DYSPHAGIA ODYNOPHAGIA HEARTBURN AND OTHER ESOPHAGEAL SYMPTOMS

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					    DYSPHAGIA, ODYNOPHAGIA
       HEARTBURN, AND OTHER
        ESOPHAGEAL SYMPTOMS
                                                                                  oel E. Richter



DYSPHAGIA, 93                                HEARTBURN (PYROSIS), 95                       CHEST PAIN, 97
Mechanisms, 93                                Symptom Complex, 95                           Mechanisms, 98
Classification, 94                            Mechanisms, 97                               RESPIRATORY ; EAR, NOSE, AND THROAT;
                                             GLOBUS SENSATION, 97                          AND CARDIAC SYMPTOMS, 99
ODYNOPHAGIA, 95
                                              Mechanisms, 97




O    ccasional esophageal complaints are common and usu-
ally are not harbingers of disease . A recent survey of healthy
                                                                    Mechanisms

subjects in Olmsted County, Minnesota, found that 20%,              Several mechanisms are responsible for dysphagia . The oro-
regardless of gender or age, experienced heartburn at least         pharyngeal swallowing mechanism and the primary and sec-
weekly .' Surely every middle-aged American adult has had           ondary peristaltic contractions of the esophageal body that
one or more episodes of heartburn or chest pain and dyspha-         follow usually transport solid and liquid boluses from the
gia when swallowing dry or very cold foods or beverages .           mouth to the stomach within 10 seconds (see Chapter 32,
Frequent or persistent dysphagia, odynophagia, or heartburn         section on coordinated esophageal motor activity) . If these
immediately suggests an esophageal problem that necessi-            orderly contractions fail to develop or progress, the accumu-
tates investigation and treatment . Other, less specific symp-      lated bolus of food distends the lumen and causes the dull
toms of possible esophageal origin include globus sensation,        discomfort that is dysphagia . Some people fail to stimulate
chest pain, belching, hiccups, rumination, and extraesopha-         proximal motor activity despite adequate distention of the
geal complaints such as wheezing, coughing, sore throat, and        organ.' Others, particularly the elderly, generate low-ampli-
hoarseness, especially if other causes have been excluded . In      tude primary or secondary peristaltic activity that is insuffi-
particular, gastroesophageal reflux disease may manifest with       cient for clearing the esophagus . 6 A third group has primary
these "atypical" complaints and should not be missed, be-           or secondary motility disorders that grossly disturb the or-
cause it is readily treatable (see Chapter 33, section on           derly contractions of the esophageal body . Because these
symptoms) .                                                         motor abnormalities may not be present with every swallow,
                                                                    dysphagia may wax and wane (see Chapter 32, sections on
                                                                    achalasia and spastic disorders of the esophagus) .
DYSPHAGIA                                                              Mechanical narrowing of the esophageal lumen may in-
                                                                    terrupt the orderly passage of a food bolus despite adequate
Dysphagia, from the Greek phagia (to eat) and dys (diffi-           peristaltic contractions . Symptoms also vary with the degree
culty, disordered), refers to the sensation of food being hin-      of luminal obstruction, associated esophagitis, and type of
dered in its passage from the mouth to the stomach . Most           food ingested . Although minimally obstructing lesions cause
patients say that food "sticks," "hangs up," or "stops" or that     dysphagia only with large, poorly chewed solid boluses of
they feel that the food "just won't go down right ." Occa-          such foods as meat and dry bread, lesions that totally ob-
sionally they complain of associated pain . Dysphagia always        struct the esophageal lumen are symptomatic for both solids
indicates malfunction of some type in the esophagus, al-            and liquids . Gastroesophageal ref ux disease may produce
though associated psychiatric disorders can amplify this            dysphagia by multiple mechanisms, including the syndrome
symptom .                                                           of "nonobstructive" dysphagia 7 (see Chapter 33, section on
    Dysphagia is a common symptom, present in 12% of                symptoms) . Difficulty swallowing in this situation usually
patients admitted to an acute care hospital and in over             results from intermittent acid-induced motility disturbances
 50% of those in a chronic care facility . 2 An accurate, de-       sometimes associated with mild to moderate esophageal in-
 tailed history suggests its etiology and enables the phy-          flammation. Finally, abnormal sensory perception within the
 sician to correctly define the cause in 80% to 85% of              esophagus may lead to dysphagia. Because some normal
 patients.3 4
           °
                                                                    subjects experience the sensation of dysphagia when the
                                                                                                                                93
	




