FUNCTIONAL GASTROINTESTINAL DISORDERS

MOTILITY DISORDERS OF THE OROFARINX AND ESOPHAGUS

MOTILITY DISORDERS OF THE ORO-FARINX

AND ESOPHAGUS

The oropharynx and proximal esophagus are composed of striated muscle and are under central nervous system control. The distal esophagus is predominantly composed of smooth muscle controlled by the enteric nervous system and vagus nerve.

MOTILITY DISORDERS OF THE ORO-FARINX

AND ESOPHAGUS

I.

Oropharyngeal swallowing disorders

Esophageal motility disorders Esophageal involvement in systemic disease

II.

III.

I. ORO-PHARYNGEAL SWALLOWING
DISORDERS

Estimates of the prevalence of dysphagia among individuals older than 50 years of age range from 16% to 22% of which most are attributed to oropharyngeal dysfunction as opposed to esophageal dysfunction

The consequences of oro-pharyngeal dysphagia are severe: dehydration, malnutrition, aspiration, choking, pneumonia, and death. As our population continues to age, oro-pharyngeal dysphagia will become an increasing problem

EVALUATION OF ORO-PHARYNGEAL
DYSPHAGIA 1. Does the patient describe dysphagia as opposed to globus sensation or xerostomia? 2. Is dysphagia oropharyngeal or esophageal in origin? 3. Is the dysphagia secondary to a structural or functional disorder? 4. Is there an underlying related or causative disorder? 5. Should therapy be directed toward the underlying etiology or the dysphagia itself?

EVALUATION OF ORO-PHARYNGEAL
DYSPHAGIA

Examination of the oral cavity, head, and neck for masses, lymph nodes, goiter, and evidence of previous surgery or radiation therapy will help define structural abnormalities associated with dysphagia. Neurological examination may indicate cranial nerve dysfunction, neuromuscular disease, cerebellar dysfunction, or an underlying movement disorder.

FURTHER TESTS

If the etiology of oropharyngeal dysphagia is not readily apparent after initial evaluation; The first task in the evaluation of suspected oropharyngeal dysphagia is to distinguish between structural and functional etiologies. Structural abnormalities that may result from trauma, surgery, tumors, caustic injury, congenital anomalies, or acquired deformities are identified by endoscopic or radiographic examination. Functional abnormalities can be attributable to dysfunction of either intrinsic musculature, peripheral nerves, or central nervous system control mechanisms.

FURTHER TESTS

Endoscopy is useful to identify tumors, webs or hypopharyngeal diverticula. Barium studies may define areas of obstruction and hypopharyngeal diverticula, but add little structural information to endoscopic exams. After structural defects have been excluded, videofluoroscopy is used for a functional evaluation of swallowing:
1 inability or excessive delay in initiation of pharyngeal swallowing; 2 aspiration; 3 nasopharyngeal regurgitation; 4 residue of the ingestate within the pharyngeal cavity after swallowing.

FURTHER TESTS

Intralumenal manometry can quantify:

the strength of pharyngeal contraction; the completeness of upper esophageal sphincter (UES) relaxation relaxation; and the relative timing of these events.

STRUCTURAL ETIOLOGIES OF OROPHARYNGEAL DYSPHAGIA Cervical webs; Pharyngeal or crico-pharyngeal strictures or tumors; Post-radiotherapy; Goiter; Prominent cervical osteophytes; Cricopharyngeal bars; Acquired hypopharyngeal diverticula.

ACQUIRED HYPOPHARYNGEAL DIVERTICULA

most commonly in men after the age of 60; the most common type, Zenker diverticulum, originates in the midline posteriorly at Killians dehiscence, a point of pharyngeal wall weakness between the oblique fibers of the inferior pharyngeal constrictor and the transverse cricopharyngeus muscle.

ACQUIRED HYPOPHARYNGEAL DIVERTICULA

ACQUIRED HYPOPHARYNGEAL DIVERTICULA

Other locations of acquired pharyngeal diverticula include:

the lateral slit separating the cricopharyngeus muscle from the fibers of the proximal end of the esophagus through which the recurrent laryngeal nerve and its accompanying vessels run to supply the larynx; at the penetration of the inferior thyroid artery into the hypopharynx; at the junction of the middle and inferior constrictor muscles.

ACQUIRED HYPOPHARYNGEAL DIVERTICULA

Hypopharyngeal diverticula are often asymptomatic until they enlarge sufficiently to store a significant amount of food or liquid. In most instances, symptoms are of:

dysphagia, halitosis, post-swallow regurgitation, even aspiration of material from the pharyngeal pouch.

ACQUIRED HYPOPHARYNGEAL DIVERTICULA TREATMENT

Cricopharyngeal myotomy with or without a diverticulectomy.

Good or excellent results can be expected in 80% 100% of Zenker patients treated by transcervical myotomy combined with diverticulectomy or diverticulopexy

Whether or not a cricopharyngeal bar in the absence of a diverticula requires treatment is less clear.

Dilation with a large caliber bougie may be efficacious in relieving dysphagia and this is certainly a reasonable treatment option prior to myotomy.

FUNCTIONAL ETIOLOGIES OF OROPHARYNGEAL DYSPHAGIA

Neurological causes (virtually any disease of the central nervous system can potentially cause dysphagia):

Cerebrovascular accidents; Poliomyelitis (bulbar) (60% of cases); Amyotrophic lateral sclerosis; Parkinson disease (only 15%20% of patients with Parkinson disease complain of swallowing problems, but more than 95% have demonstrable defects videofluoroscopically); Medullary (astrocytomas, medullo) or vagal tumors.

FUNCTIONAL ETIOLOGIES OF OROPHARYNGEAL DYSPHAGIA

Muscular diseases (virtually any disorder affecting skeletal muscles can result in dysphagia):
Oculopharyngeal dystrophy (syndrome characterized by progressive dysphagia and palpebral ptosis); Myotonic dystrophy; Myasthenia gravis.

generally, dysphagia progresses slowly and may ultimately lead to starvation, aspiration pneumonia, or asphyxia.

