Functional

Dyspepsia

Division of Gastroentero - Hepatology

Departmen of Internal Medicine
Medical Faculty, North Sumatera University
Medan - Indonesia
 Dyspepsia - Definition

A group of symptoms which alert

clinicians to consider disease of the
upper gastrointestinal tract

(British Society of Gastroenterology, 1996)

 Functional Dyspepsia -
Definition
Chronic or recurrent upper GI symptoms not
explained by biochemical or structural abnormalities
(does not imply that there is no physiological basis)
Appropriate evaluation using standard diagnostic
tests reveals no abnormalities
Also known as nonulcer dyspepsia, essential
dyspepsia, idiopathic dyspepsia

(Talley N. Scand J Gastro 1991;182:7)

 Dyspepsia

Functional Non-GI
Dyspepsia Causes of Symptoms
(cardiac disease,
muscular pain, etc.)

Structural Dyspepsia
(GERD, PUD, pancreatic
disease, gallstones, etc.)
 What is Dyspepsia?
Epigastric pain
Indigestion
Fullness
Early satiety
Bloating
Belching
Nausea
Retching
 Symptoms of Functional
Dyspepsia
Ulcer-like Dominant Dysmotility-like Dominant

Nocturnal
pain Nausea
Localized Heartburn Bloating
epigastric
Retrosternal Early satiety
burning
burning Worse
Better with food
with food
 Why is Dyspepsia
Important?
Prevalence is 25% - 40% per year
Accounts for 5% of all PCP referrals
Accounts for 50% of gastroenterologists
workload
$2 Billion is spent on acid-suppressing
drugs each year in the US
Pathophysiology of
Functional
Dyspepsia
 What are the possible
causes of functional
dyspepsia?
Altered enteric visceral perception
(hyperalgesia)
Altered enteric motor function
Altered CNS function
Helicobacter pylori
 Pathogenesis &
Pathophysiology of Dyspepsia

Behavioural factors
Gastritis
H. pylori infection

Increased
visceral Altered
perception motility
 Mechanisms Underlying
Increased Sensory Perception
Reduced
descendin
g inhibition

Increased
sensory
input
 Mechanisms Underlying
Altered Motility in Dyspepsia
Stress
Behavioural
Factors

Local Factors:
Gastritis
H. pylori infection

Abnormal Motility
Decreased antral motility
Impaired fundal relaxation
 Putative Pathogenesis of
Dyspepsia
Stress

ANS Imbalance
Increased Sensitivity

Sensory Inhibition
.
Increased
Low Grade
.. Sensitivity
Afferent
Activity Inflammation
HP Infection Impaired Motor Activity

Accommodation

Altered Motor & Sensory Function

DYSPEPSIA
Helicobacter pylori
in Functional
Dyspepsia
 Is H. pylori a Factor in
Functional Dyspepsia?
Controversial
Some evidence
- biological plausibility
- prevalence (45% to 70% in
dyspeptics, 13% to 60% in controls)
- eradication studies
 H. pylori Eradication
Studies
in Functional Dyspepsia
No Benefit from Length of Benefit from Length of
H. pylori Follow-up H. pylori Follow-up
Eradication (yr) Eradication (yr)
Veldhuyzen van Zanten, 1995 0.5 Lazzaroni, 1996 0.5
Elta, 1996 3 Trespi, 1994 0.5
Schutze, 1996 1 McCarthy, 1995 1
Sheu, 1996 1
 Testing for H. pylori
Test Sensitivity Specificity Cost Comments
C13 or C14 90% to 100% 96% to 100% ++ Limited - requires
urease breath hospital nuclear
test medicine department
Serology 91% to 98% 75% to 80% + Widely available
through commercial
labs and Public Health
Capillary 85% to 90% 75% to 80% + Office test, must be
blood serology purchased by doctor administered

Endoscopic 99% 99% ++++ Requires specialist

biopsy Invasive

(Cutler A. Gastro 1995;109:136.

Megraud F. Scand J Gastro 1996;215:57)
 Suspected Functional
Dyspepsia - Who to
Investigate?
Over 50 years of age, with new onset
of symptoms
Failed therapy
Cancer fear
Symptoms that are severe as
perceived by patient or physician
AGA Guidelines Step 1
AGA Guidelines Step 2

Alarm Symptoms:
Weight loss
Progressive
dysphagia
Recurrent vomiting
Evidence of GI bleed
Family history of
malignancy
AGA Guidelines Step 3
AGA Guidelines Step 4
Proposed Mechanisms of
Hyperalgesia
Central Hyperalgesia

Pain Loss of
Descending
Inhibition

Peripheral Signals
 Proposed Mechanisms of
Hyperalgesia
Drug Effects on the CNS-Enteric Nervous System
Pain Perception
Cortex
Pharmacological
Options
Spinal Cord opiates, tricyclics
Descending inhibitory fibres 5HT3 antagonists

- ANS. Input Clonidine

2nd order neurons opiates
Dorsal horn nucleus 5HT3 antagonists

Substance P
Dorsal root ganglion CGRP antagonists
Sensory
NSAIDs
nerve endings in gut opiates
5HT3 antagonists
 Altered Enteric
Motor Function in
Functional
Dyspepsia
 Upper GI Motility in
Functional Dyspepsia
Impaired reflex fundal relaxation
Impaired gastric compliance/receptive relaxation
to food ingestion
Weak postprandial antral contractions
Delayed gastric emptying
Small bowel motor dysfunction
Upper GI Motility in Functional
Dyspepsia
Abnormal Fundic Relaxation in Response
Abnormal Fundic Relaxation in Response
to Meal in Functional Dyspepsia