                              ~A71Ef4TS WWiTH   SYMPTOMS AND SIGNS

distal esophagus is distended by a balloon, as well as by                    sodes during a meal indicate a concomitant tracheobronchial
other intraluminal stimuli, an aberration in visceral percep-                aspiration. Pain is infrequent ; dysphagia predominates .
tion could explain dysphagia in patients who have no defina-                    Other symptoms are less frequent and may be progres-
ble cause .' This mechanism also may apply to the amplifica-                 sive, constant, or intermittent . Swallowing associated with a
tion of symptoms in patients with spastic motility disorders,                gurgling noise may suggest the presence of Zenker diverticu-
among whom the prevalence of psychiatric disorders is                        lum (see Chapter 31, section on diverticula ; also Chapter 20,
high. 9                                                                      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 may
Classification
                                                                             result from recurrent laryngeal nerve dysfunction or intrinsic
                                                                             muscular disease, both of which cause ineffective vocal cord
Dysphagia is readily classified into two distinct types : oro-
                                                                             movement . Weakness of the soft palate or pharyngeal con-
pharyngeal and esophageal (Table 6-1) . The former is
                                                                             strictors causes dysarthria and nasal speech as well as pha-
caused by abnormalities that affect the fine-tuned neuromus-
                                                                             ryngonasal regurgitation . Finally, unexplained weight loss
cular mechanism of the pharynx and upper esophageal
                                                                             may be the only clue to a swallowing disorder ; patients
sphincter (UES) ; the latter stems from one of a variety of
                                                                             avoid eating because of the difficulties encountered .
disorders that affect the esophageal body .

Oropharyngeal Dysphagia                                                      Esophageal Dysphagia

