(20) Pathology of the upper GI tract Flashcards
Describe the normal oesophagus
- 25cm long muscular tube
- mostly lined by squamous epithelium (stratified squamous)
What type of epithelium lines most of the oesophagus?
Mostly squamous (stratified squamous)
What are the 2 sphincters in the oesophagus?
- cricopharyngeal (upper end)
- gastro-oesophageal junction (lower end)
How much of the oesophagus is situated below the diaphragm?
The distal 1.5-2cm
The distal 1.5-2cm of the oesophagus is satiated below the diaphragm. What is it lined with?
Glandular (columnar) mucosa
The squamo-columnar junction of the oesophagus is usually located where?
40cm from the incisor teeth (at the level of the diaphragm)
Name the 3 main layers of the oesophageal wall
- muscularis propria
- submucosa
- mucosa (lamina propria and epithelium)
What is oesophagitis?
Inflammation of the oesophagus
What are the 2 classifications of oesophagitis?
- acute
- chronic
What are the 2 main aetiological classifications of oesophagitis?
- infectious
- chemical
What are the infectious causes of oesophagitis?
- bacterial
- viral (HSV1, CMV)
- fungal (candida)
What are the chemical causes of oesophagitis?
- ingestion of corrosive substances
- reflux of gastric contents
What is the commonest form of oesophagitis?
Reflux oesophagitis
What is reflux oesophagitis caused by?
Reflux of gastric acid (gastro-oesophageal reflux)
and/or bile (duodeno-gastric reflux)
What are the risk factors for reflux oesophagitis?
- defective lower oesophageal sphincter
- hiatus hernia
- increased intra-abdominal pressure
- increased gastric fluid volume due to gastric outflow stenosis
What is the leading clinical symptom of reflux oesophagitis?
“heartburn”
What is a hiatus hernia?
Abnormal bulging of a portion of the stomach through the oesophageal opening in the diaphragm
What are the 2 different types of hiatus hernia?
- sliding hiatus hernia
- para-oesophageal hernia
What happens to the position of the lower oesophageal sphincter in a sliding hernia?
It raises above the diaphragm (usually at the level of/just below)
Which of the 2 types of hiatus hernia gives reflux symptoms?
Sliding hiatus hernia
What symptom does a para-oesophageal hernia give?
Strangulation
What happens to the normal mucosa in reflux oesophagitis? (histology)
Squamous epithelium
- basal cell hyperplasia
- elongation of papillae
- increased cell desquamation
Lamina propria
- inflammatory cell infiltration (neutrophils, eosinophils, lymphocytes)
What are the complications associated with reflux oesophagitis?
- ulceration
- haemorrhage
- perforation
- benign stricture (segmental narrowing)
- Barrett’s oesophagus
What is the cause of Barrett’s oesophagus?
Longstanding reflux
What are the risk factors for Barrett’s oesophagus?
- same as for reflux (+ male, Caucasian, overweight)
What do you see macroscopically in Barrett’s oesophagus?
Proximal extension of the squamo-columnar junction (the junction occurs higher up in the oesophagus, under the junction is “Barrett’s oesophagus”)
What do you see histologically in Barrett’s oesophagus?
Squamous mucosa replaced by columnar mucosa - “glandular metaplasia”
More inflammatory cells in lamina propria, mucous secreting glands in lamina propria, goblet cells in the columnar epithelium
What are the different types of columnar mucosa?
- gastric cardia type
- gastric body type
- intestinal type = “specialised Barrett’s mucosa”
Barrett’s oesophagus is a premalignant condition with an increased risk of what?
Developing adenocarcinoma
What is recommend for patients with Barrett’s oesophagus?
Regular endoscopic surveillance for early detection of neoplasia (increased risk of adenocarcinoma)
What are the 4 stages of disease progression in Barrett’s oesophagus?
- Barrett’s oesophagus
- low-grade dysplasia
- high-grade dysplasia
- adenocarcinoma
How common is oesophageal cancer?
8th most common cancer in the world
What are the 2 histological types of oesophageal cancer?
- squamous cell carcinoma
- adenocarcinoma
What percentage of oesophageal cancers in the UK are squamous cell carcinomas compared to other countries?
