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Dewa Ayu Agung Anggita Ningrat

Pembimbing : Depart. Of Gastroenterology


Hadassah Hospital

Definisi

Sandler RS et al. Bowel habits in young adults not seeking health care. Dig Dis Sci 1987; 32: 841-5
Lembo A et al. Chronic constipation. N Engl J Med 2003; 349: 1360-8
Sandler Rs et al. Demographic and dietary determinants of constipation in the US population.
Am J Public Health. 1990 ; 80: 185-9.

Definition
Patients Outlook

In older adults straining to defecate


most common
Decreased frequency < 2% F
< 3% M

Whitehead et al JAGS 1989

Rome III criteria for Functional


Constipation (4/2006)
2 or more of 6 symptoms present for the last 3
mo with an onset more than 6 mo earlier
more than 25% of bowel movements:

Straining
Lumpy or hard stools
Sensation of incomplete evacuation
Sensation of anorectal obstruction/blockage
Manual maneuvers to facilitate defecation

less than 3 bowel movements per week.

Definition of
Normality
Constipation Is A Symptom Not
A Disease
99% of population have between 3 bowel
movements per week and 3 bowel
movements per day
Conell et al BMJ, 1965

Epidemiology Prevalence

Chronic constipation is a common selfreported bowel symptom that affects


2 - 30% of people in Western countries

Lembo A, Camilleri M. Chronic constipation N Engl J Med 2003; 349: 1360-1368

Prevalence is highest when constipation


is self reported

Pare p et al. An epidemiological survey of constipation in canada: definitions, rates, demographics,


and predictors of health care seeking. Am J Gastroenterol. 2001 ; 96: 3130-7

When Rome II criteria are applied to


constipation prevalence is reduced

Higgins pd et al. Epidemiology of constipation in North America: a systematic review. Am J


Gastroenterol. 2004; 99: 750-9. Review

Epidemiology Incidence

Little is known about the incidence


The incidence in Olmsted county 50/1000
person-years. The rate of disappearance
31/1000 person-years

Talley NJ et al. Onset and disappearance of gastrointestinal symptoms and functional gastrointestinal
disorders. Am J Epidemiol. 1992; 15; 136: 165-77

12.5% of elderly people entering a nursing


home had constipation
7% developed constipation within 3m

Robson KM et al. Development of constipation in nursing home residents. Dis Colon Rectum. 2000 ;
43: 940-3

Epidemiology
Constipated patients seen by:
31% - general practitioner
20% - internist
15% - pediatricians
9% - surgeons
9% - obstetricians - gynecologists
4% - gastroenterologist
Sonnenberg A et al. Physician visits in the United States for constipation: 1958 to 1986.
Dig Dis Sci. 1989; 34: 606-11
Sonnenberg A et al Epidemiology of constipation in the United States. Dis Colon Rectum. 1989;
32: 1-8.

Risk Factors

Female gender
Advanced age
Non white ethnicity
Low level of income and education
Low level of physical activity
Medications

Gender

F/M 2-3/1

Harari D et al. Bowel habit in relation to age and gender. Findings from the
National Health Interview
Survey and clinical implications. Arch Intern Med. 1996; 156: 315-20

Infrequent bowel movements (e.g.


once a week) exclusively in
women

Heaton KW et al. Defecation frequency and timing, and stool form in the
general population: a
prospective study. Gut. 1992; 33: 818-24

Age

15-30% among the elderly report


constipation

Dukas l et al. Association between physical activity, fiber intake, and other lifestyle variables and
constipation in a study of women. Am J Gastroenterol. 2003; 98: 1790-6

almost half of nursing homes residents


50-74% use laxatives daily

Read et al, J Clin Gastroenterol, 1995


Stewart et al, AJG 1992

Elderly seek more medical assistance

Age

Contributing factors: decreased food intake,


reduced mobility, weakening of abd.
Muscles, chronic illnesses, psychological
factors, medications

Merkel IS et al. Physiologic and psychologic characteristics of an elderly population with chronic
constipation. Am J Gastroenterol. 1993; 88: 1854-9
Talley NJ et al. Constipation in an elderly community: a study of prevalence and potential risk factors.
Am J Gastroenterol. 1996; 91: 19-25

