PEPTIC ULCER DISEASEPresenting by:

Dr. Aiydarus Ali AhmedGeneral Medine and Surgery

Banadir University - Faculty of Medicine

Mogadishu-Somalia

Fowzi_7@hotmail.com

Background

• Peptic ulcer disease (PUD) is a

common disorder that affects

millions of individuals in the world

each year, with a major impact on

health care costs.

• In the last two decades, major

advances have been made in the

understanding of the

pathophysiology of PUD,

particularly regarding the role of

Helicobacter pylori infection and

nonsteroidal anti-inflammatory

drugs (NSAIDs).

• This has led to important changes

in diagnostic and treatment

strategies, with the potential for

improving the clinical outcome and

decreasing health care costs.

DEFINITION

• An ulcer is defined as disruption of the mucosal

integrity of the stomach and/or duodenum leading

to a local defect or excavation due to active

inflammation.

• Ulcers occur within the stomach and/or duodenum

and are often chronic in nature.

Epidemiology• Peptic ulcer is very common among the population.

• Ulcers can develop at any age

• They most often occur from early middle age onwards (

30 - 50), with gastric ulcers being more common in

elderly people ( > 60).

• Affect both men and women.

• May be acute or chronic

• Acute ulcers are often multiple, produce no symptoms

and usually heal without scarring.

• Chronic ulcers are deeper, usually occur individually and

usually produce symptoms. They leave a scar when they

heal.

Sites

• Esophagus

• Stomach

• First part of the duodenum (80%).

TypesGastric ulcer:

Type I:

(Lesser curve)

(Normal acid)

Type II:

(Pre-pyloric)

(Hyper-acidity)

Duodenal:

(1st part)

(Hyper-acidity)

Etiology of PUD

A) Normal

B) Increased Attack

*Hyperacidity

*Pepsin.

*NSAIDs.

C) Weak defense

*Helicobacter pylori

*Stress, drugs, smoking

Etiology & Pathogenesis

1. Helicobacter pylori infection

2. NSAIDs & Aspirin

3. Acid/Pepsin

4. Smoking

5. Genetics

6. Psychological factors

Nonsteroidal anti-inflammatory drugs, NSAIDs

Etiology & Pathogenesis

Cont…

• The most important contributing factors are H pylori,NSAIDs, acid, and pepsin.

• Additional aggressive factors include smoking, ethanol, bile acids, aspirin, steroids, and stress.

• Important protective factors are mucus, bicarbonate, mucosal blood flow, prostaglandins, hydrophobic layer, and epithelial renewal.

– Increased risk when older than 50 d/t decrease protection

• When an imbalance occurs, PUD might develop.

Pathogenesis of Ulcers

Aggressive Factors Acid, pepsin

Bile salts

Drugs (NSAIDs)

H. pylori

Defensive Factors Mucus, bicarbonate layer

Blood flow, cell renewal

Prostaglandins

Phospholipid

Free radical scavengers

Therapy is directed at enhancing host defense or

eliminating aggressive factors; i.e., H. pylori.

Aggressive Factors

Acid/Pepsin

H. pylori infection

NSAIDs

Smoking

Defensive Factors Mucus-bicarbonate barrier

Barrier of apical membrane

Mucosal blood flow

Prostaglandins

Epithelial cell restitution

Defensive

Factors

Aggressive

Factors

Aggressive Factors + Defensive Factors

I II

III

Figure 3. A, Protective factors; B, hostile factors.

Dictum No acid, no ulcer

No acid, no Hp, no ulcer

No Hp, No NSAIDs, no ulcer

Evolving Knowledge

Two Common Forms of Peptic Ulcer

H.pylori – associated: 70-85%

NSAIDs – associated: 10-25%

Non-Hp, Non-NSAID Ulcer: 5-30%

1. Helicobacter pylori in Peptic

Ulcer

•It is found in the gastric antrum of the stomach

•95%of duodenal ulcers & 85% of gastric ulcers

• In most people H. pylori causes antral

gastritis associated with depletion of

somatostatin (from D cells) and gastrin

release from G cells.

