PEPTIC ULCER

Definitions
Definitions

• Ulcer:

A lesion on an epithelial surface (skin or mucous membrane)

caused by superficial loss of tissue

• Erosion:

A lesion on an epithelial surface (skin or mucous membrane)

caused by superficial loss of tissue, limited to the mucosa
 Definitions
Definitions

• Peptic Ulcer

An ulcer of the alimentary tract mucosa, usually in the

stomach or duodenum, & rarely in the lower esophagus,
where the mucosa is exposed to the acid gastric secretion

• It has to be deep enough to penetrate the muscularis

mucosa
Peptic
Peptic Ulcer
Ulcer Disease
Disease
 Gastric
Gastric Mucosa
Mucosa &
& Secretions
Secretions

• The inside of the stomach is bathed in about 2 liters of gastric

juice every day
Thejuice
• Gastric gastroduodenal mucosal
is composed of digestive integrity
enzymes & is
determined
concentrated by protective
hydrochloric acid,(defensive) & tear
which can readily damaging
apart
the toughest food (aggressive)
or microorganismfactors
 Gastric
Gastric Mucosa
Mucosa &
& Secretions
Secretions

The Defensive Forces The Aggressive Forces

Bicarbonate Helicobacter pylori
When the layer
Mucus aggressive factors increase or the
HCl acid
defensive factors decrease, Pepsins
mucosal damage
Mucosal blood flow
NSAIDs
will result, leading to erosions & ulcerations
Prostaglandins
Bile acids
Growth factors Ischemia and hypoxia.
Smoking and alcohol
 Because of Imbalance

• Imbalance primarily between Aggressive factors

and Defensive factors:

n s ive
Defe rs, e.g.
facto s,
u
muc , PG
3
HCO
r e s s ive
Ag g , e , g,
r s
facto epsin,
p
acid, .
tc
bile e
 What may contribute imbalance ?
• Helicobacter pylori
• NSAIDs
• Ethanol
• Tobacco
• Severe physiologic
stress (Burns, CNS trauma,
Surgery, Severe medical illness)
• Steroids
 Negative
Negative Feedback
Feedback Regulation
Regulation of
of Acid
Acid Secretion
Secretion

Antral distention
Protein content
intragastric PH

Gastrin release

somatostatin secretion Increased gastric acid secretion

CGPR release Intragastric PH

CGPR= calcitonin gene related peptide

 Pathophysiology
Pathophysiology

• A peptic ulcer is a mucosal break, 3 mm or greater in size with

depth, that can involve mainly the stomach or duodenum.
 Pathophysiology
Pathophysiology

Two major variants in peptic ulcers are commonly encountered

in the clinical practice:

1) Duodenal Ulcer (DU)

2) Gastric Ulcer (GU)

 Phases of gastric secretion
Phase Stimuli Pathway
Cephalic (stimulate) Sight, smell, taste or 1) Vagus (M3 receptors)
thought of food 2) Histamine (H2 receptor)
3) Gastrin
Gastric (stimulate) Food in the stomach 1) Stretch: local reflex (M3
receptors)
2) Chemical substances in food
(gastrin)
3) Increase pH: Inhibition of
somatostatin (GHIH) release
Intestinal (inhibit) Chyme in the
duodenum
 What is Peptic Ulcer ?
• A peptic ulcer disease or PUD is an ulcer (defined as mucosal
erosions equal to or greater than 0.5 cm) of an area of the
gastrointestinal tract exposed to the acid and pepsin secretion

• Gastritis is the precursor to PUD and it is clinically difficult to

differentiate the two
– Stomach (called gastric ulcer)

– Duodenum (called duodenal ulcer)

– Esophagus (called Esophageal ulcer)

– Meckel's Diverticulum (called Meckel's Diverticulum ulcer)

 Recurrence
Recurrence

Risk factors for recurrence include:

• Non-ulcer dyspepsia

• Persistence of chronic gastritis after eradication therapy

• Female gender
• Intellectual disability

• Younger age

• High rates of primary infection

• Higher urea breath test values

ABLES A Z et al. American Family Physician. 2007

 Duodenal Vs Gastric Ulcers
Duodenal
• Age: 25-75 years
• Gnawing or burning upper abdomen
pain relieved by food but reappears 1-
3 hrs after meals
• Worse pain when stomach empty
• Bleeding occurs with deep erosion
– Hematemesis
– Melena
Gastric
• Age: 55-65 years
• Relieved by food but pain may persist
even after eating
• Anorexia, wt loss, vomiting
• Infrequent or absent remissions
• Small % become cancerous
• Severe ulcers may erode through
stomach wall
 Why Ulceration Occurs?
• High [H+] in the gastric lumen

• Require defense mechanisms to protect oesophagus and stomach

• Oesophagus – LES

• Stomach: a number of mechanisms

– Mucus secretion: slows ion diffusion

– Prostaglandins: I2 and E2 (alcohol, aspirin, and other drugs)

– Bicabonate ions

– High Blood Flow (nitric oxide)

 H. pylori
• Gram (-) rod with flagella
• H pylori is most common cause of PUD
• Transmission route fecal-oral
• Secretes urease → convert urea to
ammonia
• Produces alkaline environment enabling
survival in stomach
• Almost all duodenal and 2/3 gastric ulcer
pt’s infected with HP
• Considered class 1 carcinogen → gastric
cancer
• Higher prevalence in Low SES
 Who are they ?

Nobel Laureates
of Medicine –
2005

Discovery of
H. pylori & its
role in peptic
ulcer

Barry J Marshall J. Robin Warren

 Differentiating between
between H.
H. pylori
pylori
and NSAID-induced ulcer

Ulcers associated with H. Ulcers associated with

NSAIDs
pylori

• More often in stomach

• More often in • Often deep
duodenum • More severe GI bleeding

• Often superficial • Sometimes asymptomatic

• Less severe GI bleeding

Drugs of Ulcer
treatment
 Misoprostol Ranitidine
PGE2 Gastrin
Histamine
+ _ Proglumide
ACh _

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
Peptic
Peptic Ulcers
Ulcers

Therapy Purpose

Therapy is directed at
enhancing host defense or
eliminating aggressive
factors; i.e., H. pylori
 Classification
1. Acid Neutralizing agents: (ANTACIDS)
• Systemic: Sodium Bicarbonate and Sod. Citrate
• Nonsystemic: Magnesium hydroxide, Mag. Treisilicate, Aluminium hydroxide
gel, Magaldrate and calcium carbonate

2. Reduction in Gastric acid secretion:

• H2 antihistamines: Cimetidine, Ranitidine, Famotidine,
Nizatidine and Roxatidine
• Proton pump inhibitors: Omeprazole, Lansoprazole Pantoprazole,
Rabeprazole and Esomeprazole
• Anticholinergics: Pirenzepine, Propantheline and Oxyphenonium
• Prostaglandin analogue: Misoprostol
 Classification – contd.
3. Ulcer protectives: Sucralfate, Colloidal Bismuth
sudcitrate

4. Anti-H. pylori Drugs: Amoxicillin, Clarithromycin,

metronidazole, tinidazole and tetracycline
 Antacids
• Weak bases that neutralize acid
• Also inhibit formation of pepsin
(As pepsinogen converted to pepsin at acidic pH)
• Acid Neutralizing Capacity:
– Potency of Antacids
– Expressed in terms of Number of mEq of 1N HCl
that are brought down to pH 3.5 in 15 minutes by
unit dose of a preparation (1 gm)
 Antacids - The Oldest
Oldest Remedy
Remedy
• Sodium Bicarbonate:

– Potent neutralizing capacity and acts instantly

– ANC: 1 gm = 12 mEq

• NOT USED ANYMORE FOR ITS DEMERITS:

– Systemic alkalosis

– Distension, discomfort and belching – CO2

– Rebound acidity

– Sodium overload
 Antacids
• Present day antacids :
– Aluminium Hydroxide (ANC 1-2.5mEq/g)
– Magnesium Hydroxide (ANC 30 mEq) – milk of magnesia
– Magnesium trisilicate (ANC 1mEq/g)
• Duration of action : 30 min when taken in empty stomach and 2 hrs
when taken after a meal
• Side effects :
– Aluminium antacids – constipation (As they relax gastric smooth muscle & delay
gastric emptying) – also hypophosphatemia and osteomalcia
– Mg2+ antacids – Osmotic diarrhoea
• In renal failure Al3+ antacid – Aluminium toxicity
& Encephalopathy
(Magaldrate – hydrated hydroxy magnesium aluminate)
 Antacids – contd.
• Simethicone: Decrease surface tension thereby reduce
bubble formation - added to prevent reflux

• Alginates: Form a layer of foam on top of gastric

contents & reduce reflux

• Oxethazaine: Surface anaesthetic

 Therapeutic Questions
• Is it rational to combine Aluminium hydroxide and
magnesium hydroxide in antacid preparations ?

