DYSPHAGIA, ODYNOPHAGIAHEARTBURN, AND OTHERESOPHAGEAL SYMPTOMS

Occasional esophageal complaints are common and usu-ally are not harbingers of disease . A recent survey of healthysubjects in Olmsted County, Minnesota, found that 20%,regardless of gender or age, experienced heartburn at leastweekly.' Surely every middle-aged American adult has hadone or more episodes of heartburn or chest pain and dyspha-gia when swallowing dry or very cold foods or beverages .Frequent or persistent dysphagia, odynophagia, or heartburnimmediately suggests an esophageal problem that necessi-tates investigation and treatment . Other, less specific symp-toms of possible esophageal origin include globus sensation,chest pain, belching, hiccups, rumination, and extraesopha-geal complaints such as wheezing, coughing, sore throat, andhoarseness, especially if other causes have been excluded . Inparticular, gastroesophageal reflux disease may manifest withthese "atypical" complaints and should not be missed, be-cause it is readily treatable (see Chapter 33, section onsymptoms) .

DYSPHAGIA

Dysphagia, from the Greek phagia (to eat) and dys (diffi-culty, disordered), refers to the sensation of food being hin-dered in its passage from the mouth to the stomach . Mostpatients say that food "sticks," "hangs up," or "stops" or thatthey feel that the food "just won't go down right ." Occa-sionally they complain of associated pain . Dysphagia alwaysindicates malfunction of some type in the esophagus, al-though associated psychiatric disorders can amplify thissymptom .

Dysphagia is a common symptom, present in 12% ofpatients admitted to an acute care hospital and in over50% of those in a chronic care facility . 2 An accurate, de-tailed history suggests its etiology and enables the phy-sician to correctly define the cause in 80% to 85% ofpatients.3 ° 4

Mechanisms

Several mechanisms are responsible for dysphagia . The oro-pharyngeal swallowing mechanism and the primary and sec-ondary peristaltic contractions of the esophageal body thatfollow usually transport solid and liquid boluses from themouth to the stomach within 10 seconds (see Chapter 32,section on coordinated esophageal motor activity) . If theseorderly contractions fail to develop or progress, the accumu-lated bolus of food distends the lumen and causes the dulldiscomfort that is dysphagia. Some people fail to stimulateproximal motor activity despite adequate distention of theorgan.' Others, particularly the elderly, generate low-ampli-tude primary or secondary peristaltic activity that is insuffi-cient for clearing the esophagus . 6 A third group has primaryor secondary motility disorders that grossly disturb the or-derly contractions of the esophageal body . Because thesemotor abnormalities may not be present with every swallow,dysphagia may wax and wane (see Chapter 32, sections onachalasia and spastic disorders of the esophagus) .

Mechanical narrowing of the esophageal lumen may in-terrupt the orderly passage of a food bolus despite adequateperistaltic contractions . Symptoms also vary with the degreeof luminal obstruction, associated esophagitis, and type offood ingested. Although minimally obstructing lesions causedysphagia only with large, poorly chewed solid boluses ofsuch foods as meat and dry bread, lesions that totally ob-struct the esophageal lumen are symptomatic for both solidsand liquids . Gastroesophageal ref ux disease may producedysphagia by multiple mechanisms, including the syndromeof "nonobstructive" dysphagia7 (see Chapter 33, section onsymptoms) . Difficulty swallowing in this situation usuallyresults from intermittent acid-induced motility disturbancessometimes associated with mild to moderate esophageal in-flammation. Finally, abnormal sensory perception within theesophagus may lead to dysphagia. Because some normalsubjects experience the sensation of dysphagia when the

oel E. Richter

93

DYSPHAGIA, 93 HEARTBURN (PYROSIS), 95 CHEST PAIN, 97

Mechanisms, 93 Symptom Complex, 95 Mechanisms, 98

Classification, 94 Mechanisms, 97 RESPIRATORY; EAR, NOSE, AND THROAT;

ODYNOPHAGIA, 95 GLOBUS SENSATION, 97 AND CARDIAC SYMPTOMS, 99

Mechanisms, 97

~A71Ef4TS WWiTH SYMPTOMS AND SIGNS

distal esophagus is distended by a balloon, as well as byother intraluminal stimuli, an aberration in visceral percep-tion could explain dysphagia in patients who have no defina-ble cause.' This mechanism also may apply to the amplifica-tion of symptoms in patients with spastic motility disorders,among whom the prevalence of psychiatric disorders ishigh. 9

Classification

Dysphagia is readily classified into two distinct types : oro-pharyngeal and esophageal (Table 6-1) . The former iscaused by abnormalities that affect the fine-tuned neuromus-cular mechanism of the pharynx and upper esophagealsphincter (UES) ; the latter stems from one of a variety ofdisorders that affect the esophageal body .

