2. Peptic ulcer
• discontinuity of the mucosa of the GIT that is
usually deep penetrate muscularis mucosa
• This is one of the features to differentiate
ulcers from erosions.
3. • Remember that mucosa is made up of 3 parts :
• 1. The epithelial lining → which varies as you go
through the duct
• 2. The lamina propria → loose areolar
connective tissue.
• 3. Muscularis mucosa →the small layer which
made from inner circular, outer longitudinal.for
secretion.
6. • Jejunum used to be
affected in the past
because the treatment of
peptic ulcer was mainly
surgical.
• particularly after
complications (when
there is fibrosis of
duodenal ulcer or closure
of pyloric antrum), and
therefore one of the usual
operations that was done
is the gastro-jejunustomy;
when we connect the
jejunum to the stomach,
so this was the cause of
the jejunual ulceration
stromal ulcer (ulcer that occur at the site of
the anastomosis).
Acute ulcer shows no evidence of fibrosis.
7.
8. Due to NSAID
Repeated use of high doses of corticosteroids
Chronic renal failure , hypercalcemia:there’ll be more (H) ions secretions to
replace the calcium lead to higher acidity
psychological stress
9. prostaglandins
• the mucosa is protected
by the layer of mucus. You
can see that the PH in the
lumen is 1-2, while at the
level of the mucosa is
almost 7 which means
that it is almost protected
whenever there is mucus
and bicarbonate (this is
done by prostaglandins).
- extend from muscularis mucosa all the
way to lamina propria
- In each pit > you will see 5-7 gastric
gland open there
10. Regenerative (adult stem
cell):
- distinguished using
electron microscope.
- quiescent.
- heterochromatic(coiled)
ncleus, but they are very rich
in RER.
Parietal (Oxyntic):
- Pyramidal in shape.
- approximately half of the
size of this cell is
mitochondria (eosinophilic)
Chief (Zymogenic):-
Produce zymogen>proenzyme
(pepsinogen & g. lipase).
-Columnar cells with basophilic (RER)
-Mostly in the lower part of the gland
small pits in the cardia >>>>>> go to the body
>> pits will grow larger >>in Pyloric region >>
the pits are the longest.
foveolarcompartmentglandularcompartment
14. DNES Cells (diffuse neuro-
endocrine system cells )
- Diffuse : along the gut : from the esophagus , more in
the stomach, more in the small intestine, even in the
large intestine>>so diffuse ).
- Or APUD cell ) عبود خاليا(>>>>( amine precursor
uptake and decarboxylation) “old name”.
- the only unicellular endocrine gland
- They secrete products into the blood.
- 13 different types along the GIT.
- * Most common is G cells.
- Since they are endocrine, they are Located in the
base of the gland( most basal part).
15. • H.pylori (-) is the main cause or the etiologic
factor .
• most of the patients who are having duodenal
ulcer in 95% of them H.pylori is present, while
those of gastric ulcer only about 70% do have
H.pylori and the other 30% are usually
explains the NSAID uses.
Peptic ulcer
17. • the flagella will help H.pylori to dig deep in the
mucosa to have a more alkaline media in
order to resist the acid distraction .
H.pylori has certain enzymes
and cytotoxins that affect the
mucosa which result in
distraction
The urease enzyme of H.pylori
is quite useful clinically,
because it will help us to
diagnose or to detect the
presence of H.pylori by
radioactive carbon
produce phospholipases that destroy the
bicarbonate
-fastidious slow-growing organism.
18. • patient has received a radiolabeled urea then
he will expire radioactive carbon which means
that the patient has H.pylori.
• the ammonia will help H.pylori to survive the
acidic environment of the gastric mucosa.
(urease Will increase the PH this allows the
bacteria to colonize the mucosa). only colonize
stomach “especially in antrum”.
20. • Breath test is more likely to be used in hospitals
as a follow up treatment.
• to diagnose the patient we use endoscope, if the
ulcer is duodenal or gastric, f it is gastric; a biopsy
should be taken because of the possibility of
malignant ulcer.
• Also fecal antigen test can be used because it is
cheap as well as serology tests: Poor in children,
in elderly, for epidemiologic or surveillance tool.
• Blood culture has no role in diagnosis because
it’s not invasive.
21. Also it has
• VacA (vaculating toxin):destructing mucosal
barrier.
• Cag A (cytotoxin Antigen A)
22. History about H.pylori
• (they discovered it in 1979, in 1982 it was
approved and until 1995 to make people
accept the idea of infection).
23.
