Acid Related Disorders

M. Amer Khatib, MD
Assistant Professor in Medicine and
Gastroenterology
University of Jordan

Acid Related Disorders

Peptic ulcer disease (PUD)
Gastric Ulcers (GU)
Duodenal Ulcers (DU)

Gastro Esophageal Reflux Disease (GERD)

Peptic Ulcer Disease (PUD)

Definition:
Defects in the gastrointestinal mucosa that extend
through the muscularis mucosae

 PUD is an important cause of morbidity and

health care costs estimates of expenditures
related to work loss, hospitalization, and
outpatient care (excluding medication costs)
are $5.65 billion per year in the United States.
1/8 of Americans are suffering from PUD.

PUD
Clinical Presentation
Dyspepsia
DU: The "classic" symptoms occur when acid is
secreted in the absence of a food buffer.
symptoms occur two to five hours after meals or on an
empty stomach.
Symptoms also occur at night, between 11 PM and 2 AM,
when the circadian stimulation of acid secretion is
maximal.

GU: Has classically been associated with more

severe pain occurring soon after meals, with less
frequent relief by antacids or food.

PUD
Clinical Presentation

Postprandial belching
Bloating
Epigastric fullness
Anorexia
Early satiety
Nausea and occasional vomiting

Silent Ulcers in 1-2% of asymptomatic population

20 % of complicated ulcers present without symptoms
more frequent in elderly patients and individuals consuming
nonsteroidal antiinflammatory drugs (NSAIDs)

Presentation of more complicated cases

Penetrating ulcers:
a shift from the typical vague visceral discomfort to
a more localized and intense pain that radiates to
the back and is not relieved by food or antacids.

Perforation:
sudden development of severe, diffuse abdominal
pain.

Pyloric outlet obstruction:

Vomiting is the cardinal feature present in most
cases.

Hemorrhage:
may be heralded by nausea, hematemesis,
melena, or dizziness.

Pathophysiology

PUD
Causes

H Pylori
Nonsteroidal antiinflammatory drugs
Gastric acid hypersecretion
Familial aggregation

PUD
Causes

H Pylori
Nonsteroidal antiinflammatory drugs
Gastric acid hypersecretion
Familial aggregation

Helicobacter pylori
Spiral-shaped, gram-negative
bacterium with four to six unipolar
sheathed flagella.
The organism was first named
Campylobacter-like (curved rod)
organism, then Campylobacter
pylori. Its name was later changed
to H. pylori.
Its helical shape and flagella,
assist its movement through the
gastric mucus layer.

Prevalence of H. Pylori in peptic ulcer

Copyright Science Press Internet Services

H. pylori colonize the human

gastric mucus layer
through a combination
of flagellae mediated
motility and adherence
to carbohydrate
receptor structure, in
order to avoid clearance
by the shedding of cells
and mucus.

By secretion of the
Once the microbes have gained enough of
vacuolating cytotoxin,
nutrients, they will return to the protective
the microbes can utilize
mucus layer, and by doing so, they will
the cell as a source of
escape the PMN-cells. There is subsequently
nutrition. However, such
an equillibrium process in between adhering
disturbances will also
and free-floating microbes, where the
recruit white blod cells,
process is driven by parameters such as
a situation that
adherence properties, toxin secretion,
eventually results in a
metabolic efficacy and probably many
state of chronic
additional still unrecognized factors.
inflammation.

Genetic predispostion
Antral H. Pylori infection

Increased
inflammatory cells and
cytokines

Decrease
mucosal defense

Increase parietal cell

mass and sensitivity
Decrease antral
somatostatin
Increase Gastrin release

Ulcer formation
Increase acid output
Gastric metaplasia and
colonization

Environmental factors
Duodenitis

PUD
Causes

H Pylori
Nonsteroidal antiinflammatory drugs
Gastric acid hypersecretion
Familial aggregation

PUD
Causes

H Pylori
Nonsteroidal antiinflammatory drugs
Gastric acid hypersecretion
Familial aggregation
Risk of ulcer formation from NSAIDs:
Increase with Increasing age, particularly >60
Higher NSAID dose
Past history of gastroduodenal toxicity from NSAIDs
or peptic ulcer disease
Concurrent use of glucocorticoids, anticoagulants,
bisphosphonates, or other NSAIDs

NSAIDs inhibit the COX enzyme, which

exists in two forms
Arachidonic acid
COX-1
(constitutive)

COX-2
(induced by inflammatory stimuli)

COX-2 selective NSAIDs

Non-selective NSAIDs

Prostaglandins

Gastrointestinal cytoprotection
Platelet activity

Prostaglandins

Inflammation
Pain
Fever
Adapted from Vane & Botting 1995

Systemic effects of NSAIDs

may lead to gastric mucosal damage
NSAIDs
Altered inflammatory
mediator production
(e.g. decreased
prostaglandin, increased
tumour necrosis factor)

Increased neutrophil
endothelial adhesion

Capillary obstruction

Neutrophil release of
proteases and oxygenderived free radicals

Ischaemic/hypoxic cell
injury

Endothelial and
epithelial injury
Mucosal ulceration

Wallace 1997

PUD
Causes

H Pylori
Nonsteroidal antiinflammatory drugs
Gastric acid hypersecretion Zollinger-Ellison syndrome
Familial aggregation
DU and no Helicobacter pylori present

