Week 6 Upper Tract GI Flashcards
What is the length of the oesophageus and what is it normally lined with?
25 cm long muscular tube mostly lined by squamous epithelium
Where are the spincters of the oesophagus found?
Sphincter at upper end (cricopharyngeal) and lower end (gastro-oesophageal junction)
What part of the oesophagus is lined by glandular mucosa?
Distal 1.5-2 cm are situated below the diaphragm and lined by glandular (columnar) mucosa
Where is the squamo-columnar junction situated?
The squamo-columnar junction is usually located at 40 cm from the incisor teeth
What is Oesophagitis?
Inflammation of the oesophagus
What is the classifications of oesophagitis?
Acute
Chronic
What is the aetiology of oesophagitis?
Infectious–> not common unless you are immunocompromised
Bacterial, viral (HSV1, CMV), fungal (candida)
Chemical
Ingestion of corrosive substances
Reflux of gastric contents –> gastro reflux disease most common type
What is the commenst form of oesophagitis?
Reflux oesophagitis
What is the cause of reflux oesophagitis?
Caused by reflux of gastric acid (gastro-oesophageal reflux) and/or bile (duodeno-gastric reflux)
What are the risk factors of Reflux oesophagitis?
Defective lower oesophageal sphincter
Hiatus hernia part of the stomach will herniate through the diaphragm to the thorax
Increased intra-abdominal pressure
Increased gastric fluid volume due to gastric outflow stenosis
What is the main clinical symptom of reflux oesophagitis and what is the possible complications?
Heart burn is the main symptom.
Ulceration Haemorrhage Perforation Benign stricture (segmental narrowing) Barrett’s oesophagus
Whata are the two types of hiatus hernia?
Sliding Hiatus Hernia
Paraesophageal hiatus hernia
What are the symptoms of sliding and paraesophageal hiatus hernia?
Sliding –> reflux symptoms
Para-oesophageal hernia –> strangulation which can lead to a lack of blood to that area and can get necrosis
What are the epithelial changes that takes place in reflux oesophagitis?
Squamous epithelium –> Basal cell hyperplasia, elongation of papillae, increased cell desquamation
Lamina propria –>Inflammatory cell infiltration (neutrophils, eosinophils, lymphocytes)
What is the cause of Barrett’s oesophagus?
Longstanding reflux
Risk factors of Barrett’s oesophagus?
Same as for reflux (male, Caucasian, overweight)
What is the macroscopic features of Barretts oeophagus?
Proximal extension of the squamo-columnar junction = caused by metaplasia = change from normal squamous lining to a columnar lining in the stomach –> this is trying to combat the acid content
What is the histological change in Barrett’s oeophagus?
Squamous mucosa replaced by columnar mucosa > “glandular metaplasia
What are the types of columnar mucosa in Barrett’s oeophagus?
Get a type of gastric epithelium that represents
Gastric cardia type
Gastric body type
Intestinal type = “specialised Barrett’s mucosa”
What is the importance of specialised barrett’s mucosa in terms of diagnosis?
Characteristic feature of Barrett’s oesophagus = Confirm diagnostic when you find this in the oesophageal tube
What is adenocarcinoma?
A malignant tumour formed from glandular structures in epithelial tissue
Barret’s oesophagus increases the risk of what disease?
Barret’s oesophagus is a premalignant condition with an increased risk of developing adenocarcinoma of the oesophagus
How is neoplasia of the oesophagus detected?
Regular endoscopic surveillance is recommended for early detection of neoplasia
What is a treatment if you get adenocarcinoma of the oesophagus?
Replacement of the esophagostomy= remove it and then replace with colon
What is the disease progression from Barrett’s oesophagus too adenocarcinoma?
Barrett’s oesophagus –> low grade dysplasia –> high grade dysplasia –> adenocarcinoma
What are the two histological types of oesophageal carcinoma?
Squamous cell carcinoma –> originating from the normal oesophageal epithelium
Adenocarcinoma –> following on from Barrett’s, originating from glandular epithelium
Where is incidence of adenocarcinoma highest?
Risen in industrial country due to increase in number of overweight people.
There is a ratio of 7;1 for males/female preponderance.
Hight incidence among caucasions
What is the aetiology of adenocarcinoma?
Barrett’s oesophagus
tobacco, obesity
Where is adenocarcinoma found and what is the macroscopic profile?
Finally how does spread and staging?
