Peptic ulcer disease

Professor Alaa El-Suity

 Acute peptic ulcer

Troubles waste the stomach

like rust waste iron
 Pathology

 Abnormal sites
Jejunum & oesophagus
(+ Stomach & duodenum)

 Multple small superficial ulcers

 Aetiology
1- Stress
2- Steroids & NSAIDs
3- Surgery (prolonged surgery,
neurosurgery)
4- severe trauma
5- severe sepsis
6- severe burn
 Clinical features
 Acute epigastric pain
 Vomitinig & haematemesis
 Perforation (may be)
 Burn  Curling ulcer
 Neurosurgery  Cushing ulcer

“After every end is a new beginning,

and every beginning has an end”
Chronic peptic ulcer
 Incidence
 Ulcer incidence is about 1% per year in H.P.
positive people, a rate that is 6-10x higher than
non-infected individuals.
 NSAID use as well as HP infection rates increase
with age. This may explain shifting trends in
incidence.
 Another factor is the prevalence of smoking.Rates
of smoking are declining in younger people,
particularly men, possibly influencing the male to
female ratio. Previously a predominant male
disease,currently with nearly comparable gender
ratio in latest studies.
 Gastric ulcer

Pathophysiology, pathogenesis,
Aetiology,pathology
 Pathophysiology
 The first line of defense is mucus and
bicarbonate secretion. It stabilizes the pH
between the lumen and the surface epithelial
cells. Mucus gel in patients with HP infection
was found to be structurally weak. Duodenal
mucus as wel as bicarbonate secretion is
reduced in patients who smoke.
 The second line of defense is the intrinsic
epithelial cell defense.The mucosal surface is a
barrier to acid back diffusion thus maintaining
normal intra cellular pH.
 Pathophysiology
 With the exception of ZE ulcer disease should
be regarded as a reduction in normal mucosal
defense. Considering the aggressive nature of
acid /pepsin environment , ulcer disease is
surprisingly uncommon.
 Factors such as HP, NSAIDS disrupt these
normal defense mechanisms. Smoking
interferes with healing and secretory regulation.
 Pathophysiology
 The third line of defense is the rich mucosal
blood flow. The blood provides a buffer for acid
neutralization as well as adequate nutrition for
the metabolic demand to maintain mucosal
integrity.
 Gastric mucosa has the ability to repair minor
injury and therefore prevent progression to deep
ulcers.Restitution has been evident within one
hour.
 Pathogenesis: HP infection.
 Described in humans in the first decade of the 20th
century. Only in 1983 was it described in association with
ulcer disease.
 HP’s natural habitat is the human stomach. Without
treatment infection is lifelong.
 In developing countries most children are infected by the
age of 10. In developed countries there is a clear age
related increase.
 IT has not been proven why most patients with HP do not
develop ulcer disease.
 HP resides in the stomach but causes duodenal ulcers
probably by colonizing pockets of metaplastic gastric
mucosa.
 Pathogenesis : NSAIDS
 NSAIDs impair normal mucosal defense.
 10-20% of patients will develop gastric ulcers and
4-10 % duodenal ulcers within 3 months of taking
NSAIDS. Not all endoscopic ulcers are clinically
symptomatic and trials generally overstate the risk.
Probably closer to 1% in the first three months.
 NSAID users develop gastric ulcers twice as
common as duodenal ulcers. (HP more duodenal).
 NSAID ulcers not usually associated with gastritis
as is the case with HP infection. When NSAID use
is stopped these ulcers do not recur.
 So, the aetiology of gastric ulcer:
1) Chronic atrophic gastritis
2) Infection with H.pylori
3) NSAIDs
4) Spicy food
5) Duodenogastric reflux
6) Mucosal ischemia
 Pathology
A. Location and Type of gastric Ulcer:
 Type 1: Primary gastric ulcer. Associated with diffuse
antral gastritis.
 Type 2: Gastric ulcers with duodenal ulcers, most likely
secondary to duodenal ulcers.
 Type 3: Prepyloric or channel ulcer.
 Type 4: Proximal stomach or gastric cardia.

Acid hyper secretion common among type 2 and 3 ulcers.

