What are functional bowel disorders?

GASTROENTEROLOGY

1993;104:1196-1201

VIEWPOINTS ON DIGESTIVE DISEASES What Are Functional Bowel Disorders? JAIME

ZIGHELBOIM

and

Division of Gastroenterology

T

he irritable

NICHOLAS

and Internal

bowel

J. TALLEY

Medicine,

syndrome

Mayo Clinic and Mayo Foundation,

(IBS)

is the

most

widely recognized functional bowel disorder, but is it a disease? The Oxford English Dictionary con-

siders

disease

comfort;

to be “absence

inconvenience;

Disease

of ease; uneasiness; annoyance;

has been more specifically

something evidence

with

This

psychological

different

refers to the subjective

based

illness,

state of the person

feels aware of not being well, and from sickness, is a state of social assumes

the illness

intestinal

disease.

pathophysiology

dysfunction

where

have shed enough

Experience

there

medical

can indicate studies

light, in our opin-

history,

the

if well enough than

organic

l), accurate

possible.’

epide-

that have surveyed random indicate that approximately

15%20%

IBS.‘y3 In industrialized

of adults

have

that IBS is usually

but long-term

adults

studies

in the community

Because

are generally

IBS is so common,

be a normal

a lifelong

of the natural

condi-

history

in

lacking.

it has been implied

experience.

However,

that

it depends

on one’s definition of normal. The high prevalence of a condition is inadequate to label it a nondisease. For Helicobacterpylori gastritis

example, mon

in the general

argue

population,

that this is a normal

tomatic

persons.

theoretical

For many

reasons

to usually

be a smooth

by degrees.

those

death)

of a condition

present

with

there

in asympare no good

that distinct

popula-

there appears

as disease is acquired

been argued that the sound-

ease is to label

who

even

exist; rather,

for distinguishing

because

now

diseases

transition

It has therefore

est approach

com-

condition

for believing

tions of well and ill people

is extremely yet few would

who

disease

suffer

from

from

as diseased

and

Using such criteria,

IBS to a physician

nondis-

disability

(or those

people

are indeed

dis-

eased.

Pathophysiological Level of the Gut

Abnormalities

at the

Data from

properly designed studies samples of the population

tions, women are more affected and each year at least 2 million

tion,

Minnesota

who do not as nondiseased.

data to support

(Table

have become

we do our

this fact.

that IBS rather

disease is the likely diagnosis

and

but Not Normal

are adequate

view that the standard

miological

the individual

and we believe

by not recognizing

A Common

structured,

which

New data on the epidemiology

a disservice

Because

who

role. It is our thesis that IBS is a real

ion, to justify this viewpoint, patients

on dys-

from

has been presumed

it must

to infer that

function,

and/or

is somewhat

disturbance.”

defined

bodily

of physiological

function. which

is wrong

dis-

Rochester,

Unfortunately,

there continues

to be a polariza-

na-

tion of thought regarding the pathogenesis of IBS; this was clearly illustrated in an editorial in Lancet, which

than men (Figure l), office visits are made

stated “. . . at one end of the scale is the belief that the primary disorder is almost entirely psychiatric . . . at

for IBS in the United States. Although by definition IBS is a relapsing and remitting disorder, the prevalence of IBS remains remarkably stable over time when repeated surveys are obtained. It has been estimated in a population-based study in Olmsted County, Minnesota, that over a 12- to 20-month period, 9% of subjects who were initially free of IBS symptoms developed IBS, whereas a similar number of subjects who initially fulfilled the criteria for IBS spontaneously lost their symptoms on follow-up.3 Why some develop typical symptoms of IBS while approximately equal numbers appear to recover each year is unclear; indeed, it

the other end of the scale is the notion that irritable bowel syndrome is an organic disorder of gut function.“’ However, several abnormalities in the gut have been linked

to IBS.

Visceral hypersensitivity.

