Mahmoud TanashThis lecture

Dr. Niazi Abu-farsakh

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Peptic Ulcer Disease ( PUD )

Definition
It is ulcer ( loss of continuity of an epithelial tissue ) in an area that
secretes acid & pepsin, which is greater than 4-5 mm & could be acute
or chronic . NO acid no ulcer
Erosion : less than 5 mm , smaller , more superficial than ulcer and can
occur in acid and non-acid secreting area , & heals rapidly usually 48-72 h .

Location
As we said peptic ulcer occur in areas that contain acid & pepsin
mainly :
1- 1st part of duodenum duodenal bulb
2- stomach ( esp. lesser curvature ) ,
And less common areas like lower esophagus , gastrojujenal
anastomosis after surgery & meckel's diverticulum .
Meckel's diverticulum : is a congenital diverticulum in the terminal
ileum contains gastric cells which secrete acids that may cause ulcer &
sometimes cause severe bleeding in pediatrics .

Causes
Why some pt. develops PU while other does not ?
There are 3 main causes of PUD :
1- Helicobacter pylori .
2- NSAIDs .
3- Hypersecretory state of acid ( Zollinger-Ellison Syndrome ) .

Pathogenesis
Imbalance between aggressive & defensive factors.

Dr. Niazi Abu-farsakh

Mahmoud Tanash

ZOLLINGER-ELLISON SYNDROME
This is a rare disorder characterized by the triad of severe peptic
ulceration, gastric acid hypersecretion and a non-beta cell islet tumour of
the pancreas ('gastrinoma'). It probably accounts for about 0.1% of all
cases of duodenal ulceration. The syndrome occurs in either sex at any
age, although it is most common between 30 and 50 years of age.

- Sometimes ulcer occurs without relation to the mechanism of acid

secretion like in Malignancy , sarcoidosis & crohns disease .

The aggressive factors :

1- Acid secretion : by parietal cells in the fundus of stomach , but
this is under control of nervous & endocrine ( e.g Gastrin )
or paracrine a factor as :
(GRP: increase secretion of acid, Somatostatin: decreases secretion of acid
and Histamine : stimulates secretion of acid)
And as we said we never find peptic ulcer with low acid secretion ,so as
MAO ( Maximum Acid Output)rate increase the possibility of ulcer will
increase . If stomach pH > 2.5 we willnot get ulcer , and if you find pt. with
Achlorhydra ( absence ofacid secretion ) with ulcer in the stomach this is n
ot peptic ulcer ,so this ulcer may do to malignancy or other possibility .
2- Pepsin .

The defensive factors :

1- Prostaglandin , the most imp. One that protects the gastric
mucosa , so drugs that inhibit its synthesis ( e.g. NSAIDs ) will
cause mucosal damage .
2- Mucosal blood flow .
3- Mucus gel layer .
4- Bicarbonate in the mucosa .
5- Epithelial junction between the gastric cells that prevent acid ions
to damage the sub epithelial layers .
6- Regeneration of the epithelial layer in gastric mucosa .
7- Growth factors : EGF

Dr. Niazi Abu-farsakh

Epidemiology of PUD
-

Mahmoud Tanash

Prevalence : 5-10 % of population .

H. pylori more in people with low socioeconomic state .
Most of cases are duodenal or gastric ulcers .
Duodenal ulcer more in males , Gastric ulcer male = female .
Hx. Of PUD increase risk by 3-4 times .
Cigarette smoking also increase the risk .
Emotional disturbances ( e.g. stress ) increase the risk , because
stress 1- increase acid secretion in the stomach up to 3 times & 2decrease blood supply to the stomach .
Any person with mental or physical stress ( e.g. pt. in the
hospital ) is liable for PUD .

Symptoms of PUD :
- Epigastric pain , which is very localize .
- Dyspepsia , pt. tell you I feel tired after the meal .
- Some pt. come without symptoms , others come with
complications .
- The clinical picture is suggestive but not diagnostic .

signs :
- Epigastric tenderness.
- Signs related to complications.

Diagnosis :
- Endoscopy is the best diagnostic test in PUD .
- Barium meal is less helpful . we give the pt. 150-300 cc of barium
sulfate not like barium swallow that we give only 50 cc .
- Any other method is useless , like ultrasound that used by some
private doctors .
- No role for serum Gastrin in usual ulcer, indicated if ZE is suspected.
- Every gastric ulcer should be biopsied to exclude malignancy , but
in duodenal ulcer is not needed because it is unlikely to become
malignant .
- Gastric cells make contraction around the ulcer , so in endoscopy
you have to balloon properly .

Dr. Niazi Abu-farsakh

Mahmoud Tanash

This is how ulcer appears

on radiology

These are pictures of endoscopy

These are erosions

Dr. Niazi Abu-farsakh

Mahmoud Tanash

Helicobacter Pylori
H. Pylori found in : ( to be memorized )
-

20-50 % of healthy people .

All Pt. with chronic active gastritis .
More than 90 % of pt. with duodenal ulcer .
50-80 % of pt. with gastric ulcer .
90 % of pt. with gastric adenocarcinoma .
80-85 % of pt. with gastric lymphoma .
90 % of pt. with MALToma .