Type 1 an 4 pathophysiologycally the same.
B. Size: more than 3 cm  giant ulcer 
3-26% is suspicious
C. Ulcer Crater: filled with granulation tissue
D. Base: is bulged outside the lumen.
E. Intraoperatively: Petechial hge appear on
rubbing the serosa ( chronic inflammatory
process)
F. mucosal conversion.
 Duodenal ulcer

Pathogenesis, aetiology,
pathology

Dr.S.Mani
 Pathogenesis: hyperacidity
 Adequate acid necessary for duodenal
ulcers.
 Remember “no acid, no ulcer” withstood
the test of time. Acid is a important co-
factor in the developing of both duodenal
and gastric ulcers.
 So, the aetiology of hyper acidity:
1) Genetic factor: Large parietal cell mass
in blood group O personnel.
2) Stress: hurry, worry, work.
3) Infection with H.pylori.
4) Endocrinal causes:
- ZE syndrome
- MEN
- Hypercalcaemia
 Pathology
A. Site of ulcer
- Anterior bulbar 95%  perforate
- Posterior bulbar 5%  bleed
- Ant. & post  kissing ulcer
B. Size: smaller than gastric ulcer
C. Ulcer Crater: filled with granulation tissue
D. Base: is bulged outside the lumen.
E. Intraoperatively: Petechial hge appear on
rubbing the serosa ( chronic inflammatory
process)

Never turn malignant

“Attitude determines altitude”
Clinical presentation of chronic
peptic ulcer
 Clinical Presentation
 Patients present with dyspepsia, epigastric pain
and or discomfort. Acid may irritate nerve
endings or peristaltic waves passing the ulcer
may cause discomfort.
 But there is great overlap in symptoms with non
ulcer dyspepsia. 20% of patients will present
with serious complications without previous ulcer
symptoms.
 It is said that gastric ulcers present with pain
associated or closely followed by eating ,where-
as duodenal ulcer pain is relieved by food.
 Clinical Presentation
 These two pain processes are very non specific.
 Pain tend to be chronic and recurrent. The two can
generally not be differentiated on clinical grounds
alone.
 Generally gastric ulcers present from age 50-65,
where as duodenal ulcers present in the thirties.
 Other non specific symptoms are nausea, weight
loss, heart burn fatty food intolerance and bloating.
 Melena alone more frequently associates duodenal
ulcers. Gastric ulcers present with hematemesis or
melena in equal frequency.
 Clinical Presentation
 Ulcers may also present with a perforation.
This occurs in 5-10% of patients.
 Gastric outlet obstruction usually develops
in the context chronic ulcer disease. Seen
in <5% of patients.
 Duodenal versus Gastric ulcers

Gastric Duodenal
Normal/hypo-secretion of Hyper-secretion
gastric acid
Pain 1-2 hrs pc meals Pain 2-4 hrs pc meals
Food aggravates pain Food may relieve pain
Vomiting common Vomiting not common
More likely to hemorrhage – Less likely to hemorrhage, but if
manifests as hematemesis occurs, likely to manifest as
melena
Diagnosis of chronic peptic ulcer
 1) Esophagogastroduodenoscopy

 Fiberoptic endoscope allows

direct visualization of
esophagus, stomach and
duodenum

 Biopsy
 detection of H.pylori
 Malginancy in gastric
ulcer
Dr.S.Mani
Dr.S.Mani
 2) Barium studies

 Gastric ulcer  Niche

& notch

 Duodenal ulcer 
deformed duodenal
cap or its trifoliate
apperance
 Benign. lesser curvature gastric ulcer. Red arrows point to
Hampton's Line, a thin, straight line at neck of ulcer in profile view
which represents the thin rim of undermined gastric mucosa
  duodenal ulcer,
colored barium

Dr.S.Mani
3) Estimation of gastrin hormone by
radioimmunoassay
 Differential diagnosis of
chronic peptic ulcer
1) Gastric cancer.
2) Chronic cholecystitis.
3) Chronic pancreatitis.
4) Hiatus hernia
 Complications of duodenal ulcers
1) Haemorrhage
2) Perforation
3) Pyloric stenosis

Complications of Gastric ulcers

As above +
4) Hour glass stomach
5) Tea-pot stomach
6) Malignancy
Treatment of Peptic Ulcer

Dr Alaa El-Suity
“Choice not chance determines
destiny”

‫االختيار و ليس الحظ هو ما ُيحدد المصير‬

 Medical Management of ulcers
 Conservative therapy:  Pharmaceutical:
 Rest: Both physical  Antibiotics
and emotional To eradicate H. Pylori infections
Recurrence of ulcer is 75-90% as high
 Dietary modifications with infection
 Elimination of
smoking  Antiacids
Initial drugs of choice
 Long term follow up
 Histmaine H2 receptor antagonists
care
Histamine is the final intracellular
activator of HCL secretion
 Anticholinergic:
Stop the cholinergic stimulation of HCl
secretion and slow gastric motility
Not commonly used, if used need to
be used with caution in pts with
Glaucoma
 Misoprostol Ranitidine
PGE2 Gastrin
Histamine _
ACh + Proglumide
_