SWALLOWING THERAPY

Following characterization of a patients swallow dysfunction, the radiographic study should proceed to test selected compensatory or therapeutic treatment strategies. Compensatory treatments include:
postural changes (head turning in patients with hemiparesis), modifying food delivery or consistency or the use of prosthetics.

Therapeutic strategies designed to alter the physiology of the swallow, usually by improving the range of motion of oral or pharyngeal structures using voluntary control of oropharyngeal movement during swallow.

DETECTION OF SEVERE ASPIRATION

Oropharyngeal dysphagia associated with aspiration is responsible for an estimated 40 000 deaths a year as a result of aspiration pneumonia; Videoflouroscopy is believed to be the most sensitive test for detecting aspiration, detecting instances not evident by bedside evaluation
radiographic aspiration has a positive predictive value of only 19%68% and a negative predictive value of 55% 97% for pneumonia; its detection dictates that compensatory swallowing strategies, non-oral feeding (/tracheostomy?) or corrective surgery be instituted.

II. ESOPHAGEAL MOTILITY DISORDERS

Neuromuscular function of the esophagus (motility) has the consistent objective of emptying the esophagus:
primary esophageal peristalsis empties swallowed material from the esophagus; secondary peristalsis eliminates air or fluid refluxed from the stomach; the upper esophageal sphincter contracts during inspiration to exclude inspired air from the digestive tract; elements of the esophagogastric junction (EGJ) contract during transient increases of intra-abdominal pressure, preventing gastroesophageal reflux.

ESOPHAGEAL MOTILITY DISORDERS

A basic characteristic is the failure to preserve esophageal emptiness. Retained material within the esophagus, or the excessive entry of material into the esophagus, is abnormal. Such dysfunction can be categorized as:

disorders of peristalsis; disorders of sphincter competence.

or

EVALUATION OF ESOPHAGEAL
DYSPHAGIA

Esophageal (as opposed to oropharyngeal dysphagia) is suggested by the absence of:

associated aspiration, cough, nasopharyngeal regurgitation, dry mouth, pharyngeal residue following swallow, co-occurring neuromuscular dysfunction.

On the other hand, the associated conditions of:

heartburn, esophagopharyngeal regurgitation, chest pain, odynophagia, intermittent esophageal obstruction

suggest esophageal dysphagia.

EVALUATION OF ESOPHAGEAL
DYSPHAGIA

an important limitation of the patient history in esophageal dysphagia is that patient identification of the location of obstruction is of limited accuracy (only about 60%).

Therefore, an evaluation for cervical dysphagia should encompass the entire esophagus.

EVALUATION OF ESOPHAGEAL
DYSPHAGIA

Another important consideration in patient management is that esophageal motility disorders are much less common than mechanical or inflammatory etiologies of dysphagia (tumors, strictures, rings, and peptic, pill, or infectious esophagitis). Historical points suggestive of a motor disorder are
difficulty with both solids and liquids; as opposed to difficulty with only solids, which is more suggestive of mechanical obstruction.

DIAGNOSTIC TESTING IN ESOPHAGEAL

DISEASE

Endoscopy

should be the first test ordered for evaluating new-onset dysphagia when structural causes requiring either dilation or biopsy are being considered. with excellent specificity for strictures and tumors;

however, it has the potential to miss subtle obstructing lesions, such as webs and rings; it will also provide very limited information regarding peristaltic function.

DIAGNOSTIC TESTING IN ESOPHAGEAL

DISEASE

Contrast studies

if stricture or tumor is not suspected

upper endoscopy is not readily available. this imaging technique has the added benefit of providing information regarding UES function, peristalsis, and bolus clearance through the EGJ.

or

DIAGNOSTIC TESTING IN ESOPHAGEAL

DISEASE

Manometry

the only technique that can define the contractile characteristics of the esophagus in an attempt to identify pathological conditions; assesses the integrity, rate of progression, and morphology of the contractile complex (amplitude, duration, repetitive contractions); both the magnitude of EGJ pressure and EGJ relaxation characteristics are measured with manometry.

DIAGNOSTIC TESTING IN ESOPHAGEAL

DISEASE

Impedance monitoring

method to assess intralumenal bolus transit without fluoroscopy; validation studies of multichannel intralumenal impedance against videofluoroscopy have shown excellent concordance in ascertaining bolus transit, reporting agreement in 97% of swallows analyzed.

ACHALASIA

the most easily recognized and best defined motor disorder of the esophagus; initially labeled cardiospasm reflecting the observation that it was caused by a functional obstruction of the esophagus at the cardia sphincter with no obstructing lesion evident;

= failure to relax.

ACHALASIA

Epidemiology

estimated incidence of 1/100 000 population per year; the disease affects both sexes equally and usually presents in adult life, being most common between the ages of 25 and 60.
Reports of familial clustering of achalasia raise the possibility of genetic predisposition;

ACHALASIA

Neuropathology
(1) failure of the LES to relax completely with swallowing; (2) aperistalsis in the smooth muscle esophagus.

The resting LES pressure elevated in about 60% of achalasia cases. If there are nonperistaltic, spasm-like contractions in the esophageal body, the disease is referred to as vigorous achalasia.

These physiological alterations are thought to result from damage to the innervation of the smooth muscle esophagus (including the LES) (loss of ganglion cells within the myenteric Auerbachs plexus).

ACHALASIA

Neuropathology
there is increasing evidence consistent with an immunemediated process; A multitude of evidence supports impaired physiological function of postganglionic inhibitory innervation in the smooth muscle esophagus of achalasics.

ACHALASIA

Clinical presentation
dysphagia, regurgitation, chest pain, weight loss, aspiration pneumonia (approx. 10% of achalasics).

The onset of dysphagia is usually gradual with the duration of symptoms averaging 2 years at presentation . Dysphagia severity fluctuates but eventually plateaus.

ACHALASIA

Clinical presentation
It is paradoxical that many achalasics complain of heartburn, even after the onset of dysphagia; ambulatory 24-h esophageal pH studies of achalasics have only shown periods of esophageal acidification caused by the bacterial fermentation of retained food in the esophagus rather than discrete gastroesophageal reflux events.