• The subsequent hypergastrinaemia

stimulates acid production by parietal cells,

but in the majority of cases this has no

clinical consequences.

• In a minority of patients (perhaps smokers)

this effect is exaggerated, leading to

duodenal ulceration . The role of H. pylori

in the pathogenesis of gastric ulcer is less

clear but H. pylori probably acts by

reducing gastric mucosal resistance to

attack from acid and pepsin.

• In approximately 1% of infected people, H.

pylori causes a pangastritis leading to

gastric atrophy and hypochlorhydria. This

allows bacteria to proliferate within the

stomach; these may produce mutagenic

nitrites from dietary nitrates, predisposing

to the development of gastric cancer

A, H. pylori resident on the gastric epithelium; B,

electron micrograph

• Specifically, the presence of antral-

predominant gastritis is associated with

DU formation; gastritis involving

primarily the corpus predisposes to the

development of GUs, gastric atrophy,

and ultimately gastric carcinoma .

Figure 3. Natural History of Helicobacter pylori Infection.

2. NSAIDs & Peptic Ulcer

• Apart from H pylori infection,

NSAID (or aspirin) use is the

other major identifiable risk

factor for PUD. Accounts for the

majority of H pylori–negative

ulcers.

• Second most common cause of

PUD.

NSAIDs

• Prostaglandins have important

several mechanisms to protect gastric

mucosa. They stimulate bicarbonate &

mucus secretion from the gastric

mucosa. Also they increase the

microvasculature of the mucosa. All

these mechanisms are called the

mucosal barrier.

• NSAIDs act by inhibiting cyclo-

oxygenase enzyme (COX) leading to

decrease prostaglandins at the site of

inflammation.

• NSAIDs decrease gastric and duodenal

prostaglandins, so mucosal erosions &

ulcerations will occur.

• The cyclo-oxygenase enzyme (COX)

has 2 types, COX-2, which is present

at sites of inflammation and COX-1,

which is present in the stomach. So

COX-2 inhibitors will not affect the

gastrointestinal mucosa.

Prostaglandin synthesis and mechanism of action Cox-2 inhibitors.

What exactly are NSAIDs?

3. Acid /Pepsin

By definition, peptic ulcer is caused by

autodigestion of acid and pepsin

Activity of pepsin is pH-depedent

Pepsinogen pepsin pH< 4

Maintaining activity pH< 4

Usual therapy toward suppression of acid

4. Smoking & Peptic UlcerIncreasing incidence of peptic ulcer

Delaying healing of ulcer

Increasing relapse and complication

Mechanisms:

Facilitating bile

reflux

Decreasing mucosal

blood supply

Inhibiting synthesis

of PGs

5. Genetics & Peptic Ulcer

Familial Clustering Genetic factors

Environment factor : H. pylori infection

Concordance of peptic ulcer is more

common in monozygotic that dizygotic

twins.

Peptic ulcer occurs in a few rare inherited

syndromes.

Gastrinoma

Mastocytosis

Genetics & Peptic Ulcer

6. Psychological Factor in Peptic Ulcer

Controversial

Possible mechanisms

through vagal mechanisms,

Stimulating acid secretion

Decreasing mucosal blood supply

Pathogenesis of peptic ulcer disease.

Signs and symptoms

• Gastric ulcer: Usually sufferers are above age 40

1. Periodical pain occurs immediately after food and finally pain persists

2. Pain is felt over the umbilicus and left to midline and no radiation of pain is felt

3. Pain is relieved by vomiting or alkali foods

4. Fear of eating due to pain

5. Weight loss due to reduced intake

6. Hametemesis (blood vomiting) may be present

7. Sensation of feeling fullness, indigestion and heartburn noticed immediately after eating.

• Duodenal ulcer: Usually sufferers are between age group of 20-50.

