Chronic Inflammation and Carcinogenesis Flashcards
A 4 step guide for a microbe to cause an infection would be:
- colonise the host
- evade host defenses
- proliferate
- cause damage
Name the 6 mechanisms of damage
- exotoxins
- degradative enzymes
- acute inflammatory damage
- post-infection autoimmune damage
- chronic inflammatory damage
- carcinogenesis
Describe what Peptic Ulcer Disease is and the symptoms one can expect from it
Peptic ulcer disease is a condition in which there is a break in the lining of the stomach or small intestine
Symptoms include:
- upper abdominal pain
- belching
- vomiting
- weight loss
- bleeding
For a long time, peptic ulcer disease was treated for with ________.
antacids
H. pylori has been estimated to have infected __% of the world’s population
50%
Days-weeks after infection wit H. pylori can result in:
Superficial active gastritis
Months-years after infection wit H. pylori (if left untreated) can result in:
Chronic active gastritis
Decades (earlier) after infection wit H. pylori can result in: (3)
Antral gastritis, pangastritis, chronic active gastritis
Decades (later) after infection wit H. pylori can result in: (3)
Duodenal gastric metaplasia, atrophy intestinal metaplasia, chronic active gastritis
Final stage effects of infection with H. pylori include: (3)
duodenal ulcer, gastric cancer/ulcer, MALT lymphoma
Describe the motility of H. pylori and how it is achieved, as well as why this is significant.
A flagellum allows H. pylori to swim rapidly to the mucous layer of the stomach following ingestion in order to survive
Describe the shape of H. pylori and why this is significant.
H. pylori is helical in shape, which combnined with ‘screw-like’ movement, allows it to penetrate the stomach’s mucous layer.
How does H. pylori counterract stomach acid?
H. pylori uses urease to produce a ‘cloud’ of ammonia in order to neutralise acid.
What does H. pylori do when it reaches the mucous layer of the stomach?
It crosses the mucous layer of the stomach by causing it to de-gel by raising the pH
What does H. pylori do once it crosses the mucous layer of the stomach?
It attaches to the gastric epithelium via Lewis b carbohydrate receptor with BabA adhesin
___ is poorly recognised by TLR4, resulting in low levels of ____ production.
LPS is poorly recognised by TLR4, resulting in low levels of cytokine production.
Flagellum subunits are poorly recognised by ____, resulting in low levels of ____ production.
Flagellum subunits are poorly recognised by TLR5, resulting in low levels of cytokine production.
Vacuolating toxin A (VacA) inhibits: (3)
- phagosomal maturation
- T/B cell proliferation
- iNOS generation
H. pylori is coated with ______ and ______ in order to mimic the host
H. pylori is coated with plasminogen and cholesterol in order to mimic the host
Chronic infection + inflammation results in a loss of _____ of cells in the inflamed area
function
What is an ulcer, and what are the 3 types of ulcers?
An ulcer is a lesion found on the mucous membrane.
- Peptic ulcer - in lining of stomach or duodenum, where hydrochloric acid and pepsin are present
- Gastric ulcer - in stomach
- Duodenal ulcer - in duodenum
List the order of the sections of the stomach, starting from the end of the esophagus to the beginning of the small intestine (9)
- esophagus
- cardia
- cardial notch
- fundus
- body
- pyloric antrum
- pyloric canal
- pylorus
- duodenum
Describe the process of stomach acid production (4)
- See food/think of food
- G (gamma) cells produce gastrin
- ECL cells produce histamine
- Parietal cells produce acid
What is the purpose of somatostatin cells?
Acts to inhibit the function of G cells to halt production of more acid via negative inhibition
How would H. pylori infection of the antrum affect the function of the stomach?
Inflammation leads to loss of function of somatostatin cells which relieves inhibition of G cells, causing increased gastrin and thus acid production.
Excess acid leaks into the duodenum, which causes inflammation of the duodenum, resulting in duodenal ulcers and acid hypersecretion.
How would H. pylori infection of the corpus of the stomach affect its function?
Inflammation results in loss of parietal cells. As parietal cells are required to make acid, acid production becomes halted.
This results in the development of intestinal-like cells within the stomach, leading to further inflammation and resulting in gastric ulcers and hyposecretion.
H. pylori exposure is c______.
carcinogenic.
Low acid production results in _____ which becomes ____ ______, finally leading to _____ _____.
Low acid production results in pangastritis which becomes atrophic gastritis, finally leading to gastric cancer.
High acid production results in _____-______ _____ which ultimately becomes ____ ____ ______.
High acid production results in antral-predominant gastritis which ultimately becomes peptic ulcer disease.
What is the cag pathogenicity island?
A >30kb region of genetic material that houses 28 virulence genes - mostly codes for type 4 secretion system (T4SS) which allows bacteria to secrete proteins into host cells - in particular CagA
cagA is a ____ secreted from bacteria
protein
Disease symptoms following the absence of vacA are:
Unchanged proportion for mild gastris, slightly decreased other symptoms with the exception of carcinoid which increased.
Disease symptoms following the absence of cag are:
Absence of all severe disease symptoms , leaving only mild gastritis
_____ is important in causing various forms of severe diseases associated with heliobacter pylori
cag
H. pylori cagA is ______ in the gastric cell
phosphorylated
CagA-P stimulates phosphorylation cascades - list the 4 resulting effects
- Apoptosis - especially neutrophils
- Morphological change - barrier disruption
- Cytokine production - inflammation
- Cell proliferation
CagA promotes the release of _____ from mitochondria
reactive oxygen species (ROS)
What is the function of urease in H. pylori?
Neutralises gastric acid, gastric mucosal injury via ammonia
Name an exotoxin and its function when it comes to H. pylori
vacuolating toxin (vacA) - causes gastric mucosal injury
Name 3 secretory enzymes which play a role in H. pylori infection
mucinase, protease, lipase - gastric mucosal injury
What is the function of lipopolysaccharides on H. pylori?
Helps to adhere to host cells, inflammation
What function do outer proteins serve on H. pylori?
Help to adhere to host cells
What is T4SS?
A pill like structure for the injection of effectors
Give an example of an effector in H. pylori infection, and its functions
cagA - actin remodelling, IL-8 induction, host cell growth and apoptosis inhibition
The initial test for H. pylori is:
The breath/sniff test - if stinky = infected lol
What is the first-line therapy for H. pylory infection?
One-week “triple therapy” - proton pump inhibitor such as omeprazole + antibiotics such as clarithromycin and amoxicillin
Acid hypersecretion –> ____ ulcers
Acid hypersecretion –> duodenal ulcers
Acid hyposecretion –> ____ ulcers
Acid hyposecretion –> gastric ulcers
Acid ____secretion –> gastric ulcers
Acid hyposecretion –> gastric ulcers
Acid ____secretion –> duodenal ulcers
Acid hypersecretion –> duodenal ulcers