Children

Common in children < 4y age, 2-3%


Fecal retention & fecal soiling

Diet and physical


Activity

Increased consumption of fiber decreases


colonic transit time, increases stool weight
and frequency
Nurses Health Study 62,036 women aged 3661
Women on highest quintile of fiber intake and
exercised daily were 68% less likely to report
constipation.
Effects of exercise in studies conflicting
results
Dehydration identified as a risk factor. The
benefit of increased fluid has not been studied
thoroughly

Medications
Opiods
Diuretics
Antidepressants
Antihistamines
Antispasmodics
Anticonvulsants
Aluminum antacids
NSAIDS

Economic Impact

2.5 million physicians visits (USA)


92000 hospitalizations
85% of visits - laxatives prescribed
Several hundreds million dollars in the
USA
Cost of annual investigation 6.9 billion $
Greatest cost of investigation is attributed
to colonoscopy

Epidemiology

9.7% people > 65y in Israel (1995)


40% of them > 75y

Levy N et al. Bowel habits in Israel. A cohort study.J Clin Gastroenterol. 1993; 16: 295-9

Pathophysiology

At least 4 case-control studies have shown


that women with severe constipation have a
normal:

dietary fiber intake


fluid intake
level of exercise
Preston DM, Lennard-Jones JE. Severe chronic constipation of young women: idiopathic slow transit
Constipation. Gut 1986; 27:4148
Muller-Lissner SA, et al. Myths and misconceptions about chronic constipation. Am J Gastroenterol
2005;100:232242
Klauser AG, et al. Nutrition and physical activity in chronic constipation. Eur J Gastroenterol Hepatol
1992;4:227233
Brown WJ, et al. Leisure time physical activity in Australian women: relationship with well being and
symptoms. Res Q Exerc Sport 2000; 71:2 06216.

Pathophysiology
Colonic Function - Luminal
Contents
Colonic contents food residue, bacteria and

fiber
Bran increased stool weight and decreased
colonic transit time in healthy volunteers
d/t increased bulk that stimulates propulsive
motor activity and particulate nature
Coarse bran 20gr/d reduced colonic transit
time by 1/3 compared to fine bran that had no
affect

Kirwan WO et al. Action of different bran preparations on colonic function. Br Med J. 1974
26;4(5938):187-9.

Ingestion of inert plastic particles of the same


size increased fecal output by x3 times their
own weight & decreased colonic transit time

Tomlin J et al. Laxative properties of indigestible plastic particles. BMJ. 1988; 297: 1175-6

Pathophysiology
Absorption of water and
sodium
Colon absorbs 1000-1500ml water daily

and leaves 100-200ml of fecal water


daily
Water & electrolytes absorption is
normal in constipated patients
Slow transit could allow more time for
increased water & electrolytes
absorption

Aichbichler BW et al. A comparison of stool characteristics from normal and constipated people.
Dig Dis Sci. 1998 ; 43: 2353-62

Pathophysiology
Diameter and length

A wide or long colon may lead to slow


colonic rate.
Only a small fraction have megacolon or
megarectum.
Width of more than 6.5 cm at the pelvic brim
is associated with constipation

Pathophysiology
Motor Function
Normal colonic transit hrs to days (35
hrs)
In some constipated patients transit is
slow
Decreased high-amplitude peristaltic
contractions (mass movements) in some
patients

Innervation and the Interstitial


cells of Cajal

Slow transit constipation related to


autonomic dysfunction
Abnormal numbers of myenteric plexus
neurons.
Decrease in neurotransmitter substance
P and increase in VIP or NO.
ICC are intestinal pacemakers reduced
number and abnormal morphology

Pathophysiology
Defecatory Function

Blunted gastrocolic reflex

Bassotti G et al. Colonic motility in man: features in normal subjects and in patients with chronic
idiopathic constipation. Am J Gastroenterol. 1999; 94: 1760-70

When an urge to defecate is resisted retrograde


movement of stool may occur and prolong transit
time

Klauser AG et al. Behavioral modification of colonic function. Can constipation be learned? Dig Dis Sci.
1990; 35: 1271-5.