Neuromuscular diseases that affect the hypopharynx and up-                   Various motility disorders or mechanical obstructing lesions
per esophagus produce a distinctive type of dysphagia . The                  can cause esophageal dysphagia . Most patients complain of
patient is often unable to initiate swallowing and repeatedly                difficulty "transporting" food down the esophagus, noting
has to attempt to swallow . A food bolus cannot be propelled                 the sensation of food "hanging up" somewhere behind the
successfully from the hypopharyngeal area through the UES                    sternum . If this symptom is localized to the lower part of the
into the esophageal body. The resulting symptom is oropha-                   sternum, the lesion probably is in the distal esophagus ; how-
ryngeal, or transfer, dysphagia . The patient is aware that the              ever, dysphagia frequently may be referred to the neck or
bolus has not left the oropharynx and specifically locates the               substernal notch from that site in some patients .
site of symptoms to the region of the cervical esophagus .                      To understand the syndrome of esophageal dysphagia, the
Dysphagia within 1 second of swallowing is suggestive of                     answers to three questions are crucial : 10 (1) What type of
an oropharyngeal abnormality .' In this situation, a liquid                  food causes symptoms? (2) Is the dysphagia intermittent or
bolus may enter the trachea or the nose rather than the                      progressive? and (3) Does the patient have heartburn? On
esophagus . Some patients describe recurrent bolus impaction                 the basis of these answers, it often is possible to distinguish
that requires manual dislodgment . In severe cases, saliva                   the cause of dysphagia as either a mechanical or a neuro-
cannot be swallowed, and the patient drools . Coughing epi-                  muscular defect and to accurately postulate the cause (Fig .
                                                                             6-1) .
                                                                                Patients who report dysphagia with both solids and liq-
Table 6-1 1 Common Causes of Dysphagia                                       uids probably have an esophageal motility disorder . When
                                                                             food impaction develops, it frequently can be relieved by
    OROPHARYNGEAL                               ESOPHAGEAL
                                                                             various maneuvers, including repeated swallowing, raising
Neuromuscular                        Mechanical Obstruction                  the arms over the head, throwing the shoulders back, and
Cerebrovascular accident             Benign strictures                       using the Valsalva maneuver. In addition to dysphagia, most
Parkinson disease                    Webs and rings (Schatzki)               patients with achalasia complain of bland regurgitation of
Brainstem tumors                     Neoplasm
                                                                             undigested food, especially at night, and of weight loss . In
Multiple sclerosis                   Diverticula
Amyotrophic lateral sclerosis        Vascular anomalies                      contrast, patients with spastic motility disorders commonly
Peripheral neuropathies (i .e .,       Aberrant subclavian artery (dys-      complain of chest pain and sensitivity to either hot or cold
  poliomyelitis)                          phagia lusoria)                    liquids . Patients with scleroderma of the esophagus usually
Mechanical Obstruction                  Enlarged aorta (dysphagia aortica)   have Raynaud's phenomenon and severe heartburn . In these
Retropharyngeal abscess              Motility Disorders
Zenker diverticulum                  Achalasia                               patients, mild complaints of dysphagia can be caused by
Cricopharyngeal bar                  Spastic motility disorders              either a motility disturbance or esophageal inflammation, but
Cervical osteophyte                  Scleroderma                             severe dysphagia nearly always signals the presence of a
Thyromegaly                          Chagas disease                          peptic stricture (see Chapter 32, sections on achalasia, spas-
Skeletal Muscle Disorders            Miscellaneous
                                                                             tic disorders of esophagus, and systemic diseases of esopha-
Polymyositis                         Miscellaneous
Muscular dystrophies                 Diabetes                                gus) .
  Myotonic dystrophy                 Alcoholism                                 In patients who report dysphagia only after swallowing
  Oculopharyngeal dystrophy          Gastroesophageal reflux                 solid foods and never with liquids alone, a mechanical ob-
Myasthenia gravis                                                            struction is suspected . When a luminal obstruction is of
Metabolic myopathies
Miscellaneous
                                                                             sufficiently high grade, however, it may be associated with
Decreased saliva                                                             dysphagia for both solids and liquids . If food impaction
  Medications, radiation                                                     develops, the patient frequently must regurgitate for relief .
  Sjogren syndrome                                                           Episodic and nonprogressive dysphagia without weight loss
Alzheimer disease
                                                                             is characteristic of an esophageal web or a distal esophageal
Depression
                                                                             ring (i .e ., Schatzki ring). The first episode typically occurs
	




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



                                                                                                             Dysphagia
                                                                       Difficulty initiating swallows                          Food stops or "sticks"
                                                                       (includes coughing, choking,                                after swallowed
                                                                          and nasal regurgit a ti on)
                                                                          Oropharyngeal Dysphagia                                 Esophageal Dysphagia




                                                                                 Solid food Only                                     Solid or liquid food
Figure 6-1 . Diagnostic algorithm for the symptomatic
assessment of the patient with dysphagia . Important dif-                    Mechanical Obstruction                               Neuromuscular Disorder
ferentiating symptoms are included within the boxes .
(Modified from Castell DO, and Donner MW . Evalua-                                                                                                          Progressive
                                                                  Intermittent                       Progressive      Intermittent
tion of dysphagia : A careful history is crucial . Dysphagia
2 :65, 1987 .)
                                                                                     Chronic heartburn                               Chronic Heartburn
                                                                                       No weight loss

                                                                                                         Age > 50     Chest Pain                   Bland regurgitation
                                                                  Bread/Steak
                                                                                                        Weight loss                                     Weight loss