M3 _ H2
Adenyl
PGE cyclase
+ Gastrin
+ receptor + receptor

Ca++ ATP cAMP Ca++

+ + +

Protein Kinase
(Activated)
+ +
K
K +H
Parietal cell
Proton pump
_ Lumen of stomach
Omeprazole Gastric acid _ Antacid
 Antacids

 Weak bases that neutralise acid

 Also inhibit formation of pepsin
(As pepsinogen converted to pepsin at acidic pH)
 Present day antacids :
Aluminium Hydroxide
Magnesium Hydroxide
 Antacids – cont…

Duration of action :
 30 min when taken in empty stomach
 2 hrs when taken after a meal
Side effects :
 Al3+ antacids – constipation (As they relax gastric
smooth muscle & delay gastric emptying)
 Mg2+ antacids – Osmotic diarrhoea .
 In renal failure Al3+ antacid – Aluminium toxicity
&
Encephalopathy
 Now answer this question

 Is it rational to combine aluminium hydroxide

and magnesium hydroxide in antacid
preparations ?
 Answer

 Combination provides a relatively fast and

sustained neutralising capacity .
(Magnesium Hydroxide – Rapidly acting
Aluminium Hydroxide - Slowly acting )

 Combination preserves normal bowel function.

(Aluminium Hydroxide – constipation
Magnesium hydroxide – diarrhoea )
 Histamine H2 Receptor Antagonist
 Reversible competitive inhibitors of H 2 receptor

 Highly selective, No action on H1 or H3 receptors

 Very effective in inhibiting nocturnal acid

secretion ( as it depends largely on Histamine )
 Cimetidine Ranitidine Famotidine Nizatidine

Bioavailability 80 50 40 >90
Relative Potency 1 5 -10 32 5 -10
Half life (hrs) 1.5 - 2.3 1.6 - 2.4 2.5 - 4 1.1 -1.6
Duration of 6 8 12 8

action (hrs)
Inhibition of 1 0.1 0 0
CYP 450
Dose mg(bd) 400 150 20 150
 H2 Blockers–Side effects & Interactions

 Extremely safe drugs

 Cimetidine causes gynecomastia, galactorrhea

(as it is antiandrogenic & increases prolactin level)
 Cimetidine inhibits Cytochrome P-450 &
increases conc. of Warfarin, Theophylline,
Phenytoin, Ethanol. S
 Proton Pump Inhibitors

 Most effective drugs in antiulcer therapy

 Irreversible inhibitor of H+ K+ ATPase

 Prodrugs requiring activation in acid environment

 Proton Pump Inhibitors

Omeprazole 20 mg o.d.
Esomeprazole 20 - 40 mg o.d.
Lansoprazole 30 mg o.d.
Pantoprazole 40 mg o.d.
Rabeprazole 20 mg o.d.
 Now answer this question
 It is given in the previous slides that the half life of
proton pump inhibitors is 1.5 hours only and
these drugs are generally given once daily. How
this can be justified ?

 Answer :

P.P.I - Irreversible inhibitors of H +K+ATPase

(Hit and run drugs)
 P.P.I. – Side effects & Interactions

 Extremely safe drugs

 Causes hypergastrinemia which leads to

carcinod tumor in rats
 But no evidence of such tumors in man

 Inhibit CYP 450 & hence metabolsim of

warfarin, phenytoin, etc
 Pantoprazole & Rabeprazole have no significant
interactions
 Now Answer this Question

A patient comes to your clinic at midnight

complaining of heart burn. You want to relieve his
pain immediately. What drug will you choose?
 Answer :
Antacids

Explanation :
Antacids neutralise the already secreted
acid in the stomach. All other drugs act by
stopping acid secretion and so may not relieve
symptoms atleast for 45 min.
 Mucosal Protective Agents

Dr.S.Mani
 Mucosal Protective Agents

 Sucralfate

 Misoprostol

 Colloidal Bismuth compounds

 Sucralfate

 Salt of sucrose

 Taken on empty stomach 1 hr. before meals

 Concurrent antacids, H2 antagonist avoided

( as it needs acid for activation )