• How to avoid formation of insoluble complexes of

drugs by antacids, that are not absorbed ?
 Answers (!)
• Interactions can be avoided by taking antacids 2 hrs
before or after ingestion of other drugs
• Combination provides a relatively fast and sustained
neutralizing capacity
– (Magnesium Hydroxide – Rapidly acting
– Aluminium Hydroxide - Slowly acting )
• Combination preserves normal bowel function
– (Aluminium Hydroxide – constipation
– Magnesium hydroxide – diarrhoea )
 The
The Reality
• Not part of Physician prescribed regimen – frequency of
dosing and rebound acidity

• Over the counter (OTC) drug for symptomatic relief of

dyspepsia

• May only be prescribed for very short term:

– Non-ulcer dyspepsia and minor episodes of heart burn

– As adjuvant in GERD – quick relieve

Sucralfate – ulcer protective

• Salt of sucrose complexed to sulfated aluminium hydroxide (basic

aluminium salt)
• MOA:
– In acidic pH polymerises to viscous gel that adheres to ulcer crater - more on
duodenal ulcer
– Precipitates protein on surface proteins and acts as physical barrier
– Dietary proteins get deposited on this layer forming another coat
– Delays gastric emptying and causes gastric PG synthesis – protective action
 Sucralfate –– contd.
contd.
• Taken on empty stomach 1 hr. before meals
• Concurrent antacids, H2 antagonist avoided (as it needs acid for
activation)
• Uses:
– NSAID induced ulcers
– Patients with continued smoking
– ICU
– Topically – burn, bedsore ulcers, excoriated skins

• Dose: 1 gm 1 Hr before meals

• ADRs: Constipation, hypophosphatemia
Chemical
Chemical reactions
reactions of
of antacids
antacids with
with HCl
HCl
in
in the
the stomach
stomach
 Antacids
Capsules & Tablets:

• Powders

• Chewable tablets

• Suspensions

• Effervescent granules and tablets

 H22 Antagonists
• Cimetidine, Ranitidine, Famotidine, Roxatidine, Nizatidine and
• MOA:
– Reversible competitive inhibitors of H2 receptor
– Highly selective, no action on H1 or H3 receptors
– All phases of gastric acid secretion
– Very effective in inhibiting nocturnal acid secretion (as it depends largely on
Histamine )
– Modest impact on meal stimulated acid secretion (as it depends on gastrin,
acetylcholine and histamine)
– Volume of pepsin content and IF are also reduced
– Volume reduced by 60 – 70% - anti ulcerogenic effect
– No effect on motility
 H22 antagonists
• Kinetics:
– All drugs are absorbed orally adequately
– Bioavailability upto 80 %
– Absorption is not interfered by presence of food
– Can cross placental barrier and reaches milk
– Poor CNS penetration
– 2/3rd of the drugs are excreted unchanged in bile and urine
• Preparations: available as tablets, injections
H22 antagonists - ADRs
• Extremely safe drugs and well tolerated
• Main ADRs are related to Cimetidine:
– Antiandrogenic effects
– Increases prolactin secretion and inhibits degradation of estradiol by liver
– Cytochrome P450 inhibition – theophylline, metronidazole, phenytoin,
imipramine etc.
– Antacids

• Others:
– Headache, dizziness, bowel upset, dry mouth
– Bolus IV – release histamine – bradycardia, arrhythmia, cardiac arrest
– Elderly - precaution
 H22 antagonists - Uses
Promote the healing of gastric and duodenal ulcers
• Duodenal ulcer – 70 to 90%
• Gastric Ulcer – 50 to 75% (NSAID ulcers))
• Stress ulcer and gastritis
• GERD
• Zollinger-Ellison syndrome
• Prophylaxis of aspiration pneumonia
• Urticaria
Doses:
• 300 mg/40 mg/150 mg at bed time of R, F, Rox respectively for healing
• Maintenance: 150/20/150 mg BD of R, F, Rox
 H22 blockers
blockers Tablets
Tablets in
in Peptic
Peptic ulcer
ulcer
Cimetidine 800mg bedtime /400mgBd 400mg bedtime