                                                                    Lower                 Peptic        Carcinoma       Diffuse           Scleroderma    Achalasia
                                                                  Esophageal             Stricture                    Esophageal
                                                                      Ring                                              Spasm




during a hurried meal, often with alcohol . The patient notes                       cannot eat or even swallow their own saliva . Odynophagia
that the bolus of food sticks in the lower esophagus ; it often                     usually reflects a severe inflammatory process that involves
can be passed by drinking large quantities of liquids ; after                       the esophageal mucosa or, in rare instances, the esophageal
relieving the obstruction, the patient can finish the meal                          muscle . The most common causes of odynophagia include
without difficulty . The offending food frequently is a piece                       caustic ingestion, pill-induced esophagitis, radiation injury,
of bread or steak, hence the description "steakhouse syn-                           and infectious esophagitis (Candida, herpes, and cytomega-
drome ."" Initially, the episode may not be repeated for                            lovirus) (Table 6-2) . In these diseases, dysphagia also may
weeks or months, but then the episodes recur more fre-                              be present, but pain is the dominant complaint . Odynophagia
quently . Daily dysphagia, however, is likely not caused by a                       is a rather infrequent complaint of patients with gastroesoph-
lower esophageal ring (see Chapter 31, section on rings and                         ageal reflux disease and, when present, usually is associated
webs) .                                                                             with a severe ulcerative esophagitis . In rare cases, a nonob-
    If solid food dysphagia is clearly progressive, the major                       structive esophageal carcinoma can produce odynophagia .
differential diagnosis is peptic esophageal stricture and car-
cinoma. In about 10% of patients with gastroesophageal re-
flux disease, benign esophageal strictures gradually develop .                      HEARTBURN (PYROSIS)
Most of these patients have a long history of associated
heartburn . Weight loss seldom is noticed with benign lesions                       Heartburn is probably the most common gastrointestinal
because these patients have a good appetite and convert their                       (GI) complaint in the Western population .' 12,13 This symp-
diet to high-calorie soft and liquid foods to maintain weight .                     tom reaches its maximal frequency during pregnancy, when
Patients with carcinoma differ from those with peptic stric-                        25% of patients may have daily heartburn . 12 It is not surpris-
ture in several ways . As a group, the cancer patients are                          ing, then, that most people do not consider heartburn a
older and present with a history of rapidly progressive dys-                        medical problem and seldom report it to their physicians .'
phagia . They typically do not have a history of heartburn or,                      They seek relief with over-the-counter antacids, accounting
if so, it is a symptom of the past but not the present . Most                       for most of the $1 billion-per-year sales of these nonpre-
cancer patients have anorexia and more weight loss than the                         scription drugs . In patients who take antacids daily, this may
severity and duration of their dysphagia indicates (see Chap-                       be a dangerous habit ; one study found that more than one
ter 35, section on symptoms) . True dysphagia may be seen                           half of these patients had endoscopic evidence of erosive
in patients with pill, caustic, or viral esophagitis ; however,                     esophagitis . 14
the predominant complaint of patients with these acute
 esophageal injuries is usually odynophagia (see Chapter 23,
 section on caustic agents, and Chapter 34, section on infec-                       Symptom Complex
 tions and medications) .
                                                                                    Heartburn, the classic manifestation of gastroesophageal re-
                                                                                    flux disease, is a commonly used but frequently misunder-
ODYNOPHAGIA                                                                         stood word . It has many synonyms, including "indigestion,"
                                                                                    "acid regurgitation," "sour stomach," and "bitter belching ."
The second symptom specific for esophageal involvement is                           The physician should listen for these descriptors if the pa-
odynophagia-pain with swallowing . This symptom may                                 tient does not readily admit to the complaint of heartburn .
range from a dull retrosternal ache on swallowing to a stab-                        Heartburn usually is described as a sensation of burning
bing pain with radiation to the back so severe that patients                        discomfort behind the breastbone . The description of "burn-
                   ;AC   TO PATIENTS WITH SYMPTOMS AND SIGNS