Afferent information from the gastrointestinal tract is carried by both vagal and spinal afferents, and many patients with IBS have an altered visceral distention threshold, although the mechanisms remain unexplained. An altered threshAbbreviations used in this paper: IBS, Irritable 0 1993 by the American Gastroenterological 0016-5085/93/$3.00

bowel syndrome. Association

April1993

Table 1. Rome Definition of the Irritable Bowel Syndrome

during

Continuous or recurrent symptoms for at least 3 months Abdominal pain or discomfort, relieved with defecation, and/or associated with a change in frequency and/or consistency of stool: and An irregular (varying) pattern of defecation at least 25% of the time (two or more of) Altered stool frequency (>3 bowel movements/day or <3 bowel movements/week); Altered stool form (lumpy/hard or loose/watery stool); Altered stool passage (straining or urgency, or a feeling of incomplete evacuation); Passage of mucus; and Bloating or feeling of abdominal distention.

prolonged

of patients Balloon num

Adapted with permission.2o

distention

conduction

of

the

conscious

threshold

sensorial

modulation

input,

at a central

or

in the

an

with

level could

all explain

IBS have an abnormally Several

studies

“sensitive”

have documented

of patients colon

with

or rectum.

that balloon

disten-

tion of different segments of the colon causes pain in 50%60% of IBS patients compared with less than 10% of controls’ (Figure U). Balloon distention in the rec-

(Figure

motility

abnormalities

symptoms motility

that rectal sensitivity nant

bowel

varies depending

on the predomi-

activity.

to episodes

By applying

stimuli,

different

lecystokinin-octapeptide, of the ileum,

for any kind of uncomfortable

or alternatively

chological

tendency

such as infusions

intestinal with

dysmotility

of cho-

recordings motor

contractions; were

could

be the result

to exaggerate

contractions.‘4 Diarrhea. Whole

has been of small

with IBS have also shown

of postprandial

of clustered pain

pain. l3

IBS but not in controls.’

ambulatory

in patients

duration

abnormal-

of abdominal

a high fat meal, and balloon

distention

motility

These motor

with

activity

a

and

68% of all episodes

associated

with

periods

of

clustered

The lowered threshold for colonic distention reflect a more generalized phenomenon

ered tolerance

of small

in patients

ities have been linked

episodes

patterns

waves and clus-

of abdominal

habit.

could

stimulus

in

suggests

to

ileal propulsive

shorter

This

correlated

more frequently

nant

7% of those

instances,

occur

72-hour

group.”

specific

ters of jejunal pressure

bowel

some

is

with

in controls:

in patients

with only

In

are closely

Abdominal pain. Two

bowel

There

of patients

in IBS.

Continuous

compared

2B).7

disturbances.

unmasked

IBS patients

activity the small

and symptoms.

that a subgroup

tum was also found to elicit the sensations of gas, stool, urgency, and discomfort in 57% of diarrhea-predomithe constipation-predominant

abdomi-

of motor

may arise from

disturbances

evidence

IBS than

Colonichypersensitivi~. A subgroup

with functional

perception

IBS, the pain

motility

specific

altered

hypersensitivity.

and duode-

the presenting

in the small bowel suggests that in some

cur in some patients

these an altered

jejunum,

bowel rather than, or in addition to, the colon. Esophageal and possibly gastric hypersensitivity may also oc-

convincing

receptors,

of patients

in 6 1%

17% of controls.

to reproduce

nal pain.’ The enhanced patients

with

of the ileum,

pain in two-thirds and distention

ileal contractions

IBS compared

has also been found

IBS have old of gut-wall

propagated

with

Motility

visceral

1197

FUNCTIONAL BOWEL DISEASE

in IBS of low-

transit

times

somatic

shorter

in patients

of a psy-

the painfulness

addition,

have

diurnal

gut, small

been

found

bowel,

and colonic

to

significantly

be

with diarrhea-predominant migrating

motor

complex

IBS.’ In intervals

of

any aversive stimulus. These hypotheses, however, have not stood the test of time. Despite an increased perception

to rectosigmoid

pared

with

controls,

ences

in their

there

tolerance

and no correlation

distention

to ice water

between

in IBS com-

were no significant hand

psychometric

differ-

I

us. females

immersion measures

of

psychological distress and tolerance for colonic distention.” Extracolonic h_ypersensitivi$ Some patients with IBS show an increased awareness of proximal and distal small bowel motor activity. Thus, episodes of abdominal discomfort coincided with duodenal activity fronts in 45% of patients with IBS compared with 10% of controls.‘* These perceived activity fronts were of higher amplitude than nonperceived activity fronts. In another study,‘3 cramping abdominal pain occurred

xl-29

3039

4049

M-59

60-69

70-79

so

Age groups

Figure 1. Prevalence of IBS in the United States (n = 1,163) and United Kingdom (n = 1.620) by gender and age groups. Data from Talley et al.4,5 and Jones and Lydeard.’

