Gastrointestinal Pathology Flashcards
What is Helicobacter Pylori
- Gram-negative microaerophilic bacterium
- May play a role in natural gastric ecology
- Can exist in two form in the human stomach: spiral and coccoid forms
- Bacterium was responsible for most cases of gastric and peptic ulcers
What is the entrance and top part of the stomach called and what cells do they contain
Cardia, Fundus, respectively
They contain mucus secreting cells
What is the middle part of the stomach called and what cells does it contain
Body
They contain parietal cells that secrete acid
They also contain chief cells that secrete pepsinogen
What is the end of the stomach called and what cells does it contain
Antrum
Contains cells that secrete the hormone gastrin
What is the role of mucus secreting cells
The mucus coats and protects the epithelial cells from the acid content
What is the role of the cells that line the body of the stomach
The acidity enhances the activity of the pepsin and therefore protects the stomach from the pathogens
What is the role of Gastrin
Increases the release of acid
What are the 4 layers of the stomach
1) Mucosa
2) Submucosa
3) Muscularis externa
4) Serosa
What does the Mucosa layer consist of
The surface epithelium
Lamina Propria
Muscularis Mucosae
What does the Muscularis Externa layer consist of
Oblique layer
Circular layer
Longitudinal layer
What is the survival strategy of Helicobacter pylori
- Migrate to the regions with less acidic pH - burrows down into the mucus layer that coats the stomach lining (this lining is closer to neutral pH)
- Release of urease to turn urea into ammonia, to neutralise the gastric acid and allow colonisation
- Adherence to the gastric mucosa
What does ammonia do for the bacteria
Ammonia neutralises the gastric acid around the bacterium, creating a protective cloud so it can survive.
This local increase in pH also irritates and damages the stomach lining, contributing to inflammation and ulcer formation
How does H. pylori attach to the gastric mucosa
It utilises:
- lipoprotein A-B
- group antigen-binding protein:
This binds to Lewis B antigens (especially on blood group A individuals - hence they are more susceptible to infection and complications) - OipA (Outer inflammatory protein A):
Involved in triggering inflammation
Associated with more virulent strains
What are the virulence factors of H. pylori
Exotoxin-vacuolating cytotoxin A (vacA)
Cytotoxin-associated Gene A (cagA)
What does vacA do
secreted into the environment around the bacteria.
Forms pores in host cell membranes
→ Causes vacuole formation (big, bubble-like structures inside cells, hence “vacuolating”).
Disrupts mitochondrial function
→ Leads to cell injury and apoptosis (programmed cell death).
Modulates the immune response
→ Suppresses T-cell activation and proliferation (weakening the immune system’s ability to clear H. pylori).
What does cagA do
Interferes with intercellular attachment, cagA is injected into the gastroepithelial cells via the T4SS where it gets phosphorylated and dirupts the cell-to-cell junctions by interacting with the E-cadherin and Beta-catenin proteins.
Induces inflammatory immune response: this causes gastritis/chronic inflammation, MALT lymphoma and adenocarcinoma
What are the clinical syndromes associated with HP
1) Functional dyspepsia/GERD
2) Gastritis
3) Peptic ulcer
What is GERD
gastroesophageal reflux disease, is a condition where stomach acid frequently flows back up into the esophagus, causing heartburn
No clear understanding of the role that HP has on it but the symptoms improve with eradication
What is gastritis
inflammation of the stomach lining associated with mucosal damage.
Acute inflammation turns into chronic with prominent lymphocytic infiltrate
What is a peptic ulcer
Open sores on the inner lining of the stomach and the upper part of the small intestine
VacA m1 is possibly associated with an increased risk of peptic ulcer disease
What is the Type A gastritis
Cause: Auto-immune (against parietal cells and intrinsic factor)
Pathology: chronic atrophic gastritis with intestinal metaplasia
Main site: fundus/body of the stomach
Key features: ↓ Acid (hypochlorhydria), ↓ Intrinsic factor → B12 deficiency (pernicious anemia), ↑ Gastrin
What is Type B gastritis
Cause: Bacterial
Pathology: Chronic active gastritis
Main site: Antrum (first) → can later spread to body of the stomach
Key features: risk of ulcers, intestinal metaplasia, cancer
What is Type C gastritis
Cause: chemical, bile reflux, drugs
Pathology: Foveolar hyperplasia, oedema, telangiectasia and lack of inflammatory cells
Main site: Antrum (mainly)
Key features: Chemical injury to mucosa; less inflammatory cells, more foveolar hyperplasia
How would you assess a gastric biopsy
Look at the extent, quantity and type of inflammation:
- mild
- focal
- predominantly lymphocytic
The extent and quantity of atrophy (glandular density) and possible metaplasia
