Upper GI Diseases Flashcards
What are the names of the 2 oesophageal sphincters?
1) Upper end - cricopharyngeal
2) Lower end - gastro-oesophageal junction
What epithelium lines the oesophagus?
Mostly stratified squamous
BUT
distal 1.5-2cm are situated below the diaphragm
lined by glandular (columnar) mucosa
How far from the incisors is the squamo-columnar junction usually located?
40cm
Normal oesophageal histology involved what 3 layers?
1) Mucosa - made up of epithelium and underlying lamina propria
2) Submucosa
3) Muscularis propria
Which histological layer of the oesophagus contains the major blood vessels and lymphatics?
The submucosa
What is oesophagitis?
Inflammation of the oesophagus
What are the 2 classifications of oesophagitis?
Acute or chronic
What are the 2 main causes of oesophagitis?
1) Infections
2) Chemical (ingestion of corrosive substances, or reflux of gastric contents)
What 4 infectious agents can cause oesophagitis?
1) Bacteria
2) Viral - HSV1
3) Viral - CMV
4) Fungal - candida
What is the most common cause of oesophagitis?
Reflux oesophagitis
What is reflux oesophagitis?
Oesophagitis caused by reflux:
of gastric acid (gastro-oesophageal reflux)
bile (duodeno-gastric reflux)
What is the leading clinical symptom of reflux oesophagitis?
Heart burn
What are the 4 main risk factors for reflux oesophagitis?
1) Defective lower oesophageal sphincter
2) Hiatus hernia
3) Increased intrabdominal pressure (obesity)
4) Increased gastric fluid volume due to gastric outflow stenosis (Eg. antral tumour)
What is the most common complication of a para-oesophageal hernia?
Strangulation (compromised blood supply to that part of the stomach - can get ischaemia and necrosis of stomach)
What 4 changes are seen histologically in the squamous epithelium/lamina propria in reflux oesophagitis?
1) Basal cell hyperplasia (rather than being 1/2 layers thick normally, this is due to increased proliferation and cell turnover)
2) Elongation of papillae (lamina propria papillae normally project 1/3 way into epithelium, project further)
3) Increased cell desquamation (squamous epithelium is normally 8-15 layers thick, much thinner)
4) Inflammatory cell infiltration into lamina propria (neutrophils, eosinophils, lymphocytes)
What are the 5 main complications of reflux disease?
1) Ulceration - erosion of the epithelium and then underlying layers
2) Haemorrhage - ulceration gets to submucosa and hits vessels
3) Perforation
4) Benign stricturing - if get some healing by fibrosis can then get stricturing leading to segmental narrowing and dysphagia
5) Barrett’s oesophagus
What is the cause of Barrett’s oesophagus?
Long standing reflux
What are the 3 risk factors for Barrett’s oesophagus?
Same as for reflux disease
1) Male
2) Caucasian
3) Obese
How does Barrett’s oesophagus appear macroscopically?
Proximal extension of the squamo-columnar junction
Histologically what is Barrett’s oesophagus?
METAPLASIA:
Squamous epithelium replaced by glandular (columnar) mucosa
At what level is the squamo-columnar junction of the oesophagus normally seen?
Level of the diaphragm
What 3 types of columnar mucosa can be seen in Barrett’s oesophagus but which is most typical and almost diagnostic of Barrett’s oesophagus?
1) Gastric cardia type
2) Gastric body type
3) Intestinal type = most typical of Barrett’s oesophagus
What cells are found in the intestinal mucosa and not in the gastric mucosa which are highly suggestive of Barrett’s if seen in the oesophagus?
Goblet cells
Is Barrett’s oesophagus a malignant condition?
No but it is considered a premalignant condition with an increased risk of developing adenocarcinoma
What screening procedure is required in patients with Barrett’s oesophagus?
Regular endoscopic surveillance
Early detection of neoplasm
What are the 4 steps in the progression from Barrett’s oesophagus to adenocarcinoma, and the main histological features of each?
1) Barrett’s oesophagus - intestinal type epithelium, see goblet cells, normal nuclei basally located
2) Low grade dysplasia - More complex architecture, less basally located nuclei more atypical
3) High grade dysplasia - Distorted architecture and atypical nuclei
4) Adenocarcinoma - All features of dysplasia and cells breaking through basement membrane to invade other structures
How common is oesophageal cancer compared to other cancers?
8th most common in the world
What are the histological types of oesophageal cancer?
1) Squamous cell carcinoma - originating from the normal oesophageal epithelium
2) Adenocarcinoma - following on from Barrett’s, originating from glandular epithelium
In the UK is squamous or adenocarcinoma more common, how does this compare to other countries?
Adenocarcinoma more common (could be due to obesity - risk factor for Barrett’s)
Other countries squamous is more common
Whats the main cause of adenocarcinoma and what are the other 2 possible risk factors?
1) Barrett’s oesophagus
Other risk factors with a link:
Tobacco, obesity
What is the normal site of an adenocarcinoma?
Lower oesophagus
How would the macroscopic appearance of a polypoidal, ulcerated adenocarcinoma differ?
