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
Dyspepsia

Non-GI
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

Nocturnal
pain
Localized
epigastric
burning
Better
with food

Dysmotility-like Dominant

Heartburn

Nausea
Bloating

Retrosternal Early satiety

burning
Worse

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
perception

Altered
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
Afferent
Activity

Low Grade
Inflammation
HP Infection

.
..

Sensitivity

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
H. pylori
Eradication

Length of Benefit from Length of

Follow-up
H. pylori
Follow-up
(yr)
Eradication
(yr)

Veldhuyzen van Zanten, 1995 0.5

Lazzaroni, 1996

0.5

Elta, 1996

Trespi, 1994

0.5

Schutze, 1996

McCarthy, 1995

Sheu, 1996

Testing for H. pylori

Test

Sensitivity Specificity Cost

C13 or C14
urease breath
test

90% to 100% 96% to 100%

hospital nuclear
medicine department

Serology

91% to 98% 75% to 80%

through commercial
labs and Public Health

Comments

++

Limited - requires

Widely available

Capillary
85% to 90% 75% to 80%
+
blood serology purchased by doctor administered

Office test, must be

Endoscopic
biopsy

Requires specialist

99%
Invasive

99%

++++

(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

Peripheral Signals

Loss of
Descending
Inhibition

Proposed Mechanisms of
Hyperalgesia
Drug Effects on the CNS-Enteric Nervous System
Cortex
Spinal Cord
Descending inhibitory fibres
- ANS. Input
2nd order neurons
Dorsal horn nucleus
Dorsal root ganglion
Sensory
nerve endings in gut

Pain Perception
Pharmacological
Options
opiates, tricyclics
5HT3 antagonists
Clonidine
opiates
5HT3 antagonists
Substance P
CGRP antagonists
NSAIDs
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

Functional
dyspepsia

Impaired fundic
accommodation
with a
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
pathogenesis of functional
the
Anxiety
dyspepsia:
Depression

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

BID

Bismuth 2 tabs qid

Metronidazole 250 mg qid
Tetracycline 500 mg qid

Alternate
PPI - BMT

Choice of Investigation for

Ulcer-like Dyspepsia
Endoscopy

UGI Series

More expensive

Less expensive

Issues of access/waiting
lists can be a problem

Easy access, usually short

waiting time

Allows for biopsy

(cancer, Hp)

If cancer is found, endoscopy

will be needed

Allows diagnosis of
mucosal lesions (erosions)

Often misses mucosal lesions

Preferred investigation for

dyspepsia

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
cyclic
cyclic therapy
therapy

Investigate
Investigate
Test
Test H.
H. pylori
pylori
Gastroscopy
Gastroscopy or
or UGI
UGI
+
+

--

Eradicate
Eradicate
Success
Success

Failure
Failure

Consider
Consider H
H22
antagonists,
antagonists, tricyclics
tricyclics

Differential Diagnosis

Functional Dyspepsia (60%)

PUD (25%)
GERD
Biliary Pain
Chronic Abdominal Wall Pain
Gastric CA
Esophageal CA
Other Abdominal Malignancy
Gastroparesis

Pancreatitis
Carbohydrate Malabsorption
Meds (NSAIDS, Narcotics,
etc.)
Infiltrative Diseases
Metabolic Disturbances
Hepatoma
Ischemic Bowel Disease
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