CP11-1 Upper GI Pathology Flashcards
What are 3 main pathologies affecting the oesophagus?
Oesophagitis and gastro-oesophageal reflux
Barrett’s oesophagus
Oesophageal carcinoma
What are 3 pathologies affecting the stomach?
Acute and chronic gastritis
Peptic ulceration
Gastric carcinoma
What is an example of a pathology affecting the small bowel?
Coeliac disease
What cells make up the oesophagus?
Mainly stratified squamous epithelium until the distal portion around the level of the diaphragm where the cells become squamocolumnar (squamocolumnar junction) before becoming normal columnar epithelium of the stomach lining
What is oesophagitis?
Inflammation of the oesophagus. Can be acute or chronic.
What causes oesophagitis?
Usually viral e.g. HSV or CMV, or fungal like candida
Can also be chemical via ingestion of corrosive substances or due to reflux of gastric contents.
What is reflux oesophagitis?
Inflammation of the oesophagus due to reflux of gastric acid or bile.
What are risk factors for reflux oesophagitis?
Defective lower oesophageal sphincter
Hiatus hernia
Increased intra-abdominal pressure e.g. from pregnancy
Increased gastric fluid volume due to outflow stenosis.
What is the main symptom of reflux oesophagitis?
‘Heartburn’
How does reflux oesophagitis affect the histology of the oesophagus?
Basal cell hyperplasia
Elongation of papillae
Increase cell desquamation
Inflammation
Ulceration if severe
What are some complications of reflux oesophagitis?
Ulceration
Haemorrhage
perforation
Bengin stricture (segmental narrowing)
Barrett’s oesophagus
What is Barrett’s oesophagus?
Metaplastic transition of epithelium, to columnar mucosa (like in intestines with goblet cells) from stratified squamous, in the oesophagus due to longstanding gastro-oesophageal reflux
What are risk factors for Barrett’s oesophagus?
Male
Caucasian
Overweight
How does the oesophageal epithelium look under the microscope and histological with Barrett’s oesophagus?
Proximal extension of the squamocolumnar junction with the squamous mucosa replaced by columnar mucosa- glandular metaplasia
What does Barrett’s oesophagus increase risk of?
Adenocarcinoma
How does Barrett’s oesophagus progress to an adenocarcinoma?
Barrett’s oesopagus —> low grade dysplasia —> high grade dysplasia xx> adenocarcinoma
How are patients with Barrett’s oesophagus monitored for neoplasia?
Via regular endoscopic surveillance
What are the two main types of oesophageal carcinoma?
Squamous cell carcinomas
Adenocarcinomas
What is the epidemiology of oesophageal carcinoma?
8th most common cancer globally
30% of oesophageal carcinomas are squamous in the UK
Who is most likely to get an oesophageal adenocarcinoma? Males or females?
Males
What causes oesophageal adenocarcinomas?
Barrett’s oesophagus
What are risk factors for oesophageal SCC?
Tobacco and alcohol
Nutrition
Thermal injury e.g. hot drinks
HPV infection
Male
Ethnicity = black
What part of the oesophagus doe SCC usually develop?
In middle and lower third of the oesophagus (less than 15% in upper third)
How can an oesophageal SCC look macroscopically?
Polypodial
With structuring
Ulceration
What system is used to stage GI cancers?
TNM staging
( T = primary Tumour staging, N = lymph Node staging, M= distant Metastases)
What is the pathogenesis of gastritis?
Increased acid in the stomach causes impaired defences e.g. ischaemia, shock, delayed emptying, duodenal reflux or impaired regulation of pepsin secretion.
What can cause increased acid in the stomach disrupting the balance between aggressive and defensive forces of the stomach?
Excessive alcohol
Drugs
Heavy smoking
Ingestion of corrosive substances
Radiation
Chemotherapy
Infection e.g. h.pylori
What is the cause of acute gastritis?
Usually chemical injury e.g through NSAIDs or alcohol
Initial response to H. Pylori infection
What can Acute gastritis cause for the stomach?