ZIGHELBOIM AND TALLEY

1198

GASTROENTEROLOGY Vol. 104, No. 4

6 _

60

.rg

-

50 -

Controls IBS(n=25) (n=rn)

40

20

60

60

P 85 z tz 04-

100

1273 140

160

-

160 MDP

Distension of rectosigmoid (mL)

@ W.l_BoI

Functional dyspepsia (n=20) Controls (n=20)

-

f2

+4

+6

lntragastric

@

+8

+10

+12

+14

pressure (mm Hg)

CC-l18104Bo2 Figure 2. Heightened visceral sensitivity to balloon distention. Note the similarity in shape of the curves for rectosigmoid distention in patients with IBS using a latex balloon (A) and gastric distention for patients with functional dyspepsia using the barostat (6) compared with controls, despite the different methodologies applied. Reproduced with permission from Whitehead et aL8 and Mearin et al.’

in the small bowel are significantly shorter in patients with diarrhea when compared with patients with constipation-predominant IBS or controls.‘4 in fast colonic contractions lasting <15

An increase seconds and

accelerated

pellets

passage

the ascending umented

of radiolabeled

and transverse

in patients

with diarrhea-predominant

Using the barostat, we have resistance to stretch was greater nant

IBS than

was induced the colon, greater

resin

in healthy by lower

a tendency

subjects,

distending

and rectal pressures

for preprandial

using the barostat

IBS.’

noted that the rectal in diarrhea-predomi-

in diarrhea-predominant

controls

from

colon have also been doc-

urgency

in IBS. In

motility

IBS than

to be

in healthy

has also been documented,

as exemplified

by a higher

lesser changes

in tone in response

fasting

motility

index

and

to food ingestion.15

These results suggest that small bowel and/or colonic motility and transit are altered in a subset of patients with

IBS and diarrhea. Constipation. Small

times

have

patients

been

with

compared

shown

bowel

and whole

to be significantly

constipation-predominant

with controls,

and a paucity

retention lumbar men.16

Certain sorbitol,

IBS

when

luminal

protrusion

contents,

excess

of the abdo-

such as lactose,

fructose,

fatty acids, and bile acids, can induce

some

individuals

with

atic improvement mechanisms

IBS can experience

with

strict

by which

dietary

symp-

endogenous

or exogenous

factors

might

cause exacerbations

could

include

brush

border

carbohydrates),

enzyme

net stimulation

lyte secretion (e.g., fatty creased colonic contractility suspect that persons

acids,

lu-

of symptoms

deficiencies

of water bile

The

(e.g.,

and electro-

acids),

and

in-

(e.g., fatty acids).’ We also

with visceral

be particularly susceptible, careful testing.

symptom-

exclusions.

minal

hypersensitivity

but this hypothesis

may requires

Imagined or Real Symptoms? Patients

in

of high ampli-

of the diaphragm,

or voluntary

toms of gastrointestinal distress in susceptible individuals, especially bloating and diarrhea.’ In addition,

gut transit longer

of gas, depression lordosis,

healthy

persons,

nal pain, bloating,

with

IBS

symptoms

have

real

symptoms.

of IBS including

and a feeling

of incomplete

In

abdomievacua-

tude propagated colonic contractions has also been observed.’ However, there are no published studies on regional colonic transit in patients who fulfill strict criteria for the diagnosis of IBS and who complain of

tion can be induced by antidiarrheal therapy with loperamide. Outpatients with IBS also tend to have more to complain of than do those with IBS who have not presented for medical care. Thus, pain, bloating, ur-

constipation.

gency, and feelings of incomplete evacuation are more frequent or severe in patients than nonpatients with IBS.” Moreover, in two independent samples of women who were nonpatients, a factor analysis suggested that IBS exists as a distinct entity in the community because a core set of symptoms, composed of three of the four major Manning symptom criteria, clustered together in the two samples.‘*

Bloating. This

common symptom remains largely unexplained, but visible abdominal distension has recently been objectively documented in female patients with IBS using a computed tomography technique.16 Visible distension could be related to changes in intestinal muscle tone, although the actual mechanism remains unknown; it was not found to be due to

FUNCTIONAL

April 1993

Another

issue that is often

of manometric clinical

raised

abnormalities

relevance

relates

or just epiphenomena?

