Dyspepsia Dr. H. Rustam Effendi YS, SpPD-KGEH

Division of Gastroenteroenterology and Hepatology

Department of Internal MedicineMedical Faculty, North Sumatera University

Adam Malik Hosptal,-Pirngadi HospitalMedan – Indonesia

Kuliah Mhs. FKUSU, Semester 5, 16 Oct.2012.09.00-10.00

What is Dyspepsia?■ Symptoms of : Pain/discomfort pada upper

abdomen, 12 minggu dalam 12 bulan terakhir (Rome II criteria).

• Epigastric pain• Indigestion• Fullness /postprandial fullness• Early satiety (cepat kenyang)• Bloating (gembung)• Belching (sendawa)• Nausea• Retching/vomiting (muntah)■

Dyspepsia

• A group of symptoms which alert clinicians to consider disease of the upper gastrointestinal tract

(British Society of Gastroenterology, 1996)

Dyspepsia

FunctionalDyspepsia

(Nonulcer dyspepsia)

Non-GICauses of Symptoms

(cardiac disease,muscular pain, etc.)

Structural Dyspepsia/Organic(GERD, PUD, pancreatic

disease, gallstones, etc.)

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 (no identifiable cause on diagnostic evaluation)

• Also known as nonulcer dyspepsia, essential dyspepsia, idiopathic dyspepsia

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

Symptoms of Functional Dyspepsia

Nocturnal painLocalized epigastric burningBetter with food

Heartburn

Retrosternal burning

NauseaBloatingEarly satietyWorse with food

Ulcer-like Dominant Dysmotility-like Dominant

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

Symptom complex results primarily from interplay of :

GI motility disturbances,: -delayed GEmp time

Altered visceral sensation:- hypersensitivity to gastric distention

and maladaptive psychologic responses. Other notable contributing factors include

altered mechanism at brain-gut axis and triggers by acute gastrointestinal infection.

Genetic polymorphisms predisposing to functional dyspepsia have also been recently suggested.

Pathogenesis & Pathophysiology of Dyspepsia

• Increasedvisceralperception

• Alteredmotility

• Behavioural factors

• Gastritis• H. pylori infection

Mechanisms Underlying Increased Sensory Perception

Increasedsensory input

Reduced descending inhibition

Mechanisms Underlying Altered Motility in DyspepsiaStressBehaviouralFactors

• Decreased antral motility

• Impaired fundal relaxation

Abnormal Motility

Local Factors:GastritisH. pylori infection

Sensory Inhibition Sensitivity

Putative Pathogenesis of Dyspepsia

Stress

Increased Sensitivity

Increased AfferentActivity

ANS Imbalance

Impaired Motor ActivityAccommodation

Altered Motor & Sensory Function

DYSPEPSIA

Low GradeInflammation± HP Infection

. ..

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

Veldhuyzen van Zanten, 19950.5 Lazzaroni, 1996 0.5Elta, 1996 3 Trespi, 1994 0.5Schutze, 1996 1 McCarthy, 1995 1

Sheu, 1996 1

No Benefit from Length of Benefit from Length of

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

Testing for H. pylori

C13 or C14 90% to 100% 96% to 100% ++ Limited - requiresurease breath hospital nucleartest medicine department Serology 91% to 98% 75% to 80% + Widely available

through commerciallabs and Public Health

Capillary 85% to 90% 75% to 80% + Office test, must beblood serology purchased by doctor administered

Endoscopic 99% 99% ++++ Requires specialistbiopsy Invasive

Test Sensitivity Specificity Cost Comments

(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

Central Hyperalgesia

Pain

Peripheral Signals

Loss of Descending Inhibition

Proposed Mechanisms of Hyperalgesia

Spinal CordDescending inhibitory

fibres- ANS. Input2nd order neuronsDorsal horn nucleus

Dorsal root ganglionSensorynerve endings in gut

Pain Perception Cortex

Drug Effects on the CNS-Enteric Nervous System

PharmacologicalOptions opiates, tricyclics5HT3 antagonists

Clonidine opiates5HT3 antagonists

Substance PCGRP antagonists

NSAIDs opiates5HT3 antagonists

Proposed Mechanisms of Hyperalgesia

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 DyspepsiaAbnormal Fundic Relaxation in Response

to Meal in Functional Dyspepsia

Normal

Impaired fundic accommodationwith a redistribution of food to antrum

Fundic accommodation or receptive relaxation

Meal

Functionaldyspepsia

(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

• Anxiety • 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

Psychological factors to be considered in

the pathogenesis of functional dyspepsia:

H. pylori Eradication Regimens

(All given for one week)Treatments of Choice

PPI - AC BID Amoxicillin 1 g bidClarithromycin 500 mg

bidPPI - MC BID Metronidazole 500 mg bid Clarithromycin 250 mg bid

Regimen PPI Antibiotics

AlternatePPI - BMT BID Bismuth 2 tabs qid

Metronidazole 250 mg qid

Tetracycline 500 mg qid

Choice of Investigation for Ulcer-like Dyspepsia

More expensive Less expensiveIssues of access/waiting Easy access, usually shortlists can be a problem waiting timeAllows for biopsy If cancer is found, endoscopy(cancer, Hp) will be neededAllows diagnosis ofOften misses mucosal lesionsmucosal lesions (erosions)Preferred investigation forAlternative, especially if dyspepsia access is a concern

Endoscopy UGI Series

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 treatment and specific management

based on dominant symptom complex

Follow-up within 3 to 6 weeks

Ulcer-like

Dysmotility-like

Management of Ulcer-like Functional Dyspepsia

Ulcer-like Symptoms Dominant

Education/lifestyle modification

Test Hp

+ -

Eradicate Hp

Success Failure

Trial of acid suppression

Investigate Trial of prokinetic

Reassess

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 modification

Test H. pylori

+ -

Continue withcyclic therapy

Success Failure

Investigate

Trial of prokinetic medication

Eradicate

Gastroscopy or UGI

Success FailureConsider H2antagonists, 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