Table 6-2 1 Common Causes of Odyn op hagia                                                 Heartburn is predictably aggravated by multiple factors,
                                                                                        particularly food (Table 6-3) . Thus it is most frequently
   Caustic Ingestion                                                                    noted within 1 hour after eating, particularly after the largest
   Acid
                                                                                        meal of the day . Foods high in fats, sugars, chocolate, on-
   Alkali (lye, Drano)
   Pill-Induced Esophagitis
                                                                                        ions, or carminatives may aggravate heartburn by decreasing
   Antibiotics (especially doxycycline)                                                 lower esophageal sphincter (LES) pressure ." Other foods
   Potassium chloride, slow release                                                     commonly associated with heartburn, including citrus prod-
   Quinidine                                                                            ucts, tomato-based foods, and spicy foods, do not affect LES
   Iron sulfate
   Zidovudine
                                                                                        pressure . They directly irritate the inflamed esophageal mu-
   NSAIDs                                                                               cosa, 16 by pathogenetic mechanisms that include titratable
   Radiation Esophagitis                                                                acidity, low pH, or high osmolarity . 11 Many beverages, in-
    Infectious Esophagitis                                                              cluding citrus juices, soft drinks, coffee, and alcohol, also
    Healthy persons
                                                                                        cause heartburn, by a variety of mechanisms . 15 Wine drink-
      Candida albicans
      Herpes simplex                                                                     ers may have heartburn after hearty red wines but not after
    HIV patients                                                                         delicate white wines . Retiring, especially after a late meal or
      Fungal (Candida, histoplasmosis)                                                   snack, brings it on within 1 to 2 hours and, in contrast to
      Viral (herpes simplex, cytomegalovirus, HIV, Epstein-Barr virus)
                                                                                         peptic ulcer disease, does not awaken the person in the early
      Mycobacteria (tuberculosis, avium-complex)
      Protozoan (Cryptosporidium, Pneumocystis carinii)
                                                                                         morning . Some patients say that their heartburn is more
      Idiopathic ulcers                                                                  pronounced while they lie on the right side . 18
    Severe Ulcerative Esophagitis Secondary to GERD                                         Maneuvers that increase intra-abdominal pressure, includ-
    Esophageal Carcinoma                                                                 ing bending over, straining at stool, lifting heavy objects,
     NSAIDs, nonsteroidal anti-inflammatory drugs ; HIV, human immunodeficiency
                                                                                         and performing isometric exercises, may aggravate heart-
virus ; GERD, gastroesophageal reflux disease .                                          burn . Running also may aggravate heartburn, whereas sta-
                                                                                         tionary bike riding may be good exercise for those with
                                                                                         gastroesophageal reflux disease . 19 Because nicotine lowers
                                                                                         LES pressure and air swallowing relaxes the sphincter, ciga-
ing," "hot," or "acidic" sensation is typically used by pa-
tients unless the discomfort of heartburn becomes so intense                             rette smoking exacerbates the symptoms of reflux . 20, 21 Emo-
that pain is experienced . In those situations, patients com-                            tions such as anxiety, fear, and worry may exacerbate heart-
monly complain of both heartburn and pain . The burning                                  burn, probably through the amplification of symptoms rather
sensation often begins inferiorly and radiates up the entire                             than by increase in the amount of acid reflux .l, 22 Some
retrosternal area to the neck, occasionally to the back, and                             heartburn sufferers complain that certain drugs may initiate
rarely into the arms . The patient usually signifies the rela-                           or exacerbate their symptoms, either by reducing LES pres-
tionship with the open hand moving from the epigastrium to                               sure and peristaltic contractions (e.g ., theophylline, calcium
the neck or throat . This should be contrasted with the sta-                             channel blockers) or by directly irritating the inflamed
tionary clenched-fist gesture of the patient suffering from                              esophagus (e .g ., aspirin ; see Table 6-3) .
 coronary chest pain . Heartburn caused by acid reflux is usu-                              Heartburn may be accompanied by the appearance of
 ally relieved, albeit only transiently, by the ingestion of                             fluid in the mouth, either a bitter acidic material or a salty
 antacids, baking soda, or milk .                                                        fluid. Regurgitation describes the complaint of a bitter acidic



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

                      LOW LES                            DIRECT MUCOSAL                        INCREASED INTRA-
                      PRESSURE                               IRRITANT                        ABDOMINAL PRESSURE                    OTHERS