Oropharyngeal Dysphagia

Neuromuscular diseases that affect the hypopharynx and up-per esophagus produce a distinctive type of dysphagia . Thepatient is often unable to initiate swallowing and repeatedlyhas to attempt to swallow . A food bolus cannot be propelledsuccessfully from the hypopharyngeal area through the UESinto the esophageal body. The resulting symptom is oropha-ryngeal, or transfer, dysphagia . The patient is aware that thebolus has not left the oropharynx and specifically locates thesite of symptoms to the region of the cervical esophagus .Dysphagia within 1 second of swallowing is suggestive ofan oropharyngeal abnormality .' In this situation, a liquidbolus may enter the trachea or the nose rather than theesophagus . Some patients describe recurrent bolus impactionthat requires manual dislodgment . In severe cases, salivacannot be swallowed, and the patient drools . Coughing epi-

Table 6-1 1 Common Causes of Dysphagia

OROPHARYNGEAL

ESOPHAGEAL

NeuromuscularCerebrovascular accidentParkinson diseaseBrainstem tumorsMultiple sclerosisAmyotrophic lateral sclerosisPeripheral neuropathies (i .e .,

poliomyelitis)Mechanical ObstructionRetropharyngeal abscessZenker diverticulumCricopharyngeal barCervical osteophyteThyromegalySkeletal Muscle DisordersPolymyositisMuscular dystrophies

Myotonic dystrophyOculopharyngeal dystrophy

Myasthenia gravisMetabolic myopathiesMiscellaneousDecreased saliva

Medications, radiationSjogren syndrome

Alzheimer diseaseDepression

Mechanical ObstructionBenign stricturesWebs and rings (Schatzki)NeoplasmDiverticulaVascular anomalies

Aberrant subclavian artery (dys-phagia lusoria)

Enlarged aorta (dysphagia aortica)Motility DisordersAchalasiaSpastic motility disordersSclerodermaChagas diseaseMiscellaneousMiscellaneousDiabetesAlcoholismGastroesophageal reflux

sodes during a meal indicate a concomitant tracheobronchialaspiration. Pain is infrequent ; dysphagia predominates .

Other symptoms are less frequent and may be progres-sive, constant, or intermittent . Swallowing associated with agurgling noise may suggest the presence of Zenker diverticu-lum (see Chapter 31, section on diverticula; also Chapter 20,section on diverticula of esophagus) . Recurrent bouts of pul-monary infection may reflect spillover of food into the tra-chea from inadequate laryngeal protection . Hoarseness mayresult from recurrent laryngeal nerve dysfunction or intrinsicmuscular disease, both of which cause ineffective vocal cordmovement . Weakness of the soft palate or pharyngeal con-strictors causes dysarthria and nasal speech as well as pha-ryngonasal regurgitation . Finally, unexplained weight lossmay be the only clue to a swallowing disorder ; patientsavoid eating because of the difficulties encountered .

Esophageal Dysphagia

Various motility disorders or mechanical obstructing lesionscan cause esophageal dysphagia . Most patients complain ofdifficulty "transporting" food down the esophagus, notingthe sensation of food "hanging up" somewhere behind thesternum . If this symptom is localized to the lower part of thesternum, the lesion probably is in the distal esophagus ; how-ever, dysphagia frequently may be referred to the neck orsubsternal notch from that site in some patients .

To understand the syndrome of esophageal dysphagia, theanswers to three questions are crucial : 10 (1) What type offood causes symptoms? (2) Is the dysphagia intermittent orprogressive? and (3) Does the patient have heartburn? Onthe basis of these answers, it often is possible to distinguishthe cause of dysphagia as either a mechanical or a neuro-muscular defect and to accurately postulate the cause (Fig .6-1) .