Pathophysiology
Adverse life events, in particular sexual or
physical abuse, or death or separation
from a parent, during childhood,
more common in women with functional
disorders, including severe constipation
Drossman DA, Talley NJ, et al. Sexual and physical abuse and gastrointestinal illness. Review and
recommendations. Ann Intern Med 1995;123:782794.
Drossman DA, et al. Health status by gastrointestinal diagnosis and abuse history
Gastroenterology 1996;110:9991007.
Olden KW, Drossman DA. Psychologic and psychiatric aspects of gastrointestinal disease
Med Clin North Am 2000;84:13131327.
Kamm MA. Chronic pelvic pain in womengastroenterological, gynaecological, or psychological?
Int J Colorect Dis 1997;12:5762

Pathophysiology

Depression and anxiety

Eating disorder

Mason H, Kamm MA et al. Psychological morbidity in women with idiopathic constipation


Am J Gastroenterol 2000; 95:28522857
Emmanuel AV, Kamm MA et al. Anorexia nervosa in gastrointestinal practice
Eur J Gastroenterol Hepatol 2004;16:11351142.

Pathophysiology

Behavioral - school toilet avoidance

Pelvic trauma such as childbirth or


hysterectomy

Roy AJ, Kamm MA. Et al. Behavioural treatment (biofeedback) for Constipation following
hysterectomy. Br J Surg 2000;87:100105.

Classification
Secondary
Functional

Secondary
Constipation
Colon motility

Mechanical conditions
Congenital - agangliosis
Metabolic disorders
Neurologic disorders
Drug induced

Mechanical Obstruction

Anal Stenosis
Colorectal cancer
Extrinsic compression
Rectocele/sigmoidocele
stricture

Metabolic
Constipation
Diabetes mellitus

Hypothyroidism
Hypercalcemia
Hypokalemia
Uremia
Porphyria
Heavy metal poisoning
Panhypopituitarism
Pheochromocytoma
Pregnancy

Neurogenic Constipation

Parkinson`s disease
Dementia
Multiple sclerosis
Trauma to brain / spinal cord
Chagas disease
Amyloidosis
Intestinal peudo-obstruction
Shy Drager syndrome
Shy Drager syndrome
CVA

Drug Induced Constipation

Analgetics
Anesthtetics
Anticholinergics
Antacids
Anticonvulsants
Anti-Parkinsonians
MAO inhibitors
Opiates
Muscle paralyzers
Diuretics
Ganglionic inhibitors
Hematinics
Parasympatholytics
Psychotherapeutic drugs
Ca chanell blockers
barium
Bismuth

FUNCTIONAL
CONSTIPATION

Colonic motility

Irritable Bowel
Syndrome

Rome III criteria

15-20% of general population


Up to 33% - constipation predominant

Colon in IBS hypersegmentation and spastic areas

Physiologic Findings

Normal transit 59%


Slow transit - 13%
Defecatory disorders 25%
Combination - 3%

Nyam DC et al. Long-term results of surgery for chronic constipation. Dis Colon Rectum. 1997;
40: 273-9

Normal Transit
Constipation
Psychologic profile :
anxiety
depression
somatization
obsessive personality
Ashraf W et al. An examination of the reliability of reported stool frequency in the diagnosis of
idiopathic constipation.Am J Gastroenterol. 1996;91:26-32

Anorectal sensory & motor dysfunction


Normal physiologic testing

Colonic mass movements barium enema

Colonic mass movements colon manometry

Slow Transit
Constipation

Most common in young women


Usually < 1 bowel movement / w
Intractable symptoms
Unresponsive to fiber or laxatives
Disordered colonic motor function
Delayed emptying of proximal colon &
Fewer HAPCs

Bharucha AE. Treatment of Severe and Intractable Constipation.Curr Treat Options


Gastroenterol.
2004;7:291-298
Bassotti G et al. Impaired colonic motor response to eating in patients with slow-transit
constipation.
Am J Gastroenterol. 1992;87:504-8

Colon inertia
Colon motor activity fails to
increase after meals, bisacodyl,
neostigmine

Colon inertia

Defecation process - I

Defecation process - II

Defecatory Disorders

Disorders of the anorectum and Pelvic


Floor :
Stricture
Neoplasia
Hirschprungs disease
Chiarioni G, et al. Biofeedback benefits only patients with outlet dysfunction, not patients with isolated slow transit
constipation
Gastroenterology 2005; 129: 86-97
Bharucha AE, et al. Functional anorectal disorders Gastroenterology 2006; 130: 1510-1518