                                                       Certain foods                               Bending over                Supine position
            Certain foods
                                                          Citrus products                          Lifting                     Lying on right side
              Fats
                                                          Tomato-based products                    Straining at stool          Red wine
              Sugars
                                                          Spicy foods                              Exercise                    Emotions
              Chocolate
              Onions                                      Coffee
              Carm i natives                           Medications
              Coffee                                      Aspirin
              Alcohol                                     NSAIDs
            Cigarettes                                    Tetracycline
            Medications                                   Quinidine
               Progesterone                               Potassium chloride
               Theophylline                                 tablets
               Anticholinergic agents                     Iron salts
               Adrenergic agonists
               Adrenergic antagonists
               Diazepam
               Meperidine
               Nitrates
               Calcium channel blockers

     LES, lower esophageal sphincter ; NSAIDs, nonsteroidal anti-inflammatory drugs .
                                                      DYSPHAGIA, ODYNOPHAGIA, .HEAKTRURN,   AND OTHEN ESOPMA(s6r4 L . . : Y,ymh
                                                                                                                        ;



fluid in the mouth that is common at night or when the               frequency of the heartburn complaints ; and interaction of
patient bends over . The regurgitated material comes from the        pepsin with acid (see Chapter 33, section on pathogenesis of
stomach and is yellow or green, which suggests the presence          gastroesophageal reflux disease)    .24, 32



of bile . It is important to distinguish regurgitation from vom-
iting, which is the primary complaint of some patients . The
absence of nausea, retching, and abdominal contractions sug-         GLOBUS SENSATION
gests regurgitation rather than vomiting . Furthermore, the
regurgitation of bland material is atypical for acid reflux          Globus sensation is a feeling of a lump or tightness in the
disease and suggests the presence of an esophageal motility          throat, unrelated to swallowing . Up to 46% of the general
disorder (i .e ., achalasia) or delayed gastric emptying . In one    population have experienced the globus sensation at one
study, the researchers found that the presence of heartburn          time or another." This particular sensation accounts for 3%
and acid regurgitation together as dominant complaints had a         of consultations to throat specialists, 33 predominantly by
sensitivity of 78% and a specificity of 60% for the presence         middle-aged women. The sensation can be described as a
of gastroesophageal reflux disease, as defined by prolonged          "lump," "tightness," "choking," or "strangling" feeling as if
esophageal pH monitoring. 23 Water brash is an uncommon              something is caught in the throat. The globus sensation is
and frequently misunderstood symptom that should be used             present between meals, and swallowing of solids or large
to describe the sudden filling of the mouth with clear,              liquid boluses may give temporary relief . Dysphagia and
slightly salty fluid . This fluid is not regurgitated material but   odynophagia are not present . Frequent dry swallowing and
rather secretions from the salivary glands as part of a protec-      emotional stress may worsen the globus sensation .
tive, vagally mediated reflex from the distal esophagus .24

                                                                     Mechanisms
Mechanisms
                                                                     Evidence for physiologic and psychologic abnormalities in
The physiologic mechanisms that produce heartburn are, sur-          patients with the globus sensation has been inconsistent and
prisingly, poorly understood . Although the reflux of gastric        controversial . Although frequently suggested, UES dysfunc-
acid is most commonly associated with heartburn, the same            tion has not been directly identified as the cause of the
symptom may be elicited by esophageal balloon distention, 25         globus sensation . Modern manometric studies have consist-
reflux of bile salts '26 and acid-induced motility distur-           ently shown the UES to be functioning normally, 34 and the
bances . 27 The best evidence that the pain mechanism is             sphincter does not appear to be hyper-responsive to esopha-
probably related to the stimulation of mucosal chemorecep-           geal distention, acidification, or mental stress        Further-
                                                                                                                             .14, 35



