Peptic
Ulcer disease

Contents

Peptic
Ulcer disease

•       Etiology

•       Risk factor

•       Pathogenesis

•       Symptoms

•       Treatment 

Objectives
 

At the end of this lecture, student will be able to

•       Define  peptic ulcer disease

•       Explain the  etiology of peptic ulcer disease

•       Describe the pathophysiology of
peptic ulcer disease

Peptic Ulcer

•       Breach in the mucosa of the
alimentary tract, which extends through the muscularis mucosa into the
submucosa or deeper

•       Chronic  and most often solitary, lesions

•       Any 
portion of gastrointestinal tract exposed to the aggressive action of acid-peptic
juices

•       Erosion of GI mucosa resulting
from  digestive action of HCl and pepsin

Duodenal
vs gastric ulcers

	DUODENAL	GASTRIC
INCIDENCE	More common	Less common
ANATOMY	First part of duodenum – anterior wall	Lesser curvature of stomach
DURATION	Acute or chronic	Chronic
MALIGNANCY	Rare	Benign or malignant

Peptic
ulcer

     Imbalance
between aggressive & protective factors

Aggressive factors

•      
Gastric acid

•      
Proteolytic enzyme

Protective factors

•      
Mucosal layer

•      
Bicarbonate secretion

•      
Prostaglandins

Risk
factors of peptic ulcers

•       Helicobacter
pylori

•       Non
Steroidal Anti-inflammatory Drugs

•       Steroid
therapy

•       Smoking
and Excess alcohol intake

•       Genetic
factors

•       Zollinger
Ellison syndrome – rare syndrome caused by gastrin-secreting tumour

•       Blood
group O   and Hyperparathyroidism

Pathophysiology of peptic ulcers

Gastric acid and pepsin

•       Potential for producing mucosal
damage is related to the secretion of gastric (hydrochloric) acid and pepsin

•       Hydrochloric acid  – parietal cells – receptors for histamine,
gastrin, and acetylcholine

•       Increased acid secretion – duodenal
ulcers –  HP infection

•       Patients with ZES  have gastric acid hypersecretion resulting
from a gastrin-producing tumor

•       Patients with gastric ulcer – normal
or reduced rates of acid secretion

Mucosal defense mechanisms

•       Protect the gastroduodenal mucosa
from noxious endogenous and exogenous substances

•       Bicarbonate barrier protect the
stomach from the acidic contents

•       Epithelial cell restitution, growth,
and regeneration

•       Maintenance of mucosal integrity and
repair is mediated by the production of endogenous prostaglandins         

H. pylori infection

Mechanisms
include:

1)     
Direct
mucosal damage

2)     
(b)
Alterations in the host immune/inflammatory  
response

3)     
Hypergastrinemia
leading to increased acid secretion        

•       Virulence factors (vacuolating
cytotoxin, cytotoxin-associated gene protein, and growth inhibitory factor)

•       Elaborating bacterial enzymes
(lipases, proteases, and urease), and adherence

•       Lipases and proteases degrade
gastric mucus

•       Ammonia produced by urease – toxic
to epithelial cells

•       Bacterial adherence enhances uptake
of toxins into gastric epithelial cells

NSAID Induced

•       Direct or topical irritation of the
gastric epithelium and 

•       Systemic inhibition of endogenous
mucosal prostaglandin synthesis

•       Inhibit both COX-1 and COX-2 to
varying degrees

•       Neutrophil adherence may damage the
vascular endothelium

•       Lead to a reduction in mucosal blood
flow

•       Liberate oxygen-derived free
radicals and proteases      

Symptoms of peptic ulcers

•       Abdominal pain that is often
epigastric  – burning –   vague discomfort, abdominal fullness, or
cramping

•        A typical nocturnal pain that awakens the
patient from sleep

•        Severity of ulcer pain varies from patient to
patient

•       May be seasonal, occurring more
frequently in the spring or fall

•       Episodes of discomfort usually occur
in clusters lasting up to a few weeks followed by a pain-free period or
remission lasting from weeks to years

•       Heartburn, belching, and bloating
often accompany the pain

•        Nausea, vomiting, and anorexia

Complications
of peptic ulcers

•       Obstruction
– pyloric stenosis and duodenal stenosis

•       Hemorrhage
– blood in stools; if chronic – leads to anemia

•       Perforation

•       Malignant
transformation to carcinoma

Summary

•       Ulcers are defined as a breach in
the mucosa of the alimentary tract, which extends through the muscularis mucosa
into the submucosa or deeper

•       Etiological factors are helicobacter
pylori infection, nonsteroidal anti-inflammatory drugs, critical illness,
hypersecretion of gastric acid , viral infections ,vascular insufficiency

•       HP infection alters host
inflammatory response and damages epithelial cells directly by cell-mediated
immune system whereas NSAID cause direct irritation to epithelium and decrease
PGE2