Normal Fundic
accommodatio
n or receptive
relaxation

Meal

Impaired fundic
accommodation
Functional with a
dyspepsia redistribution of
food to antrum
(Gilja O. Dig Dis Sci 1996;41:689)
Delayed Gastric Emptying in
Functional Dyspepsia

Studies have found delayed gastric

emptying for solids, in 30% to 82%
of patients with functional
dyspepsia
 Small Bowel Motor
Dysfunction in Functional
Dyspepsia
In patients with more severe
symptoms
Hyperactive or uncoordinated
duodenal contractions
Absent or abnormal migrating
myoelectrical complexes
(Kerlin P. Gut 1989;30:54)
Altered CNS Function
in Functional
Dyspepsia
 CNS Factors
Psychological factors to be considered
in
the pathogenesis of functional
Anxiety
Depressiondyspepsia:
Sexual abuse
Sleep deprivation
Stressful events
The role of psychological factors in functional dyspepsia
is not as clearly established as it is in IBS
 H. pylori Eradication
Regimens
(All given for one week)
Treatments of Choice
Regimen PPI Antibiotics
PPI - AC BID Amoxicillin 1 g bid
Clarithromycin 500 mg bid
PPI - MC BID Metronidazole 500 mg bid
Clarithromycin 250 mg bid

Alternate
PPI - BMT BID Bismuth 2 tabs qid
Metronidazole 250 mg qid
Tetracycline 500 mg qid
 Choice of Investigation for
Ulcer-like Dyspepsia
Endoscopy
More expensive
Issues of access/waiting
lists can be a problem
Allows for biopsy
(cancer, Hp)
Allows diagnosis of
mucosal lesions (erosions)
Preferred investigation for
dyspepsia
UGI Series
Less expensive
Easy access, usually short
waiting time
If cancer is found, endoscopy
will be needed
Often misses mucosal lesions
Alternative, especially if
access is a concern
 Investigation of
Dysmotility-like Dyspepsia
Investigations are frequently normal
Reserved for patients with severe
symptoms, vomiting dominant,
unresponsive to therapy
Solid-phase gastric emptying test
may be useful
Management of
Functional
Dyspepsia
Management of Functional
Dyspepsia
Functional Dyspepsia

General
General treatment
treatment and
and specific
specific
management
based
based on
on dominant
dominant symptom
symptom complex
complex

Ulcer-like
Ulcer-like Dysmotility-like
Dysmotility-like

Follow-up
Follow-up within
within 3
3 to
to 6
6
weeks
weeks
Management of Ulcer-like
Functional Dyspepsia
Ulcer-like Symptoms Dominant

Education/lifestyle
Education/lifestyle
modification
modification

Test
Test Hp
Hp

+
+ --

Eradicate
Eradicate Hp
Hp Trial
Trial of
of acid
acid suppression
suppression
Reassess
Reassess

Success
Success Failure
Failure
Investigate
Investigate Trial
Trial of
of prokinetic
prokinetic
Lifestyle Modification for
Patients with Functional
Dyspepsia
Small frequent meals
Stop smoking
Reduce alcohol
Reduce caffeine
Avoid irritating foodstuffs
Maintain an ideal weight
Review medications
Acid Suppression Therapy
for Ulcer-like Functional
Dyspepsia

H2-receptor antagonist for 4 weeks

OR
Proton pump inhibitor for 2 weeks
Management of Dysmotility-like Functional
Dyspepsia
Dysmotility-like Symptoms Dominant

Educate/lifestyle
Educate/lifestyle modification
modification

Trial
Trial of
of prokinetic
prokinetic
medication
medication
Success
Success Failure
Failure

Continue
Continue with
with Investigate
Investigate
cyclic
cyclic therapy
therapy
Test
Test H.
H. pylori
pylori
Gastroscopy
Gastroscopy or
or UGI
UGI
+
+ --

Eradicate
Eradicate
Consider
Consider HH22
Success
Success Failure
Failure antagonists,
antagonists, tricyclics
tricyclics
 Differential Diagnosis
Functional Dyspepsia (60%) Pancreatitis
PUD (25%) Carbohydrate Malabsorption
GERD Meds (NSAIDS, Narcotics,
Biliary Pain etc.)
Chronic Abdominal Wall Pain Infiltrative Diseases
Gastric CA Metabolic Disturbances
Esophageal CA Hepatoma
Other Abdominal Malignancy Ischemic Bowel Disease
Gastroparesis Systemic Disorders
Parasites
 Pathophysiology of FD
Increased gastric acid
H. pylori infection
GI dysmotility (antral hypocontractility)
Decreased perception threshold
Autonomic dysfunction
Decreased gastric accommodation
Gastric myoelectric activity
Psychological factors
Psychological Treatment for
FD
4 trials have evaluated CBT,
hypnotherapy, or psychotherapy
All show statistically improvement at 1
year
Cochrane Meta-analysis- insufficient
evidence as all trials likely underpowered