Pelvic floor Weakness

Rectocele
Descending perineal syndrome
Solitary rectal ulcer syndrome
Mucosal intussusception
Rectal prolapse

Anatomical abnormalities
leading to constipation

Anismus
Other names:
Rectum

Spastic pelvic floor


Non-relaxing puborectalis synd.
Pelvic floor dyssynergia

Anal
Canal

Puborectal sling
Internal
sphincter
External
sphincter

External anal sphincter and


puborectal muscles contract
during straining

Puborectal sling

Roberts JP et al. Evidence from dynamic integrated proctography to redefine anismus.


Br J Surg. 1992; 79: 1213-5
Rao SS et al. Manometric tests of anorectal function in healthy adults. Am J Gastroenterol. 1999;94:773-83

Acquired
Learned behavior to avoid discomfort
Usually older adults

Symptoms

Infrequent BM
Ineffective excessive straining
Need for manual manuvers
Symptoms do not correlate with testing

Rome III Diagnostic Criteria for


Functional Defecation
Disorders
The patient must satisfy diagnostic criteria for
functional constipation
During repeated attempts to defecate must have at
least 2 of the following:
a. Evidence of impaired evacuation, based on balloon
expulsion test or imaging
b. Inappropriate contraction of the pelvic floor muscles
(ie, anal sphincter or puborectalis) or less than 20%
relaxation of basal resting sphincter pressure by
manometry, imaging, or EMG
c. Inadequate propulsive forces assessed by
manometry or imaging

Fecal Impaction

42% in geriatric depts.


19% in geriatric population in the
community

Increased rectal compliance


Abnormal rectal sensation

Megarectum

Investigation - I
Should be reserved to patients with refractory
constipation or with alarming signs & symptoms
History

Alarming Signs & Symptoms

Hematochezia
Weight loss 10 pounds
Family history of colon cancer or
inflammatory bowel disease,
Anemia
Positive fecal occult blood tests
Acute onset of constipation in elderly
persons

Investigation - I

Physical examination
Blood tests
Endoscopy

Investigation - II

Symptom diary
Colonic transit study
Anorectal manometry
Balloon expulsion test
Electromyography
Proctography / defecography
Endoanal ultrasound
Rectal compliance
Rectal sensory testing

Colonic transit study radio-opaque markers

Wireless Motility Capsule

SmartPill Wireless PH and Pressure


recording capsule Assesses colonic
motility with no irradiation
Gastric and small bowel transit
Before surgery

Proctography:
Squeeze angle

Resting angle

Proctography:
Normal defecation

Anismus

Balloon Expulsion Test

The rectum is distensed with 50ml


balloon
The inability to expel it defecatory
dysfuncion

Anorectal manometry
Maximal Voluntary Squeeze Pressure

RP

10 - 20

IS

Squeeze

Relax
Regression
Amplitude

Peak
Amplitude

Procedure:
Patient squeezes as hard as possible
for 10-20 sec.
Repeat the squeeze once or twice with
more than 30 sec. between squeezes

ES

50%

Duration 50% > 5


Duration

Slope = Fatigue Rate

RectoAnal Inhibitory Reflex (RAIR)


cmH2O
Balloon

30 ml

RP
Inflation Reflex

30 ml
40
50

50 ml

40 ml

IS

Amplitud
e
Duration

Balloon

Syringe 100 ml

10-20

3- 5

Procedure: 1- 2
Inflate rectal balloon with 10 ml of air
Within 3-5 sec. of inflation, air should be
completely withdrawn
Repeat and increase volume by 10 ml
until the RAIR is obtained
Testing sequence: 10, 20, 30, 40, 50 ml

Inhibitory Reflex

10-20

ES
Time

Sphincter Electromyography

Amplitude

Urethral Sphincter
m. Bulbocavernous

Urethral Sphincter

Amplitude
Duration
Single Potentials
Polyphasic Potentials

Duration

Recording
with needle EMG
Automatic MUP analysis

Anal Sphincter

Nerve Conduction
Pudendal Nerve

Responses are inverted by


rotation of the electrode!