Patients who report dysphagia with both solids and liq-uids probably have an esophageal motility disorder . Whenfood impaction develops, it frequently can be relieved byvarious maneuvers, including repeated swallowing, raisingthe arms over the head, throwing the shoulders back, andusing the Valsalva maneuver. In addition to dysphagia, mostpatients with achalasia complain of bland regurgitation ofundigested food, especially at night, and of weight loss. Incontrast, patients with spastic motility disorders commonlycomplain of chest pain and sensitivity to either hot or coldliquids . Patients with scleroderma of the esophagus usuallyhave Raynaud's phenomenon and severe heartburn . In thesepatients, mild complaints of dysphagia can be caused byeither a motility disturbance or esophageal inflammation, butsevere dysphagia nearly always signals the presence of apeptic stricture (see Chapter 32, sections on achalasia, spas-tic disorders of esophagus, and systemic diseases of esopha-gus) .

In patients who report dysphagia only after swallowingsolid foods and never with liquids alone, a mechanical ob-struction is suspected . When a luminal obstruction is ofsufficiently high grade, however, it may be associated withdysphagia for both solids and liquids . If food impactiondevelops, the patient frequently must regurgitate for relief .Episodic and nonprogressive dysphagia without weight lossis characteristic of an esophageal web or a distal esophagealring (i .e ., Schatzki ring). The first episode typically occurs

Figure 6-1 . Diagnostic algorithm for the symptomaticassessment of the patient with dysphagia . Important dif-ferentiating symptoms are included within the boxes .(Modified from Castell DO, and Donner MW . Evalua-tion of dysphagia : A careful history is crucial . Dysphagia2:65, 1987 .)

DYSPHAGIA, ODYNOPHAGIA, HEARTBt'RN, AND ONse'?p'SG 1P ;k

Intermittent

Bread/Steak

LowerEsophageal

Ring

during a hurried meal, often with alcohol. The patient notesthat the bolus of food sticks in the lower esophagus ; it oftencan be passed by drinking large quantities of liquids ; afterrelieving the obstruction, the patient can finish the mealwithout difficulty. The offending food frequently is a pieceof bread or steak, hence the description "steakhouse syn-drome."" Initially, the episode may not be repeated forweeks or months, but then the episodes recur more fre-quently. Daily dysphagia, however, is likely not caused by alower esophageal ring (see Chapter 31, section on rings andwebs) .

If solid food dysphagia is clearly progressive, the majordifferential diagnosis is peptic esophageal stricture and car-cinoma. In about 10% of patients with gastroesophageal re-flux disease, benign esophageal strictures gradually develop .Most of these patients have a long history of associatedheartburn. Weight loss seldom is noticed with benign lesionsbecause these patients have a good appetite and convert theirdiet to high-calorie soft and liquid foods to maintain weight .Patients with carcinoma differ from those with peptic stric-ture in several ways. As a group, the cancer patients areolder and present with a history of rapidly progressive dys-phagia. They typically do not have a history of heartburn or,if so, it is a symptom of the past but not the present . Mostcancer patients have anorexia and more weight loss than theseverity and duration of their dysphagia indicates (see Chap-ter 35, section on symptoms). True dysphagia may be seenin patients with pill, caustic, or viral esophagitis ; however,the predominant complaint of patients with these acuteesophageal injuries is usually odynophagia (see Chapter 23,section on caustic agents, and Chapter 34, section on infec-tions and medications) .

ODYNOPHAGIA

The second symptom specific for esophageal involvement isodynophagia-pain with swallowing . This symptom mayrange from a dull retrosternal ache on swallowing to a stab-bing pain with radiation to the back so severe that patients

Progressive

Chronic heartburnNo weight loss

Dysphagia

Difficulty initiating swallows(includes coughing, choking,

and nasal regurgit a ti on)Oropharyngeal Dysphagia

Esophageal Dysphagia

Solid food Only

Solid or liquid food

Food stops or "sticks"after swallowed

Mechanical Obstruction

Neuromuscular Disorder

Age > 50

Intermittent

Progressive

Chest PainWeight loss

Chronic Heartburn

Peptic

Carcinoma

Diffuse

Scleroderma Achalasia

Stricture

EsophagealSpasm

Bland regurgitationWeight loss

cannot eat or even swallow their own saliva . Odynophagiausually reflects a severe inflammatory process that involvesthe esophageal mucosa or, in rare instances, the esophagealmuscle. The most common causes of odynophagia includecaustic ingestion, pill-induced esophagitis, radiation injury,and infectious esophagitis (Candida, herpes, and cytomega-lovirus) (Table 6-2) . In these diseases, dysphagia also maybe present, but pain is the dominant complaint . Odynophagiais a rather infrequent complaint of patients with gastroesoph-ageal reflux disease and, when present, usually is associatedwith a severe ulcerative esophagitis . In rare cases, a nonob-structive esophageal carcinoma can produce odynophagia .