 Misoprostol

 PGE1 analogue

 Modest acid inhibition

 Stimulate mucus & bicarbonate secretion

 Enhance mucusal blood flow

 Approved for prevention of NSAID induced ulcer

 Diarrhoea & cramping abd. pain – 20 %

 Not so popular as P.P.I are more effective &

better tolerated
 Colloidal Bismuth Compounds

 Coats ulcer, stimulates mucus & bicarbonate

secretion
 Direct antimicrobial activity against H.pylori

 May cause blackening of stools & tongue

 Not used for long periods – bismuth toxicity

 Now answer this question

 A pregnant lady (first trimester) comes to you

with peptic ulcer disease. Which drug will you
prescribe for her ?
 Answer :

Antacids or Sucralfate

 Explanation ;
H2 antagonists cross placenta and are also
secreted in breast milk. Safety of Proton pump
inhibitors not established in pregnancy.
Misoprostol causes abortion .
 Can you identify these people ?

Nobel prize
Medicine –
2005

Discovery
of H.pylori &
its role in
ulcer

Barry J Marshall J. Robin Warren

Eradication of H.pylori
 Triple Therapy

 The BEST among all the Triple therapy regimen is

Omeprazole / Lansoprazole - 20 / 30 mg bd
Clarithromycin - 500 mg bd
Amoxycillin / Metronidazole - 1gm / 500 mg bd

 Given for 14 days followed by P.P.I for 4 – 6 weeks

 Short regimens for 7 – 10 days not very effective

Now you have learnt about drugs used for
treating peptic ulcer ? Are there any drugs that
can cause peptic ulcer ?

Drugs causing peptic ulcer

 Non Steroidal Anti Inflammatory Drugs
(NSAIDs)
 Glucocorticoids

 Cytotoxic agents
Surgical Management of
ulcerations
 (I) Chronic gastric ulcer
 Main line of ttt in type I & IV ulcers.
 WHY?
1- Persistent mucosal defect
2- May be silent for long time, then turn
malginant
 (I) Chronic gastric ulcer
(1)
Gastroduodenostomy
(Billroth I)
 Removal of the lower
portion of stomach and
small portion of
duodenum and
connects remaining of
stomach to duodenum
 (I) Chronic gastric ulcer
(2) Subtotal gastrectomy
 removal distal third of
stomach, reconnecting to
duodenum or jejunum

(3) Sleeve gastrectomy

(pauchet’s gastrectomy)
 In cardiac ulcer
 (II) Chronic duodenal ulcer
 ttt is essentially medical.
 Indications of surgery:
1- Failure of medical ttt for > 8 wks
2- Recurrence after medical ttt with
intractable pain, interfering with life style
3- Risk & cost of medical ttt > 5 yrs = Risk &
cost of operation
 (II) Chronic duodenal ulcer
(1) HSC
 Preserve antral pump
( by preservation of nerve of Latter jet)
 No drainage operation

(2) Trunkal vagotomy (& drainage)

No need for gastrectomy in uncomplicated
duodenal ulcer
 (II) Chronic duodenal ulcer
Drainage operation
1- gastrojujenostomy
- anterior / posterior
- short loop / lomg loop
- iso-peristaltic / anti-peristaltic
- anti colic / retro colic
2- pyloroplasty
Longitudinal incision that is sutured
transversely
Complications
 Complications of duodenal ulcers
1) Haemorrhage
2) Perforation
3) Pyloric stenosis

Complications of Gastric ulcers

As above +
4) Hour glass stomach
5) Tea-pot stomach
6) Malginancy
 Complications: Pyloric obstruction

Pathogenesis
 Caused by inflammation or edema of the
pylorus

 Stomach cannot empty  abdominal

bloating, N & V
 Complications: Pyloric obstruction
Clinical features
 Pain
 Vomiting
 Loss of apetite
 Loss of weight
 Loss of perriodicity
 +ve succusion splash
 Auscultopercussion test
 Persistent vomiting Hyponatraemia,
hypokalemia,hypochloraemia, hypomagnesaemia,
metabolic alkalosis, hypocalcaemia (gastric tetany),
paradoxical aciduria
 NO PALPABLE MASS
Dr.S.Mani
 Complications: Pyloric obstruction
Paradoxical aciduria
With normal serum Na, body can
compensate for metabolic alkalosis by
renal secretion of excess Hco3 along with
Na.
In pyloric stenosis, there is hyponatraemia,
so body compensate for metabolic
alkalosis by renal secretion of excess
Hco3 along with H ions.
 Complications: Pyloric obstruction
Investigations
1- Barium studies
2- Gastroscopy
3- Electrolyte profile
4- ECG for hypokalaemia
Pyloric obstruction
Hen’s Peak
 Complications: Pyloric obstruction
Other causes of pyloric stenosis
1- Congenital
2- Cicatrized duodenal ulcer
3- Cancer pylorus
4- Pyloric mucosal diaphragm
 Complications: Pyloric obstruction
Treatment
(Mainly surgical)
(1) VAG + CG
(2) VAG + antrectomy + Billroth II reconstruction
( end to side anastomosis)