ACHALASIA

Radiography
The characteristic radiograph is of a dilated intrathoracic esophagus with impaired emptying, an airfluid level, absence of a gastric air bubble, and an LES that tapers to a point giving the distal esophagus a beak-like appearance. With long-standing achalasia the esophagus may assume a sigmoid configuration, and in some instances an airfluid level, mediastinal widening, and an outline of the dilated esophageal wall are even evident on a plain chest film.

Note that the characteristic radiographic findings depend upon esophageal dilation; as dilation is not always present in achalasia, the sensitivity of the radiograpic examination is limited.

ACHALASIA

Manometry

The defining manometric features of achalasia are:

aperistalsis incomplete LES relaxation.

In cases of achalasia that are established by all available clinical criteria, these features are present more than 90% of the time. Given that esophageal aperistalsis also occurs with disorders other than achalasia, including GERD, collagen vascular diseases, and diabetes, the diagnosis of achalasia is highly dependent on accurately detecting impaired LES relaxation.

ACHALASIA

Manometry

Despite utilizing state-of-the-art techniques, there are achalasia variants with atypical features of either peristalsis or LES relaxation, confounding their diagnosis. Achalasia variants:
high amplitude esophageal body contractions (vigorous achalasia) retained peristalsis in most of the esophagus with only a short segment of aperistalsis retained deglutitive LES relaxation impaired deglutitive relaxation but intact transient LES relaxations

ACHALASIA

Classic achalasia

ACHALASIA

Vigorous achalasia

ACHALASIA

Achalasia with intact peristalsis

ACHALASIA

Endoscopic findings
Typical endoscopic findings include retained food or saliva, dilation, and atony of the esophageal body. With progressive dilation and stasis, erythema, friability, and superficial ulcerations may be seen. Whitish plaques covering the epithelial surface may be seen as the result of Candida overgrowth The achalasic LES has a pinpoint appearance and does not open with air insufflation.

Nonetheless, the instrument should pass easily through the sphincter into the stomach with minimal pressure. Resistance, or a feeling of stiffness as the endoscope crosses the EGJ, should immediately raise the suspicion of malignancy (pseudoachalasia). Also, equivocal mucosal abnormalities of the EGJ, evident on forward viewing or retroflexed inspection, should always be biopsied.

ACHALASIA

Differential diagnosis

esophageal spasm;
esophageal involvement in Chagas disease (Trypanosoma cruzi) - the chronic phase of the disease develops many years after infection and results from destruction of autonomic ganglion cells throughout the body, including the heart, gut, urinary tract, and respiratory tract (megaureter, cardiomyopathy, megaduodenum, megacolon, megarectum), with LES dysfunction occurring late in the course of the disease. post-fundoplication; pseudoachalasia.

PSEUDOACHALASIA

It is important to emphasize that neither the radiographic nor the manometric features of achalasia are specific for idiopathic achalasia or achalasia associated with Chagas disease; tumor-related pseudoachalasia accounts for up to 5% of cases with manometrically defined achalasia; tumor infiltration (especially carcinoma in the gastric fundus) can completely mimic the functional impairment seen with idiopathic achalasia; more likely with:
progressive age (> 50 years), abrupt onset of symptoms (< 1 year), early weight loss in excess of 7 kg.

PSEUDOACHALASIA

pancreatic, oat cell, hepatoma, bronchogenic, esophageal squamous cell, prostate, and lymphoma cases have been reported; these tumors produce an achalasia syndrome by infiltrating the wall of the esophagus at the EGJ, in essence causing a malignant obstruction at the LES with proximal esophageal dilation. pseudoachalasia has also been reported to result from esophageal infiltration by amyloid, eosinophilic gastroenteritis, and sarcoidosis. although often speculated in the literature, it is less certain, and certainly much less common, that an achalasic syndrome occurs as a paraneoplastic syndrome without direct tumor stenosis of the EGJ.

ACHALASIA MANAGEMENT

Because the underlying neuropathology cannot be corrected, treatment of achalasia is directed at:
compensating for the functional abnormalities; preventing complications.

Peristalsis rarely returns with therapy. LES pressure can be reduced by:

pharmacological therapy, botulinum toxin injection, forceful dilation, POEM or surgical myotomy.

ACHALASIA

Risk of squamous cell cancer

the relative risk of developing squamous cell cancer has been estimated to be 33-fold higher than in the nonachalasic population; because the tumors often arise in a greatly dilated esophagus, symptoms can be delayed and the neoplasms are large and advanced at the time of detection.

These considerations raise the issue of surveillance endoscopy in achalasics to detect early squamous cell cancer.

SPASTIC DISORDERS OF THE ESOPHAGUS

SPASTIC DISORDERS OF THE ESOPHAGUS

Clinical presentation The major symptoms of spastic disorders are

dysphagia - reported by 30-60% of patients with spastic disorders (usually intermittent in occurrence, sometimes related to swallowing specific substances or liquids at extreme temperature, usually not progressive and weight loss is rare.) and chest pain - reported by 80-90% of patients with spastic disorders (high prevalence of psychiatric diagnosis, particularly anxiety and depression; evidence also exists suggesting a lower visceral pain threshold in this group; symptoms compatible with the irritable bowel syndrome may be seen in more than 50% of these patients).

Regurgitation is infrequent.

SPASTIC DISORDERS OF THE ESOPHAGUS

Esophageal chest pain is very similar to angina:

usually described as crushing or squeezing in character, often radiating to the neck, jaw, arms, or midline of the back. pain episodes may last from minutes to hours; swallowing is usually not impaired during these episodes. severe pain episodes may require narcotics or nitroglycerin for relief, further confusing the distinction between esophageal and cardiac pain.

The mechanism producing pain is poorly understood; transient ischemia, lumenal distension, and altered visceral sensitivity have all been hypothesized.