tors is the sensitivity of the esophagus to the presence of          more, esophageal distention can cause a globus sensation
acid during its perfusion or by monitoring pH . The location         unrelated to the degree of rise in UES pressure," and stress-
of these receptors is not known and probably is not superfi-         induced increases in UES pressure are not associated with a
cial because topical anesthetics fail to alter the pain re-          globus sensation in normal subjects or in patients complain-
sponse . 2
        R                                                            ing of this symptom . 34 Heartburn has been reported in up to
   The correlation of discrete episodes of acid reflux and           90% of patients with the globus sensation . 36 Documentation
symptoms, however, is poor . For example, postprandial gas-          of esophagitis or abnormal gastroesophageal reflux by esoph-
troesophageal reflux is common in healthy people, but symp-          ageal pH monitoring, however, is found in fewer than 25%
toms are rare . Intraesophageal pH monitoring of patients            of patients . 37 Balloon distention of the esophagus produces
with endoscopic evidence of esophagitis typically shows ex-          the globus sensation at lower balloon volumes in globus
cessive periods of acid reflux, but fewer than 20% of these          sufferers than in controls, which suggests that the perception
reflux episodes are accompanied by complaints . 29 Moreover,         of esophageal stretch may be heightened in these patients . 35
one third of patients with Barrett esophagus, the most ex-              Psychological factors may be important in the genesis of
treme form of gastroesophageal reflux disease, are acid in-          the globus sensation . The most commonly found psychiatric
sensitive .30 Therefore, symptoms must require more than             diagnoses include anxiety, panic disorder, depression, hypo-
esophageal contact with acid . Mucosal disruption with in-           chondriasis, somatization, and introversion . 38 Indeed, globus
flammation may be a contributory factor, but on endoscopy,           is the fourth most common symptom of patients with soma-
the esophagus appears normal in most symptomatic patients .          tization disorders .39 A combination of biologic factors, hypo-
The histologic appearance of the mucosa obtained by biopsy           chondriacal traits, and learned fear after a choking episode
shows that some of these patients have polymorphonuclear             provides a framework for misinterpretation of the symptoms
leukocytes, others have only reparative changes, and many            and intensifies the globus symptoms or the patient's anxi-
have a normal esophagus . Results of one study suggest that          ety . 40
hydrogen ion concentration could be crucial in symptom
production. 31 One group found that all 25 patients with re-
flux disease experienced heartburn during intraesophageal in-        CHEST PAIN (Table 6-4)
fusion of solutions having pH values of 1 .0 and 1 .5, but
only one half had heartburn with solutions having pH values          Recurrent chest pain of esophageal origin that mimics an-
of 2 .5 to 6 .0 . Other factors that possibly influence the report   gina pectoris is not surprising, in view of the proximity of
of heartburn include the acid clearance mechanism ; salivary         the two organs and their shared neural pathways . Esophageal
bicarbonate concentration ; volume of refluxed acid, as mea-         disorders are probably the most common causes of noncar-
sured by duration and proximal extent of reflux episodes ;           diac chest pain . Of the approximately 500,000 patients who
                              PATtENIS Wlft3 SYMPTOMS AND SI NS


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

                     CHARACTERISTICS                                  DESCRIPTION                         N              %              N               %
            Quality                                               Tight, heavy                           48              92             15              83
            Location                                              Retrosternal                           51              98             18             100
            Radiation                                             To left arm                            28              38              6              33
            Duration                                              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§

