lec 7 Flashcards
types of peptic ulcer.
Gastric and duodenal ulcers
Causes of peptic ulcer
(1) Helicobacter Pylori (HP) infection,
(2) Use of non-steroid anti-inflammatory Drugs (NSAIDs)
(3) Stress-relatedmucosal disease (SRMD)
Stress-relatedmucosal disease (SRMD) includes
stress-related injury (superficialmucosal damage)
stress ulcers (focal deep mucosal damage).
Both types of Stress-relatedmucosal disease (SRMD) are caused by
mucosal ischemia
Stress-related mucosal damage onset is
usually acute
Both types of Stress-relatedmucosal disease (SRMD) show a propensity ميلfor
the acid-producing body and fundus
Stress-related mucosal damage is thought to be caused by factors such as
low mesenteric perfusion rather than HP or NSAIDs
Stress-related mucosal damage in a
small proportion of patients may progress to deep ulceration and hemorrhage
Less common causes of peptic ulceration include
- Zollinger- Ellison syndrome (ZES),
- cancer chemotherapy/ radiation,
- illicit-drug
illicit-drug cause
vascular insufficiency.
ZES is caused
by a gastrin-producing tumor called a gastrinoma found in pancreases and
results in gastric acid hyper-secretion.
Helicobacter pylorus normally resides in
in the human stomach
Helicobacter pylorus is transmitted via
the fecal-oral route or
through ingestion of fecal-contaminated water or food
Helicobacter pylorus Infection is more common in developing countries because
of crowded conditions and
the presence of contaminated food and water
Helicobacter pylorus Cellular active infection is usually
asymptomatic and
leads to chronic active gastritis
Helicobacter pylorus colonization does not necessarily reflect an
active infection since the organism can attach itself to the gastric epithelium without invading
cells
Helicobacter pylorus Cellular invasion is
necessary for an active infection
Helicobacter pylorus are
(a) gram-negative
(b) micro-aerophilic
(c) rod shape
(d) S-shaped bacterium
(e) multiple flagella
) multiple flagella that initially invade the
gastric antrum but migrates to the more
proximal sections
Helicobacter pylori causes
75% of gastric ulcers
90% of duodenal ulcers
mucosa-associated lymphoid tissue (MALT) lymphoma
adenocarcinoma
The outcome of the disease depends on
environmental factors,
the host and
the bacterium
Bacterial factors in Helicobacter pylori pathogenesis
- Urease and survival under acidic stomach conditions
- Flagella and movement toward epithelium cells
- Adhesins and attachment to cellular surface receptors
- Toxin and host tissue damage
Intra-bacterial urease activity
is regulated by the proton-gated urea channel (UreI)
Extra-bacterial urease activity
one note
UreI
permits urea entry
only under acidic conditions (5.0-7.0 pH
Urease will
liquefy the mucous and
Decrease elasticity
make Hp to swim easily through it
Flagella considered
early stage colonization/virulence factor
movement toward epithelium cells
Helicobacter pylori moves through the gastric mucosa gel layer
to the basal layer where the pH value is close to 7.0 by the
action of 4–7 polar
Adhesins
1.attach to the surface of the bacterium
2.can recognize the structures of glycans expressed on the surface of gastric epithelial cell
3.
the interaction of bacterial adhesins with cellular receptors
1.protects the bacteria from displacement
from the stomach by forces such as those
generated by peristalsis and gastric emptying
2.bacteria get metabolic substrates and
nutrients to improve growth through
releasing toxins to damage the host cells
Types of adhesin
- Blood group antigen binding adhesin (BabA & BabB)
- sialic acid-binding adhesin (SabA)
- Neutrophil activating protein A (NAP)
- Heat shock protein 60 (Hsp60)
- Adherence-associated lipoproteins (AlpA & AlpB)
- Lacdinac-binding adhesin (LabA)
Blood group antigen binding adhesin (BabA & BabB)
The structure of the BabA receptor is like the O type blood antigen, and the statistics
of epidemiology reveal the correlation between type O blood and gastric related diseases
Cytotoxin-associated gene A (CagA) associated with
acute gastritis, gastric ulcer, and gastric cancer development
The Cytotoxin-associated gene A pathogenicity island (cag A PAI) is located on
chromosome in H. pylori, It is 35–40 kilobase pairs of DNA (kb), It contains more than 30 genes It represents the pathogenicity island of H. pylor
cag A PAI It contains
cagI and cagII region
cagI and cagII contain a gene involve
in coding
Type IV secretion system (T4SS
The cagA gene is found
within cagI, but not cagII.
Type IV secretion system (T4SS)
forms needle-like pili, who’s binding to the integrin in injection of the Cag A
oncoprotein.
ما هي فوائد
Disruptions of tight junctions للبكتيريا
a) allow the bacterial cells access to the basement membrane
b. beneficial for colonization and persistence at the host epithelial surface
ما هي اضرار Disruptions of tight junctions للخلايا ال host
abnormal receptor activation \+ stimulation of signaling pathways involved in inflammation, proliferation, migration, and invasion
Disruptions of tight junctions causes
- expose extracellular matrix proteins
2. abnormal receptor activation
ما الذي يحدد الconsequences of disease and result in disease development
stimulation of signaling pathways involved in inflammation, proliferation, migration, and invasion
The pathogenicity of bacteria that colonize the human mucosa is influenced by
H.P capacity to invade and survive within epithelial cellsالبكتيريا كلها جوا الHOST
2.Helicobacter pylori internalization the virulence proteins Cag A and Vac Aالبكتيريا تدخل العامل الامراضي
The multiplication of Helicobacter pylori within cells provides
- resistance to antibiotic
2. impact on its biological life cycle
Helicobacter pylori capacity to invade and survive within epithelial
cells
- ability and rates of Helicobacter pylori positive correlation disease severity gastric cancer and ulcers were higher than the rate of strains found in gastritis
- بس دخل بتحيط نفسها بحويصله تتكاثر داخلها
اهمية وجود الحويصلة
- the location of replication
2. the degradation of the replicating bacteria after fusion with lysosomes
CagA can alter host cell signaling in
phosphorylation-dependent
2.phosphorylation-independent manner
phosphorylation-dependent affects the:
.1host cell adhesion, spreading, and migration of
2.Host cell induction of Nitric oxide and Cyclooxygenase (COX-2
3.stimulating the gastric epithelium cells to secrete
IL-8 (Interleukin-8) 2.NF-κB
4. سلايد 15
phosphorylation-independent manner
the proliferation and inflammation of cells (neutrophil
infiltration) via the Akt signaling pathway, which activates NF- κB and β-cateni
The effects of Vacuolating cytotoxinA (Vac A)]
1.membrane channel formation
2.vacuolization
3.Previous studies also indicate that VacA may affect
4.It also can induce acute inflammatory
responses t
The effects of Vacuolating cytotoxinA (Vac A)]
1.membrane channel formation
2.vacuolization
3.Previous studies also indicate that VacA may affect
4.It also can induce acute inflammatory
responses t
5.disturb epithelial barrier,