Localisation:
Lower oesophagus –> see the barest metaplasia
Macroscopy:
Plaque-like, nodular, fungating, ulcerated, depressed, infiltrating
Spread and staging:
Same as squamous cell carcinoma
How common is oesophageal carcinoma in the world?
It is the 8th most common cancer
What is more common squamous carcinoma or adenocarcinoma in the UK?
Adenocarcinoma?
What are the risk factors of Squamous carcinoma?
Tobacco and alcohol Nutrition (potential sources of nitrosamines) Thermal injury (hot beverages) HPV Male Ethnicity (black)
What is the location of squamous carcinoma?
Middle and lower third (
What system is used for staging cancer and what does each part mean?
Use the TNM system
T–> depth of invasion of the primary tumour
N–> Regional lymph nodes
M –> distant metastasis
What are the different grades of T in the TNM system for Squamous carcinoma and adenocarcinoma staging?
pT1: tumour invades lamina propria, muscularis mucosae or submucosa
pT2: tumour invades muscularis propria thick muscle layer
pT3: tumour invades adventitia through the muscularis propria
pT4: tumour invades adjacent structures move outside the eosophageus
What are the different grades of N and M in the TNM system for Squamous carcinoma and adenocarcinoma staging?
pN0: no regional lymph node metastasis
pN1: regional lymph node metastasis 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
M0: no distant metastasis
M1: distant metastasis
What are the 4 anatomcal regions of the stomach?
Cardia
Fundus
Body
Antrum
What are the 3 histological regions with different functions?
Cardia
Body
Antrum
What type of glands are found in the cardia and antrum of the stomach?
Mucous glands
What type of glands are found in the body of the stomach?
Body get specialist glands that produce the enzymes to digest
Normally how does a stomach balance beteen the aggressive acid and defences forces?
Surface mucous
Bicarbonate secretion
Mucosal blood flow Regenerative capacity Prostaglandins
What is a cause of increased aggression in the stomach?
Excessive alcohol- Drugs --> NSAIDS Heavy smoking Corrosive Radiation Chemotherapy Infection
What is a cause of impaired defences of the stomach?
Ischaemia --> reduction in mucosal blood flow Shock Delayed emptying Duodenal reflux Impaired regulation of pepsin secretion
Describe the type of bacteria H. Pylori is and its structure?
Gram negative spiral shaped bacterium
2.5-5.0 micrometres long
4 to 6 flagellae
Lives on the epithelial surface protected by the overlying mucus barrier
What is the actions of H.pylori?
Damages the epithelium leading to chronic inflammation of the mucosa
More common in gastric antrum than body
Results in glandular atrophy lead to replacement fibrosis over time and intestinal metaplasia
What are the complications of H.pylori?
Gastric ulcer = 2-5%
Duodenal ulcer = 10-15%
What is the 3 main aetiology category that causes chronic gastritis?
Autoimmune
Bacterial infection
Chemical injury
What is the pathogenic mechanism of autoimmune chronic gastritis?
Anti-parietal cell and anti-intrinsic factor antibodies
Sensitised T lymphocytes
What is the histological findings of autoimmune chronic gastritis?
Glandular atrophy in body mucosa intestinal metaplasia
What is the main histological findings of chronic gastritis caused by Bacterial infection?
1) Active chronic inflammation
2) Multifocal atrophy: Antrum> body intestinal metaplasia
What is the pathogenic mechanism for chronic Gastritis causd by NSAIDS and bile reflux?
NSAIDS –> disruption of the mucus layer
Bile reflux –> Degranulation of mast cells
Histological findings of oedema, vasolidation or paucity of inflammatory cells in chronic gastritis is due to?
Oedema –> NSAIDS
Vasolidation –> bile reflux
paucity of inflammatory cells –> Alcohol
What two cancers can be caused by H.pylori?
Gastric cancer
MALT lymphoma
What is peptic ulcer?
Localised defect extending at least into submucosa
What are the 3 major sites of peptic ulcers?
First part of duodenum Junction of antral and body mucosa Distal oesophagus (GOJ)
What is the 5 main aetiological factors of peptic ulcers?
Hyperacidity H. pylori infection Duodeno-gastric reflux Drugs (NSAIDs) Smoking
What are the histological findings of acute gastric ulcers?
Full-thickness coagulative necrosis of mucosa (or deeper layers)
Covered with ulcer slough (necrotic debris + fibrin + neutrophils)
Granulation tissue at ulcer floor
What are the histological findings of chronic gastric ulcers?