Erosions
Haemorrhage
How soon does acute gastritis heal?
Quickly
What causes chronic gastritis?
Autoimmune problems e.g. due to anti-parietal and anti-intrinsic antibodies
Bacterial infection e.g. h. Pylori
Sustained chemical injury due to NSAIDs, bile reflux potentially alcoholism, causing direct injury
What can h. Pylori lead to in chronic gastritis?
Gastric ulcers (in 2-5%)
Duodenal ulcers (in 10-15%)
Gastric cancer and MALT lymphoma
What is h.pylori?
What is peptic ulcer disease?
Localised defect/ ulceration of the stomach extending at least into the submucosa.
Where are common sites of peptic ulcer disease?
First part of duodenum
Junction of antra, and body mucosa
Distal oesophagus
What causes peptic ulcer disease?
Hyperacidity
H. Pylori infection
Duodeno-gastric reflux
Drugs (NSAIDs)
Smoking
How do gastric ulcers and duodenal ulcer differ?
What are come complications of peptic ulcers?
What is the most common gastric cancer?
Adenocarcinomas
What are some less common gastric cancers?
Endocrine tumours
Lymphomas
Stromal tumours
What increases risk of adenocarcinoma of gastro-oesophageal junction?
Being a white make
Have gastrooesophafeal reflux
Incidence increasing reccentky
What increases risk of developing an adenocarcinoma in the body/antrum of the stomach?
H.pylori infection
Diet high in salt and low in fruit and veg
Decreased incidence recently
What is the epidemiology of gastric adenocarcinomas?
5th most common cancer globally, 17th in UK accounting for 2% of all new cancer cases
Steady decline over past decades
What is the aetiology of gastric adenocarcinomas?
Diet - high in smoked/cured meat or fish and pickled by vegetables
H. Pylori infection
Bile reflux
Hydrochlorhydria
Genetics (~1% of cases)
Gastric ulcers
What are the macroscopic subtypes of gastric adenocarcinomas?
Superficial exophytic
Flat or depressed
Superficial excavated
Exophytic
Linitis plastics
Excavated
Polypodial
Ulcerated
What are the microscopic subtypes of gastric cancer?
Intestinal = well or moderately differentiated, may undergo intestinal metaplasia and adenoma steps
Diffuse type = poorly differentiated, scattered growth, associated with cadherin loss/mutation, can be hereditary
What percentage of gastric adenocarcinomas are caused by a germline mutation in E-cadherin?
Around 1%
What is coeliac disease?
An immune mediated enteropathy which is triggered by ingestion of gluten containing cereals in genetically predisposed individuals
What is the epidemiology of coeliac disease?
0.5-1% of people in UK
Commonly affects adults between 30-60
What is the pathogenesis of coeliac disease?
Reaction to gliadin inducing epithelial cells to express IL-15. Increased production of IL-15 causes activation and proliferation of CD8+ intraepithelial lymphocytes which are cytotoxic and kill enterocytes.
CD8+ intraepethial lymphocytes do NOT recognise gliadin directly
How is coeliac disease diagnosed?
With non-invasive serologic tests performed before biopsy e.g. IgA antibodies to TTG, IgA or IgG antibodies to delaminated gliadin and anti-endomysial antibodies
Tissue biopsy is diagnostic
How is coeliac disease treated?
With gluten free diet
What are long term complication of coeliac disease if it’s not treated?
Anemia
Female infertility
Osteoporosis
Cancer - enteropathy associated T-cell lymphoma and small intestinal adenocarcinomas
What are some diseases associated with coeliac disease?
Dermatitis herpetiformis in 10% of patients
Lymohocytic gastritis and colitis
If a patient with coeliac disease still gets symptoms when adhering to a gluten free diet, what might they have?
Cancer
How does the intestine present histologically with coeliac disease?
Vilous atrophy
Crypt elongation
Increased IELs
Increased lamina propria inflammation
What are enterocytes?
Intestinal cells involved in absorption of nutrients