24. • This is a picture to show you how H.pylori can result
in excess acid secretion,
• you can see the disruption of somatostatin secreting
cell, this will lead to reduction of somatostatin
hormone, then this will lead to increase in gastrin
secretion which eventually increase acid production
that will reach the duodenum to cause ulcerations.
(-) inhibit gastrin
secretion
25. • H.pylori infection is more common in
industrialized countries than developed
countries, due to oral hygiene or the type of
food.
histologically identical to the fundus
pepsinogen I
mucus secreting cells.
Intrinsic factors
more
26. Pathology and Clinical features
• This disease is characterized by lymphocytic &
plasma cell infiltrate in lamina propria.
• cryptitis when the lymphocytic infiltrate is in
the crypt wall
• crypt abscess when the lymphocytic infiltrate
is inside the crypt (more sever).
Many lymphoid tissues in the mucosa of the
stomach, there is some sort of
destruction in the crypts. The overall
architecture of the mucosa is disrupted.
27.
28. Treatment
• Relief symptoms (pain & dyspepsia):
Some patients have H.pylori without peptic
ulcer disease or some patients have no
H.pylori but they suffer from peptic ulcer
symptoms (dyspepsia, heartburn….), so
these patient have non-ulcer dyspepsia
usually occurs in obese people and people
who eat a lot.
29. • Heal ulcer.
• Prevent recurrence
In the past the recurrence was very great
because the only treatment was H2-blockers
but nowadays the recurrence rate has been
reduced
recurrence may occur especially in patients who
have very severe form of excessive acid
secretion as in Zollinger–Ellison syndrome.
Treatment Cont.
30.
31. • Prevent complications (hemorrhage and
perforation).
Nowadays there is no surgery for peptic ulcer,
unless there is hemorrhage or perforation.
due to the presence of effective treatment for
peptic ulcer, therefore the patient will not
develop any complications.
• Eradicating H. pylori and Restoring balance
Treatment Cont.
33. • 2 antimicrobial agents + acid suppressor
(proton pump inhibitor)
clarithromycin + Amoxicillin or metronidazole
This treatment usually takes 7-10 days some
patients may take it for 2 weeks to eradicate
the infection .not healing the ulcer.
34. • we should take another course of proton
pump for one month or one month and a half
to heal the ulcer
35.
36. SIDE-EFFECTS OF H. PYLORI
ERADICATION THERAPY
• 1- Diarrhea followed by the use of
antibacterial agent specially
this might progress to pseudomembranous
colitis.
(The treatment of pseudomembranous colitis
is
penicillin(amoxicillin
Cl.difficile
vancomycin or
metronidazole
37.
38. • 2-Metallic taste :
by Metronidazole
Also the patients how take alcohol with
metronidazole they will have Flushing and
vomiting (disulfiram-like reaction).
39. If chronic gastritis isn't treated well, it will progress
to peptic ulcer disease; but if it's left untreated,
there will be an expansion of the lymphoid cells and
it will progress to gastric lymphoma.(it's the only
type of lymphoma that can be treated by
antibiotics)but in late stages, it will be resistant.
40. chronic gastritis
• we look for five histologic features; chronicity,
activity” intra-epithelial lymphocytic
infiltrate”, atrophy, intestinal metaplasia
(presence of goblet cells in the stomach )and
dysplasia.
• Dysplasia: we look whether it's present or not.
Why gastric atrophy, intestinal metaplasia?
When there is an atrophy The intestinal
metaplasia will take place Try to compensate
for the loss of glandular epithelium.
43. • For those that stimulate acid secretion, when
they are activated they will activate protein
kinase which initiate the action or the function
of the proton pump (which is the main pump
that secrets acid into the lumen), this is why
the proton pump inhibitors are the best
suppressor of acid secretion.
• there is some sort of interaction between
these receptors (they can stimulate each
other).
48. • They are effective in neutralizing the acidity, but
clinically we prefer Magnesium hydroxide
[Mg(OH)2].and Aluminum hydroxide, because
their neutralization is acceptable.
• unlike Sodium bicarbonate[NaHCO3] with HCl to
form CO2, it neutralizes the acid to a very high
PH very rapidly, and usually this result in CO2
production and therefore gases will occur in the
abdomen, as well as Na will be absorbed into the
body causing water to be absorbed, and this may
lead to problems in patients with heart failure,
kidney problems or hypertension.
50. • Generally, these drugs are used in
combinations.
because Aluminum compound lead to
Constipation(Air Condition), while Magnesium
compound may lead to Diarrhea (Must go to
toilet)and therefore to overcome this effect
either constipation or diarrhea they are
usually given in combination.
51.