SPASTIC DISORDERS OF THE

ESOPHAGUS

SPASTIC DISORDERS OF THE

ESOPHAGUS

Treatment
similar to those of coronary artery disease there is a paucity of data on the medical treatment of esophageal spasm

nitrates; calcium channel blockers; botulinum toxin injected at the level of the EGJ; anxiolytics (trazodone);

pneumatic dilation has been used in DES patients with severe dysphagia; if dysphagia becomes so severe that weight loss is observed or if pain becomes unbearable, surgical therapy consisting of a Heller myotomy across the LES with proximal extension of the incision to include the involved area of spasm should be considered.

III. ESOPHAGEAL INVOLVEMENT IN SYSTEMIC

DISEASE

Esophageal dysmotility occurs as a manifestation of several disease processes with the potential to affect smooth muscle or the autonomic nervous system:
collagen vascular diseases (scleroderma); infiltrative diseases (amyloidosis or malignancies); metabolic disorders (thyrotoxicosis, diabetes); caustic injury as occurs with gastroesophageal reflux disease.

FUNCTIONAL DYSPEPSIA

FUNCTIONAL DYSPEPSIA

also referred to as idiopathic or nonulcer dyspepsia;

the most common type of dyspepsia encountered in primary care and gastroenterology practice ; it occurs in approximately 25% of the population each year, but most affected people do not seek medical care;

with an extensive differential diagnosis and a heterogeneous pathophysiology.

FUNCTIONAL DYSPEPSIA (ROME III CRITERIA)

One or more of:

Bothersome postprandial fullness Early satiation Epigastric pain Epigastric burning

AND

No evidence of structural disease (including at upper endoscopy) that is likely to explain the symptoms.

These criteria should be fulfilled for the last three months with symptom onset at least six months before diagnosis. Two subcategories (postprandial distress syndrome and epigastric pain syndrome) were also recognized but their main value lies currently in research.

FUNCTIONAL DYSPEPSIA (PATHOPHYSIOLOGY)

Gastric motor function

Delayed gastric emptying has been found in approximately 30% of patients; Antral hypomotility has been found in a similar proportion of patients; Up to 10% of patients have fast gastric emptying; Gastric compliance is lower in patients with functional dyspepsia than in healthy controls.

Visceral sensitivity (visceral hyperalgesia)

Patients with dyspepsia are also more sensitive to acid infusion into the duodenal bulb; Both mechanoreceptor dysfunction (peripheral mechanism) and aberrant processing of afferent input in the spinal cord or brain (central mechanism) may play a role.

FUNCTIONAL DYSPEPSIA (PATHOPHYSIOLOGY)

Helicobacter pylori infection

rather unconvincing findings; H. pylori may cause altered smooth muscle dysfunction or lower the discomfort threshold to gastric distension due to the induction of an inflammatory response; at best, only a minority of patients with functional dyspepsia will benefit from H. pylori eradication conclusion was supported by a systematic review of 21 randomized controlled trials, which found that NNT = 14. anxiety, somatization, neuroticism, and depression are increased in this group compared with healthy controls.

Psychosocial factors

FUNCTIONAL DYSPEPSIA (DIAGNOSIS)

There are no diagnostic tests for functional dyspepsia. As a result, the diagnosis is made from the characteristic clinical history and the exclusion of other causes of dyspepsia.

FUNCTIONAL DYSPEPSIA (DIAGNOSIS)

FUNCTIONAL DYSPEPSIA (DIAGNOSIS)

Questions to ask in patients with dyspepsia

Peptic ulcers - Does the patient have a previous history of ulcers? Does the patient take nonsteroidal antiinflammatory drugs? Is the patient a smoker? Gastroesophageal reflux disease - Does the patient complain of heartburn or regurgitation? Are symptoms worse when the patient is lying down? Does the patient have a chronic cough or hoarseness? Biliary tract disease - Does the patient have episodic upper abdominal pain lasting at least one hour? Does pain occur after meals? Is the pain associated with meals or belching? Pancreatitis - Does the pain radiate to the patient's back? Is the pain abrupt, is it unbearable in severity, or does it last for many hours without relief? Does the patient have a history of heavy alcohol use? Is there a family history of pancreatitis? Cancer - Is the patient over 50 years of age? Has the patient had a recent significant weight loss? Does the patient have trouble swallowing? Is the patient a smoker? Does the patient have longstanding gastroesophageal reflux disease? Irritable bowel syndrome - Does the patient fulfill the Rome or Manning criteria for irritable bowel syndrome (eg, pain relieved with defecation, more frequent stools at the onset of pain, loose stools at the onset of pain, visible abdominal distention, passage of mucus, sensation of incomplete evacuation)? Metabolic disorders/delayed gastric emptying - Does the patient have a medical history of diabetes mellitus, hypothyroidism or hyperthyroidism, or hyperparathyroidism? Medications - Is the patient currently taking medications commonly associated with dyspepsia (eg, iron, NSAIDs, bisphosphonates, some antibiotics)?

FUNCTIONAL DYSPEPSIA (DIAGNOSIS)

FUNCTIONAL DYSPEPSIA (TREATMENT)

Treatment of patients with functional dyspepsia is controversial and often disappointing, a sharp contrast to the therapy of peptic ulcer disease. The goal is to help patients accept, diminish, and cope with symptoms rather then eliminate them:

explanation, validation that the symptoms are not imaginary, evaluation and management of relevant psychosocial factors, dietary advice, medications that might contribute to symptoms (such as NSAIDs) should be substituted or discontinued whenever possible.

FUNCTIONAL DYSPEPSIA (TREATMENT)

DRUGS:

Proton pump inhibitors (relative risk reduction of about 10%; the benefit was proved in those with ulcer-like or reflux-like symptoms; there was no significant benefit in patients with dysmotility-like symptoms); H2 receptor antagonists (better quality trials showed reduced efficacy of H2 receptor antagonists therapy); Prokinetic agents (domperidone; associated with a 50 percent reduction in symptoms compared with placebo; RRR 50%); Antidepressants (a therapeutic trial should begin with a low dose, adjusting the dose upward while observing for daytime sedation or other side effects; if the patient responds in a few weeks, continue the drug for a few months before stopping); Psychological therapy (cognitive-behavioral therapy, hypnotherapy, or psychotherapy) has benefited selected patients; Complementary and alternative medicine.

