DISPEPSIA

Primary regions of gastric

acid-related disease

Acid reflux
Oesophagitis
Strictures
Barrett’s
oesophagus
Oesophageal Gastritis
adenocarcinoma
Peptic ulcer
disease
(Includes NSAID-
induced ulcers)
Functional
dyspepsia
Duodenitis
Duodenal ulcer
Defines :
 Abdominal symptoms : discomfort, pain,
aching, bloating, fullness, burning, or
indigestion
Definition of dyspepsia (Rome II)

Pain or discomfort occurring

in the upper abdomen

Dyspepsia subgroups
 Ulcer-like (predominantly pain)
 Dysmotility-like (predominantly discomfort)
 Unspecified (non-specific, no predominant
symptom)

Talley et al., Gut 1999; 45(Suppl II): II37–42.

Malfertheiner, Eur J Gastroenterol Hepatol 1999; 11(Suppl 1): S25–9.
Dyspepsia covers a range of symptoms

DYSPEPSIA
GORD PAIN OR DISCOMFORT IBS
centred in upper abdomen

UNINVESTIGATED INVESTIGATED

ORGANIC FUNCTIONAL
(or idiopathic)
(use of the term ‘non-ulcer’
is discouraged)

Talley et al., Gut 1999; 45(Suppl II): II37–42.

Dyspepsia:
the size of the problem

15–25% of the general population experience dyspepsia within

a 12-month period
Much more common than peptic ulcer
Up to 5% of primary care visits are due to dyspepsia
Most patients have no detectable abnormality on radiological
upper GI series or endoscopy
Endoscopy findings and symptoms do not correlate

Talley, J Clin Gastroenterol 2001; 32: 286–93.

Locke, Ballieres Clin Gastroenterol 1998; 12: 435–42.
Paré, Can J Gastroenterol 1999; 13: 647–54.
van Bommel et al., Postgrad Med J 2001; 77: 514–18.
Talley et al., BMJ 2001; 323: 1294–7.
Dyspepsia:
pathogenic mechanisms

Dysmotility
H. pylori infection/ Altered gastric
inflammation acid secretion

Mechanisms of
dyspepsia

Psychosocial Gut hypersensitivity

factors
Witteman & Tytgat, Netherlands J Med 1995; 46: 205–11.
Talley et al., BMJ 2001; 323:1294–7.
Tack et al., Curr Gastroenterol Rep 2001; 3: 503–8.
Dyspepsia:
symptom assessment

Nature of symptoms Severity of

Character symptoms
Radiation
Timing, duration
and frequency
Modifying factors
Assessment
of symptoms

Patient’s degree Alarm features

of distress

Paré, Can J Gastroenterol 1999; 13: 647–54.

Table. Causes of chronic dyspepsia
Disease Clues on clinical evaluation

Functional (non-ulcer) dyspepsia Young patient; no alarm features

Chronic peptic ulceration NSAID use; Helicobacter pylori-positive serologically;
smoker; history of bleeding or anemia
Gastro-oesophageal reflux Heartburn or acid regurgitation dominant complaint
Gastric cancer Advanced age at onset; alarm features such as
weight loss; H.pylori positive serologically
Miscellaneous:
Biliary tract disease Biliary type pain
Chronic pancreatitis Constant pain; radiates to back; alcohol abuse;
diabetes mellitus
Only postprandrial pain; afraid to eat; weight loss;
Intestinal angina smoker
Diabetes mellitus History of diabetes; other diabetic complications
Drugs Theophylline; iron; potassium; digoxin; antibiotics
Important to distinguish the terms:
 Dyspepsia encompasses all relevant upper
abdominal symptoms regardless of their underlying
cause
 Uninvestigated D : refers to new onset or recurrent
D for which no diagnostic investigation yet have
been performed and therefore a specific diagnosis
has not been determined
 Functional D: refers to persistent or recurrent D for
which diagnostic investigation (including endoscopy)
has not determined an obvious organic cause of
symptoms
Uninvestigated dyspepsia
vs functional dyspepsia

Uninvestigated dyspepsia
 All symptomatic patients, regardless of whether a
cause
has been sought

Functional dyspepsia
 Symptomatic patients in whom
an organic cause has been
sought and excluded

Talley et al., Gut 1999; 45(Suppl II): II37–42.