UK = 30% Germany = 60% France/Spain = >80% China/Japan = >95%
The incidence of adenocarcinoma of the oesophagus has risen dramatically in what countries?
Industrialised countries
Which gender is most at risk of adenocarcinoma of the oesophagus?
Males
Male/female ratio = 7:1
Also higher incidence among Caucasians
What is the aetiology of adenocarcinoma of the oesophagus?
- Barrett’s oesophagus
- tobacco
- obesity
Where does adenocarcinoma occur?
Lower oesophagus
What does the lower oesophagus look like macroscopically in adenocarcinoma?
- plaque-like
- nodular
- fungating
- ulcerated
- depressed
- infiltrating
There is wide geographical variation in incidence of squamous carcinoma of the oesophagus. In which countries is incidence high?
- Iran
- China
- South Africa
- Southern Brazil
What are the risk factors for squamous carcinoma of the oesophagus?
- tobacco
- alcohol
- nutrition (potential source of nitrosamines)
- thermal injury (hot beverages)
- HPV
- male
- ethnicity (black)
Where do squamous carcinomas occur in the oesophagus?
Middle and lower third (
What is squamous carcinoma of the oesophagus preceded by?
Squamous dysplasia
change from normal squamous epithelium to high grade squamous dysplasia
In TNM staging, what does pT mean?
Depth of invasion of the primary tumour
In TNM staging, what does pT1 mean?
Tumour invades lamina propria, muscularis mucosae or submucosa
In TNM staging, what does pT2 mean?
Tumour invades muscularis propria
In TNM staging, what does pT3 mean?
Tumour invades adventitia
/into subserosa
In TNM staging, what does pT4 mean?
Tumour invades adjacent structures
through serosa (peritoneum)
In TNM staging, what does N and M mean?
N = regional lymph nodes M = distant metastasis
In TNM staging, what does pN0, pN1, pN2 and pN3 mean?
pN0 = no regional lymph node metastases
pN1 = regional lymph node metastases in 1 or 2 nodes
pN2 = regional lymph node metastasis in 3 to 6 nodes
pN3 = regional lymph node metastasis in 7 or more nodes
In TNM staging, what does M0 and M1 mean?
M0 = no distant metastasis
M1 = distant metastasis
What are the 4 anatomic regions of the stomach?
- cardia
- fundus
- body
- antrum
Which regions of the stomach are histologically different with different functions?
- cardia
- body
- antrum
What normally happens in the stomach?
- balance of aggressive (acid) and defensive forces
- surface mucous
- bicarbonate secretion
- mucosal blood flow
- regenerative capacity
- prostaglandins
What causes increased aggression in the stomach? (can go on to cause gastritis)
- excessive alcohol
- drugs
- heavy smoking
- corrosive
- radiation
- chemotherapy
- infection
What caused impaired defences in the stomach? (can go on to cause gastritis)
- ischaemia
- shock
- delayed emptying
- duodenal reflux
- impaired regulation of pepsin secretion
Give 6 main causes of chronic gastritis
ABC
- autoimmune
- bacterial infection (H. pylori)
- chemical injury
- NSAIDs
- bile reflux
- alcohol
What is the pathogenic mechanism behind autoimmune chronic gastritis?
- anti-parietal cell antibodies
- anti-intrinsic factor antibodies
- sensitised T cells
What are the histological findings in autoimmune chronic gastritis?
Glandular atrophy in body mucosa
Intestinal metaplasia
What is the pathogenic mechanism behind chronic gastritis caused by bacterial infection?
- cytotoxins
- liberation of chemokines
- mucolytic enzymes
- ammonia production by bacteria urease
- tissue damage by immune response
What are the histological findings in chronic gastritis caused by bacterial infection?
- acute chronic inflammation
- multifocal atrophy: antrum > body
- intestinal metaplasia
What is the pathogenic mechanism behind chronic gastritis caused by chemical injury?
Direct injury
What are the histological findings in chronic gastritis caused by chemical injury?
Foveolar hyperplasia
What is the pathogenic mechanism behind chronic gastritis caused by NSAIDs?
Disruption of the mucus layer
What are the histological findings in chronic gastritis caused by NSAIDs?