HEARTBURN (PYROSIS)

Heartburn is probably the most common gastrointestinal(GI) complaint in the Western population .' 12,13 This symp-tom reaches its maximal frequency during pregnancy, when25% of patients may have daily heartburn . 12 It is not surpris-ing, then, that most people do not consider heartburn amedical problem and seldom report it to their physicians .'They seek relief with over-the-counter antacids, accountingfor most of the $1 billion-per-year sales of these nonpre-scription drugs. In patients who take antacids daily, this maybe a dangerous habit; one study found that more than onehalf of these patients had endoscopic evidence of erosiveesophagitis . 14

Symptom Complex

Heartburn, the classic manifestation of gastroesophageal re-flux disease, is a commonly used but frequently misunder-stood word . It has many synonyms, including "indigestion,""acid regurgitation," "sour stomach," and "bitter belching ."The physician should listen for these descriptors if the pa-tient does not readily admit to the complaint of heartburn .Heartburn usually is described as a sensation of burningdiscomfort behind the breastbone. The description of "burn-

;AC TO PATIENTS WITH SYMPTOMS AND SIGNS

Table 6-2 1 Common Causes of Odyn ophagia

Caustic IngestionAcidAlkali (lye, Drano)Pill-Induced EsophagitisAntibiotics (especially doxycycline)Potassium chloride, slow releaseQuinidineIron sulfateZidovudineNSAIDsRadiation EsophagitisInfectious EsophagitisHealthy persons

Candida albicansHerpes simplex

HIV patientsFungal (Candida, histoplasmosis)Viral (herpes simplex, cytomegalovirus, HIV, Epstein-Barr virus)Mycobacteria (tuberculosis, avium-complex)Protozoan (Cryptosporidium, Pneumocystis carinii)Idiopathic ulcers

Severe Ulcerative Esophagitis Secondary to GERDEsophageal Carcinoma

NSAIDs, nonsteroidal anti-inflammatory drugs ; HIV, human immunodeficiencyvirus ; GERD, gastroesophageal reflux disease .

ing," "hot," or "acidic" sensation is typically used by pa-tients unless the discomfort of heartburn becomes so intensethat pain is experienced. In those situations, patients com-monly complain of both heartburn and pain . The burningsensation often begins inferiorly and radiates up the entireretrosternal area to the neck, occasionally to the back, andrarely into the arms . The patient usually signifies the rela-tionship with the open hand moving from the epigastrium tothe neck or throat. This should be contrasted with the sta-tionary clenched-fist gesture of the patient suffering fromcoronary chest pain . Heartburn caused by acid reflux is usu-ally relieved, albeit only transiently, by the ingestion ofantacids, baking soda, or milk .

Heartburn is predictably aggravated by multiple factors,particularly food (Table 6-3) . Thus it is most frequentlynoted within 1 hour after eating, particularly after the largestmeal of the day . Foods high in fats, sugars, chocolate, on-ions, or carminatives may aggravate heartburn by decreasinglower esophageal sphincter (LES) pressure ." Other foodscommonly associated with heartburn, including citrus prod-ucts, tomato-based foods, and spicy foods, do not affect LESpressure. They directly irritate the inflamed esophageal mu-cosa, 16 by pathogenetic mechanisms that include titratableacidity, low pH, or high osmolarity . 11 Many beverages, in-cluding citrus juices, soft drinks, coffee, and alcohol, alsocause heartburn, by a variety of mechanisms . 15 Wine drink-ers may have heartburn after hearty red wines but not afterdelicate white wines . Retiring, especially after a late meal orsnack, brings it on within 1 to 2 hours and, in contrast topeptic ulcer disease, does not awaken the person in the earlymorning. Some patients say that their heartburn is morepronounced while they lie on the right side . 18

Maneuvers that increase intra-abdominal pressure, includ-ing bending over, straining at stool, lifting heavy objects,and performing isometric exercises, may aggravate heart-burn. Running also may aggravate heartburn, whereas sta-tionary bike riding may be good exercise for those withgastroesophageal reflux disease . 19 Because nicotine lowersLES pressure and air swallowing relaxes the sphincter, ciga-rette smoking exacerbates the symptoms of reflux . 20, 21 Emo-tions such as anxiety, fear, and worry may exacerbate heart-burn, probably through the amplification of symptoms ratherthan by increase in the amount of acid reflux .l, 22 Someheartburn sufferers complain that certain drugs may initiateor exacerbate their symptoms, either by reducing LES pres-sure and peristaltic contractions (e.g ., theophylline, calciumchannel blockers) or by directly irritating the inflamedesophagus (e.g ., aspirin; see Table 6-3) .

