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Approch to the Patientconstipation Hernomo

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APPROACH TO THE PATIENT WITH CONSTIPATION

HERNOMO KUSUMOBROTOGastro-Hepatology Center Airlangga University School of Medicine Soetomo Hospital Surabaya

DEFINITION Constipation is passage of small amounts of hard, dry bowel movements, usually fewer than three times a week. People who are constipated may find it difficult and painful to have a bowel movement. Other symptoms of constipation include feeling bloated, uncomfortable, and sluggish.

DEFINITIONConstipation is a symptom rather than a disease and is the most common digestive complaint in the United States.

A standard set of criteria has been suggested that includes at least 2 of the following symptoms present for at least 3 months: 1. Hard stools 2. Straining at defecation 3. Sensation of incomplete evacuation at least 25% of the time 4. Two or fewer bowel movements per week

EPIDEMIOLOGY In the US : - > 4 million people have frequent constipation, - a prevalence of about 2%. - estimated 2.5 million physician visits per year. Most patients with constipation can be treated medically, resulting in complete success or improvement. However, a small percentage of patients are quite debilitated as a result of constipation. Some patients with functional constipation (ie. colonic inertia) require total abdominal colectomy with ileorectal anastomosis.

EPIDEMIOLOGYConstipation Affects people of color : whites = 1.3 : 1. Male : female, approximately 1 : 3. Can occur in all ages, from newborns to elderly persons. An age-related increase in the incidence of constipation exists, with 30-40% of adults older than 65 years citing constipation as a problem.

Age-specific increase in the prevalence of constipation in the US, by age and sex12 -

Age-specific Prevalence (Percent)

10 86-

Men Women

42-

0-

0-44

45-64

65-74

75+

Constipation Increases With Age And Is More Common In WomenPhysician visits per 100,000 population Physician Visits Per 100,000 Patients60 50 40 30 20 10 0 0-4 5-14 15-24 25-44 45-64 65-74 75+ 4500 4000 3500 3000 2500 1500 1000 500 0-

I I I I I I 0-9 10-19 20-39 40-59 60-64 65+

AGE GROUP

ENGLAND AND WALESMALES FEMALES

USA

PATHOPHYSIOLOGY The hard and dry stools of constipation occur when the colon absorbs too much water. This happens because the colon's muscle contractions are slow or sluggish, causing the stool to move through the colon too slowly

SEROTONIN(5-hydroxytryptamine = 5-HT)5-HT is found in the enteric nervous system where it has been implicated in controlling gastrointestinal motor function. A number of receptor or recognition sites has been identified in the gut, i.e. : 5-HT1, 5-HT2, 5-HT3 and 5-HT4 But recently most attention has focused on the 5-HT3 and 5-HT4.

The functional role of the 5-HT3 receptor remains incompletely understood, but it is probably involved in the modulation of colonic motility and visceral pain in the gut. A number of selective 5-HT3 antagonists have been developed including : ondansetron, granisetron, tropisetron, renzapride and zacopride. While the substituted benzamide prokinetics (for example, metoclopramide and cisapride) also block 5-HT3 receptors in high concentration, their prokinetic action is believed to be on the basis of their agonist effects on the putative 5-HT4 receptors.(Talley, 1992)

5-HT3 and 5-HT4 5-HT3 modulation of colonic motility and visceral pain in the gut. 5-HT4 stimulates motility throughout the GI tract, and has a key role in the modulation of visceral sensitivity.

95% of the Bodys 5-HT is Found in the GI TractCNS 5%

GI tract 95% enterochromaffin cells neuronal

Gershon. Aliment Pharmacol Ther 1999;13(suppl 2):1530

Distribution and Function of 5-HT4 Receptors in the GI Tract Present on enteric nerves and non-neuronal tissue (entero-chromaffin cells, enterocytes and smooth muscle cells) Stimulation (initiation)of the peristaltic reflex Modulation of smooth muscle tone Stimulation of intestinal CI-/H2O secretion Modulation of visceral sensitivity/pain via direct inhibition of spinal afferents.

The enteric nervous system (ENS) and its connections with the CNSSpinal cord Brain stem

Spinal afferent fibre Sympathetic preganglionic fibres Sympathetic postganglionic fibres Afferent and efferent fibres of the vagus nerve

Longitudinal muscle Myenteric plexus Circular muscle Submucosa with submucosal plexus Muscularis mucosae Mucosa Interstitial cell of Cajal ENS

5-HT receptor receptor-mediated effectsImmune cells EC cellsIntrinsic afferent (5HT4) Extrinsic afferents (5HT3) ENS3 3 3 3

= 5-HT receptors

3 3Na+ ClNa+ ClK+

Secretion Ach/VIP

Motor responseMucosal afferent Muscle mechanoreceptor

Role of 5-HT in Motor Activity

Interneurons

Excitatory motor neuron (contraction) 5-HT receptors 5-HT

Sensory neuron

Inhibitory motor neuron (relaxation)

Enterochromaffin cells

Grider JR et al. Gastroenterology 1998;115:370380

Tegaserod Stimulates the Peristaltic Reflex Through Activation of Intrinsic Sensory PathwaysTegaserod triggers the peristaltic reflex in human, rat and guinea pig intestine (MEC 5nM)

ACh/SP Motor neurons 5-HT4 receptor Tegaserod CGRP

VIP/PACAP/NOS Motor neurons

Release of CGRP, VIP, SP (MEC 10nM)

5-HT

Enterochromaffin cells

Grider JR et al. Gastroenterology 1998;115:37080

ETIOLOGY

A.