Oedema
What are the pathogenic mechanisms of chronic gastritis caused by bile reflux?
Degranulation of mast cells
What are the histological findings in chronic gastritis caused by bile reflux?
Vasodilatation
What are the histological findings in chronic gastritis caused by alcohol?
Paucity of inflammatory cells
In what year was H. pylori discovered?
1984
What type of bacterium is Helicobacter pylori?
Gram negative spiral shaped bacterium
2.5-5 micrometers long
4 - 6 flagellae
Where does H. pylori live in the stomach?
On the epithelial surface protected by the overlying mucus barrier
What does H. pylori do?
Damages the epithelium leading to chronic inflammation of the mucosa
Results in glandular atrophy, replacement fibrosis and intestinal metaplasia
Where in the stomach is H. pylori found?
More common in the antrum than in the body
Give 5 complications that H. pylori can cause
- gastric ulcer
- gastric cancer
- MALT lymphoma
- pre-pyloric gastric ulcer
- duodenal ulcer
What is peptic ulcer disease?
Localised defect extending at least into the submucosa
What are the major sites of peptic ulcer?
- first part of duodenum
- junction of antrum and body mucosa
- distal oesophagus (GOJ)
What are the main etiological factors of peptic ulcer disease?
- hyperacidity
- H. pylori infection
- duodeno-gastric reflux
- drugs (NSAIDs)
- smoking
What is the histology of an ACUTE gastric ulcer?
- full-thickness coagulative necrosis of mucosa (or deeper layers)
- covered with ulcer slough (necrotic debris + fibrin + neutrophils)
- granulation tissue at ulcer floor
What kind of necrosis do you get in an acute gastric ulcer?
Coagulative
An acute gastric ulcer is covered with ulcer slough, what does this consist of?
- necrotic debris
- fibrin
- neutrophils
What type of tissue is at the floor of an acute gastric ulcer?
Granulation tissue
What is the histology of a CHRONIC gastric ulcer?
- clear-cut edges overhanging the base
- extensive granulation and scar tissue at ulcer floor
- scarring often throughout the entire gastric wall with breaching of the muscularis propria
- bleeding
What type of tissue is at the ulcer floor in a chronic gastric ulcer?
Extensive granulation and scar tissue
Where do you get scarring in a chronic gastric ulcer?
Often throughout the entire gastric wall with breaching of the muscularis propria
Give 4 complications of peptic ulcers
- haemorrhage
- perforation
- penetration into an adjacent organ (liver, pancreas)
- stricturing
Haemorrhage is a potential complication of peptic ulcer. What may it lead to?
Acute or chronic
May lead to anaemia
Perforation is a potential complication of peptic ulcer. What may it lead to?
Peritonitis
Stricturing is a potential complication of peptic ulcer. What is the deformity known as?
Hour-glass deformity
What is the relative incidence of gastric ulcer compared to duodenal ulcer?
Gastric = 1
Duodenal = 3
What is the age distribution of gastric ulcer compared to duodenal ulcer?
Gastric = increases with age
Duodenal = increased up to 35 years
What are the acid levels in gastric ulcer compared to duodenal ulcer?
Gastric = normal or low
Duodenal = elevated or normal
What proportion of gastric ulcer is associated with H. pylori gastritis compared to duodenal ulcer?
Gastric = 70%
Duodenal = 95-100% (predom. antrum)
What is the localisation of gastric ulcer compared to duodenal ulcer?
Gastric = lesser curve, antrum-corpus junction, pre pyloric
Duodenal = bulbus (prox. 2cm)
Blood group in gastric ulcer compared to duodenal ulcer?
Gastric = A
Duodenal = O
What is the most common gastric cancer?
Adenocarcinoma
Give 3 other types of gastric cancer, other than adenocarcinoma
- endocrine tumours
- MALT lymphomas
- stromal tumours (GIST)
How common is gastric adenocarcinoma?
5th most common cancer in the world
There is wide geographic variation in gastric adenocarcinoma. In which countries are there high rates?
- Eastern Asia
- Andean regions of South America
- Eastern Europe
Steady decline over the past decades
What are the main aetiological factors of gastric adenocarcinoma?
