Gastric

Physiology and Pep3c Ulcer

Disease
Gary E Wild, MD.PhD.FRCP(C)

Role of Gastric Acid

Nutrient absorption
Iron
B12

Defense against blood borne pathogens

Prevention of small intestinal bacterial
overgrowth

Gastric Acid Secre1on

Stimulation
Gastrin
Acetylcholine
Histamine

Inhibition
Somatostatin
Prostaglandins

Parietal Cell Physiology

Gastric Defences

Mucus layer
Bicarbonate layer
Epithelial cells
Adequate blood flow

Mucosal Defense Mechanisms

MUCOSAL DEFENSE MECHANISMS

Stephanie L. Hansel
Mayo Clinic Gastroenterology and Hepatology Board Review: Peptic Ulcer Disease
(Adapted from Soll AH. Peptic ulcer and its complications. In: Feldman M, Sleisenger MH, Scharschmidt BF, editors. Sleisenger & Fordtrans gastrointestinal and liver disease: pathophysiology, diagnosis, management. Vol 1. 6th ed. Philadelphia [PA]: WB Saunders Company; c1998. p. 620-78. Used with permission.)

Consequences of Gastric Acid

Hypersecre1on
Peptic ulceration
Esophagitis
Steatorrhea (fat maldigestion)
Secondary to inactivation of lipase inactivation by
acid

Pep1c Ulcer Disease

200,000 to 400,000 people affected annually.
Accounts for 10% of costs for digestive
diseases.
0.1 to 0.3% incidence.

Pep1c Ulcer Disease

Etiology & Pathogenesis

Aggressive Factors
Acid/Pepsin
l H. pylori infection
l NSAIDs
l Smoking

Defensive Factors

l Mucus-bicarbonate barrier

l Barrier of apical membrane

l Mucosal blood flow
l Prostaglandins
l Epithelial cell restitution

Aggressive
Factors
III

Aggressive Factors + Defensive Factors

Defensive
Factors

II

Evolving Paradigm
Dictum
g No

acid, no ulcer
g No acid, no Hp, no ulcer
g No Hp, No NSAIDs, no ulcer

Clinical Features of Pep1c Ulcers

Endoscopy is diagnostic test of choice
Asymptomatic
Diagnosed during evaluation of anemia

Symptomatic
Abdominal pain
Bleeding (15%)
Advanced age
NSAID use

Perforation
Penetration to adjacent organ (pancreas)
Gastric outlet obstruction

Endoscopy versus Radiography

l Endoscopy has a greater accuracy of

establishing diagnosis than radiography.

l Endoscopy can take biopsies for
histology, ruling out malignancy, and
detection of Hp.
l Hemostatic therapy can be performed at the time of
Endoscopy.
l Cost
l Risk

Pep1c Ulcer Disease Risk Factors

Major (90%)
Helicobacter pylori infection
NSAIDs (Non steroidal anti-inflammatory drugs).
Minor(10%).
Acid hypersecretion state (Zollinger Ellison Syndrome)
Crohns disease
Malignancy
Cytomegalovirus infection
Cocaine
Smoking
Alcohol
Diet
Stress

NSAID Medica1ons as Risk Factor for Pep1c

Ulcer Disease
17 million people take NSAID daily in USA.
200000 will have serious adverse event
including bleeding
16000 deaths
3% of NSAID users develop serious GI
complications mediated through direct topical
injury to mucosa
20% develop asymptomatic ulcers or
gastropathy in the firsy year of use.

NSAID agents and Other Drugs

Low dose ASA

Cyclooxygenase-2 inhibitors
NSAID + H pylori synergy
Corticosteroids when co-administered with
NSAIDs
Bisphosphanates
Antiplatelet agents

Management of Pep1c Ulcer Disease

PPI (proton pump inhibitor) therapy is the
cornerstone of management. Long term
therapy may be needed in patients who
require NSAIDs
NSAID use should be assessed and
alternatives sought.
Evaluation and treatment of H pylori.
Endoscopic management of bleeding
Surgery
Failure of response to medical therapy
For complications

Medical Therapy
Aims of Treatment
l Removing underlying cause of
peptic ulcer
l Relieving symptoms
l Healing ulcer
l Preventing relapse of ulcer
l Avoiding complications

