Histo: Upper GI Disease Flashcards
What is a key histological feature of the oesophageal mucosa?
Presence of submucosal glands
what is the Z-line?
The point in the oesophagus at which the epithelium transitions from being squamous to being columnar
What does the body and fundus of the stomach have in abundance?
Specialised glands responsible for producing acid and enzymes
Which part of the stomach tends to be affected by H. pylori-associated gastritis?
Pylorus and antrum
What are the three layers of the gastric mucosa?
- Columnar epithelium
- Lamina propria
- Muscularis mucosa
Where do cells proliferate in the intestinal lining?
In the crypt
What happens to cells after they proliferate in the crypt?
They migrate upwards to the tip of the villous and shed at the top.
What is the normal villous: crypt ratio?
2:1
What does the 2:1 villous to crypt ratio depend on?
The height of the villi and the depth of the crypts.
How does the proportion of crypts change if the villi are shorter?
The crypts take up a bigger proportion of the total length.
What happens to the crypts when the villi get damaged?
The crypts will proliferate to replace the damaged villi.
What does the presence of goblet cells in the stomach signify?
Intestinal metaplasia
NOTE: goblet cells are NOT normally seen in the stomach
What is the characteristic histological feature of acute oesophagitis?
Presence of lots of neutrophils- hallmark of acute inflammation
This is usually caused by GORD
The redness is a cardinal sign of inflammation
What can acute oesophagitis result in?
- Ulceration
- Fibrosis
Complications
* Haemorrhage
* Perforation
* Stricture
* Barrett’s oesophagus
What does ulceration of the oesophagus produce?
produces a necrotic slough, inflammatory exudate and granulation tissue
Define Barrett’s oesophagus.
Metaplastic process by which the normal sqaumous epithelium of the lower oesophagus is replaced by columnar epithlieum
NOTE: this is also known as columnar-lined epithelium (CLO)
What further degree of metaplasia is associated with an even greater risk of cancer than Barrett’s oesophagus?
Intestinal metaplasia - goblet cells become visible
NOTE: metaplasia is reversible
Describe the histological route to cancer
Metaplasia –> Dysplasia –> Cancer
Why is metaplasia not technically pre malignant? What can metaplasia lead to?
Metaplasia is NOT technically pre-malignant because it is REVERSIBLE
However, once you have metaplasia you can progress to dysplasia
Define dysplasia.
Changes showing some of the cytological and histological features of malignancy but with no invasion through the basement membrane.
What histological stage does the screening process for Barrett’s oesophagus aim to identify?
the screening process for Barrett’s oesophagus is aimed at identifying patients at the dysplastic stage
What is adenocarcinoma?
Adenocarcinoma is when the abnormal cells invade through the basement membrane
Why is adenocarcnioma difficult to remove for surgeons?
adenocarcinomas can spread underneath the columnar epithelium - this is a massive issue for surgeons because they don’t know exactly where to stop cutting
What is squamous carcinoma of the oesophagus associated with? Which area does it affect? Where is it common?
- Smoking and alcohol
- It tends to affect the middle/lower oesophagus
- Invades into the submucosa
- It is the most common type of oesophageal cancer in Africa
What are the hallmark histological features of squamous cell carcinoma of the oesophagus?
Cells produce keratin (normal oesophageal squamous epithelium is non-keratinised)
Intercellular bridges
What is this slide showing
Squamous cell carcinoma at bottom
Prognosis of oesophageal carcinoma
o Poor prognosis
o Diagnosis at the pre-invasive stage is important
How is eosinophilis oesophagitis treated?
- Steroids
- Allergen removal
NOTE: this is associated with an allergic reaction (asthma of the oesophagus). It is due to allergy to food causing muscle spasm and dysphagia.
What is the commonest cause of oesophageal varices?
- Cirrhosis of the liver (Most common)
- Portal vein thrombosis
List some causes of chronic gastritis
- Autoimmune (body, auto-antibodies e.g. antiparietal)
- Bacterial (H. pylori)
- Chemical (NSAIDs, bile reflux)
o NOTE: this can be remembered as ‘the ABC of chronic gastritis’: Autoimmune, Bacteria, Chemical)
NOTE: the key inflammatory cells in chronic gastritis are lymphocytes
Which inflammatory cells would you see in chronic gastritis.
lymphocytes = chronic inflammation
NOTE: the presence of co-existing acute processes can mean that you may also see a lot of neutrophils
What is mucosa-associated lymphoid tissue and what is their presence indicative of?
- Chronic gastritis caused by H. pylori infection induces lymphoid tissue in the stomach -It induces the development of lymphoid follicles in germinal centres
- The presence of lymphoid follicles in a stomach biopsy, is highly suggestive of H. pylori infection (normal stomach mucosa does not contain lymphoid follicles)
- This is important because it is associated with an increased risk of lymphoma
Name a key virulence factor/toxin that enables H. pylori to cause chronic infection.
Cag-A positive H. pylori has a needle-like appendage that injects toxins into intercellular junctions allowing bacteria to attach more easily
Associated with chronic inflammation.
Does Helicobacter pylori directly invade the epithelium in gastritis?
No, H. pylori binds to epithelial cells and injects toxins but does not directly invade the epithelium.