1. Periodicity of pain is very marked

2. Pain is felt above umbilicus and right to the midline and it may radiate to back

3. Pain appears 1-2 hours after food i.e. Pain is felt when the stomach gets empty, so the pain is often felt during middle of the night or sleep which disturbs sleep

1. Pain is usually better after taking food

2. No weight loss will be there since patient feels better with eating and goes on eating

3. Black or bloody stools (melena) may be present

Differentials

• Biliary Colic

• Cholecystitis

• Cholelithiasis

• Gastritis, Acute

• Gastritis, Chronic

• Gastroesophageal Reflux Disease

• Mesenteric Artery Ischemia

• Myocardial Ischemia

• Pancreatic Cancer

• Pancreatitis, Acute

• Pancreatitis, Chronic

WORKUP

• Lab Studies:

–In most patients with

uncomplicated PUD, routine

laboratory tests are usually

unhelpful.

–Documentation of PUD depends on

radiographic and endoscopic

confirmation.

– If the diagnosis of PUD is unclear or

complicated and PUD is suspected,

obtaining CBC, liver function tests

(LFTs), amylase, and lipase might be

useful

Imaging Studies

• Upper gastrointestinal series

–Double-contrast radiography performed by an experienced radiologist might approach the diagnostic accuracy of upper GI endoscopy.

–However, it has been replaced largely by diagnostic endoscopy, when available.

–It is not as sensitive as endoscopy

for the diagnosis of small ulcers

(<0.5 cm).

–It does not allow for obtaining a

biopsy to rule out malignancy in

the setting of a gastric ulcer or to

assess for H pylori infection in the

setting of a gastroduodenal ulcer.

A, X-ray of gastric ulcer in the antrum; B, corresponding

illustration of a gastric ulcer.

A, Duodenal ulcer; B, corresponding x-ray.

Peptic ulcers; A. malignant; B. benign.

Other Tests

• Detection of H pylori infection is

essential in all patients with peptic

ulcers.

• Endoscopic or invasive tests

include a rapid urease test,

histopathology, and culture.

–Rapid urease tests are considered

the endoscopic diagnostic test of

choice.

–The presence of H pylori in

gastric mucosal biopsy

specimens is detected by testing

for the bacterial product urease.

–One or more 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.

–Obtain histopathology, often

considered the criterion standard

for the diagnosis of H pylori, if

the rapid urease test result is

negative and a high suspicion for

H pylori persists (presence of a

duodenal ulcer).

–Culture primarily is used in

research studies and is not

available routinely for clinical

use.

• Nonendoscopic or noninvasive

tests include serum H pylori

antibody detection, fecal antigen

tests, and urea breath tests.

–Antibodies (immunoglobulin G

[IgG]) to H pylori can be

measured in serum, plasma, or

whole blood.

–Urea breath tests detect active H

pylori infection by testing for the

enzymatic activity of bacterial

urease.

–In the presence of urease

produced by H pylori, labeled

carbon dioxide (heavy isotope,

carbon-13, or radioactive isotope,

carbon-14) is produced in the

stomach, absorbed into the

bloodstream, diffused into the

lungs, and exhaled.

–Fecal antigen testing identifies

active H pylori infection by

detecting the presence of H

pylori antigens in stools.

–This test is more accurate than

antibody testing and less

expensive than urea breath tests.

• Special studies

–Obtaining a serum gastrin is

useful in patients with recurrent,

refractory, or complicated PUD

and is useful in patients with a

family history of PUD to screen

for Zollinger-Ellison syndrome.

Procedures

• Upper GI endoscopy :

–Preferred diagnostic test in the

evaluation of patients with

suspected PUD

–Highly sensitive for the diagnosis

of gastric and duodenal ulcers.

UGI Endoscopy

Gastric U. Duodenal U.

–Allows for biopsies and

cytologic brushings in the setting

of a gastric ulcer in order to

differentiate a benign ulcer from

a malignant lesion

–Allows for detection of H pylori

infection with antral biopsies for

a rapid urease test and/or

histopathology in patients with

PUD.

Complications

• Hemorrhage: Mild to severe hemorrhage is

the most common complication of peptic

ulcer disease.