Secondary constipation(dietary, structural, endocrinopathy/ metabolic, neurologic, drugs, collagen, psychologic)

B.

Functional constipation(simple, IBS, idiopathic, weak pelvic floor, chr. obstr., etc)

Secondary Causes of Functional Constipation1Metabolic and Endocrine DisordersDiabetes mellitus Hypothyroidism Hypercalcemia, hypokalemia Pregnancy Porphyria Panhypopituitarism Pheochromocytoma Glucagonoma

Neurogenic DisordersPeripheral Hirschsprungs disease Chagas disease Neurofibromatosis Autonomic neuropathy Hypoganglionosis Intestinal pseudoobstruction (myopathy, neuropathy)

Secondary Causes of Functional Constipation2CentralMultiple sclerosis Spinal cord lesions Parkinsons disease Shy-Drager syndrome Trauma to nervl erigentes Cerebrovascular accidents

CollagenSystemic sclerosis Amyloidosis Dermatomytositis Myotonic dystrophy

Drugs Associated With ConstipationAnalgesics Anticholinergics Antispasmodics Antidepressants Antipsychotics Antiparkinsonian drugs Cation-Containing Agents Iron supplements Aluminum (antacids, sucralfate) Calcium (antacids, supplements) Barium sulfate Metallic intoxication (arsenic, lead, mercury) Neutrally Active Agents Oplates Antihypertensive Ganglionic blockers Vinca alkaloids Anticonvulsants Calcium channel blockers

DIAGNOSIS1. 2. 3. 4. 5. History Physical examination (RT) Lab studies Radiology (plain photo, Ba enema) Endoscopy (proctoscopy, sigmoidoscopy, colonoscopy)

Symptoms Associated With The Term ConstipationDefecation Infrequent stools (may relate to concept of normal) No urge Stools difficult to pass (small, or large, hard; much effort needed) Ineffective straining Need to digitate Sense of incomplete evacuation Anal or perineal pain Prolapse comes down at the anus Soiling of clothes

Symptoms Associated With The Term ConstipationAbdomen Bloating (distention) Discomfort or pain, related or unrelated to defecation General Bad taste in the mouth Headache Nausea Malaise

DIAGNOSISOther studies : 1. Colonic transit study, 2. Defecography, 3. Manometry, 4. Electromyography.

Algorithm for evaluating a patient a patient with severe constipation who has not responded to simple dietary measuresDEFINE COMPLAINT INFREQUENT DEFECATIONColonic Transit Time

DEFECATORY STRAINING

Normal Normal

Colonic InertiaAnorectal Manometry

Outlet ObstructionDefecography Anorectal Manometry

Psychological Esophageal, gastric, Profile and email intestinal studies to evaluate for gastrointestinal pseudoobstruction

Normal

Abnormal Expulsion Pattern

Anatomical Hirschsprungs Abnormalities Disease

TREATMENT

1. Lifestyle changes 2. Pharmacological treatment 3. Other treatment

LIFESTYLE CHANGES

1. Dietary modification 2. Enough liquid 3. Exercise

Dietary Modification The most common cause of constipation is a diet low in fiber found in vegetables, fruits, and whole grains and high in fats found in cheese, eggs, and meats. People who eat plenty of high-fiber foods are less likely to become constipated. A low-fiber diet also plays a key role in constipation among older adults. They often lack interest in eating and may choose fast foods low in fiber. In addition, loss of teeth may force older people to eat soft foods that are processed and low in fiber.

Dietary Modification Fiber--soluble and insoluble--is the part of fruits, vegetables, and grains that the body cannot digest. Soluble fiber dissolves easily in water and takes on a soft, gel-like texture in the intestines. Insoluble fiber passes almost unchanged through the intestines. The bulk and soft texture of fiber help prevent hard, dry stools that are difficult to pass.

Merchanisms By Which Dietary Unasorbed Carpohydrate May Increase Stool Bulk. Emg, Electromyograph.(From Cumming, J. H 1999)

Unabsorbed Carbohydrate Large Bowel Microflora Well Fermenied Microbial Growth Gas production Increase Bulk in Colon Faster Transit Less water absorption Increased stool bulk

Nonstrach polysaccharides Ressistance starch Fructo-olisaccherides Polydextrose, lactulose Mucus

Poorly fermented Physical properties maintained Mechanical effect Water holding

Improved efficiency of bacterical