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
(parietal cells producing HCL and IF, chief cells producing pepsinogen)
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
What is the normal villous: crypt ratio?
2:1
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
This is usually caused by GORD
What can acute oesophagitis result in?
- Ulceration
- Haemorrhage
- Perforate
- Fibrosis
- Stricture
- Barrett’s oesophagus
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
Outline the histological stages that occur leading up to Upper GI cancer
- Metaplasia (not considered pre-malignant as is reversible)
- Dysplasia (histological and cytological changes similiar to that of cancer but no invasion of basement membrane)
- Adenocarcinoma (invasion through basement membrane occurs)
The Upper GI pathway to cancer differs from the lower GI. Upper GI is referenced as flat pathway (metaplasia –> dysplasia –> cancer). While Lower GI is referred to as Polyp pathway as often there is formation of a polyp.
Define dysplasia.
Changes showing some of the cytological and histological features of malignancy but with no invasion through the basement membrane.
What is squamous carcinoma of the oesophagus associated with?
- Smoking and alcohol
- It tends to affect the upper/middle 2/3rds of the oesophagus
- It is the most common type of oesophageal cancer in Africa
What are the main histological features of squamous cell carcinoma of the oesophagus?
Cells produce keratin (normal oesophageal squamous epithelium is non-keratinised)
Intercellular bridges
What is adenocarcinoma of the oesophagus associated with
- Bottom 1/3rd
- Associations: GORD, Barrett’s oesophagus
What are the main histological features of adenocarcinoma of the oesophagus?
Histology:
- Glandular epithelium
- Mucin
How is eosinophilic 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
Histological differences between Acute and Chronic Gastritis
Acute Gastritis = Neutrophil infiltration
Chronic Gastritis = Lymphocyte infiltration (may have some neutrophils due to co-existent acute changes)
Causes of Acute Gastritis
Chemical = Aspirin/NSAIDs, Alcohol, Corrosives
Bacterial = H. pylori, CMV
Causes of chronic gastritis
ABCD:
Autoimmune (atrophic) = i.e. antiparietal ABs
Bacteria (atrophic/non-atrophic) = H.pylori, CMV
Chemical = NSAIDs, bile reflux
D = IBD
What is mucosa-associated lymphoid tissue (MALT) and what is their presence indicative of?
- Chronic gastritis caused by H. pylori infection induces lymphoid tissue in the stomach
- The presence of lymphoid follicles in a stomach biopsy, is highly suggestive of H. pylori infection
- This is important because it is associated with an increased risk of lymphoma (MALToma)
Name a key virulence factor 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
Outline the differing outcomes of H.Pylori infection
- Non-atrophic pan-gastritis –> MALToma (due to likely chronic infection)
- Atrophic Body-predominant gastritis –> Ulcer, Adenocarcinoma
- Antrum-predominant –> duodenal ulcer
*memorise: atrophic = adenocarcinoma (A = A) while non-atrophic = MALToma *
Two Pathways that lead to development of GI cancer
- Metaplasia-Dysplasia pathway (upper GI)
- Adenoma-Carcinoma pathway (lower GI)
Define gastric ulcer.
Erosion where the depth of the loss of tissue goes beyond the muscularis mucosa (into the submucosa)
NOTE: if you only get loss of surface epithelium not past the lamina propria then it is just an erosion
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)
Perforation (peritonitis)
What changes can be seen in the stomach prior to gastic cancer
Gastric Intestinal Metaplasia = presence of goblet cells in the mucosa of the stomach.
* Occurs in response to long term damage. NOT Pre-malignant but can ldead to dysplasia (which is pre-malignant)
* associated with increased risk of cancer
Gastric Epithelial Dysplasia = abnormal epithelial pattern of growth
* some cytological / histological features of malignancy but no invasion through the basement membrane
Risk factors for gastric cancer
- Host genetic factors
- Environmental factors
- Bacterial virulence factors (Cag-A)
- Gastric phenotypes
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)
- MALToma is a type of B cell Non-Hodgkin’s Lymphoma
NOTE: if H. pylori is also present, crypts may also contain neutrophils
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
List some other pathogens that affect the duodenum.
- CMV
- Cryptosporidium
- Giardiasis
- Whipple’s disease (Tropheryma whippelii)
These are usually seen in immunosuppressed patients. Note that H. Pylori is behind almost 100% of duodenal ulcers
List some histological features of coeliac disease (that lead to malabsorption)
- Villous atrophy
- Crypt hyperplasia
- Increased intraepithelial lymphocytes (>20 per 100 enterocytes)
NOTE: the T cell response to gliadin in Coeliac disease is responsible for the damage to villi
What is lymphocytic duodenitis?
- When you get the inflammatory changes of coeliac disease (increased intraepithelial lymphocytes) but without architectural changes (loss of villi and crypt hyperplasia)
- 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
Duodenal biopsy (villous atrophy)
NOTE: duodenal biopsy will be normal in people with coeliac disease who have been following a strict gluten-free diet
Which other condition has very similar clinical and histological features to coeliac disease?
Tropical sprue
What type of lymphoma is duodenal lymphoma?
T cell lymphoma
NOTE: lymphomas in the stomach due to H. pylori are B cell lymphomas