Management of
uninvestigated
dyspepsia
 GP management of
uninvestigated dyspepsia

Alarm features (and/or >45 years?) No alarm features (and/or <45 years?)

Refer/investigate Symptom-based diagnosis

4 weeks’ therapy based on predominant symptom

Treat accordingly
Responders Non-responders/early relapses

1st-line investigation (13CUBT/stool test)

H. pylori +ve H. pylori -ve

Eradication therapy

Responders Non-responders
2nd-line investigation Increase doses/combination therapies
Stanghellini, 2001.
The Maastricht European Consensus Guidelines on the
management of dyspeptic patients in primary care

Dyspeptic patient
First primary care visit

Age <45 years* without Age 45 years or with alarm

alarm symptoms symptoms (irrespective of age)

Review patient’s history Refer to

Test for H. pylori gastroenterologist
• 13C-UBT or
• Laboratory serology
* The cut-off age may be below 45 years,
depending on regional differences in the
If H. pylori- incidence of gastric malignancy
positive,
treat the infection
The European Helicobacter Pylori Study Group 1997
When to refer

Presence of alarm symptoms

Failure to respond to appropriate therapy
Patients 45 years of age with new-onset
symptoms

Talley et al., Gut 1999; 45(Suppl II): II37–42.

Talley et al., BMJ 2001; 323: 1294–7.
Bytzer & Talley, Ann Intern Med 2001; 134: 815–22.
Treatment options in functional dyspepsia

Muco-protective Acid inhibition

agents

Functional
Functional
Dyspepsia
dyspepsia

Prokinetic H. pylori eradication

motility agents
Phytotherapeutics
Carminatives
Anti-depressants
Anti-serotoninergics
Opioids
Talley et al., Aliment Pharmacol Ther 1999; 13: 1135–48.
Talley et al., Gut 1999; 45(Suppl II): II37–42.
Nyeri Perut Berulang
(Recurrent Abdominal Pain/RAP)

 Chronic abdominal Pain (CAP) : nyeri perut

lebih dari 3 bulan terus menerus atau
kambuh-kambuhan)
 RAP : nyeri perut lebih dari 3 bulan tidak
berlangsung terus menerus namun
intermiten.
 Prevalensi :
 Anak-anak >10%
 Dewasa : 2% terutama wanita  sebagain besar
keluhan GI kronis (NUD & gangguan usus)
 CAP : biasanya fungsional : adanya gejala-
gejala nyeri perut berhubungan GI pada
pemeriksaan fisik, struktur maupun
biokimiawi tidak ditemukan kelainan
 CAP :
 FAPS / FGID  90%
 CAP  10%
 (Collins & Thomas Pediatric in Review, 2007)
Kriteria diagnostik FGID :
 Kriteria Roma III : gejala sudah terjadi seja 6
bulan dan harus aktif saat ini (harus
memenuhi kriteria selama 3 bulan)
 FGID :
 Dyspepsia fungsional
 IBS
 Kelainan kandung empedu fungsional

 (Chang, 2006; Mustafa, 2008)

Kriteria Diagnostik Roma III
Dyspepsia Fungsional (Chang, 2006)