IRRITABLE BOWEL SYNDROME

IRRITABLE BOWEL SYNDROME (IBS)

gastrointestinal syndrome characterized by:

chronic abdominal pain and altered bowel habits in the absence of any organic cause.

It is the most commonly diagnosed gastro-intestinal condition. The prevalence of IBS is approximately 10-15% of the general population.

IRRITABLE BOWEL SYNDROME (IBS)

IBS affects both young patients, and the elderly; however, younger patients and women are more likely to be diagnosed with IBS; there is an overall 2:1 female predominance;

only about 15% of those affected actually seek medical attention; nevertheless, the absolute number of patients is still so large that IBS in its various forms comprises 25-50% of all referrals to gastroenterologists.

IRRITABLE BOWEL SYNDROME (CLINICAL MANIFESTATIONS)

Chronic abdominal pain

usually described as a crampy sensation with variable intensity and periodic exacerbations; the location and character of the pain can vary widely; the severity of the pain may range from mildly annoying to debilitating; several factors, such as emotional stress and eating, may exacerbate the pain, while defecation often provides some relief.

IRRITABLE BOWEL SYNDROME (CLINICAL MANIFESTATIONS)

Chronic abdominal pain

some clinical features are not compatible with the syndrome and should prompt an investigation for organic diseases:
pain associated with anorexia, malnutrition, or weight loss this constellation is extremely rare in IBS unless there is concurrent major psychologic illness; pain that is progressive, awakens the patient from sleep, or prevents sleep.

IRRITABLE BOWEL SYNDROME (CLINICAL MANIFESTATIONS)

Altered bowel habits ranging from:

diarrhea, constipation, alternating diarrhea and constipation, normal bowel habits alternating with either diarrhea and/or constipation.

IRRITABLE BOWEL SYNDROME (CLINICAL MANIFESTATIONS)

Diarrhea

Stools generally occur during waking hours, most often in the morning or after meals. Most bowel movements are preceded by lower abdominal cramps and urgency even to the point of fecal incontinence and may be followed by a feeling of incomplete evacuation. Approximately one-half of all patients with IBS complain of mucus discharge with stools.
Large volume diarrhea, bloody stools, nocturnal diarrhea, and greasy stools are NOT associated with IBS and suggest an organic disease.

IRRITABLE BOWEL SYNDROME (CLINICAL MANIFESTATIONS)

Constipation
may last from days to months, with interludes of diarrhea or normal bowel function. Stools are often hard and may be described as pelletshaped. Patients may also experience a sense of incomplete evacuation even when the rectum is empty.

IRRITABLE BOWEL SYNDROME (CLINICAL MANIFESTATIONS)

Other gastrointestinal symptoms

Upper gastrointestinal symptoms, including gastroesophageal reflux, dysphagia, early satiety, intermittent dyspepsia, nausea, and non-cardiac chest pain, are common in patients with IBS. Patients with IBS also frequently complain of abdominal bloating and increased gas production in the form of flatulence or belching.

IRRITABLE BOWEL SYNDROME (CLINICAL MANIFESTATIONS)

Extraintestinal symptoms

Patients with IBS often complain of a broad range of non-gastrointestinal symptoms. These include:
impaired sexual function, dysmenorrhea, dyspareunia, increased urinary frequency and urgency, and fibromyalgia symptoms.

IRRITABLE BOWEL SYNDROME (PATHOPHYSIOLOGY)

GASTROINTESTINAL MOTILITY

increased frequency and irregularity of luminal contractions, prolonged transit time in constipation-predominant IBS an exaggerated motor response to cholecystokinin and meal ingestion in diarrhea-predominant IBS.

IRRITABLE BOWEL SYNDROME (PATHOPHYSIOLOGY)

VISCERAL HYPERSENSITIVITY
awareness and pain caused by balloon distention in the intestine are experienced at lower balloon volumes compared with controls, suggesting receptor hypersensitivity; about half of patients with IBS (mainly those with constipation) have a measurable increase in abdominal girth associated with bloating (sensation of abdominal fullness), although this may not be related to the volume of intestinal gas, but to the impaired transit of intestinal gas loads.

heightened sensitivity of the intestines to normal sensations is mediated by the local GI nervous system, by central modulation from the brain, or by some combination of the two.

IRRITABLE BOWEL SYNDROME (PATHOPHYSIOLOGY)

INTESTINAL INFLAMMATION

Immunohistologic investigation has revealed mucosal immune system activation characterized by alterations in:
particular immune cells (lymphocytes, mast cells) and markers (elevated levels of plasma proinflammatory interleukins)

in some patients with IBS (those with diarrheapredominant IBS and patients with presumed postinfectious IBS).

IRRITABLE BOWEL SYNDROME (PATHOPHYSIOLOGY)

ALTERATION IN FECAL MICROFLORA

The complex ecology of the fecal microflora has led to speculation that changes in its composition could be associated with diseases including IBS. Emerging data suggest that the fecal microbiota in individuals with IBS differ from healthy controls and varies with the predominant symptom.
Small intestinal bacterial overgrowth (SIBO) - associated with an increased number and/or type of bacteria in the upper GI tract, but data reporting an association between IBS and SIBO have been conflicting.

IRRITABLE BOWEL SYNDROME (PATHOPHYSIOLOGY)

FOOD SENSITIVITY

Food allergy Carbohydrate malabsorption Gluten sensitivity

GENETICS

Familial studies suggest a modest contribution of genetics to the development of IBS in some patients:
polymorphisms in the serotonin transporter gene, resulting in altered serotonin reuptake efficacy that affects intestinal peristalsis; an altered pattern of anti-inflammatory cytokine interleukin production.

IRRITABLE BOWEL SYNDROME (PATHOPHYSIOLOGY)

PSYCHOSOCIAL DYSFUNCTION Psychosocial factors may influence the expression of IBS

patients with GI symptoms report more lifetime and daily stressful events than control groups; patients with IBS exhibit increased anxiety, depression, phobias, sleep problems, and somatization; some studies report a positive association between IBS and abuse.