Ranitidine 300 mg bedtime/150mg BD 150 mg bedtime

Famotidine 40 mg bedtime 20 mg bedtime

Roxatidine 150 mg bedtime 75 mg bedtime

 Question
Your friend wants to take a H2 antagonist before he
takes alcohol to avoid gastric irritation .He consults
you .Which H2 antagonist will you ask him to take ?

Ranitidine/Famotidine/Roxatidine/Tiznidine ?
 H22 antagonists –– contd.
contd.
• Answer :

Famotidine

• Explanation :

All H2 antagonist except famotidine inhibit gastric first

pass metabolism of ethanol and increase its
bioavailability
Proton Pump Inhibitors
Omeprazole
• Most effective drugs in antiulcer therapy
• Prodrugs requiring activation in acid environment
• Block enzymes responsible for secreting HCl - binds irreversibly
to H+K+ATPase
• Prototype: Omeprazole (Prilosec)
• Examples:
– Lansoprazole
– Pantoprazole
– Rabeprazole
– Esomeprazole
 Question
• 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)

 Pharmacokinetics - PPI
 Given on an empty stomach because food affects absorption
 They should be given 30 minutes to 1 hour before food intake
because an acidic pH in the parietal cell acid canaliculi is
required for drug activation, and food stimulates acid
production
 Concomitant use of other antisecretory drugs - H2 receptor
antagonists – reduces action
 Highly protein bound and rapidly Metabolized by the liver by
CYP2C19 and CYP3A4 – dose reduction necessary in severe
hepatic failure
 Excreted in Kidneys minimally (no dose reduction needed in
renal failure and elderly)
 Adverse Effects
 The most common are GIT troubles in the form of nausea,
abdominal pain, constipation, flatulence, and diarrhea
 Subacute myopathy, arthralgias, headaches, and skin
rashes
 Prolonged use:
 Gynaecomastia, erectile dysfunction
 Leucopenia and hepatic dysfunction
 Vitamin B12 deficiency
 Hypergastrinemia which may predispose to rebound hypersecretion of
gastric acid upon discontinuation of therapy and may promote the growth of
gastrointestinal tumors (carcinoid tumors )
• Therapeutic uses:
1. Gastroesophageal reflux disease (GERD)
2. Peptic Ulcer - Gastric and duodenal ulcers
3. Bleeding peptic Ulcer
4. Zollinger ellison Syndrome
5. Prevention of recurrence of nonsteroidal antiinflammatory drug
(NSAID) - associated gastric ulcers in patients who continue NSAID
use.
6. Reducing the risk of duodenal ulcer recurrence associated with H.
pylori infections
7. Aspiration Pneumonia
PPI – Dosage schedule
schedule

• Omeprazole 20 mg o.d.

• Lansoprazole 30 mg o.d.

• Pantoprazole 40 mg o.d.

• Rabeprazole 20 mg o.d.

• Esomeprazole 20 - 40 mg o.d.
 Muscarinic antagonists
Atropine:
– Block the M1 class receptors
– Reduce acid production
– Abolish gastrointestinal spasm
Pirenzepine and Telenzepine
Mechanism of action:
• Reduce meal stimulated HCl secretion by reversible blockade of muscarinic (M1)
receptors on the cell bodies of the intramural cholinergic ganglia
(receptors on parietal cells are M3).