proposed

criteria

to test

symptoms

to manometric

the

Cohen

validity

events,”

the evidence more

overall

supports

data are needed.

which

response

trials

tients

with

disease)

of patients organic

can

also

must

although

controlled

ther-

IBS, it is clear that pa-

similar

that

that

the placebo

(e.g., inflammatory

achieve

rates.’ We conclude symptoms

with

disease

link,

although

has been high in randomized,

apeutic

are consid-

we believe

a causal

Finally,

has

of attributing

ered in Table 2; based on these criteria,

placebo

in many

truly originate

patients

bowel response with

IBS,

although

diagnostic selection

criteria

for psychiatric

bias (only

studying

ill-

patients

referred to psychiatrists or specialist treatment centers) may partly account for the findings.’ However, psychopathological turns

out often

ganic diseases ulceration primarily bowel

disturbances

have similarly

erroneously)

been

in the past, including

linked

(and as it

to many

chronic

or-

duodenal

(which we now recognize to probably be an infectious disease) and inflammatory

disease.

Indeed,

frequent

clinic

attenders

itively

influence

a minority

of persons

care, and it has been documented

the decision

symptoms

to seek health

for care have more psychologithose

have

interpreted

this data to suggest

be classified

as a gastrointestinal

not rather

as a psychiatric

however, tation tend

because

in IBS: Evidence

to have

bowel tients

more

factors

chronic

health

patients

Rather,

that patients

with IBS are more sensitive

of the bowel

than

responsive being

to somatic

more sensitive

pain

even

at least in some cases, objective function

disease marker,

to distension

at the same time

although activity

as

Furthermore,

abnormalities

and studies

tility patterns and myoelectric specific or discordant.

shown

but are not more

pain.“‘l

have been documented,

an accepted

are just for bodily

reproducibly

controls

to visceral

in which

that the symptoms

these

it has been

pa(e.g.,

care presen-

a low threshold

matched

of

disease).

there is no evidence or that

and

discomfort.

of motor we still lack

of colonic

mo-

have been non-

One Disease or Many Diseases? In clinical recognize

care.’

those

Clustered contractions in the small intestine Abnormal transit time in small and large intestine Hypersensitivity to distension in colon and small intestine Motility change is associated with a symptom and precedes the development of the symptom Pain coincides with clustered intestinal contractions Constipation associated with slow transit Diarrhea associated with rapid transit Bloating and pain can be reproduced with gut distension Abnormal motility must be able to be confirmed with another independent measure in the same patient Relief of symptoms occurs when the motor dysfunction is corrected Abnormal motor activity absent during sleep, as are symptoms Prokinetics slows transit in IBS and improves diarrhea Cisapride may accelerate colonic transit and may improve constipation in IBS

reflux)

bowel

with

of

examples

to physicians

also influence

complainers

to a physician

diseases in which

to present

of IBS are imagined

but

abnormalities are other

gastroesophageal

In summary,

often pos-

A major alteration in motility is objectively shown

there

(e.g., inflammatory

problem

also affects presen-

demonstrable

not

Some

that IBS should

who come

gastrointestinal

elect

not.‘,’

This is not tenable,

severity

Indeed,

organic

often

have

disturbance.6

symptom

function.”

common

are

for a Causal

who

for care, and patients

practice,

at least

with

chiatric Events

of IBS

than

three

predominant

disease,

for the highly chiatric

we believe distinct

we can clearly

groups

physiological

those with predominant Table 2. Manometric Link

symptoms

that those who present

more likely to have psychological disturbances no matter what the final diagnosis, suggesting that psychological factors rather than causing

1199

cal disturbances

tation

ing functional gastrointestinal complaints; approximately 50% of outpatients with IBS have been shown

with

DISEASE

for medical

psychosocial

Psychiatric disorders have traditionally been considered to be of paramount importance in explain-

ness,

present

symptomatic

in the gut.

Not All in the Mind

to fulfill research

Only

to the role

in IBS; are these truly of

BOWEL

psychological

of patients: disturbances,

distress

or psy-

and those with both; this may account variable

abnormalities

rates of physiological

and psy-

that have been reported

in the

various published series, which have usually only evaluated selected patient groups. Because patients with IBS always have erratic symptoms and may have an alternating physiological

bowel

pattern,

disturbances

it is conceivable

that

also vary in subgroups

the with

different symptoms. Thus, the term “IBS” probably encompasses several quite different diseases with different underlying pathophysiological mechanisms.