One unifying hypothesis concerning the role of stress and psycho neuroticism in IBS is based upon corticotropin releasing factor (CRF), a peptide released from the paraventricular nucleus and considered to be a major mediator of the stress response. Data suggest that overactivity in the brain CRF and CRF-receptor signaling system contributes to anxiety disorders and depression. Intravenous administration of CRF increases abdominal pain and colonic motility in IBS patients to a higher degree than normal controls. Furthermore, this response can be blunted by the administration of a CRF receptor antagonist with no effect on the hypothalamus-pituitary-adrenal axis

IRRITABLE BOWEL SYNDROME (DIAGNOSTIC CRITERIA - ROME III)

Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months with symptom onset at least 6 months prior to diagnosis associated with 2 or more of the following: (1) Improvement with defecation ; (2) Onset associated with a change in frequency of stool; (3) Onset associated with a change in form (appearance) of stool.

IRRITABLE BOWEL SYNDROME (DIAGNOSTIC CRITERIA - ROME III)

Supportive symptoms that are not part of the Rome III criteria include:

abnormal stool frequency (3 bowel movements per week or >3 bowel movements per day), abnormal stool form (lumpy/hard or loose/watery), defecation straining, urgency, a feeling of incomplete bowel evacuation, passing mucus bloating.

IRRITABLE BOWEL SYNDROME (DIAGNOSTIC CRITERIA - ROME III)

Four subtypes of IBS are recognized:

IBS with constipation (hard or lumpy stools 25 percent / loose or watery stools <25 percent of bowel movements) IBS with diarrhea (loose or water stools 25 percent / hard or lumpy stools <5 percent of bowel movements) Mixed IBS (hard or lumpy stools 25 percent / loose or watery stools 25 percent of bowel movements) Unsubtyped IBS (insufficient abnormality of stool consistency to meet the above subtypes)

IRRITABLE BOWEL SYNDROME (DIAGNOSTIC APPROACH)

It is important to exclude other causes. Routine laboratory studies (complete blood count, chemistries) are normal in IBS. "Alarm" or atypical symptoms which are not compatible with IBS include:
Rectal bleeding Nocturnal or progressive abdominal pain Weight loss Laboratory abnormalities such as anemia, elevated inflammatory markers, or electrolyte disturbances [3].

Patients with one of these alarm symptoms require further imaging studies and/or colonoscopy.

IRRITABLE BOWEL SYNDROME (DIAGNOSTIC APPROACH)

In patients who have:

symptoms suggestive of IBS, no alarm symptoms no family history of inflammatory bowel disease or colorectal cancer

a limited number of diagnostic studies can rule out organic illness in the majority of patients and a sizable number require no testing at all. this limited diagnostic approach rules out organic disease in over 95% of patients.

IRRITABLE BOWEL SYNDROME (DIAGNOSTIC APPROACH)

Diarrhea predominant IBS:

Stool cultures There is little role for stool cultures in patients with chronic diarrhea. The one exception may be Giardia in patients with possible exposure. Celiac disease screening Screening for celiac disease with serum IgA antibody to tissue transglutaminase should be performed in patients with diarrhea-predominant IBS. In a meta-analysis of 14 studies focusing on unselected adults who met diagnostic criteria for IBS, celiac disease was four times as likely as in controls without IBS; the absolute proportion of patients who fulfilled criteria for IBS and had celiac disease was approximately 4%. Twenty-four hour stool collection should be considered if osmotic or secretory diarrhea or malabsorption is suspected. Colonoscopy or flexible sigmoidoscopy and biopsy Many causes of chronic diarrhea such as microscopic colitis require endoscopic evaluation.

IRRITABLE BOWEL SYNDROME (DIAGNOSTIC APPROACH)

Constipation predominant IBS:

Radiography A plain film of the abdomen can detect retained stool and suggest the diagnosis of constipation. Flexible sigmoidoscopy and colonoscopy should be performed if a structural lesion is suspected. Colonoscopy is preferred in patients who are older than 50 because of the increased risk of colon cancer in this age group.

IRRITABLE BOWEL SYNDROME (DIAGNOSTIC APPROACH)

Mixed IBS - performing screening tests based upon the patient's clinical history. A more extensive evaluation should be considered in patients who have had a change or progression of symptoms or do not respond to general treatment measures (refractory symptoms).

IRRITABLE BOWEL SYNDROME (TREATMENT)

IBS is a chronic condition with no known cure. As a result, the focus of treatment should be on relief of symptoms and addressing the patient's concerns. An important question to answer is why the patient is seeking help at this time.

recent exacerbating factors (medications, dietary changes), concerns about serious illness, stressors, requests for opiates psychiatric comorbidities

IRRITABLE BOWEL SYNDROME (TREATMENT)

The most important component of treatment lies in the establishment of a therapeutic physician-patient relationship. The doctor should be non-judgmental, establish realistic expectations with consistent limits, and involve the patient in treatment decisions. Patients with established, positive physician interactions have fewer IBS-related follow-up visits. Patients should be informed of the chronic and benign nature of IBS, and also informed that the diagnosis (if well-established) is not likely to be changed, and that he or she should have a normal life span.

IRRITABLE BOWEL SYNDROME (TREATMENT)

Dietary modification

A careful dietary history may reveal patterns of symptoms related to specific foods. A number of dietary interventions have been proposed but their efficacy has not been well established (true or placebo effect??):

Exclusion of gas-producing foods (beans, onions, celery, carrots, raisins, bananas, apricots, prunes, brussel sprouts, wheat germ, pretzels, and bagels) Food allergies - there are no reliable means to identify such individuals Gluten sensitivity Carbohydrate malabsorption - the theory holds that fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) in patients with IBS or IBD enter the distal small bowel and colon where they are fermented, leading to symptoms and increased intestinal permeability; Fiber - some improvement has been demonstrated in patients with IBS whose primary complaints are abdominal pain and constipation .

IRRITABLE BOWEL SYNDROME (TREATMENT)

Physical activity
After 12 weeks, there was a trend toward more patients in the physical activity arm showing clinical improvement in the severity of IBS symptoms compared with the control group Also, patients in the physical activity arm were less likely to have clinically significant worsening of their IBS symptoms.