WHY NOT B I?

 drawbacks of B II:
1- Non physiological
2- Predispose to postgastrectomy complications
“Knowledge is the only treasure that
increases on sharing”

‫المعرفة هي الكنز الوحيد الذي يزداد بالمشاركة‬

 Complications: Perforation
 GI contents empty into peritoneal cavity

 Manifested by:
 Sudden, sharp mid-epigastric pain which can shortly
spread to all abdomen
 Rigid, tender, board-like abdomen
 Patient assumes the fetal position to reduce tension
on muscles

 Can lead to shock

 It is a surgical emergency
 Complications: Perforation
Stages of perforation
1- stage of chemical peritonitis
2- stage of reaction
3- stage of bacterial peritonitis

The end results is

- Septicaemia & shock
- Facies hippochratica
- MODS
 Complications: Perforation
Investigations
1-Plain x-ray, erect: gas under diaphragm
(70%)
2- U/S: free fluid & gases
3- C.T: to exclude other causes of acute
abdomen ( in absence of gases)

Dr.S.Mani
Complications: Perforation

Differential diagnosis:
Other causes of acute abdomen
 Complications: Perforation

Management
 NGT to prevent additional spillage of GI
contents in peritoneum
 Replace blood, fluid, electrolytes
 Antibiotics
 I & O, NPO
 SURGERY: Urgent
A- Open: Closure with interrupted sutures
and placement of omental patch)
B- Laparoscopy: beneficial in both diagnosis
and treatment.

 Definitive ulcer surgical ttt is not required,

as the general condition of pt is bad
 Perforated GU VS perforated DU

Dr.S.Mani
 Complications: Hemorrhage
site
1- granulation tissue in ulcer crater
2- Small vessels running in wall.
3- Gastroduodenal artery in DU
or left gastric artery in GU

Fatal hge
 Complications: Hemorrhage
Manifested by:
 Orthostatic hypotension,  BP, HR, cool,
clammy skin overt bleeding

 Hematemesis (bloody vomit) – bright red or coffee

ground (more likely with gastric ulcer)

 Melena (bloody or tarry [black] stool) – more likely

with duodenal ulcer

  Hgb,  Hct
Complications: Hemorrhage

 Diiferential diagnosis:
other causes of haematemesis
 Complications: Hemorrhage
Investigations

1- Endoscopy

2- Celiac angiography( in doubtful site of bl.)

 Complications: Hemorrhage
Management
(A) Initial management:
 Monitor S/S
 Determine rate amount of blood loss (Hct/hct),
 Replace blood, fluid and electrolyte loss

(B) Emergency endoscopy to rule out diagnosis

 Complications: Hemorrhage
(C)
 saline lavage with adrenaline 1/20000 via NGT
 O2
 I.V H2 blocker or I.V PPP
 Endosopic cauterization
 Sclerotherapy (ethanolamine oleate)
 Failure  open surgery & under running of the bleeding
ulcer bed or ligation of the big vessel
(D)If the general condition of pt is good 

Dr.S.Mani Definitive ulcer surgical ttt

 Complications of gastric operations
1- Haemorrage
2- Stomal obstruction
3- duodenal blow out
4- Reccurent ulcer
5- Dumping syndrome
 Dumping syndrome
(post cibal syndrome)
 A complication of gastric surgery

 S&S
 vertigo, sweating, palpitations, syncope, pallor, tachycardia

 occurs after eating

 D/t rapid emptying of hypertonic stomach contents into small intestine
 fluid shifts into gut abd. distention and cramps and S/S of 
plasma volume.
 Later get rapid elevation of blood glucose followed by insulin secretion
and hypoglycemia

 Management
 Small frequent meals
  fat,  protein,  CHO meals
 liquid between (not with) meals
 Lie down after meals