What is the sequence of conditions that can result from H. pylori associated gastritis?
CLO (columnar-lined oesophagus ) → IM (intestinal metaplasia) → Dysplasia.
What is the increased risk of adenocarcinoma due to H. pylori associated gastritis?
8 times increased risk.
What type of lymphoma can be a consequence of H. pylori associated gastritis?
Lymphoma (MALToma).
How does the treatment of H. pylori infection with antibiotics impact cancer risk?
It drastically reduces the risk of cancer.
List some other cause of gastritis.
Infection
*CMV
* Strongyloides
( tend to occur in immunocompromised individuals )
IBD
* Crohn’s disease
What are the two pathways that lead to the development of GI cancer?
- Metaplasia-Dysplasia pathway (e.g. oesophageal cancer)
- Adenoma-Carcinoma pathway (e.g. colon cancer)
Define gastric ulcer.
The depth of the loss of tissue goes beyond the muscularis mucosa (into the submucosa)
NOTE: if you only get loss of surface epithelium with or without involvement of the lamina propria then it is an erosion, NOT an ulcer)
What is the difference between acute and chronic ulceration?
Chronic ulcers are accompanied by scarring and fibrosis
What must you do with all gastric ulcers?
They should all be biopsied to rule out malignancy.
List some complications of gastric ulcers.
Bleeding (anaemia, shock-massive haemorrhage)
Perforation (peritonitis)
What signifies the presence of intestinal metaplasia in the stomach?
The presence of goblet cells in the mucosa of the stomach.
What causes intestinal metaplasia in the stomach?
It occurs in response to long-term damage.
What is the association between intestinal metaplasia and cancer?
Increased risk of cancer.
What characterizes gastric epithelial dysplasia?
An abnormal epithelial pattern of growth.
What features are present in gastric epithelial dysplasia?
Some cytological and histological features of malignancy.
Is there invasion through the basement membrane in gastric epithelial dysplasia?
No
Risk factors for gastric cancer
Epidemiology of gastric cancer
- High incidence in Japan, Chile, Italy, China, Portugal and Russia
- More common in MALES
What type of cancer is gastric cancer?
- 95% adenocarcinoma
- 5% squamous cell carcinoma, lymphoma (MALToma), gastrointestinal stromal tumour (GIST), neuroendocrine tumours
What are the two main morphological subtypes of gastric adenocarcinoma? What are their key features?
- Intestinal: well-differentiated, presence of big gland containing mucin
- Diffuse: poorly differentiated, composed of single cells with no attempt at gland formation
Name two types of diffuse adenocarcinoma of the stomach.
- Linitis plastica
- Signet ring cell carcinoma
What is the overall survival rate of gastric cancer?
15%
What is gastric lymphoma?
- Lymphoma of the gastric mucosa that is driven by chronic inflammation (H. pylori gastritis)
- Consists of lots of B lymphocytes (marginal zone)
NOTE: if H. pylori is also present, crypts may also contain lots of neutrophils
* If you treat H. pylori, the lymphoma could be reversed
What causes duodenitis and duodenal ulcers?
- Caused by increased acid produced in the stomach that spills into the duodenum
- It can also occur due to chronic inflammation and gastic metaplasia with H. pylori infection
Why does the intestinal epithelium change to look more like gastric epithelium in duodenitis?
gastric epithelium is well designed to deal with acid
List some other pathogens that affect the duodenum.
- CMV
- Cryptosporidium
- Giardiasis
- Whipple’s disease (Tropheryma whippelii)
List some histological features of malabsorption.
- Villous atrophy
- Crypt hyperplasia
- Increased intraepithelial lymphocytes (>20 per 100 enterocytes) - normal range is less than 20 per 100 enterocytes
NOTE: the T cell response to gliadin in Coeliac disease is responsible for the damage to villi. Crypt hyperplasia occurs in an attempt to regenerate the damaged villi
What are the architectural and inflammatory changes In coeliac disease?
Architectural - loss of villi and crypt hyperplasia
inflammatory - increased intraepithelial lymphocytes
What is lymphocytic duodenitis?
- When you get the inflammatory changes (increased intraepithelial lymphocytes) without architectural changes
- Many people with this condition either have coeliac disease or will go on to develop coeliac disease
How is coeliac disease diagnosed?
Antibodies: anti-tTG, anti-endomysial
Anti antibodies of:
* Endomysial Antibodies
* Tissue Transglutaminase Antibodies
Duodenal biopsy
NOTE: duodenal biopsy will be normal in people with coeliac disease who have been following a strict gluten-free diet
Biopsy
* ON gluten rich diet showing villous atrophy
* OFF gluten rich diet showing normal villi
To see biopsy changes would need to be eating gluten for a month prior otherwise false negative
Which other condition has very similar clinical and histological features to coeliac disease?
Tropical sprue
Differentiate because coeliac is to do with diet and this is to do with tropics (eg. Argentina)
What type of lymphoma is duodenal lymphoma?
T cell lymphoma
NOTE: lymphomas in the stomach due to H. pylori are B cell lymphomas
What do patients with coeliac disease have an increased risk of?
GIT cancers
Where are MALTomas associated with coeliac disease found?
duodenum