52. • Calcium carbonate is also good but the
problem with it is that if it’s taken with excess
milk in some individuals, it results in a
condition or a syndrome called milk-alkaline
syndrome, where the patient feels headache
with nausea and abdominal discomfort and
vomiting so it is not well-recommended.
53.
54. The indications
• 1- To relieve pain.
• 2- Promote healing of duodenal ulcer.
• 3- To prevent stress ulcers.
• 4- Prevent hyperphosphatemia in patients
having kidney failure .
(aluminum hydroxide, because in the intestine it
will be converted into aluminum phosphate,
so it will drain all the phosphate into the
stool), so this will lead to hypophosphatemia.
58. MOA
• have a short half-life but they have long
duration of action, because they irreversibly
block the activity of the proton pump enzyme
(H/K ATPase). unlike H2 blockers, which are competitive in
their activity.
59. • The coating is removed in the alkaline
duodenum,and the prodrug, a weak base, is
absorbed and transported to the parietal cell.
• There, it is converted to the active drug and
forms a stable covalent bond with the H+/K+-
ATPase enzyme.
by combining with their SH group.
Sulfonamide
60. • It takes about 18 hours
for the enzyme to be
resynthesized, and acid
secretion is inhibited by
more than 90% during
this time.
• involving the basal as well
as the stimulated (basal
stimulation mainly occur
at night).
61. The indications:
• 1- Definitely to treat peptic ulcer disease
• 2- Stress ulcer whether treatment or prophylaxis.
• 3- Gastroesophageal reflux disease (GERD).
• 4- Erosive esophagitis.
• 5- Prevention of NSAID induced ulcers.
• 6- Hyper-secretory states ()
they are more effective than H2 blockers because the acid
secretion is very high so it need a very effective treatment.
Zollinger-Ellison
syndrome
62. • Proton pump inhibitor is by far better than
either of the two so they are preferred to treat
GERD and erosive esophagitis.
63. acid is required for its absorption in a complex
with intrinsic factor.
64.
65. • Omeprazole and Esomeprazole are enzyme inhibitors.
• they will interfere with the metabolism of certain
drugs, particularly those which have narrow
therapeutic index (e.g. Diazepam, phenytoin and
warfarin).
• because they inhibit the enzyme if they are given with
clopidogrel (anti-platelet agent) it results in decreasing
its effect; because clopidogrel is a prodrug so it has to
be converted to its active drug in order to be effective.
• so patients with cardiac problems who receive PPI with
clopidogrel are more liable for cardiac attacks or
ischemic attacks.
70. • They competitively block histamine (H2)
receptors which means that one single dose
may not be enough.why?? reversible
71. • so the duration of action will be shorter than
that of PPI; the general protocol of the
treatment by these drugs was by giving them
4 times a day.
• Nowadays, they reached a conclusion that the
main cause of the ulcer is the secretion that
occurs during night and therefore if these
drugs are prescribed, they are given usually at
supper & bedtime to suppress the basal acid
secretion.
72. • The other difference between PPI and H2
blockers is the incidence of recurrence. In the
past, when we were using H2 blockers the
incidence was much greater than the
incidence nowadays with PPI, probably it is
not due to the difference of their mechanism
of action, but it is due to the fact that we are
eradicating the causative organisms and
therefore the recurrence rate has been greatly
reduced.
73.
74. The indication
• Promote healing of duodenal and gastric ulcers.
(recurrence is more common)
• Provide long-term treatment of pathological GI hyper
secretory conditions.
Some schools think that in cases of hyper secretory
conditions, if we would like to use the drug for a very long
time, they prefer the H2 blockers over PPI; because the side
effects and interactions of H2 blockers were very well
known, but PPI when they are introduced, their side effects
and interactions were not be known at that time.
• Reduce gastric acid production and prevent stress ulcers.
(PPIs are preferred).
The use of these agents has decreased with
the advent of PPIs
75. • Interaction = same PPI
Patients with NSAID-induced ulcers?? PPI
76. Adverse reactions:
• Headache, bowel upset, nausea, vomiting (all
H2 blockers can cause them).
• CNS effects; restlessness, confusion,
convulsions in elderly patients especially If
these drugs were given in excess or IV.
77. • done by cimetidine only :
Gynecomastiain male, galactorrhea(continuous
release/discharge of milk)in female, and
reduced sperm count (this is due to anti-
androgenic effect of cimetidine) so it should
not be given to health adult male patients
practically if they are newly married or they
are going to get married.
80. Sucralfate
• It’s a complex of aluminum hydroxide and
sulphated sucrose, so because it has aluminum
hydroxide, it can prevent the absorption of
antimicrobial agents.