• Symptoms include hematemesis (vomiting

of fresh blood or "coffee ground" material);

passage of bloody or black tarry stools

(hematochezia and melena, respectively);

and weakness, orthostasis, syncope, thirst,

and sweating caused by blood loss.

• Other Complications:

–Perforation

–Penetration

–Obstruction

Prognosis

• When the underlying cause is

addressed, the prognosis is

excellent. Most patients are

treated successfully with the cure

of H pylori infection, avoidance

of NSAIDs, and the appropriate

use of antisecretory therapy.

• Cure of H pylori infection

changes the natural history of

the disease, with a decrease in

the ulcer recurrence rate from

60-90% to approximately 10-

20%.

TREATMENT

• Given current understanding of the

pathogenesis of PUD, the majority

of patients with PUD are treated

successfully medically with cure of

H. pylori infection and/or

avoidance of NSAIDs, along with

appropriate use of antisecretory

therapy.

• A number of treatment options exist

for patients presenting with

symptoms suggestive of PUD or

ulcerlike dyspepsia, including

empiric antisecretory therapy,

empiric triple therapy for H pylori

infection, endoscopy followed by

appropriate therapy based on

findings, and H pylori serology

followed by triple therapy for

infected patients.

• Breath testing for active H pylori

infection may be used.

• Perform endoscopy early in

patients older than 45-50 years and

in patients with associated so-

called alarm symptoms, such as

dysphagia, recurrent vomiting,

weight loss, or with signs of

bleeding.

MEDICATION

• Treat all patients with peptic ulcers

and associated H pylori infection

with triple therapy, which results in

a cure rate of infection and healing

in approximately 85-90% of cases.

• In addition to effectiveness,

consider compliance, adverse

effects, drug interactions, and cost

when choosing a regimen.

• Treat NSAID-induced ulcers with

cessation of NSAIDs, if possible,

and an appropriate course of

standard ulcer therapy with a

histamine 2 (H2)–receptor

antagonist or a proton pump

inhibitor.

• If NSAIDs are continued, prescribe

a proton pump inhibitor.

• H pylori–negative ulcers that are

not caused by NSAIDs can be

treated with appropriate

antisecretory therapy, either H2-

receptor antagonists or proton

pump inhibitors.

• Begin testing for other causes.

• Drug Category: Triple therapies

for H pylori infection -- Triple

therapy for 14 days is considered

the treatment of choice for H pylori

infection.

• Two forms of triple therapy are

available, including proton pump

inhibitor–based triple therapy and

bismuth-based triple therapy.

• Proton pump inhibitor–based triple

therapy consists of a proton pump

inhibitor and 2 antibiotics, each bid

for 2 weeks.

• In the setting of an active ulcer,

continue qd proton pump inhibitor

therapy for additional 2 weeks.

Eradication of H.pylori

(Triple therapy for 2 weeks)• Proton pump inhibitor–based

triple therapy consists:

– Omeprazole (Prilosec): 20 mg PO

bid

Clarithromycin (Biaxin): 500 mg

PO bid

Amoxicillin (Amoxil): 1 g PO bid

2

weeks

• Omeprazole (Prilosec): 20

mg PO bid

• Clarithromycin (Biaxin):

500 mg PO bid

• Metronidazole (Flagyl):

500 mg PO bid

2

weeks

• Omeprazole (Prilosec): 20 mg PO bid

• Amoxicillin (Amoxil): 1 g PO bid

• Metronidazole (Flagyl): 500 mg PO bid

2

weeks

Diet

• Soft bland diet. It is better to be small and

frequent.

• Avoid irritant foods and smoking.

• Avoid excessive milk intake as it may

increase acidity due to its calcium content.

H2 Blockers:

For 4.-6 weeks to ensure ulcer healing)

• Ranitidine (ZantaC®) 300 mg/D.

• Famotidine (Antodine®) 20-40 mg/D .

PPI ( For 4 -8 Weeks)

• Omeprazole 20 mg/D.

• Pantoprazole 40 mg/D.