- diet (smoked/cured meat or fish, pickled vegetables)
- H. pylori infection
- bile reflux (eg. post Billroth II operation)
- hypochlorhydria (allows bacteria growth)
- around 1% hereditary
What are the specific aetiological factors of adenocarcinoma of GOJ?
- white males
- associated with GO reflux
- no association with H. pylori infection
- no associated with diet
- increased incidence in recent years
What are the specific aetiological factors of adenocarcinoma of the gastric body/antrum?
- association with H. pylori infection
- association with diet (salt, low fruit and vegetables)
- no association with GO reflux
- decreased incidence in recent years
Describe the genetic pathway from normal mucosa to intestinal type cancer (well differentiated type)
Normal mucosa - intestinal metaplasia - adenoma - cancer intestinal type (well-differentiated)
Mutations eg.
- K-ras mutation
- APC mutation
- p53 mutation
- pS2 reduction
- p73 LOH
- reduced p27 expression
- CpG methylation
(3 different pathways)
Describe the genetic pathway from normal mucosa to diffuse type cancer (poorly differentiated type)
Normal mucosa - cancer diffuse type (poorly differentiated)
Mutations eg. - p53 mutation - CpG methylation - cyclin E overexpression etc
Give 6 macroscopic subtypes of gastric adenocarcinoma
- superficial exophytic
- falt or depressed
- superficial excavated
- exophytic
- linitis plastica
- excavated
What are the 2 main histological subtypes of gastric adenocarcinoma
- scattered growth (diffuse type - signet ring cell cancer)
- non-scattered growth (intestinal type - tubular adenocarcinoma)
What does HDGC stand for?
Hereditary diffuse type gastric cancer
Which mutation causes HDGC?
Germline CDH1/E-cadherin mutation
Hereditary diffuse type gastric cancer comes with an increased risk of what?
Other cancers
What could be a possible preventative measure against HDGC?
Prophylactic gastrectomy
What is coeliac disease also known as?
- Coeliac sprue
- gluten sensitivity enteropathy
What is Coeliac disease?
Immune mediated enteropathy
How common is coeliac disease?
Prevalence of 0.5-1%
What is gliadin? (coeliac disease)
- alcohol soluble component of gluten
- contains most of the disease-producing components
What does gliadin do? (coeliac disease)
Induces epithelial cells to express IL-15
This leads to activation and proliferation of CD8+ IELs (intraepithelial lymphocytes)
What do CD8+ intraepithelial lymphocytes (IELs) do? (coeliac disease)
They are cytotoxic and kill enterocytes
They do not recognise gliadin directly
Gliadin-induced IL15 secretion by epithelium is the mechanism
Who does Coeliac disease commonly affect?
Adults between 30 and 60 years
Why is coeliac disease difficult to diagnose?
- atypical presentations/no specific symptoms
- silent disease (positive serology/villous atrophy but no symptoms)
- latent disease (positive serology but no villous atrophy)
What does coeliac disease as a silent disease mean?
- positive serology
- villus atrophy
- no symptoms
What does coeliac disease as a latent disease mean?
- positive serology
- no villous atrophy
How does coeliac disease present in symptomatic patients?
- anaemia
- chronic diarrhoea
- bloating
- chronic fatigue
Which gender is coeliac disease most common in?
No gender preference
What other disease are associated with coeliac disease?
- dermatitis herpetiformis (10% of patients)
- lymphocytic gastritis and lymphocytic colitis
Which cancers are coeliac disease associated with?
- enteropathy-associated T cell lymphoma
- small intestinal adenocarcinoma
(beware of symptoms despite gluten-free diet)
How do you diagnose Coeliac disease?
Non-invasive serologic tests usually performed before biopsy
- IgA antibodies to tissue transglutaminase (TTG)
- IgA or IgG antibodies to deamidated gliadin
- anti-endomysial antibodies (highly specific but less sensitive)
Tissue biopsy is diagnostic (2nd biopsy after GFD)
What is the treatment for Coeliac disease?
- gluten-free diet (GFD) leads to symptomatic improvement for most patients
- reduces risk of long-term complications including anaemia, female infertility, osteoporosis and cancer