• Unpopular as a first choice because of high incidence of anticholinergic

side effects (dry mouth and blurred vision)
 Prostaglandin analogues

• Inhibit gastric acid secretion

• Exhibit ‘cytoprotective’ activity

• Enhance local production of mucus or bicarbonate

• Promote local cell regeneration

• Help to maintain mucosal blood

 Prostaglandin
Prostaglandin analogues
analogues --
Misoprostol
Actions:
Inhibit histamine-stimulated gastric acid secretion
Stimulation of mucin and bicarbonate secretion
Increase mucosal blood flow

(Reinforcing of mucous layer buffered by HCO3 secretion

from epithelial cells)
Therapeutic uses:
Prevent ion of NSAID-induced mucosal injury (rarely used
because it needs frequent administration – 4 times daily)
 Misoprostol
• Doses: 200 mcg 4 times a day (Misoprost)
• ADRs:
– Diarrhoea and abdominal cramps
– Uterine bleeding
– Abortion
– Exacerbations of inflammatory bowel disease and should be avoided
in patients with this disorder
Contraindications:
1. Inflammatory bowel disease
2. Pregnancy (may cause abortion)
 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 is

Antacids

• Explanation :

Antacids neutralize 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
 Omeprazole
Amoxicillin
Clarithromycin
Metronidazole

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
 Triple Therapy – cont …
Some other Triple Therapy Regimens are
Bismuth subsalicylate – 2 tab qid
Metronidazole - 250 mg qid
Tetracycline - 500 mg qid

Ranitidine Bismuth citrate - 400 mg bd

Tetracycline - 500 mg bd
Clarithromycin / Metronidazole - 500 mg bd
 Bismuth subsalicylate
subsalicylate
Pharmacological actions:
• Undergoes rapid dissolution in the stomach into bismuth
and salicylates
• Salicylates are absorbed
• Bismuth coats ulcers and erosions protecting them from
acid and pepsin and increases prostaglandin and
bicarbonate production
• Uses:
• Treatment of dyspepsia and acute diarrhoea
 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
Stress induced ulceration after head trauma
-Cushing’s ulcer
Stress induced ulceration after severe burns -
Curling’s ulcer
 Etiology
Etiology

 Other uncommon causes include:

– Gastrinoma (Gastrin secreting tumor)

– Stress ulceration (trauma, burns, critical illness)

– Viral infections

– Vascular insufficiency
 Etiology
Etiology

 The two most common causes of PUD are:

– Helicobacter pylori infection ( 70-80%)

– Non-steroidal anti-inflammatory drugs (NSAIDS)

1. Etiology – Helicobacter pylori
 H.pylori
H.pylori Epidemiology
Epidemiology

• One half of world’s population has H.pylori infection, with an

estimated prevalence of 80-90 % in the developing world

• The annual incidence of new H. pylori infections in

industrialized countries is 0.5% of the susceptible population
compared with ≥ 3% in developing countries
H.pylori
H.pylori as
as aa cause
cause of
of PUD
PUD
H.pylori
H.pylori as
as aa cause
cause of
of PUD
PUD

85% 95% DU
GU
 Pathogenesis
Pathogenesis of
of H.
H. pylori
pylori infection
infection

• H. pylori is Gram-negative, spiral &

has multiple flagella at one end

• Transmitted from person-to-person

by Oro–oral or feco-oral spread

• No reservoir in animal or water

supply
 Pathogenesis
Pathogenesis of
of H.
H. pylori
pylori infection
infection

• The Flagellae make it motile,

allowing it to live deep beneath
the mucus layer

• It uses an adhesin molecule to

bind to epithelial cells Where the
pH there is close to neutral
 Pathogenesis
Pathogenesis of
of H.
H. pylori
pylori infection
infection

• Any acidity is buffered by the

organism's production of the
enzyme urease, which catalyzes the
production of ammonia (NH3) from
urea & raises the pH there

• The bacterium stimulates chronic

gastritis by provoking a local
inflammatory response.
 Pathogenesis
Pathogenesis of
of H.
H. pylori
pylori infection
infection

In the cellular level:

• H. pylori express cagA & vacA
genes
• cagA gene  signals to the
epithelial cells involving:
- Cell replication,
- Apoptosis, &
- Morphology
 Pathogenesis
Pathogenesis of
of H.
H. pylori
pylori infection
infection

In the cellular level:

• vacA gene  producing
a pore-forming protein, which
has many destructing effect to
the epithelium like:
-↑Cell permeability & efflux
of micronutrients,
- Induction of apoptosis, &
- Suppression of local cell
immunity
 Pathogenesis
Pathogenesis of
of H.
H. pylori
pylori infection
infection

