L16 Chronic infection and carcinogenesis Flashcards
What is peptic ulcer disease?
Break in the lining of stomach/small intestine
What are the symptoms of peptic ulcer disease?
Upper abdominal pain, belching (gas/bloating), bomiting, weight loss, bleeding
What is the history behind the disease being discovered?
Used to be related with stress, treated with antacid. Barry Marshall proved it was du to infection by drinking a culture, followed by antibiotics.
What is the organism behind peptic ulcer disease?
Helicobacter pylori (H. Pylori)
What is the H. Pylori disease spectrum? Time?
Wide range, asymptomatic to deadly
After infection, it can take decades to get serious forms of disease progression.
Superficial active gastritis -> days-weeks
chronic active gastritis -> months to years
antral gastritis/pangatritis/chronic active gastritis -> decades
dyodenal gastric metaplasia/atrophy intestinal metaplasia/chornic active gastritis -> decades
Finally leads to duodenal ulcers/gastric cancer/ulcer/MALT lymphoma
How does H. pylori survive in stomach?
Uses urease to produce a ‘cloud’ of ammonia to neutralise the stomach acid
What structure of H. pylori gives it its motility?
Flagellum to swim fast through mucus layer
Helical shape for screw like movement which allows it to penetrate the mucus
How does H. Pylori enter cells?
It raises pH, causing the mucus to de-gel as it enters in a crok-screw motion
How does H. Pylori attach to epithelial cells?
BabA adhesion molecule attaches to cell via Lewis b carbohydrate receptor.
How does H. pylori evade the immune system?
It’s LPS is poorly recognised by TLR4, and therefore less cytokines are produced. Its flagellum subunits are also poorly recognised by TLR5.
How does H. Pylori inhibit the immune system?
- Vacuolating toxin A (VacA) inhibits phagosomal maturation, T/B proliferation, and iNOS generation.
- Coating with plasminogen and cholesterol (to mask)
What is an ulcer?
A lesion in the mucous membrane
What is a peptic ulcer?
Ulcer lining the stomach or duodenum, where hydrochloric acid and pepsin are present
Which cells are found in the fundus (top of the stomach)?
Mucus secreting cells, parietal, and ECL cells (from top to bottom)
What cells are found in the antrum (bottom of the stomach)?
G cells, ECL cells, D cells (aka SST cell) - from top to bottom.
Chronic infection and inflammation –> Loss of function of cells in the inflamed area –> causes peptic ulcer disease
Describe the process by which acid is produced in the stomach, and how this process is stopped/controlled.
Thought of food causes G cells to produce gastrin. Gastrin acts on ECL and P cells. ECL cells produce histamine which acts on P cells. P cells produce acid. Build up of acid causes D cells to produce somatostatin, which acts on G cells to inhibit production of gastrin. Thus, stop acid production.
What happens when there is an infection in the antum?
Inflammation of the epithelial cells in the fundus, loss of function of D cells which produce somatostatin. No inhibition to stop acid production. Results in increased gastrin and acid hypersection. This causes acid to leak out into the duodenum –> inflammation and then duodenal ulcer
What happens when there is an infection in the body/corpus/fundus of the stomach?
Inflammation, causing loss of function of Parietal cells. Loss of acid production. Resulting in gastric ulcer and acid hyposecretion.
H. Pylori exposure is…
carcinogenic (leads to cancer) - rare
What is a cag pathogenicity island?
It’s a region of DNA (part of bacteria) involved in pathogenicity. 30kb of 28 genes which make up a type 4 secretion system (T4SS), secrete proteins into the cell, pili-like structure.
What does cagA stimulate?
Phosphorylation cascades once inside the gastric cell
What does cagA induce in the cell?
Apoptosis, morphological change, cytokine production, cell proliferation
cagA promotes release of ___ from __
ROS from mitochondria