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 are the 4 complications of peptic ulcers?
Haemorrhage (acute and/or chronic –> anaemia)
Perforation –> peritonitis –> through the full thickness of the wall
Penetration into an adjacent organ (liver, pancreas)
Stricturing –> hour-glass deformity
Is gastric or duodenal ulcer more common and what is the age distribution?
Duodenal ulcer is more common.
Gastric ulcer –> increase with age
Duodenal ulcer –> incrase up to 35 yrs
What are the acid levels in gastric and duodenal ulcers?
Gastric –> normal or low
Duoednal –> elevated or normal
How often does H.pylori caused Gastric and Duodenal ulcers?
Gastric –> 70% the other 30% is caused due to gastric cancer, chemicals, drugs
Duodenal –>95-100% ( predominatly in the antrum)
What blood groups is gastric ulcer and duodenal ulcers found in?
Gastric –> blood group A
Duodenal –> blood group O
What is the most common gastric cancer?
Adenocarcinoma
What are less frequent gastric cancers?
Endocrine tumours MALT lymphomas Stromal tumours (GIST)--> from stromal cells
How common is gastric adenocarcinoma in the world?
5th most common cacncer in the world
What are the causes of gastric adenocarcinoma?
Diet (smoked/cured meat or fish, pickled vegetables)
Helicobacter pylori infection
Bile reflux (e.g. post Billroth II operation)
Hypochlorhydria (allows bacterial growth)
~1% hereditary
What is the assoications with carcinoma of the gastroesophageal junction?
White males
- Association with GO reflux
- No association with H. pylori / diet
- Increased incidence in recent years with overweight individuals
What are the associations of carcinoma in the gastric body/atrum?
- Association with H. pylori
- Association with diet (salt, low fruit
& vegetables) - No association with GO reflux
- Decreased incidence in recent years
What is the 2 main histological subtypes of gastric cancer and whata are there features?
Diffuse types (signet ring cell carcinoma) –> worse prognosis . Poorly differentiated. Scattered growth. Cadherin loss/mutation
Intestinal type ( tubular adenocarcinoma) -well or moderately differentiated May undergo intestinal metaplasia and adenoma steps
What type of gatric cancer is hereditary and what is teh mutation?
Hereditary diffuse type gastric cancer (HDGC)
Caused by Germline CDH1/E-cadherin mutation
What is the TNM staging for gastric cancer?
pT1: intramucosal or submucosal
pT2: into muscularis propria
pT3: through muscularis propria into subserosa
pT4: through serosa (peritoneum)or into adjacent organs
pN0: no lymph node metastases
pN1: 1 to 2 lymph node metastases
pN2: 3 to 6 lymph node metastases
pN3: more than 6 lymph node met.
M0: no distant metastases
M1: distant metastases present
What is Coeliac disease and what is its estimated prevalence?
Sensitivity to Gluten
Immune mediated enteropathy
Fairly common, estimated prevalence of 0.5% to 1%
What are the 2 pathogensis causes of coeliac disease?
Reaction to GLIADIN
Alcohol soluble component of gluten
Contains most of the disease-producing components
Induces epithelial cells to express IL-15
CD8+ Intraepithelial lymphocytes (IELs)
IL15 produced by the epithelium activation / proliferation of CD8+ IELs
These are cytotoxic and kill enterocytes
CD8+ IELs do not recognise gliadin directly
Gliadin-induced IL15 secretion by epithelium is the mechanism
What is the diagnosis of Coeliac disease?
Commonly affects adults between 30 and 60 years
No geneder preference
Diagnosis is often difficult
Atypical presentations / non specific symptoms
Silentdisease
Positive serology / villous atrophy but no symptoms
Latentdisease
Positive serology but no villous atrophy
Symptomatic patients
Anaemia, chronic diarrhoea, bloating, or chronic fatigue
What other diseases and cancer is coeliac disease associated with?
Disease:
Dermatitis herpetiformis - 10% of patients
Lymphocytic gastritisandlymphocytic colitis
Cancer:
Enteropathy-associated T-cell lymphoma
Small intestinal adenocarcinoma
What is the diagnosis of coeliac disease?
Non-invasive serologic tests usually performed before biopsy
The most sensitive tests–> serology test
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) –> Gold standard
Treatment for Coeliac disease
Gluten-free diet –> symptomatic improvement for most patients
What are the long term consequences of coeliac disease if not treated?
Anaemia, female infertility, osteoporosis, and cancer