 Paling sedikit dalam waktu 3 bulan pada 6

bulan terakhir terdapat 1 atau lebih gejala
dibawah ini :
 Rasa penuh setelah makan
 Cepat kenyang
 Nyeri epigastrik
 Rasa terbakar di ulu hati
 Tidak ada penyakit yang mendasari (endoskopi
atas)
IBS (Kriteria Diagnostik Roma III)
 Paling sedikit dalam waktu 3 bulan pada 6
bulan terakhir,nyeri abdomen berulang atau
tasa tida enak di perut, yang terdiri dari 2
atau lebih gejala dibawah ini :
 Perubahan pola BAB dan / atau
 Perubahan fulmen BAB, dan / atau
 Perubahan bentuk feses
 Patofisiologi FGID  gambar 1 (Crowell,
2006)
Terapi FGID
 Tegaserol  efek pada serotonin
 IBS tipe C
 DF
 GERD
 Acute depresan : trisiklik  efek langsung pada
usus mengurangi somatisasi
 Kolesistokinin (CCK) : IBS tipe C
 Probiotik : perubahan mikroflora usus
 IBS tipe D
 Dispepsia
 Bifidobacterium
Kesimpulan
 Nyeri perut berulang sebagian besar
fungsional, pemeriksaan endoskopi
atas/bawah tidak ditemukan kelainan.
 Peranan endoskopi untuk diagnosis sangat
penting dilakukan lebih-lebih bila ada tanda-
tanda bahaya.
 Terapi sesuai gejala-gejalanya.
PEPTIC ULCER DISEASE
(PUD)
Siti Nurdjanah
Peptic Ulcer Disease (PUD)
 Peptic Ulcer (gastric and duodenal)
 Defect in the gastrointestinal mucosa that
extend through the muscularis mucosa
Pathofisiology
 PUD : the end result of an imbalance
between aggressive and defensive factors in
the gastro duodenal mucosa
 AGGRESSIVE FACTORS
Acidic
environment H. pylori
Gastric Pepsin
Mucus layer NSAIDs Bile acid
Ionic gradient
Bicarbonate layer
Neutral environment
Prostaglandins
Surface epithelial
cells

Mucosal blood
supply

PROTECTIVE FACTORS
Imbalanced between aggressive factors and protective factors
Clinical Features of PU
 Abdominal pain  common
 Epigastric pain :
 Burning
 Discomfort
 Typical pain pattern DU :
 Occurs 90 mn to 3 hr after meal  frequently relieved by
antacids or food
 Awakes the patients from sleep (midnight – 3 A.M)
 Discomfort  precipitated by food
 Nausea  weight loss
The mechanism of pain 
unknown
1. Acid – induced activation of clinical receptors in
duodenum  enhanced duodenal sensitivity to
bile acids and pepsin
2. Altered gastro duodenal motility :
Variation in the intensity or distribution of the abdominal
pain  indicative of an ulcer complication
 Dyspepsia  constant no longer relieved by food
or antacids or radiation to the back  penetrating
ulcer (pancreas)
 Sudden onset of severe  perforation
 Pain worsening with meal, nausea, vomiting of
undigested food  suggesting gastric outlet
obstruction
Diffential Diagnosis

 Non ulcer dyspepsia

 GI tumors
 GERD
 Vascular disease
 Pancreatobiliary disease
 Gastro duodenal Cohn's disease
Diagnosis
 Predictive value of abdominal pain  poor for the
presence of a gastro duodenal ulcer
 A radiographic ( barium study)
 Single-contrast barium meals sensitivity defecting DU :
80%
 Double contras  sensitivity 90%
DU : appears as a well – demarcated scarring
GU : as a discrete crater with radiating mucosal folds
originating from the ulcer margin
Diagnosis
 Endoscopy  most sensitive and specific
Gambar H. pylori
Table 1. Test for detection of H.pylori
Test Sensitivity/specifity, % Comments

INVASIVE (ENDOSCOPY/BIOPSY REQUIRED)

Rapid urease 80 - 95/95 – 100 Simple, false negative with recent use of PPIs,
antibiotics, or bismuth compounds
Histology 80 – 90/>95 Requires pathology processing and information
Time-consuming, expensive, dependent on
Culture --/-- experience; allows determination of antibiotic
susceptibility
NON-INVASIVE
Serology >80/>90 Inexpensive, convenient; not useful for early follow-up
Simple, rapid; useful for early follow-up; false
Urea breath test >90/>90 negatives with recent therapy (see rapid urease test);
exposure to low-dose radiation with 14C test
Inexpensive, convenient; not established for
eradication but promising
Stool antigen >90/>90
Table2. Drugs used in the treatment of Peptic Ulcer Disease

Drug type/Mechanism Examples Dose

Acid-suppressing drugs
Antacids Mylanta, Maalox, Tums, 100-140 meq/L 1 and
Gaviscon 3 h after meals and hs
H2 receptor antagonists Cimetidine, 400 mg bid
Ranitidine, 300 mg hs
Famotidine, 40 mg hs
Nizatidine 300 mg hs
Proton pump inhibitors Omeprazole, 20 mg/d
Lansoprazole, 30 mg/d
Rabeprazole, 20 mg/d
Pantoprazole, 40 mg/d
Esomeprazole 20 mg/d
Mucosal protective agents
Sucralfate Sucralfate 1 g qid
Prostaglandin analogue Misoprostol 200 g qid
Bismuth-containing Bismuth sub-salicylate (BSS) See anti H.pylori regimens
compounds
 Table3. Regimens Recommended for Eradication
of H.pylori Infection

