Lecture 16- Chronic Inflammation and Carcinogenesis Flashcards
What virulence factors help H.Pylori survive in the stomach?
Outer membrane protein urease produces a cloud of urea around the bacteria which produces a cloud ammonia to neutralize the stomach acid, the flagellum allows the bacteria to penetrate the mucus layer allowing protection from acid
The helical shape helps penetrate the mucus
Baba adhesion allows lewis b carbohydrate attachement to gastric epithelium
What helps H.Pylori avoid the immune system?
LPS which is poorly recognised by TLR4
Flagellum is poorly recognised by TLR5
This results in only a low level inflammatory response
What does H.Pylori do cause to damage to the host?
CagA, IL-8 is produced, Chemoattractants of neutrophils,
Inflammed tissue expresses sialated Lewis X receptor which the bacteria attach to via the SabA adhesion this results in the breaking of tight junctions
If bacteria survive the neutrophil attack then cagA and VacA result in persistant bacterial infection and chronic inflammation leading to loss of function of the cells in that region of the stomach
Ulcers are formed at the region of infection
What is the difference between gastric, peptic and duodenal ulcers?
When hydrochloric acid and pepsin are present it is called a peptic ulcer
When the ulcer is found in the stomach it is a gastric ulcer
When the ulcer is found in the duodenum it is called a duodenal ulcer
What is dyspepsia?
Chronic or recurrent pain in the upper abdomen
What occurs if H.Pylori infects the antrum?
Inflammation leads to the loss of function of somatostatin cells
this results in increased gastrin production, increased acid production, acid enters duodenum, inflammation of duodenum, gastric metaplasia- stomach - like cells in the duodenum
further colonisation by H.Pylori and inflammation
What occurs if H. Pylori infects the corpus?
Inflammation leads to loss of function of acid secreting parietal cells, continued stomach infection, inflammation
How is H.Pylori infection in the antrum treated?
Antibiotics to remove H.Pylori
Ulcers are healed suppression of acid secretion
How is H.Pylori infection in the corpus treated?
Eradicate H.Pylori by antibiotics and acid secretion will recover
How does H.Pylori cause cancer?
The impaired stomach results in less vitamin C getting absorbed, this results in the repeated inflammation and repair leading to DNA damage and mutation
The CagA toxin also functions as an carcinogenic toxin
How does CagA function as a carcinogenic toxin?
CagA is phosphorylated inside the gastric cell, this results in the stimulation of phosphorylation cascades (Apoptosis, Morphological Change, Cytokine production)
CagA also results in release of reactive oxygen species from mitochondria