Heartburn may be accompanied by the appearance offluid in the mouth, either a bitter acidic material or a saltyfluid. Regurgitation describes the complaint of a bitter acidic

Table 6-3 1 Aggravating Factors for Heartburn with Proposed Mechanisms

Calcium channel blockers

LES, lower esophageal sphincter ; NSAIDs, nonsteroidal anti-inflammatory drugs .

LOW LESPRESSURE

DIRECT MUCOSALIRRITANT

INCREASED INTRA-ABDOMINAL PRESSURE OTHERS

Certain foods Certain foods Bending over Supine position

Fats Citrus products Lifting Lying on right side

Sugars Tomato-based products Straining at stool Red wine

Chocolate Spicy foods Exercise Emotions

Onions CoffeeCarm i natives MedicationsCoffee AspirinAlcohol NSAIDs

Cigarettes TetracyclineMedications Quinidine

Progesterone Potassium chlorideTheophylline tabletsAnticholinergic agents Iron saltsAdrenergic agonistsAdrenergic antagonistsDiazepamMeperidineNitrates

fluid in the mouth that is common at night or when thepatient bends over. The regurgitated material comes from thestomach and is yellow or green, which suggests the presenceof bile. It is important to distinguish regurgitation from vom-iting, which is the primary complaint of some patients. Theabsence of nausea, retching, and abdominal contractions sug-gests regurgitation rather than vomiting . Furthermore, theregurgitation of bland material is atypical for acid refluxdisease and suggests the presence of an esophageal motilitydisorder (i .e ., achalasia) or delayed gastric emptying . In onestudy, the researchers found that the presence of heartburnand acid regurgitation together as dominant complaints had asensitivity of 78% and a specificity of 60% for the presenceof gastroesophageal reflux disease, as defined by prolongedesophageal pH monitoring. 23 Water brash is an uncommonand frequently misunderstood symptom that should be usedto describe the sudden filling of the mouth with clear,slightly salty fluid . This fluid is not regurgitated material butrather secretions from the salivary glands as part of a protec-tive, vagally mediated reflex from the distal esophagus .24

Mechanisms

The physiologic mechanisms that produce heartburn are, sur-prisingly, poorly understood . Although the reflux of gastricacid is most commonly associated with heartburn, the samesymptom may be elicited by esophageal balloon distention,25reflux of bile salts '26 and acid-induced motility distur-bances . 27 The best evidence that the pain mechanism isprobably related to the stimulation of mucosal chemorecep-tors is the sensitivity of the esophagus to the presence ofacid during its perfusion or by monitoring pH. The locationof these receptors is not known and probably is not superfi-cial because topical anesthetics fail to alter the pain re-sponse . 2 R

The correlation of discrete episodes of acid reflux andsymptoms, however, is poor . For example, postprandial gas-troesophageal reflux is common in healthy people, but symp-toms are rare . Intraesophageal pH monitoring of patientswith endoscopic evidence of esophagitis typically shows ex-cessive periods of acid reflux, but fewer than 20% of thesereflux episodes are accompanied by complaints . 29 Moreover,one third of patients with Barrett esophagus, the most ex-treme form of gastroesophageal reflux disease, are acid in-sensitive .30 Therefore, symptoms must require more thanesophageal contact with acid . Mucosal disruption with in-flammation may be a contributory factor, but on endoscopy,the esophagus appears normal in most symptomatic patients .The histologic appearance of the mucosa obtained by biopsyshows that some of these patients have polymorphonuclearleukocytes, others have only reparative changes, and manyhave a normal esophagus . Results of one study suggest thathydrogen ion concentration could be crucial in symptomproduction. 31 One group found that all 25 patients with re-flux disease experienced heartburn during intraesophageal in-fusion of solutions having pH values of 1 .0 and 1 .5, butonly one half had heartburn with solutions having pH valuesof 2.5 to 6 .0. Other factors that possibly influence the reportof heartburn include the acid clearance mechanism ; salivarybicarbonate concentration ; volume of refluxed acid, as mea-sured by duration and proximal extent of reflux episodes ;