Drug Dose
TRIPLE THERAPY
1. Bismuth subsalicylate plus 2 tablets qid
Metronidazole plus 250 mg qid
Tetracycline 500 mg qid
2. Ranitidine bismuth citrate plus, 400 mg bid
Tetracycline plus, 500 mg bid
Clarithromycin or metronidazole 500 mg bid
3. Omeprazole (lansoprazole) plus, 20 mg bid (30 mg bid)
Clarithromycin plus
500 mg bid
Metronidazole or Amoxicillin
1 gr bid
QUADRUPLE THERAPY
Omeprazole (lansoprazole) 20 mg (30 mg) daily
Bismuth subsalicylate 2 tablets qid
Metronidazole 250 mg qid
Tetracycline 500 mg qid
GASTRITIS
Gastritis
 Inflammation of the gastric mucosa  should be
reserve for histologically documented
 Gastritis :
 is not the mucosal erythema seen during endoscopy
 Is not interchangeable with “dyspepsia”
 Classification of gastritis based on:
 Time course
 Histology features
 Anatomical distribution
Table. Classification of gastritis
I. Acute Gastritis II. Chronic atrophic gastritis
A. Acute H.pylori infection A. Type A: Autoimmune body-
B. Other acute infectious gastritides predominant
1. Bacterial (other than H.pylori) B. B. Type B: H.pylori-related, antral-
2. Helicobacter helmanni predominant
3. Phlegmonous C. Indeterminant
4. Mycobacterial III. Uncommon Forms of Gastritis
5. Syphilitic A. Lymphocytic
6. Viral B. Eosinophilic
7. Parasitic C. Cohn's disease
8. Fungal D. Sarcoidosis
E. Isolated granulomatous gastritis
Acute gastritis
 The most common causes: infectious H.pylori
histologic mucosal:
 Marked infiltrate of neutrophils
 Edema
 Hyperemia
 Bacterial infection  phlegmonous gastritis: diffuse
acute inflammatory infiltrates of the entire gastric
wall.
 Causes: Streptococci, Staphylococci, E-coli,
Proteus, Haemophilus sp.
Chronic gastritis

 Histologic mucosal : inflammatory cell

infiltrate: lymphocytes, plasma cell, with very
scant neutrophil involvement.
 Distribution of inflammation: patchy,
superficial and glandular portions of the
gastric mucosa  progress  glandular
destruction, atrophy and metaplasia.
 Classification of chronic G  accoding to
histologic characteritis
 Superficial atrophic
 Gastric atrophy
 Early phase of chronic gastritis & superficial gastritis
inflammatory changes : limited to the lamina propria
of the surface mucosa, edema and cellular infiltrates
separating intact gastric glands  decrease mucus
and mitotic figures in the gland cells.
 Atropy gastritis: inflammatory infiltrate extends
deeper into the mucosa progressive distortion and
destruction of the glands.
 Gastric atrophy: glandular structures are lost
endoscopically the mucosa: substantially their,
permitting clear visualization of the underlying blood
vessels.
Type A gastritis
 Less common
 The predominant site: fundus and body, with antral
sparing
 This form associate with permicious anemia
 Antibody to parietal cell  detected in > 90% of
patients with permicious anemia and in up to 50% of
patients with type A gastritis
 Is also called autoimmune gastritis
 Gastric and plays role in feedback inhibition of
gastrin release from G cells. Achlorhydric, conpled
with relative sparing of the antral mucosa (site G
cells)  hypergastrinemia.
Type B gastritis

 Antral-predominant
 More common
 H.pylori infection is the cause of this entity
Histologically
 The quantity of H.pylori is highest and a
dense chronic inflammatory infiltrate of the
laminapropria.
 Epithelial cell infiltration with pmn lenkocytes
 Multifocal atrophic gastritis, gastric atrophy
with subsequent metaplasia  development
of gastric adenoca.