Psychosocial therapies (although their benefits remain controversial)

Behavioral treatments Hypnosis, Biofeedback, Psychotherapy

IRRITABLE BOWEL SYNDROME (MEDICATIONS)

Pharmacologic agents are only an adjunct to treatment in IBS. Furthermore, the drug chosen varies depending on the patient's major symptoms; diarrheapredominant IBS is treated differently from constipation-predominant disease.

Suggestion that the chronic use of drugs be generally minimized or avoided because of the lifelong nature of this disorder and the lack of convincing therapeutic benefit (although a high placebo effect).

IRRITABLE BOWEL SYNDROME (MEDICATIONS)

Antispasmodic agents

The selective inhibition of gastrointestinal smooth muscle reduces stimulated colonic motor activity and may be beneficial in patients with postprandial abdominal pain, gas, bloating, and fecal urgency. A meta-analysis of 23 controlled trials of smooth muscle relaxants found that they were more effective than placebo (risk difference for global improvement of 22%, and overall pain improvement of 53 versus 41%).
Administration of these medications in the treatment of IBS should be on an as needed basis and/or in anticipation of stressors with known exacerbating effects.

IRRITABLE BOWEL SYNDROME (MEDICATIONS)

Antidepressants
have analgesic properties independent of their mood improving effects A 2009 meta-analysis that included 13 placebo-controlled trials of antidepressants in 789 adults with IBS concluded that antidepressants were significantly more effective than placebo for the relief of pain and global symptoms (relative risk of IBS symptoms persisting 0.66) at a duration of therapy ranging from one to three months NNT = 4; the treatment effects were similar for SSRIs and tricyclic antidepressants.

Benzodiazepines

may be useful for short-term (less than two weeks') reduction of acute situational anxiety that may be contributing to symptoms.

IRRITABLE BOWEL SYNDROME (MEDICATIONS)

Antidiarrheal agents
loperamide was more effective than placebo for treatment of diarrhea, but not for treatment of global IBS symptoms or abdominal pain. administration on an as needed basis; should be used only cautiously in those with symptoms alternating between diarrhea and constipation.

IRRITABLE BOWEL SYNDROME (MEDICATIONS)

Lubiprostone

a locally acting chloride channel activator that enhances chloride-rich intestinal fluid secretion. Patients randomized to lubiprostone were significantly more likely to achieve an overall response (18 versus 10 percent).

Antibiotics
Some patients with IBS have shown improvement when treated with antibiotics (rifaximin) (41 versus 32%). Most of the improvement has been in symptoms of bloating, abdominal pain, or altered bowel habits. Modest benefit and relatively short-term follow-up!

IRRITABLE BOWEL SYNDROME (MEDICATIONS)

Alternative therapies

herbal medicine; probiotics, prebiotics, simbiotics; acupuncture.

SPHINCTER OF ODDI DYSFUNCTION

SPHINCTER OF ODDI
DYSFUNCTION

The sphincter of Oddi is

a muscular structure that encompasses the confluence of the distal common bile duct and the pancreatic duct as they penetrate the wall of the duodenum.

A circular aggregate of muscle fibers known as the sphincter choledochus (or sphincter of Boyden) maintains resistance to bile flow and thereby permits filling of the gallbladder during fasting and prevents retrograde reflux of duodenal contents into the biliary tree.

A separate structure, the sphincter pancreaticus, encircles the distal pancreatic duct.

SPHINCTER OF ODDI DYSFUNCTION

The term sphincter of Oddi dysfunction (SOD) has been used to describe a clinical syndrome of

biliary pancreatic

or

obstruction related to mechanical or functional abnormalities of the sphincter of Oddi.

SOD has been associated with two clinical syndromes:

biliary pain idiopathic recurrent acute pancreatitis.

SPHINCTER OF ODDI DYSFUNCTION

The term sphincter of Oddi dysfunction (SOD) two separate pathologic entities are widely recognized based upon their distinct pathogenic mechanisms:
Sphincter of Oddi stenosis; Sphincter of Oddi dyskinesia.

SPHINCTER OF ODDI DYSFUNCTION (PATHOPHYSIOLOGY)

Sphincter of Oddi stenosis is an anatomic abnormality associated with narrowing of the sphincter of Oddi.
It can result from any process leading to inflammation or scarring, such as pancreatitis, passage of a gallstone through the papilla, intraoperative trauma, infection, and adenomyosis. Sphincter of Oddi stenosis is associated with abnormal sphincter of Oddi motility and elevated basal pressure.

Sphincter of Oddi dyskinesia refers to a functional disturbance of the sphincter of Oddi, leading to intermittent biliary obstruction.

The cause of sphincter of Oddi dyskinesia is not well understood. Spasm and relaxation of the sphincter of Oddi can be induced pharmacologically with agents known to affect smooth muscle function (such as nitroglycerin), suggesting that the spasm may be influenced by local hormonal or neurologic disturbance.

SPHINCTER OF ODDI DYSFUNCTION (EPIDEMIOLOGY)

Women are significantly more likely to have functional biliary pain than men (2.3 versus 0.6 percent, odds ratio 3.3). In a second study of 49 patients with sphincter of Oddi stenosis and recurrent pancreatitis, 88 percent of the patients were female.

The median age of the patients of 43 years.

SPHINCTER OF ODDI DYSFUNCTION (CLINICAL MANIFSTATIONS)

Biliary SOD

biliary-type pain without other apparent causes. liver transaminases and alkaline phosphatase may be elevated there may be dilation of the CBD (> 8 mm)

Pancreatic SOD
Patients with pancreatic SOD present with recurrent episodes of pancreatitis. The episodes typically occur months apart and are associated with elevations in the amylase and lipase. Liver transaminases and bilirubin may also be elevated, and there may be dilation of the pancreatic duct.

SPHINCTER OF ODDI DYSFUNCTION (ROME III CRITERIA)

Functional gallbladder disorder Functional biliary sphincter of Oddi disorder Functional pancreatic sphincter of Oddi disorder

Those who fulfill the Rome III symptom-based criteria should undergo further evaluation with liver and pancreatic enzymes, ultrasound, and, for selected patients, sphincter of Oddi manometry.