DYSPHAGIA, ODYNOPHAGIA, .HEAKTRURN, AND OTHEN ESOPMA(s6r4 L . . :;Y,ymh

frequency of the heartburn complaints ; and interaction ofpepsin with acid (see Chapter 33, section on pathogenesis ofgastroesophageal reflux disease) .24, 32

GLOBUS SENSATION

Globus sensation is a feeling of a lump or tightness in thethroat, unrelated to swallowing . Up to 46% of the generalpopulation have experienced the globus sensation at onetime or another." This particular sensation accounts for 3%of consultations to throat specialists, 33 predominantly bymiddle-aged women. The sensation can be described as a"lump," "tightness," "choking," or "strangling" feeling as ifsomething is caught in the throat. The globus sensation ispresent between meals, and swallowing of solids or largeliquid boluses may give temporary relief. Dysphagia andodynophagia are not present . Frequent dry swallowing andemotional stress may worsen the globus sensation .

Mechanisms

Evidence for physiologic and psychologic abnormalities inpatients with the globus sensation has been inconsistent andcontroversial . Although frequently suggested, UES dysfunc-tion has not been directly identified as the cause of theglobus sensation . Modern manometric studies have consist-ently shown the UES to be functioning normally, 34 and thesphincter does not appear to be hyper-responsive to esopha-geal distention, acidification, or mental stress .14, 35 Further-more, esophageal distention can cause a globus sensationunrelated to the degree of rise in UES pressure," and stress-induced increases in UES pressure are not associated with aglobus sensation in normal subjects or in patients complain-ing of this symptom . 34 Heartburn has been reported in up to90% of patients with the globus sensation . 36 Documentationof esophagitis or abnormal gastroesophageal reflux by esoph-ageal pH monitoring, however, is found in fewer than 25%of patients . 37 Balloon distention of the esophagus producesthe globus sensation at lower balloon volumes in globussufferers than in controls, which suggests that the perceptionof esophageal stretch may be heightened in these patients . 35

Psychological factors may be important in the genesis ofthe globus sensation . The most commonly found psychiatricdiagnoses include anxiety, panic disorder, depression, hypo-chondriasis, somatization, and introversion . 38 Indeed, globusis the fourth most common symptom of patients with soma-tization disorders .39 A combination of biologic factors, hypo-chondriacal traits, and learned fear after a choking episodeprovides a framework for misinterpretation of the symptomsand intensifies the globus symptoms or the patient's anxi-ety . 40

CHEST PAIN (Table 6-4)

Recurrent chest pain of esophageal origin that mimics an-gina pectoris is not surprising, in view of the proximity ofthe two organs and their shared neural pathways . Esophagealdisorders are probably the most common causes of noncar-diac chest pain . Of the approximately 500,000 patients who

Table 6-4 1 Characteristics of Cardiac and Esophageal Chest Pain*

PATtENIS Wlft3 SYMPTOMS AND SI NS

*Questionnaire results from 70 patients admitted to emergency departments with anterior chest pain of cardiac or esophageal origin .tTotal N = 52 .tTotal N = 18 .§Differences between groups significant (P < .05) .Modified from Davies HA, )ones DB, Rhodes J, Newcombe RG : Angina-like esophageal pain : Differentiation from cardiac pain by history . J Clin Gastroenterol 7 :477,

1985 .

undergo coronary angiography yearly for presumed cardiacpain, nearly 30% have normal epicardial coronary arteries ;of those patients, 18% to 56% may have esophageal diseasesthat account for the symptoms . 41

Intermittent anterior chest discomfort is the sine qua nonof this syndrome. Chest pain usually is described as asqueezing or burning sensation, substernal, and radiating tothe back, neck, jaw, or arms, at times indistinguishable fromangina pain . Although it is not always related to swallowing,it can be triggered by ingestion of either very hot or verycold liquids . It frequently awakens the patient from sleepand may worsen during periods of emotional stress . Theduration ranges from minutes to hours and may be intermit-tent over several days . Although the pain can be severe,causing the patient to become ashen and perspire, it oftenabates spontaneously and may be eased with antacids . Occa-sionally, its severity requires narcotics or nitroglycerin forrelief. Close questioning reveals that most patients with thispain have other esophageal symptoms ; however, chest painis the only esophageal complaint in about 10% .41