Presence of diarrhea
Failure of the ulcer to heal with H. pylori eradication
Multiple ulcers or ulcers in unusual locations
Severe peptic ulcer disease leading to a complication (eg, bleeding
perforation, intractability)
Severe or resistant peptic esophageal disease
History of nephrolithiasis or endocrinopathies
Family history of nephrolithiasis, endocrinopathies, or peptic ulcer
disease

PUD
Causes

H Pylori
Nonsteroidal antiinflammatory drugs
Gastric acid hypersecretion
Familial aggregation

First-degree relatives of patients with DU have a threefold increase in

the prevalence of DU but not GU
Relatives of patients with GU have a threefold increase in the
prevalence of GU but not DU.
Hyperpepsinogenemia was proposed as a marker of autosomal
dominant inheritance.

Factors that influence the course of peptic ulcer

Smoking
Alcohol
Diet
Psychologic factors

Diagnosis
Barium studies
Endoscopy
Serological test

Barium Study

Folds radiating to the crater and deformities in the

region secondary to spasm, edema, and scarring
Barium within an ulcer
niche, which is
generally round or
oval

Barium Study
Sensitivity
Single contrast 50%
Double contrast 80-90%
Shallow lesions <0.5 cm in diameter are difficult to
detect reliably

Endoscopy
Sensitivity >95%
Biopsy and tissue samples are easy to obtain

One or two pieces of tissue are placed in

an agar well that contains urea and a pH
reagent.
Urease cleaves urea to liberate ammonia,
producing an alkaline pH and a resultant
color change

Serological test
ELISA technology to detect IgG or IgA
antibodies
Inexpensive
Concerns over its accuracy have limited its
use.

Treatment
Treatment of peptic ulcer begins with the
eradication of H. pylori in infected individuals
Antisecretory therapy is the mainstay of
therapy in uninfected patients.
Withdraw potential offending or contributing
agents such as NSAIDs, cigarettes, and
excess alcohol.
No evidence that addressing stressful
psychosocial situations benefits treatment
outcomes
No firm dietary recommendations are
necessary

H.Pylori eradication
Proton Pump Inhibitor (PPI) twice a day
Two antibiotics Amoxicillin 1 gm twice daily
and clarithromycin 500 mg twice daily
Metronidazole 500 mg twice daily can be
substituted for amoxicillin but only in
penicillin-allergic individuals.
High resistance to Metronidazole reported
Effective in more than 85%

Antisecretory therapy
All four H2 receptor antagonists, cimetidine,
ranitidine, famotidine, and nizatidine, induce
healing rates of
70 to 80 % for DU after four weeks
87 to 94 % after eight weeks of therapy.

Proton pump inhibitors, including omeprazole,

esomeprazole, lansoprazole, pantoprazole,
and rabeprazole, are effective in inducing
ulcer healing.
63 to 93 % for DU at two weeks
80 to 100 % at four weeks

Gastro Esophageal Reflux Disease

GERD
Reflux of gastric contents into the esophagus.
Retrosternal burning, or heartburn, is the most frequent
symptom experienced by GERD patients in general
practice, occurring in 86% of patients .
GERD symptoms have a significant negative impact on patients
quality of life.
8% of all adults suffer from heartburn or acid regurgitation two or
more times a week

Prevalence of heartburn

Clinical Presentation

Heartburn
Dyspepsia
Atypical chest pain
Regurgitation
Sleep difficulties
Dysphagia

Asthma
Hoarseness
Dental cares
Sinusitis
Laryngitis
Waterbrush

Causes of GERD
Reflux
Dysfunction in anti-reflux mechanism

Caustic material
Acid, Pepsin, bile and pancreatic secretions

Sufficient duration of contact

Inadequate clearance mechanism

Overwhelm
Overwhelm mucosal
mucosal
resistance
resistance

09047.lnk

Typical GERD symptoms

B e g in T h e r a p y
S uccess

F a ilu r e
C o n fir m D x
E ndoscopy

P o s it iv e

N e g a t iv e

A d van ce R x

p H M o n it o r in g

S uccess

F a ilu r e

P o s it iv e

p H M o n it o r in g
P o o r c o n tro l

G o o d a c id c o n t r o l

N e g a t iv e
O th e r D x

Indications for Endoscopy

Chronic reflux symptoms > 10 years
Age >40
Alarming symptoms ( wt. Loss, nausea,
vomiting & dysphagia)
Failure to respond to medical therapy

Indications for 24 pH monitoring

Normal endoscopy and:
- Typical GERD symptoms unresponsive to
anti-reflux therapy.
- Atypical chest pain.
- Extra esophageal disorders possibly related
to GERD.
Endoscopic esophagitis unresponsive to
therapy.
Prior to antireflux surgery.

Endoscopic view of erosive esophagitis

Barrett's esophagus

Antireflux surgical management

Antireflux surgical management

Endoscopic therapy of reflux disease

Endoscopic therapy of reflux disease