SPHINCTER OF ODDI DYSFUNCTION (ROME III CRITERIA)

All of the following conditions must be met:

Pain located in the epigastrium and/or right upper quadrant Episodes lasting 30 minutes or longer Recurrent symptoms occurring at different intervals (not daily) The pain builds up to a steady level The pain is moderate to severe enough to interrupt the patient's daily activities or lead to an emergency department visit The pain is not relieved by bowel movements The pain is not relieved by postural change The pain is not relieved by antacids Exclusion of other structural disease that would explain the symptoms

SPHINCTER OF ODDI DYSFUNCTION (ROME III CRITERIA)

Functional gallbladder disorder

Gallbladder is present Normal liver enzymes, conjugated bilirubin, and amylase/lipase

Functional biliary sphincter of Oddi disorder

Normal amylase/lipase Supportive criteria include elevated serum aminotransferases, alkaline phosphatase, or conjugated bilirubin (>twice the upper limit of normal) temporally related to at least two pain episodes and a dilated common bile duct (>8 mm).

Functional pancreatic sphincter of Oddi disorder

Elevated amylase/lipase

SPHINCTER OF ODDI DYSFUNCTION (MILWAUKEE CLASSIFICATION)

Biliary SOD
Type I patients present with biliary-type pain, abnormal aminotransferases, bilirubin or alkaline phosphatase (>2 times normal values) documented on two or more occasions, and a dilated bile duct (>8 mm on ultrasound). Approximately 65-95% of these patients have manometric evidence of biliary SOD. Type II patients present with biliary-type pain and one of the previously mentioned laboratory or imaging abnormalities. Approximately 50-63% of these patients have manometric evidence of biliary SOD. Type III patients complain only of recurrent biliary-type pain and have none of the previously mentioned laboratory or imaging criteria. Approximately 12-59% of these patients have manometric evidence of biliary SOD.

Pancreatic SOD
Type I patients have all three of the following criteria: pain, a dilated pancreatic duct (>6 mm in the head and >5 mm in the body) , serum amylase or lipase level >1.5 times the upper limit of normal on at least one occasion Type II patients have pain plus one other criterion Type III patients only have pain

SPHINCTER OF ODDI DYSFUNCTION (DIFFERENTIAL DIAGNOSIS)

gastroesophageal reflux disease irritable bowel syndrome functional dyspepsia cholelithiasis cholecystitis pancreatitis due to other causes

SPHINCTER OF ODDI DYSFUNCTION (DIFFERENTIAL DIAGNOSIS)

The evaluation for alternate diagnoses may include studies such as:

transabdominal ultrasound, abdominal computed tomography, magnetic resonance cholangiopancreatography, upper endoscopy, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography (ERCP).

prior to invasive testing for SOD (sphincter of Oddi manometry (SOM)).

SPHINCTER OF ODDI DYSFUNCTION (TREATMENT)

The goal of treating patients with symptomatic sphincter of Oddi dysfunction is to eliminate pain and/or recurrent pancreatitis by improving the impaired flow of biliary and pancreatic secretions into the duodenum, which can be accomplished by an approaches that is:

pharmacologic

though calcium channel blockers and nitrates may have a role in some patients, side effects are common, and, in one series, pharmacologic therapy was ineffective in approximately 50% of patients suggestion of a trial of pharmacologic treatment; however, it is infrequently successful for long-term management. The biliary or pancreatic segment of the sphincter of Oddi can be severed using electrocautery during ERCP. improvement or elimination of pain occurred in approximately 30-90%; biliary and pancreatic sphincterotomy can also be accomplished by a transduodenal surgical approach; endoscopic therapy is less invasive, has similar outcomes.

endoscopic

surgical

ROME III CRITERIA

A. Functional esophageal disorders

A1. Functional heartburn A2. Functional chest pain of presumed esophageal origin A3. Functional dysphagia A4. Globus

ROME III CRITERIA

B. Functional gastroduodenal disorders

B1. Functional dyspepsia

B1a. Postprandial distress syndrome B1b. Epigastric pain syndrome

B2. Belching disorders

B2a. Aerophagia B2b. Unspecified excessive belching

B3. Nausea and vomiting disorders

B3a. Chronic idiopathic nausea B3b. Functional vomiting B3c. Cyclic vomiting syndrome

B4. Rumination syndrome in adults

ROME III CRITERIA

C. Functional bowel disorders

C1. Irritable bowel syndrome C2. Functional bloating C3. Functional constipation C4. Functional diarrhea C5. Unspecified functional bowel disorder

D. Functional abdominal pain syndrome E. Functional gallbladder and Sphincter of Oddi (SO) disorders
E1. Functional gallbladder disorder E2. Functional biliary SO disorder E3. Functional pancreatic SO disorder

ROME III CRITERIA

F. Functional anorectal disorders

F1. Functional fecal incontinence F2. Functional anorectal pain

F2a. Chronic proctalgia F2a1. Levator ani syndrome F2a2. Unspecified functional anorectal pain F2b. Proctalgia fugax

F3. Functional defecation disorders

F3a. Dyssynergic defecation F3b. Inadequate defecatory propulsion

ROME III CRITERIA

G. Functional disorders: neonates and toddlers

G1. Infant regurgitation G2. Infant rumination syndrome G3. Cyclic vomiting syndrome G4. Infant colic G5. Functional diarrhea G6. Infant dyschesia G7. Functional constipation

ROME III CRITERIA

H. Functional disorders: children and adolescents

H1. Vomiting and aerophagia

H1a. Adolescent rumination syndrome H1b. Cyclic vomiting syndrome H1c. Aerophagia

H2. Abdominal pain-related functional gastrointestinal disorders

H2a. Functional dyspepsia H2b. Irritable bowel syndrome H2c. Abdominal migraine H2d. Childhood functional abdominal pain H2d1. Childhood functional abdominal pain syndrome

H3. Constipation and incontinence

H3a. Functional constipation H3b. Nonretentive fecal incontinence