The clinical history often does not enable the physician todistinguish between cardiac and esophageal causes of chestpain. For example, gastroesophageal reflux may be triggeredby exercise 19 and cause exertional chest pain that mimicsangina pectoris, even during treadmill testing . 43 Symptomssuggestive of esophageal origin include pain that continuesfor hours, retrosternal pain without lateral radiation, pain thatinterrupts sleep or is meal related, and pain that is relievedwith antacid agents. The presence of other esophageal symp-toms also helps in the establishment of the differential diag-nosis (see Table 6-4) . A serious complicating factor indiagnosis is that as many as 50% of patients with cardiacpain have one or more symptoms of esophageal pain .44 Thisoverlap exists because the prevalence of both cardiac andesophageal diseases-especially gastroesophageal reflux dis-ease-increases as people grow older . Both problems notonly may coexist but also may interact in producing chestpain .

Mechanisms

The specific mechanisms that produce esophageal chest painare not well understood . Chest pain that arises from theesophagus has commonly been attributed to the stimulationof chemoreceptors (acid, pepsin, bile) or mechanoreceptors(distention, spasm), although thermoreceptors (cold) alsomay be involved .

Gastroesophageal reflux causes chest pain primarilythrough acid-sensitive esophageal chemoreceptors, as dis-cussed earlier in the section "Heartburn (Pyrosis) ." Acid-induced dysmotility was once believed to be a major causeof esophageal pain . Early studies of acid perfusion in pa-tients with reflux demonstrated increased esophageal contrac-tion amplitude and duration, as well as simultaneous andspontaneous contractions, while pain was produced . 45 Morerecently, other investigators have not been able to reproducethese observations 4 6 Although diffuse esophageal spasm hasbeen reported during spontaneous acid reflux in some pa-tients, studies with modern equipment show that these motil-ity changes are infrequent during acid infusion .46 In addition,24-hour ambulatory esophageal pH and motility monitor-ing47 ' 48 has shown that spontaneous acid-induced chest painis associated with esophageal motility abnormalities in fewerthan 15% of patients with such discomfort.

Many patients with suspected esophageal chest pain haveesophageal motility disorders characterized by high-ampli-tude contractions of prolonged duration or frequent simulta-neous contractions . 49 One popular hypothesis is that theseabnormal waveforms cause pain as high intramural esopha-geal tension inhibits blood flow for a critical period of time(i .e ., myoischemia). Experimental studies by MacKenzie andcoworkers lend support to this hypothesis . 50 They found de-creased esophageal rewarming rates after cold water infu-sions in patients with symptomatic esophageal motility disor-ders in comparison with age-matched controls. Becausesimilar studies in patients with Raynaud phenomenon aredirectly correlated with blood flow, the authors theorized

CARDIACt ESOPHAGEAL*

CHARACTERISTICS DESCRIPTION N % N %

Quality Tight, heavy 48 92 15 83Location Retrosternal 51 98 18 100Radiation To left arm 28 38 6 33Duration Several hours 13 25 14 78§

Wakens patient at night 13 25 11 61 §Provocation Emotions 15 29 7 39

Meals 3 6 7 39§Recumbency 10 19 11 61 §Exercise 38 73 7 39

Relief Antacids 5 10 8 44§Nitroglycerin 14 27 7 39

Associated gastrointestinal symptoms 24 46 15 83§

that esophageal ischemia was the cause of the delayed re-warming rate . None of these patients, however, developedchest pain during the study . Furthermore, the extensive arte-rial and venous blood supply to the esophagus suggests thatcompromised blood flow is unlikely after even the mostabnormal esophageal contractions . 51

Complicating the relation between esophageal chest painand abnormal esophageal contractions is the consistent ob-servation that most of these patients are asymptomatic whenthe contraction abnormalities are identified .41 These esopha-geal motility disorders possibly are markers for more severeesophageal disturbances during chest pain. However, the re-sults of prolonged ambulatory esophageal motility studiesconfirm that this relationship is infrequent . 47, 48 In addition,amelioration of chest pain does not predictably correlatewith reduction of amplitude by either pharmacotherapy 52 orsurgical myotomy . 53 Results of more recent studies suggestthat the motility changes may represent an epiphenomenonof a chronic pain syndrome rather than the direct cause ofthe complaints .41, 48