Effects of H. pylori on gastric Hormones

- ↓ Somatostatin production from antral D-cells due to antral gastritis

- Low somatostatin will ↑Gastrin release from G-cell 
This effect is exaggerated among smokers!
hypergastrinemia
- This will stimulate acid production by the parietal cells  leading to
further duodenal ulceration.
 Carcinogenic
Carcinogenic effect
effect of
of H.
H. pylori
pylori

Host Factors
H. pylori

Other environmental
Factors

Antral gastritis Pangastritis

DU GU Gastritis Cancer
 Carcinogenic
Carcinogenic effect
effect of
of H.
H. pylori
pylori

• Epidemiologic evidence suggests that infection with HP is

associated with >2 fold increase risk of gastric cancer

• However due to uncertainty regarding the benefit of HP

eradication on reducing cancer risk, wide-spread screening for
HP in asymptomatic individuals cannot be recommended at
this time
For persons at high risk for gastric cancer (e.g.,
first degree relatives) screening can be
considered on a case by case basis

ABLES A Z et al. American Family Physician. 2007

2. Etiology -Non-Steroidal Anti-inflammatory
Drugs (NSAIDS)
 NSAIDS
NSAIDS

• Symptomatic GI ulceration occurs in 2% - 4% of patients

treated with NSAIDs for 1 year

• In view of the million of people who take NSAIDs annually,

these small percentages translate into a large number of
symptomatic ulcers

• The effects of aspirin & NSAIDs on the gastric mucosa ranges

from mucosal hemorrhages to erosions & acute ulcers
 NSAIDS
NSAIDS

 Inhibits the production of prostaglandins precursor from

membrane fatty acids resulting in:

1. Decrease mucus & HCO3 production

2. Decrease mucosal blood flow

3. Reduce cell renewal

 The drugs also generate oxygen-free radicals & products of

the lipoxygenase pathway that may contribute to ulceration
 NSAIDS
NSAIDS

 Gastric acid probably aggravates NSAID-induce mucosal

injury by

- Converting superficial injury to deeper mucosal necrosis,

- Interfering with haemostasis & platelet aggregation

- Impairing ulcer healing

 NSAIDS
NSAIDS

• Users of NSAIDs are at approximately 3 times greater relative

risk of serious adverse gastrointestinal events than nonusers
 NSAIDS
NSAIDS

 Identify risk factors:

– Age > 65 years (3.5-fold increased risk)
– Smoking
– Previous history of GI event (e.g. ulcer bleeding 4-fold increase
risk)
– Concomitant drug use
• Anticoagulants ( eg, warfarin; 3-fold increase)
• Corticosteroid ( 2-fold increase)
• Low dose aspirin alone ( 2.5-fold increase)
• Aspirin + NSAIDS (4-fold increase vs aspirin alone)
 Type
Type of
of NSAID
NSAID &
& Risk
Risk of
of Ulcer
Ulcer

Risk Group Drug Relative Risk

Low Ibuprofen 2.0
Diclofenac 4.2

Medium Naproxen 9.1

11.3
Indomethacin
Piroxicam 13.7

High Ketoprofen 23.7

Azapropazone 31.5
 Clinical
Clinical Presentation
Presentation

• Recurrent epigastric pain (the most common symptom)

– Burning
– Occurs 1-3 hours after meals
– Relieved by food  DU
– Precipitated by food  GU
– Relieved by antacids
– Radiate to back (consider penetration)
– Pain may be absent or less characteristic in one-third of
patients especially in elderly patients on NSAIDs
 Clinical
Clinical Presentation
Presentation

• Nausea, Vomiting

• Dyspepsia, fatty food intolerance

• Chest discomfort

• Anorexia, weight loss especially in GU

• Hematemesis or melena resulting from gastrointestinal

bleeding
Diagnosis of PUD
 Peptic
Peptic Ulcer
Ulcer Disease
Disease

Diagnosis:
1) Diagnosis of ulcer

2) Diagnosis of H. pylori
 Diagnosis
Diagnosis of
of PUD
PUD

In most patients routine laboratory tests are usually

Diagnosis of PUD depends mainly on endoscopic and
unhelpful
radiographic confirmation
 Doudenal
Doudenal Ulcer
Ulcer on
on Endoscopy
Endoscopy