Strategies for healing ulcer

l Eradicate

l Inhibit

H. pylori

acid secretion

l Improve mucosal defense

Surgical Therapy
l Rare event
l Indication for surgery

Perforation
Intractable bleeding
Gastric outlet obstruction
(Scarring)
Malignant transformation
l Surgical options

Establish the diagnosis

(endoscopy or UGI)
Gastric ulcer
biopsy, R/O cancer

Endoscopic follow-up
to healing

Duodenal ulcer

Assess pathogenesis:
H.pylori
NSAIDs
Smoking
Family history
Serum gastrin

Therapy:
Treat H.pylori
Acid suppression
Enhance mucosa defense

Document H.pylori eradication

Complications -Surgery
(obstruction, perforation, intractable bleeding, malignant transformation)

Treatment of Pep1c Ulcer Disease

Anti-secretory
Proton pump Inhibitors
H-2 Receptor Antagonists.
Others
Sucralfate
Misoprostol

Follow up and Maintenance Therapy

Hp ve Duodenal ulcers.
No further endoscopy or treatment

Gastric Ulcers
Repeat endoscopy to ensure healing and confirm
benign etiology.

Complicated vs uncomplicated ulcers

Consensus guidelines regarding continued
anti-secretory therapy for Hp +ve
complicated ulcers post eradication therapy.

Pep1c Ulcer Preven1on Considera1ons

Test and treat Hp in NSAID nave patients
prior to initiating long term NSAID therapy.
Prophylaxis in patients with risk factors with
PPI therapy
Avoid NSAID use if possible.

Helicobacter pylori Infec1on

Gram negative organism.

Oral interfamily transmission.
Geographic variation in prevalence.
Prevalence inversely related to socioeconomic
status.
Acquired during childhood.
Organism secretes ammonia to neutralize acid and
secretes protease to digest mucus to secure its
ecological niche.
Causes antral gastritis and by destroying
somatostatin secreting D cells acid secretion is
uninhibited.

Helicobacter pylori
Clinical Features
Asymptomatic antral gastritis seen in 95% of
infected patients which predisposes to DU (80%)
Gastric corpus predominant gastritis predisposes
to GU (50%).

Risk Factor for Gastric Neoplasia.

Group I carcinogen and major cause of gastric
cancer.
MALT lymphoma
o Regression post Hp eradication in early cases

Gastric adenocarcinoma
o Atrophic Gastritis, metaplasia, dysplasia, carcinoma
sequence.

H. Pylori and Pep1c Ulcer Disease

Patients with PUD have higher rate of
infection with H pylori compared to general
population.
Antibiotic therapy heals ulcers at same rate
as H2RA.
Ulcer recurrence is lower after Hp
eradication.
Ulcer recurrence usually associated with
failure of Hp eradication.

Why dont all patients with H.pylori

infection have peptic ulceration?
H.pylori
Virulence

Host Factor
IL-1B polymorphism

Environment
Factors

Diagnos1c Tests for H. pylori

Treatment Regimens for H pylori

Dyspepsia
Chronic or recurrent discomfort in the upper
abdomen.
Incidence and prevalence hard to determine because
poor description of symptoms by patients and
reporting/classification by MDs.
30 to 40% have organic dyspepsia with abnormal
findings at gastroscopy including esophagitis, peptic
ulcer, malignancy.
60 to 70% have functional dyspepsia with normal
endoscopic findings.
Patients with dyspepsia who have not undergone
exams are said to have uninvestigated dyspepsia.
Mediation induced dyspepsia includes: NSAIDs,
Antibiotics and bisphosphonates.

Causes of Func1onal Dyspepsia

Management of Dyspepsia
For patients < 55 years with uninvestigated newonset dyspepsia without alarm features, a test and
treat approach for H pylori infection is advocated.
For patients from an area of low H pylori prevalence
PPI therapy is recommended as first line treatment.
Endoscopy is recommended for investigation of
dyspepsia in people > 55 years because of
increased incidence of GI malignancy with advancing
age.
Alarm features include:
Anemia, weight loss, family history of UGI
malignancy

Medica1on for Dyspepsia