Other potential causes of esophageal chest pain includethe excitation of temperature receptors and luminal disten-tion . The ingestion of hot or cold liquids can produce severechest pain . It was previously believed that this was related toesophageal spasm, but studies have shown that cold-inducedpain produces esophageal aperistalsis and dilatation, whichsuggests that the cause of esophageal chest pain may beactivation of stretch receptors by acute distention .54 Suchdistention and pain are experienced with acute food impac-tion, the drinking of carbonated beverages (in some pa-tients), and dysfunction of the belch reflex . 55 Another possi-bility is that chest pain is caused by proximal distention ofthe esophagus by abnormal distal contractions or by im-paired LES functioning and emptying .56 In addition, esopha-geal chest pain in susceptible patients can be reproducedwith smaller volumes of esophageal balloon distention thanthe volumes that produce pain in asymptomatic patients .57Thus, altered pain perception may contribute to these pa-tients' reactions to pain stimuli . Anxiolytics and antidepres-sants can raise pain thresholds as well as improve moodstates. This may explain the mechanism by which thesemedications improve esophageal chest pain in the absence ofmanometric changes .58,59

RESPIRATORY; EAR, NOSE, ANDTHROAT; AND CARDIAC SYMPTOMS

Extraesophageal symptoms of esophageal diseases are sum-marized in Table 6-5. Although these symptoms may becaused by esophageal motility disorders, they are most fre-quently associated with gastroesophageal reflux disease .However, the classic reflux symptoms of heartburn and re-gurgitation often are mild or absent .

The mechanism by which gastroesophageal reflux cancause chronic cough and other extraesophageal symptoms isprobably twofold : (1) by intermittent recurrent microaspira-tion of gastric contents and (2) by a vagally mediated neuralreflex. In animal studies, the instillation of small amounts ofacid in the trachea60 or on the vocal cords 61 can producemarked changes in airway resistance as well as vocal cord

DYSPHAGIA, OD,',()PI IA-IA, HFatTB, Rf AN`I) 0'F)',1 ,ERr .E9O pj s'~

Table 6-5 I Extraesophageal Symptoms of EsophagealDiseases

ulcers. Direct evidence for aspiration is more difficult toidentify in adults, resting primarily on the presence of fat-filled macrophages in sputum, 62 radioactivity in the lungsafter the tracer is placed in the stomach overnight, 63 andhigh esophageal or hypopharyngeal acid reflux recorded by24-hour pH monitoring with dual probes .64, 65 There is betterevidence from both animal and human studies that a neuralreflex is the pathophysiologic basis for these symptoms .Acid perfusion into the distal esophagus increases airwayresistance in all subjects, but the changes are most markedin patients with asthma and heartburn .66 Dogs do not pro-duce this response after bilateral vagotomy 67 ; nor do humansafter atropine . 66 These findings suggest bronchial constrictionthat is vagally mediated .

Abnormal amounts of acid reflux recorded by prolongedesophageal pH monitoring have been identified in 35% to80% of asthmatic adults . 68 Symptoms that suggest reflux-induced asthma include the onset of wheezing at a late agewithout a history of allergies or asthma ; nocturnal cough orwheezing; asthma worsened after meals, exercise, or the su-pine position ; and asthma that is exacerbated by broncho-dilators or that is steroid dependent . Patients who experiencereflux with symptoms strongly suggestive of aspiration usu-ally have nocturnal cough and heartburn, recurrent pneu-monias, unexplained fevers, and associated esophagealmotility disorders . 69 Ear, nose, and throat complaints associ-ated with gastroesophageal reflux include postnasal drip,voice changes, hoarseness, sore throat, persistent cough, otal-gia, halitosis, dental erosion, and excessive salivation 70' 71Up to 25% of patients with gastroesophageal reflux diseasecomplain of only head and neck symptoms . 72 Examinationof the vocal cords may help in suspected acid-related prob-lems . Some patients have redness, hyperemia, and edema ofthe vocal cords and arytenoids . In more severe cases, vocalcord ulcers, granulomas, and even laryngeal cancer, all sec-ondary to gastroesophageal reflux disease, have been re-ported. Normal results of a laryngeal examination, however,are not incompatible with acid reflux-related extraesophagealsymptoms .70 Further evidence for the connection betweenesophageal stimulation and vagal reflexes can be fours"the syndrome of "swallow syncope." In this di"'lowing or pharyngeal esophageal stimu,'profound, even lethal bradycardia, presumtgal mechanism .71

RESPIRATORY EAR, NOSE, AND THROAT CARDIAC

Wheezing Chronic sore throat SyncopeBronchitis HoarsenessAspiration Burning sensation in tongueHemoptysis HalitosisApnea Otalgia

Cervical painGlobus sensationChronic coughStridorLateral neck painDental erosion