lecture 4 Flashcards
- that the properties of the host and the infectious agent determine the pathogenic consequences of infection - properties of H. pylori that contribute to disease - properties of the host that determine the outcome of H. pylori infection - pathogenesis of disease caused by infection of the gastrointestinal tract - treatment versus cure of disease
What are the three main ways an infectious agent can cause disease?
- contact with/entry into cells
- toxin release - exotoxins/endotoxins/enzymes
- induction of host responses - more damage e.g. suppuration, scarring, hypersensitivity (in some cases can be the main cause of disease).
Describe the four basic microorganisms that cause disease.
Bacteria
- 0.8-15 µm
- prokaryotes (lack membrane bound nucleus)
- single celled organism
- intracellular or extracellular
Virus
- 20-300nm
- require host biosynthetic and replicative apparatus for proliferation
- has to enter the cell
Fungi
- 2-200µm
- eukaryotes (distinct nucleus)
- yeast or filamentous hyphae
Parasites
- protozoa (1-50µm)
- single celled eukaryotes
- Helminths (3mm-10m)
- parasitic worms (multicellular organisms)
What are resident flora?
- not all microorganisms are pathogens
- microorganisms that live on or within the body in non-sterile areas
> skin
> mucous membranes
> GIT/bowel/rectum
> vagina - not subject to inflammatory or immune attacks as long as skin and mucosa are intact
- balance of homeostasis to prevent infection/disease
- antibiotic use can change resident flora
- immunocompromise (AIDS, organ transplant) can lead to opportunistic infection by normal flora
What is a pathogen?
Disease-producing microbe
Disease is caused by
- contact/entry
- toxins
- host immune response
Pathogenicity (capacity to cause disease) is determined by
- virulence factors-determine how severe the disease is
- invasiveness, ability to evade the immune system, speed of multiplication, production of toxins, adherence to host cell, degree of tissue damage
What barriers are in place to block microbial invasion?
Mechanical
- epithelial cells with tight junctions
- air flow
- movement of mucus by cilia
- tears
Chemical
- fatty acids
- enzymes/peptides
- pH
- surfactant
Normal flora - provide competition in that niche
Eyes - tears
Respiratory tract
- mucus
- cilia
Digestive system
- gastric acid
- bile
- enzymes
- mucus
- normal flora
skin
- barrier
- normal flora
urogenitory
- flushing of urine
- acidity of urine
vagina
- pH
- normal flora
Describe the morphology of a normal stomach
Stomach broken up into areas which have particular cells in them.
- Cardia - mucin secreting cells, thick mucus material (at lower oesophageal sphincter)
- Fundus - acid and enzyme secretion (top lobe) - stuff that breaks down food
- (body) Corpus - acid and enzyme secretion
- Antrum - gastrin and mucin secreting cells (just before it moves into the duodenum)
cross section: Longitudinal, circular, oblique muscles. Submucosa Muscularis mucosa Mucosa with epithelial cells and gastric pits that produce acids/enzymes that are required to digest food
Do we get infection of the gastrointestinal tract?
The GIT:
- hostile environment
- acidic-secretion of hydrochloric acid: very low pH
- mucosal barrier to prevent autodigestion
- proteases
- historically considered to be a sterile environment
- however this environment can get disease e.g. chronic gastritis, peptic ulcer, gastric lymphoma, gastric adenocarcinoma
What is chronic gastritis?
Chronic inflammation of the stomach:
The presence of chronic mucosal inflammatory changes leading eventually to mucosal atrophy and epithelial metaplasia
Few symptoms… nausea, vomiting, upper abdominal discomfort
What is a peptic ulcer?
- much more severe
- Ulcer - breach in the mucosa of the alimentary tract, which extends through the muscularis mucosa into the submucosa or deeper
- peptic ulcers occur in any part of the GIT exposed to acid/peptic juices
- epigastric gnawing, burning, or aching pain
What is gastric cancer?
Gastric adenocarcinoma
- most common malignancy of the stomach representing 90% of all gastric cancers and a leading cause of cancer related death
Lymphoma
- derived from mucosa associated lymphoid tissue (MALT therefore MALToma)
- 5% of gastric malignancies are primary lymphomas
- dense lymphocytic infiltrate within the lamina propria
- chronic inflammation
- low-grade B-cell lymphoma can become high-grade
What is the dogma of ‘no acid no ulcer’? How did this principle determine treatment and its outcomes?
- the cause of peptic ulcers was always believed to be too much acid
- if you can get rid of acid you won’t have ulcer
- early treatment
- targeted gastric acid secretion and mucosal defence mechanisms
- – inhibition of gastric acid secretion by selective blocking of the proton pumps of parietal cells
- – drugs that promote mucosal repair
- successfully heal ulcer
- ulcers tend to recur unless patient is maintained on acid suppression regime: drug company heaven - have to take my drugs forever
- why? treating the symptom but not the cause of disease
When was the role of infection in GIT disease theorised?
- 1984 paper published that stated:
“The bacteria were present in almost all patients with active chronic gastritis, duodenal ulcer, or gastric ulcer and thus may be an important factor in the aetiology of these diseases” - considered that that infection may be important in the development of GIT disease
Which bacteria causes GIT disease?
- Helicobacter pylori
Who were the pioneers in discovering the role of helicobacter?
- 1892 - Italy - Giulio Bizzozero - noticed there were bacteria inside the stomach of dogs
- 1940s - Ireland - Prof. Oliver Fitzgerald - in people who had peptic ulcers/chronic gastritis there was a predominance of/could detect enzyme called urease - particular to people who have this disease
- 1958 - Greece - Dr. John Likoudis - gave himself antibiotics to treat a peptic ulcer and cured himself, also cured many people in the surrounding districts of peptic ulcers. Tried to extend his knowledge to the big cities of greece, “let’s do a clinical trial” - but the establishment was very much of the opinion “no acid, no ulcer” and so wasn’t able to get clinical trial up
- 1970s - China - Professor Shu-Dong Xioa - regional doctor treating people with antibiotics, people from local region benefitted
- 1982 - Dr Barry Marshall and Professor Robin Warren
Who finally got the role of helicobacter recognised in the medical community and how?
- Dr Barry Marshall and Professor Robin Warren
- Nobel Prize for Physiology and Medicine 2005
- for their discovery of “the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease”
- who with tenacity and a prepared mind challenged prevailing dogmas
- Barry Marshall infected himself with H.pylori - gave himself a nice case of gastritis - took antibiotics and cured disease