Stimulation Right Side:at 8 oclock


Left Side: at 4 oclock

Record
Motor Action Potential
Lat. typ. 2.5 ms
(nl < 5 ms)

Stim.

Amp. 1 mV
St Mark s
Pudendal Electrode

Therapy - I

General measures:
Reassurance
Lifestyle modification
Diet - fiber (17-23 gr/d)
Organic constipation:
Treat specific etiology

THERAPY - II

Behavioral approach:
Relaxation techniques
Biofeedback - general / anorectal
Psychotherapy
Hypnotherapy

THERAPY - III
MEDICAL

Laxatives 1 :
Bulk methylcellulose, Psyllium,
polycarbophil

THERAPY - III
MEDICAL

Osmotic Laxatives 2 :
Poorly absorbed ions - magnesium
citrate/hydroxide/sulfate, sodium
phosphate,
Polyethylene Glycol (PEG)
Poorly Absorbed Sugars lactulose, sorbitol,
manitol

Treatment

Stimulants bisacodyl, cascara, castor


oil, casanthranol, danthron,
phenolphthalein, senna
Stool softener mineral oil, docusate
sodium

Treatment

Enemas and Suppositories


introduced to the rectum and stimulates
contraction by distention or chemical
action, softens hard stools.
Can cause damage to rectal mucosa,
hyperphosphatemia
Phosphate enema, glycerin, saline, tap
water

THERAPY - IV
MEDICAL

Prokinetics:
Cisapride / Prucalopride
Neostigmine
Colchicine
Misoprostole
Tegaserod

Botulinum toxin type-A


Lubiprostone is a chloride channel
activator approved by the FDA for the
treatment of chronic constipation

New Agents

Neurotrophins family of proteins that


promote growth of subpopulations of
sensory neurons and modulate synaptic
transmission of developing neuromuscular
junctions in xenopus. R-metHuNT-3
accelerated gastric, small bowel and
colonic transit.
Linaclotide minimally absorbed guanylate
cyclase C agonist, that reduces visceral
pain and promotes colonic transit.

Treatment

Biofeedback Training (70-78%


success)

Chiarioni G, Whitehead WE, Pezza V, Morelli A, Bassotti G.


Biofeedback is superior to laxatives for normal transit constipation due to pelvic fl oor dyssynergia
Gastroenterology 2006; 130: 657-664
Rao SS, Kinkade KJ, Schulze KS, Nygaard II, Brown KE, Stumbo PI, Zimmerman MB
Biofeedback therapy (bt) for dyssynergic constipation - randomized controlled trial
Gastroenterology 2005; 128 Suppl 2: A269
Heymen S, Scarlett Y, Jones K, Drossman D, Ringel Y, Whitehead WE
Randomized controlled trial shows biofeedback to be superior to alternative treatments for patients with
pelvic
fl oor dyssynergia-type constipation
Gastroenterology 2005; 128 Suppl 2: A266

Treatment

Patients with functional defecation


disorders are often unresponsive to
conservative medical management
Defecation training and Anrectal
biofeedback taught to relax pelvic
floor muscles during defecation
visual or auditory feedback on the
functioning of their anal sphincter
and pelvic floor muscles.
effective in 80%

Supplements, Alternative
Treatments, Lubricants, &
Combination
Laxatives
Insufficient data to
make a recommendation about the

effectiveness of herbal supplements, alternative


treatments, lubricants, or combination laxatives in
patients with CC
There are no RCTs examining the efficacy of herbal
supplements (e.g., aloe)
There are no RCTs on the efficacy of lubricants (e.g.,
mineral oil) in adult patients with CC, although there
are RCTs examining mineral oil in pediatric patients
with CC
There are no RCTs of combination laxatives (e.g.,
psyllium plus senna) available in the United States in
patients with CC

THERAPY - V
SURGERY

Anal dilatation
Anorectal myectomy
Partial division of puborectalis
Subtotal/total colectomy

Wald A. Severe constipation. Clin Gastroenterol Hepatol 2005; 3: 4325

Cheung O et al. Management of pelvic floor disorders. Aliment Pharmacol Ther 2004; 19:
48195
Muller-Lissner S et al. Myths and misconceptions about chronic constipation. Am J Gastroenterol
2005;100:23242

Colostomy
Antegrade continence enema (ACE)
Colon pacing