Normal doudenal bulb Doudenal Ulcer

Gastric
Gastric Ulcer
Ulcer on
on Endoscopy
Endoscopy

Chronic Gastric Ulcers

 Diagnosis
Diagnosis of
of H.
H. pylori
pylori

 Non-invasive
• C13 or C14 Urea Breath Test

• Stool antigen test

• H. pylori IgG titer (serology)

 Invasive
• Gastric mucosal biopsy

• Rapid Urease test

 Diagnosis
Diagnosis of
of H.
H. pylori
pylori

Non-invasive
1. C13 or C14 Urea Breath Test

The best test for the detection

of an active infection
 Diagnosis
Diagnosis of
of H.
H. pylori
pylori

Non-invasive
1) Serology for H pylori

a. Serum Antibodies (IgG) to H pylori (Not for active

infection)

b. Fecal antigen testing (Test for active HP)

 Diagnosis
Diagnosis of
of H.
H. pylori
pylori

Invasive
• Upper GI endoscopy

– Highly sensitive test

– Patient needs sedation

– Has both diagnostic & therapeutic role

 Diagnosis
Diagnosis of
of H.
H. pylori
pylori

Invasive (endoscopy)

– Diagnostic:
– Detect the site and the size of the ulcer, even small and
superficial ulcer can be detected

– Detect source of bleeding

– Biopsies can be taken for rapid urease test,

histopathology & culture
 Diagnosis
Diagnosis of
of H.
H. pylori
pylori

Invasive (endoscopy)
• Rapid urease test ( RUT)
o Considered the endoscopic diagnostic test of choice
o Gastric biopsy specimens are placed in the rapid urease
test kit. If H pylori are present, bacterial urease
converts urea to ammonia, which changes pH and
produces a COLOR change
 Diagnosis of H. pylori
Invasive (endoscopy)
* Histopathology
o Done if the rapid urease test result is negative

* Culture
o Used in research studies and is not available routinely
for clinical use
 TREATMENT OF PUD
DRUG TYPE EXAMPLES DOSE
ACID-SUPPRESSING DRUGS
 ANTACIDS MYLANTA, MAALOX, TUMS, 100-140 MEQ/L 1 H AND 3
GAVISCON H AFTER MEALS

 H2 RECEPTOR  CIMETIDINE  400 MG BID

ANTAGONIST  RANITIDINE  300 MG HS
 FAMOTIDINE  40 MG HS
 NIZATIDINE  300 MG HS
CIME-RANI-FAMO-NIZA

 PROTON PUMP  OMEPRAZOLE  20 MG/D

INHIBITORS- MOST  LANSOPRAZOLE  30 MG/D
POTENT ACID  RABEPRAZOLE  20 MG/D
INHIBITORY AGENTS  PANTOPRAZOLE  40 MG/D
AVAILABLE  ESOMEPRAZOLE  20 MG/D
REPOL
 TREATMENT OF PUD
MUCOSAL PROTECTIVE AGENTS
SUCRALFATE – ACTS SUCRALFATE 1 g qid
Drug Type Examples Dose
AS A
PHYSICOCHEMICAL
BARRIER, PROMOTE
TROPHIC ACTION BY
BINDING GROWTH
FACTORS SUCH AS EGF,
ENHANCING
PROSTAGLANDIN
SYNTHESIS,
STIMULATING MUCOUS
AND BICARBONATE
SECRETION, AND
ENHANCING MUCOSAL
 TREATMENT OF PUD
DRUG TYPE EXAMPLES DOSE

PROSTAGLANDIN MISOPROSTOL 200ΜG QID

ANALOGUE –
ENHANCEMENT OF
MUCOSAL DEFENSE
AND REPAIR
BISMUTH- BISMUTH
CONTAINING SUBSALICYLATE
COMPOUNDS – (BSS) – MOST IDELY
ULCER COATING, USED PREPARATIONS
BINDING OF PEPSIN,
STIMULATION OF
PROSTAGLANDINS,
HCO3, AND MUCOUS
 THERAPY OF H. pylori