Polypoidal - sticks out into the lumen of the oesophagus, could lead to problems with swallowing
Ulcerated - appears as an ulcer
What are the 6 possible macroscopic structures of an adenocarcinoma?
1) Plaque-like
2) Nodular
3) Fungating
4) Ulcerated
5) Depressed
6) Infiltrating
What are the 7 risk factors for squamous carcinoma of the oesophagus?
1) Tobacco
2) Alcohol
3) Nutrition (potential sources of nitrosamines)
4) Thermal injury (hot beverages)
5) HPV
6) Male
7) Ethnicity (black)
What is the normal site of a squamous carcinoma of the oesophagus?
Middle and lower third
>15% in upper third of oesophagus
In the TMN staging of oesophageal carcinoma what does the pT stand for and what are the 4 stages?
pT = depth of invasion of primary tumour
pT1: invades lamina propria, muscularis mucosae or submucosa
pT2: tumour invades muscularis propria
pT3: tumour invades adventitia
pT4: tumour invades adjacent structures
What does the N stand for in the TMN staging of oesophageal carcinoma and what are the 4 stages?
N = regional lymph nodes pN0 = 0 nodes pN1 = regional lymph node metastasis in 1 or 2 nodes pN2 = in 3-6 nodes pN3 = in 7+ nodes
What does the M stand for in TMN staging of oesophageal cancer and what are the 2 stages?
M0 = no distant metastasis M1 = distant metastasis
What are the 4 anatomical regions of the stomach?
Cardia (around oesophageal junction)
Fundus (above oesophageal opening)
Body
Antrum
What are the 3 histological regions of the stomach with different functions?
1) Cardia
2) Body
3) Antrum
The stomach is normally a balance between aggressive (acid) and defensive forces, what are those 5 defensive forces?
1) Surface mucous
2) Bicarbonate secretion
3) Mucosal blood flow
4) Regenerative capacity
5) Prostaglandins
What 7 things can lead to increased acidic forces in the stomach?
1) excessive alcohol
2) Drugs
3) heavy smoking
4) corrosive
5) radiation
6) chemotherapy
7) Infection
What 5 things can impair the defences of the stomach against acid?
1) Ischeamia
2) Shock
3) Delayed emptying
4) Duodenal reflux
5) Impaired regulation of pepsin secretion
What are the 3 main aetiologies for chronic gastritis?
ABC:
1) Autoimmune
2) Bacterial infection (H.pylori)
3) Chemical injury (NSAIDs, Bile reflux)
What is the main pathogenic mechanism behind autoimmune chronic gastritis?
Anti-parietal cell and anti-intrinsic factor antibodies and sensitised T cells
What would be the 2 main histological findings with autoimmune chronic gastritis?
1) Glandular atrophy in body mucosa
2) Intestinal metaplasia
What are the main histological findings in chronic gastritis due to bacterial infection?
1) Multifocal atrophy: antrum > body
2) Intestinal metaplasia
What is the main pathogenic mechanism behind bile reflux causing chronic gastritis?
Degranulation of mast cells
What is the main pathogenic mechanism behind NSAID’s causing chronic gastritis?
Disruption of the mucus layer
What would be the main histological findings in chronic gastritis due to a) oedema b) bile reflux?
a) NSAIDs - oedema
b) Bile reflux - vasodilation
What kind of bacteria is H pylori?
Gram negative spiral shaped bacterium - lives on the epithelial surface protected by the overlying mucus barrier
How does H pylori cause disease?
Damages the epithelium leading to chronic inflammation of the mucosa
H pylori is more commonly found in what part of the stomach?
More common in the antrum than body
What does H.pylori infection do to the stomach? 3
1) Glandular atrophy
2) Replacement fibrosis
3) Intestinal metaplasia
H.pylori infected individuals can present with what 2 kinds of ulcer, which is more common?
1) Gastric ulcer
2) Duodenal ulcer - more common
H.pylori infection can lead to what 2 cancers?
1) Gastric cancer
2) MALT lymphoma (mucosa associated lymphoid tissue)
What is peptic ulcer disease?
Localised defect in the digestive tract.
Typically the stomach or duodenum, extending at least into submucosa.
What are the 3 major sights of peptic ulcer disease?
1) First part of the duodenum
2) Junction of antral and body mucosa
3) Distal oesophagus
What are the 5 main aetiological factors contributing to peptic ulcer disease?
1) Hyperacidity
2) H.pylori infection
3) Duodeno-gastric reflux
4) Drugs NSAID’s
5) Smoking
What are the 3 histological features of an acute gastric ulcer?
1) Full thickness coagulative necrosis of mucosa (or deeper layers)
2) Covered with ulcer slough (necrotic debris + fibrin + neutrophils)
3) Granulation tissue at ulcer floor
What are the 4 histological features of a chronic gastric ulcer?
1) Clear-cut edges overhanging the base
2) Extensive granulation and scar tissue at ulcer floor
3) Scarring often throughout the entire gastric wall with breaching of the muscularis propria
4) Bleeding
What are the 4 main complications of peptic ulcers?