• Lanzoprazole 30 mg/D.

Surgical treatment of PUD

• Indication for surgery:-

– Failure of medical treatment.

– Recurrent uncontrollable hemorrhage.

– Perforation or penetration.

– Pyloric obstruction.

– Possible malignancy (See gastric carcinoma) .

Types of Surgery

1. Partial gastrectomy:

– Billroth I - the lower part of the stomach is

removed and stomach remnant is connected to

duodenum (a)

– Billroth II - the remnant of the stomach is

connected to the first loop of jejunum

(polyagastrectomy) (b).

2. Highly selective vagotomy (c)

• Partial gastrectomy - reduction of partial

cell mass by removal of part of the stomach.

(a) billroth I gastrectomy. (b) Polya (or

Billroth II) gastrectomy,

• (c) Vagotomy - can be either (i) truncal, or

(ii) highly selective with preservation of the

antral and pyloric innervation.

Treatment of Complication

• 1. Hemorrhage:• - Omeprazole: by I.V infusion or ranitidine infusion.

• - Endoscopic injection of adrenaline or use of heater

probe or laser therapy.

• - Blood transfusion: to restore the blood volume

rapidly.

• - Surgery: for resistant cases.

• 2. Perforation or penetretion: nasogastric

suction, IV fluids, antibiotics & analgesics,

surgery is performed to repair the

perforation with omental patch and drain

the abdomen.

Further Outpatient Care

• Endoscopy is required to document

healing of gastric ulcers and to rule

out gastric cancer.

• This usually is performed 6-8

weeks after the initial diagnosis of

PUD.

• Documentation of H pylori cure

with a noninvasive test, such as the

urea breath test or fecal antigen

test, is appropriate in patients with

complicated ulcers.

Prevention

• Primary prevention of NSAID-

induced ulcers includes the

following:

–Avoid unnecessary use of NSAIDs and

Use the lowest effective dose of an

NSAID.

–Use acetaminophen or nonacetylated

salicylates when possible.

Patient Care

Patient education

• Smoking delays ulcer healing

• Anticholinergics, TCAs, Ca channelblockers decrease lower oesophagealsphincter tone giving rise to GERD,eventually leading to oesophagitis.

• Patients should be warned of GIT riskbefore beginning NSAID or aspirin

• Patients sensitive to penicillin need aneradication regimen without amoxicillin

• Patients receiving eradication therapyshould be advised of the need of acombination of three drugs for a shortperiod of time.

Patient monitoring• Treatment success in peptic ulcer disease is

measured by review of the patient in termsof symptom control.

• Following eradication therapy, somepatients continue to experience symptoms ofabdominal pain.

• Patients should be reassured that thesesymptoms will resolve spontaneously.

• Anaemic patients following bleeding ulcerare prescribed iron therapy

Diagnosed peptic ulcer

H.pylori+ve H. pylori-ve

No NSAID history History NSAID use

Eradication therapy Ulcer healing therapy

1st line 4-8 weeks

Review 4-6weeks confirm ulcer healed

Resolution symptoms ulcer healed ulcer not healed

of symptoms persist

No follow-up urea breath test discontinue increase dose

treatment of ulcer healing agent

or alternative agent for 4 w

H.pylori+ve H.pylori-ve

Eradication therapy consider other Review

Review 4-6 w causes of symptoms

Resolution of symptoms symptoms persist

No follow-up consider other causes of symptoms

Future treatment

• Immunization against H. pylori will be a

future option in the management of peptic

ulcer disease.

OVERVIEW

• A peptic ulcer is disruption in a

segment of the GI mucosal integrity,

typically in the stomach (gastric

ulcer) or the first few centimeters of

the duodenum (duodenal ulcer).

• Nearly all ulcers are caused by

Helicobacter pylori infection or

NSAID use.

• Symptoms typically include burning

epigastric pain that is often relieved

by food.

• Diagnosis is by endoscopy and

testing for H. pylori. Treatment

involves acid suppression,

eradication of H. pylori (if present),

and avoidance of NSAIDs.