REGIMENS RECOMMENDED FOR ERADICATION OF H. PYLORI INFECTION

DRUG DOSE (RESPECTIVELY)
TRIPLE THERAPY
2 TABLETS QID, 250 MG QID, 500
1.BSS + METRONIDAZOLE + TETRACYCLINE
QID
2.RANITIDINE BISMUTH CITRATE +
400 MG BID, 500 MG BID, 500 MG
TETRACYCLINE + CLARITHROMYCIN OR
BID
METRONIDAZOLE
20 MG BID, 250/500 MG BID, 500 MG
3.OMEPRAZOLE (LANSOPRAZOLE) +
BID, OR 1 G BID
CLARITHROMYCIN + METRONIDAZOLE OR
AMOXICILLIN
QUADRUPLE THERAPY
20 MG (30 MG) DAILY
OMEPRAZOLE (LANSOPRAZOLE)
2 TABLETS QID
BISMUTH SUBSALICYLATE
250 MG QID
METRONIDAZOLE
500 MG QID
 SURGICAL

MANAGEMENT
DUODENAL ULCER
 RATIONALE
• EXCLUDING THE THE DAMAGING EFFECTS
OF ACID FROM THE DUODENUM

– BY DIVERSION OF ACID AWAY FROM

DUODENUM

– REDUCING THE SECRETORY POTENTIAL

OF STOMACH

– (OR) BOTH
 BILLROTH
BILLROTH 22 GASTRECTOMY
GASTRECTOMY

• BILLROTH 1ST IN 1881

• 1ST GJ IN SAME YEAR BY WOLFER

• BILLROTH 1 GASTRECTOMY+GASTRODUODENAL ANASTOMOSIS

• BILLROTH 2 GASTRECTOMY +DUODENUM CLOSED+RETROCOLIC

GJ WITH AS SMALL AN AFFERENT LOOP

• GASTROJEJUNOSTOMY
• TRUNCAL VAGOTOMY & DRAINAGE

• SELECTIVE VAGOTOMY&DRAINAGE

• HIGHLY SELECTIVE VAGOTOMY

*Image via Bing
 SURGERY-RELATED
COMPLICATIONS
• Afferent Loop Syndromes – caused by an
incomplete drainage of bile and pancreatic secretions
from an afferent loop that is partially obstructed in
patients who have undergone partial gastric resection
with Billroth II anastomosis resulting in bacterial
overgrowth secondary to stasis manifested by
abdominal pain, bloating, and diarrhea with
concomitant malabsorption of fats and vitamin B12
 SURGERY-RELATED
•
COMPLICATIONS
Dumping Syndrome – consists of a series of vasomotor and GI SSx and
occurs in Pxs who have undergone vagotomy and drainage

2 phases

- early dumping (15-30 min after meals) SSx are crampy abdominal
discomfort, nausea, diarrhea, belching, tachycardia, palpitations, diaphoresis,
light-headedness, and rarely, syncope

- late dumping (90 min – 3 h after meals) SSx are light-headedness,

diaphoresis, palpitations, tachycardia, and syncope, SSx is a result of rapid
emptying of hyperosmolar gastric contents into the small intestine, resulting
in a fluid shift into the gut lumen
 SURGERY-RELATED
COMPLICATIONS
 Postvagotomy Diarrhea – mc observed after truncal
vagotomy manifested as intermittent diarrhea that
occurs typically 1-2 h after meals

 Bile Reflux Gastropathy – present with abdominal

pain, early satiety, N/V, and mucosal erythema of the
gastric remnant in a subset of post-partial
gastrectomy patients

 Maldigestion and Malabsorption, Gastric

Adenocarcinoma
Type I

• Occur at the incisura.

• Not associated with

hyperacidity, most
patients have low acid
output.

• Associated with ABO

group “A”.
 Type II
• A combination of 2
ulcers, one in the body
of the stomach, the
other in the duodenum.
• Usually occur in
hypersecretory states.
• Associated with ABO
“O”.
Type III
• Located pre-pyloric.

• Associated with
hypersecretion.

• Type “O” blood

association.

• Typically 2-3 cm from

pylorus, can be multi.
 Type IV

• Csendes type ulcers.

• Occur high on lesser curve

at/near the GE junction.

• Not associated with

hypersecretion.

• Usually result from

defective mucosal
defense.
 Type V
• Can occur anywhere in stomach.

• Result from chronic ASA/NSAID ingestion.

 Thank U


H. pylori