Practically , you consider all pt. with duodenal ulcer have H. Pylori
without need for biopsy . And if we want to look for the organism we
have to look for the antrum of the stomach because it is the major place
for this organism .
In gastric ulcer we should take biopsy to exclude malignancy , so already
we can look for H. pylori .

Before the invasion of H. pylori from the antrum of the stomach to

the duodenum , the duodenal area has to be prepared by gastric
metaplasia .

Diagnosis of H.pylori :
1- Invasive ( with endoscopy ) :
- Gastric biopsy and staining.
- Culture of Bx specimens.
-Tests using urease enzyme in Bx specimens.

2- non-invasive ( without endoscopy ):

- Urea breath test.
- H.pylori antibodies.
- Stool antigen.
- Salivary antigen.

Dr. Niazi Abu-farsakh

Mahmoud Tanash

I took this table from Davidson to explain what the doctor said

The non-invasive methods tell you that there is H. pylori , but if you want
to see if this pathogen made ulcer we have to do the Invasive tests .

Complications of PUD :
1- Hemorrhage : 20% of PUD pt. are liable to bleeding , and this
bleeding may lead to death . This hemorrhage occur esp. in
asymptomatic pt.
2- Perforation : occur in 1% of the pt.
3- Gastric outlet obstruction : when the ulcer go & come several
times it cause fibrosis , and this lead to obstruction of the area .
4- penetration to the pancreas , so the
pain may radiate to the back .
Benign ulcer never transforms into malignancy , so the ulcer from
the beginning either benign or malignant .

Dr. Niazi Abu-farsakh

Mahmoud Tanash

These are pictures of bleeding ( red spots )

If you see a picture of air

under the diaphragm ,
this is an indication of
perforated ulcer .

PUD is a chronic episodic disease with relapsing & remission . If left

untreated 30% of the ulcers heal within 8 weeks , but the recurrence
rate is high ( 70% in 1 yr , 90% in 2 yrs ).
There is seasonal predilection of the ulcer & its complication in Autumn
& Spring esp. in April & October .

Dr. Niazi Abu-farsakh

Mahmoud Tanash

Treatment
Unlike GORD , There is no lifestyle modification in PUD , so we rely only
on drugs . Drugs of PUD are the same as drugs of GORD except the
prokinetic drugs . We use :
1- Antacids : give rapid symptomatic relieve , act in few minutes ,
cheap , need large amount to heal the ulcer ,if taken in empty
stomach they are effective for 10-50 minutes & if taken after meal
they are effective in 2-3 h .
Examples :
- Sodium bicarbonate : SE are increase in Na inward & Milk Alkali
syndrome .
- Aluminum OH : SE are constipation , dementia & may affect the
kidney .
- Magnesium OH: SE are diarrhea , renal failure & neurotoxicity .
- Calcium Carbonate: SE are constipation & rebound hyperacidity .
2- H2 blocker : we have cimetidine , ranitidine , famotedine ( trade
name is famodar ) & nesatidine .
These drugs act by preventing acid release from the parietal cells
through H2 receptors .
They suppress nocturnal acid secretion by 90% , and meal
stimulated secretion by 50% -60% .
SE : they are very safe drugs ( & cheap ) , but some can occur like
headache , mental confusion , reversible gynecomastia & impotance.
They have a lot of interactions with other drugs because some of
them are P450 enzyme stimulators .
3- PPI ( Proton Pump Inhibitors ) : Omeprazole , Lanzoprazole ,
Pantoprazole , Ramiprazole , Esoprazole & Tenatoprazole( longer duration
of action) .
They suppress acid secretion by blocking the ATPase pump that
secrete H+ outside the cell & k+ inside . Chronic use of these drugs
lead to achlorhydra .
Are there a dangerous effects of achlorhydra ?
Theoretically , yes ; because gastric acid secretion is under the
effect of Gastrin , and by feedback mech. The acid suppresses the
8

Dr. Niazi Abu-farsakh

Mahmoud Tanash

G cells that secrete Gastrin . In achlorhydra , there will be

overstimulation of the G cells which lead to hyperplasia .
Practically , the serum Gastrin will increase but without malignant
hyperplasia of the G cells .
PPI heal the duodenal ulcer by 2 weeks & all of ulcers within 2
months .
There are some drugs under investigation act like PPI by
preventing K+ to go inside the cell .
4-Eradication therapy of H.pylori :
Antibiotics ( Amoxicillin , Tetracycline , Clarithromycin &
st
Metronidazole ) , Bismuth compound & PPI are 1 line therapy .
Quinolones such as ciprofloxacin,furazolidone and rifabutin are
also used as 2nd line therapy ( rescue therapy ) .

How to treat ?
PPI + 2 or 3 antibiotics for 7-14 days .
The relapse after the eradication therapy is <10% .
5- Sucralfate : make a coat around the ulcer , but it is not better than PPI .
Healing rate: 70-80% within 8 weeks, & binds with the proteinaceous base
of the ulcer, increasing local mucosal production of PGs.
SE: constipation, nausea, reduce absorption of some drugs & binds
phosphate in the gut.
6- Prostaglandin : very expensive , less effective than H2- blockers, they
Inhibit gastric acid secretion and has cytoprotective effects, SE : abdominal
cramps, diarrhea, & not cost-effective. Indicated for prophylactic use rather
than for treatment.
7- Surgery .
Rare after introduction of effective therapeutic agents except for complications
..

Done by : MaHmOuD TaNaSh