrett oesophagus and long-standing GERD (especially if documented dysplasia)
Besides Barrett oesophagus, what other factors increase risk of oesophageal adenocarcinoma?
Tobacco
Obesity
Prior radiation
Describe the sex predilection of squamous cell carcinoma and adenocarcinoma
Both more common in men
What is the typical site of oesophageal adenocarcinoma?
Distal 1/3
May invade into gastric cardia
What is the overall 5-year survival of oesophageal adenocarcinoma?
<25% because often diagnosed late (if diagnosed when limited to mucosa or submucosa, 5-year survival is 80%)
Six risk factors for oesophageal squamous cell carcinoma
- Alcohol and tobacco
- Poverty
- Caustic oesophageal injury
- Achalasia
- Frequent consumption of very hot beverages
- Previous radiation
What is the typical site of oesophageal squamous cell carcinoma?
Upper 1/3 20%, middle 1/3 50%, lower 1/3 30%
Six normal gastroprotective factors and two normal damaging forces of the gastric mucosa
Gastroprotective factors:
1. Mucin secretion by surface foveolar cells
2. Bicarbonate secretion into mucous by surface epithelial cells
3. Mucosal blood flow (delivers O2, HCO3 and nutrients whilst removing H+)
4. Apical surface membrane transport
5. Epithelial regenerative capacity
6. Elaboration of prostaglandins
Normal damaging forces:
1. Gastric acidity
2. Peptic enzymes
Describe the pathogenesis of acute gastritis and gastric ulceration
Due to imbalance between normal gastroprotective forces and normal damaging forces, combined with superimposed injury from environmental or immunologic agents
Describe 4 causes of impaired gastroprotective defences, and 6 causes of gastric mucosal injury
Impaired defences due to:
1. Ischaemia
2. Shock
3. Delayed gastric emptying
4. Other host factors
Causes of mucosal injury:
1. H. pylori infection
2. NSAIDs, aspirin
3. Cigarettes
4. Alcohol
5. Gastric hyperacidity
6. Duodenal-gastric reflux
What causes stress ulcers?
Most commonly occur in setting of shock, sepsis, severe trauma
What are Curling ulcers and where do they typically arise?
Ulcers occurring in the proximal duodenum in association with severe burns or trauma
What are Cushing ulcers? What is the major risk associated with these ulcers?
Ulcers arising in persons with intracranial disease
High risk of perforation
What is an ulcer?
Breach in the mucosa of the alimentary tract that extends through muscularis mucosa into submucosa or deeper
Compare and contrast the appearance of acute ulcers vs peptic (chronic) ulcers
Acute:
- Rounded, <1cm in diameter
- More often occur in multiples throughout stomach and duodenum
- Arise anywhere within the stomach
- Sharply demarcated with normal adjacent mucosa
- Base often stained brown/black by acid digestion of extravasated blood
Peptic:
- Usually solitary
- More common to duodenum (rate of 4:1 duodenum:stomach) where they usually occur within few cm of pyloric valve and involve the anterior duodenal wall
- Gastric peptic ulcers typically found on lesser curvature where body meets antrum
- Sharply punched out defect with fibrosis and scarring
- Presence of chronic gastritis in other areas of mucosa
How common is malignant transformation of peptic ulcers?
Very rare
What are the three major complications of ulcers and with what relative frequency does each occur? What is responsible for the most ulcer-related deaths?
- Bleeding (15-20%; causes 25% of ulcer-related deaths)
- Perforation (5%; causes 66% of ulcer-related deaths)
- Obstruction (2%; usually caused by chronic ulcers)
What kind of microbe is H. pylori?
Spiral-shaped Gram negative bacillus
What are the four features of H. pylori which make it well-suited as a pathogen in the stomach?
- Flagella: allows motility in viscous mucus
- Urease: generates ammonia from endogenous urea to increase local gastric pH
- Adhesins: enhance bacterial adherence to surface foveolar cells
- Toxins: e.g. cytotoxin-associated gene A
With which four conditions is H. pylori associated?
Chronic gastritis
Peptic ulcer disease
Gastric carcinoma
Gastric MALToma
In what % of patients with duodenal vs gastric ulcers is H. pylori present?
85-100% of duodenal ulcers
70% of gastric ulcers
Compare and contrast the features of H. pylori-associated vs autoimmune gastritis in terms of:
- Location
- Inflammatory infiltrate
- Acid production
- Gastrin
- Other lesions
- Serology
- Sequelae
- Epidemiological associations
What is Zollinger-Ellison syndrome?
Syndrome of duodenal ulceration and diarrhoea caused by gastrin-secreting tumours of small intestine and pancreas
What morphological feature is characteristic of Zollinger-Ellison syndrome?
Increased mucosal thickening in stomach due to parietal cell hyperplasia
What are the three types of gastric polyps? Which is most common?
- Inflammatory or hyperplastic (most common; 75%)
- Gastric adenomas (10%)
- Fundic gland polyps
What causes inflammatory or hyperplastic gastric polyps?
Usually arise in setting of chronic gastritis
Risk of dysplasia in gastric polyps is linked to what?
Size of polyp
What two conditions can cause fundic polyps?
- PPI use (decreased gastric acidity stimulates gastrin secretion, resulting in glandular hyperplasia
- FAP
In what % of gastric adenomas is carcinoma present?
Up to 30%
What is the main gastric malignancy?
Gastric adenocarcinoma (>90%)
Two environmental and three host risk factors for gastric adenocarcinoma
Environmental:
1. Diet (lack of fresh fruit and vegetables)
2. Cigarette smoking
Host factors:
1. H. pylori-associated chronic gastritis
2. Autoimmune gastritis
3. Previous partial gastrectomy due to increased gastroduodenal reflux
What is the most common location for a gastric adenocarcinoma? Which location is seeing the greatest increase in incidence and why?
Pylorus/antrum (50-60%)
However incidence of gastric adenocarcinoma in the cardia is increasing (currently 25%), likely due to increased rates of Barrett oesophagus
Body/fundus 15-25%
What are the five types of gastric tumours seen?
- Polyps
- Gastric adenocarcinoma
- Gastric MALToma
- Carcinoid tumour
- Gastrointestinal stromal tumour (GIST)
What is the most common mesenchymal tumour of the abdomen?
GIST