1) Haemorrhage (acute and/or chronic - anaemia)
2) Perforation - peritonitis
3) Penetration into adjacent organ (liver, pancreas)
4) Stricturing - hour glass deformity
What is the difference in incidence between gastric ulcer and duodenal ulcer?
Duodenal ulcer 3x more common than gastric ulcer
What is the difference in age distribution between gastric and duodenal ulcer?
Gastric ulcers increase with age
Duodenal ulcer increase up to 35 years
How do acid levels differ in a gastric ulcer compared to a duodenal ulcer?
Gastric ulcer - normal or low acid levels
Duodenal ulcer - elevated or normal acid levels
What percentage of gastric ulcer and duodenal ulcers are caused by H.pylori gastritis?
70% of gastric ulcers
95-100% duodenal ulcers (predominantly antrum)
Gastric ulcers and duodenal ulcers are each more common in which blood groups?
Gastric - A
Duodenal - O
Gastric cancer is most frequently what type of cancer and can be what 3 other types less frequently?
Most frequently - adenocarcinoma
Less frequently - endocrine tumours, MALT lymphomas, Stromal tumours (can be low grade benign or high grade malignant)
What are the 4 main risk factors for gastric cancer?
1) Diet (smoked/cured meat or fish, pickled veg)
2) H pylori infection
3) Bile reflux
4) Hypochlorydia (allows bacterial growth)
Gastric adenocarcinoma of the gastro-oesophageal junction is associated with what risk factor and which group?
Associated with white males
Association with GO reflux
NO association with H.pyloir/diet
Gastric adenocarcinoma of the gastric body/antrum is associated with what risk factors?
Associated with H pylori, diet
NO association with GO reflux
What are the 2 main histological types of gastric adenocarcinoma and what are their main features?
1) Diffuse type (signet ring cell carcinoma) - poorly differentiated, scattered growth, cadherin loss/mutation
2) Intestinal type (tubular adenocarcinoma) - Well or moderately differentiated, may undergo metaplasia and adenoma steps
What histological type of gastric adenocarcinoma is hereditary gastric adenocarcinoma?
Diffuse type - hereditary diffuse type gastric cancer
Hereditary diffuse type gastric carcinoma involves a germline mutation in which gene?
E-cadherin mutation
In TMN staging of gastric adenocarcinoma what are the different T stages?
1) pT1: intramucosal or submucosal invasion
2) pT2: into muscularis propria
3) pT3: through muscularis propria into subserosa
4) pT4: through serosa (peritoneum) or into adjacent organs
In TMN staging what is the N and M stages?
N = lymph node involvement (same as oesophageal carcinoma) M = distant metastasis (0 or 1 if metastasis)
What is the estimated prevelance of ceoliac disease?
0.5-1%
What is the pathogenesis of coeliac disease?
- Gliadin (alcohol soluble component of gluten) induces epithelial cells to express IL-15/interleukine 15
- IL-15 produced by the epithelium activates and induces proliferation of CD8+ Intraepithelial lymphocytes (IELs)
- CD8+ cells are toxic and kill enterocytes
- CD8+ IELs do not recognise gliadin directly
- Gliadin induced IL15 secretion by epithelium is the mechanism
Ceoliac disease commonly affects adults of what age?
30 - 60 years
What are the 4 typical symptoms of symptomatic coeliac patients?
1) Anaemia
2) Chronic diarrhoea
3) Bloating
4) Chronic fatigue
Why is diagnosis of coeliac disease difficult?
1) Can have atypical presentations/ non specific symptoms
2) Can have silent disease - positive serology, villous atrophy but no symptoms
3) Can have latent disease - positive serology but no villous atrophy
What 2 other diseases is coeliac disease associated with?
1) Dermatitis herpetiformis - 10% of patients
2) Lymphocytic gastritis and lymphocytic colitis
What 2 cancers is coeliac disease associated with?
1) Enteropathy- associated T-cell lymphoma
2) Small intestinal adenocarcinoma
What is the gold standard diagnostic tool for coeliac disease?
Tissue biopsy (before and after having a gluten free diet)
Which non invasive serological tests are used prior to biopsy in the diagnosis of coeliac disease?
1) IgA Ab to tissue transglutaminase (TGG)
2) IgA or IgG Ab to deamidated gliadin
3) Anti-endomysial Abs - highly specific but less sensitive
What is the treatment for coeliac disease?
Gluten free diet - symptomatic treatment for most patient but also reduces the chances of long term complications
What 4 long term complications of coeliac disease are reduced by taking a gluten free diet?
1) Anaemia
2) Female infertility
3) Osteoporosis
4) Cancer
Helicobacter pylori is associated with…
Gastritis
Peptic Ulcer Disease
Gastric cancer
NSAIDs commonly cause
gastric ulcers
Gastric ulcers may harbour…
Adenocarcinoma
How common is stomach cancer in the UK?
17th most common in the UK
Coeliac disease is associated with which histopathological features?
Villous atrophy
Crypt elongation
Increased intraepithelial lymphocytes
Common presentation of coeliac disease
Diarrhoea
Bloating
Malabsorption