What Do We Now Need to Learn? Although major advances have been made in the understanding of the pathophysiology of IBS in recent years, much still needs to be learned. Although objective disturbances such as abnormal gastrointesti-

1200

nal

ZIGHELBOIM

motility

AND

TALLEY

and visceral

GASTROENTEROLOGY

hypersensitivity

have

been

understanding

of the pathogenesis.

Vol. 104,

In the future,

No. 4

new

documented in subsets of patients with IBS, it is impossible to estimate whether the individual patient who

drug therapy may be able to specifically target underlying pathophysiological or psychophysiological distur-

presents

bances.

with

IBS has these abnormalities

unless

enter a research

protocol.

ological

to date have largely been performed

studies

selected

“presenters”

patients

because

but do not seek medical

tend our physiological Whether

investigations

most of these motor occurring

toms are present, atic remission ambulatory

needs

disturbances

might

first appear

following

tive abnormalities

abnormali-

periods

even be present other

are confirmed markers”

by prolonged

before

inducing

symp-

of symptom-

and visceral

of symptoms,

be used as “disease sent epiphenomena.

to these groups.

Because

of the

potentially

even if some only repre-

a disease.

management

evidence

that distur-

for medi-

We believe

that this viewpoint

implications.

Thus, for pa-

who positively fulfill the symptom-based diagfor IBS (Table 1) and who have negative

nostic criteria

screening

now be provided

tests for organic

disease,

with confidence,

which

suring both for patient extensive investigation nostic

approach

acetylcholine, peptide,

a label can can be reas-

and physician and can make unnecessary. A positive diag-

is important

visceral

putative These

include

these peptides patterns

nervous

visceral

system,

afferent

nists,

serotonin selective

type

because

a fruitless

search

for another

disease is avoided.

Otherwise,

patients

may

be exposed

to the discomfort

and risk of multiple

en-

doscopies or barium examinations and may have the mistaken belief imprinted that some other disease is being missed. Explaining to patients the mechanisms that are suspected of producing symptoms can also help them take control of their disease. The complex pathophysiology emphasizes the need for a holistic approach, that includes taking into account the patient’s psychosocial background. Although clinical trials of specific drugs for IBS have been generally disappointing to date, this may partially reflect the heterogeneous groupings of patients that have been studied and our continued poor

large

neurons,

enhance very

neurons, neural

antagonists,

tis-

opioid

nervous antagosomatoantago-

with these promising our knowledge

limited

dor-

in the enteric

or central

and

of

with dif-

using cholecystokinin

antimuscarinics,

our currently

the treatment

presence

in different sites located

3 receptor

will hopefully

the

poly-

Immuno-

and brainstem,

of localization receptor

intestinal

afferent

mo-

serotonin,

peptide.

shown

cord,

system could be blocked

may be

cholecystokinin,

have

spinal

transmis-

of intestinal

P, vasoactive

in spinal

sues. Theoretically,

pathway

gene-related

studies

include

and hormones

perception

substance

to use more

should

afferent

peptides

and calcitonin

histochemical

be necessary

approaches

in modulating

tor activity.

agents

with IBS who present

has important

alter

may have multiple

in the management.

nists, to name a few. Studies

psychophysiological

be considered

that

ferent

If objec-

to exist in the presthey could

overwhelming

and

therapeutic

symptoms

cal care and because of the real distress that patients with IBS endure, we conclude that this condition must

limited

agents

statin,

bances exist in patients

tients

Future

sal root ganglia,

Treatment Implications pathophysiological

it will probably

sensitivity

events.

as some patients

one type of approach

implicated

and sensory

Motor

than

we need to ex-

to be documented

monitoring.

disturbances,

sion. Several

only at times when

or persist during

ence and absence

in

However,

care or even in

seeing nongastroenterologists,

ties are transient,

physi-

and not in subjects recruited at large who may experience simi-

from the community lar symptoms

Furthermore,

they

armamentarium

new

and enfor

of IBS.

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Received December 21, 1992. Accepted January 11, 1993. Address requests for reprints to: Nicholas J. Talley, M.B., Ph.D., Mayo Clinic, 200 First Street S.W., Rochester, Minnesota 55905. Supported by National Institutes of Health grant AG09440.