    *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 cardiac                                Mechanisms
pain, nearly 30% have normal epicardial coronary arteries ;
of those patients, 18% to 56% may have esophageal diseases                              The specific mechanisms that produce esophageal chest pain
that account for the symptoms . 41                                                      are not well understood . Chest pain that arises from the
   Intermittent anterior chest discomfort is the sine qua non                           esophagus has commonly been attributed to the stimulation
of this syndrome. Chest pain usually is described as a                                  of chemoreceptors (acid, pepsin, bile) or mechanoreceptors
squeezing or burning sensation, substernal, and radiating to                            (distention, spasm), although thermoreceptors (cold) also
the back, neck, jaw, or arms, at times indistinguishable from                           may be involved .
angina pain . Although it is not always related to swallowing,                               Gastroesophageal reflux causes chest pain primarily
it can be triggered by ingestion of either very hot or very                             through acid-sensitive esophageal chemoreceptors, as dis-
cold liquids . It frequently awakens the patient from sleep                             cussed earlier in the section "Heartburn (Pyrosis) ." Acid-
and may worsen during periods of emotional stress . The                                 induced dysmotility was once believed to be a major cause
duration ranges from minutes to hours and may be intermit-                              of esophageal pain . Early studies of acid perfusion in pa-
tent over several days . Although the pain can be severe,                               tients with reflux demonstrated increased esophageal contrac-
causing the patient to become ashen and perspire, it often                              tion amplitude and duration, as well as simultaneous and
abates spontaneously and may be eased with antacids . Occa-                             spontaneous contractions, while pain was produced . 45 More
sionally, its severity requires narcotics or nitroglycerin for                          recently, other investigators have not been able to reproduce
relief. Close questioning reveals that most patients with this                          these observations 4 6 Although diffuse esophageal spasm has
pain have other esophageal symptoms ; however, chest pain                               been reported during spontaneous acid reflux in some pa-
is the only esophageal complaint in about 10% .41                                       tients, studies with modern equipment show that these motil-
   The clinical history often does not enable the physician to                          ity changes are infrequent during acid infusion .46 In addition,
distinguish between cardiac and esophageal causes of chest                              24-hour ambulatory esophageal pH and motility monitor-
pain . For example, gastroesophageal reflux may be triggered                            ing47 ' 48 has shown that spontaneous acid-induced chest pain
by exercise 19 and cause exertional chest pain that mimics                              is associated with esophageal motility abnormalities in fewer
angina pectoris, even during treadmill testing . 43 Symptoms                            than 15% of patients with such discomfort.
suggestive of esophageal origin include pain that continues                                  Many patients with suspected esophageal chest pain have
for hours, retrosternal pain without lateral radiation, pain that                       esophageal motility disorders characterized by high-ampli-
interrupts sleep or is meal related, and pain that is relieved                          tude contractions of prolonged duration or frequent simulta-
with antacid agents . The presence of other esophageal symp-                            neous contractions . 49 One popular hypothesis is that these
toms also helps in the establishment of the differential diag-                          abnormal waveforms cause pain as high intramural esopha-
nosis (see Table 6-4) . A serious complicating factor in                                geal tension inhibits blood flow for a critical period of time
diagnosis is that as many as 50% of patients with cardiac                               (i .e ., myoischemia) . Experimental studies by MacKenzie and
pain have one or more symptoms of esophageal pain .44 This                              coworkers lend support to this hypothesis . 50 They found de-
overlap exists because the prevalence of both cardiac and                               creased esophageal rewarming rates after cold water infu-
esophageal diseases-especially gastroesophageal reflux dis-                             sions in patients with symptomatic esophageal motility disor-
ease-increases as people grow older . Both problems not                                 ders in comparison with age-matched controls . Because
only may coexist but also may interact in producing chest                               similar studies in patients with Raynaud phenomenon are
pain .                                                                                  directly correlated with blood flow, the authors theorized
                                                      DYSPHAGIA, OD,',()PI IA-IA,   HFatTB, Rf AN`I) 0'F)', 1 ,ERr .E9O pj s'~




that esophageal ischemia was the cause of the delayed re-             Table 6-5      I   Extraesophageal Symptoms of Esophageal
warming rate . None of these patients, however, developed                                Diseases
chest pain during the study . Furthermore, the extensive arte-
                                                                      RESPIRATORY                EAR, NOSE, AND THROAT           CARDIAC
rial and venous blood supply to the esophagus suggests that
compromised blood flow is unlikely after even the most                Wheezing                   Chronic sore throat             Syncope
abnormal esophageal contractions . 51                                 Bronchitis                 Hoarseness
    Complicating the relation between esophageal chest pain           Aspiration                 Burning sensation in tongue
                                                                      Hemoptysis                 Halitosis
and abnormal esophageal contractions is the consistent ob-
                                                                      Apnea                      Otalgia
servation that most of these patients are asymptomatic when                                      Cervical pain
the contraction abnormalities are identified .41 These esopha-                                   Globus sensation
geal motility disorders possibly are markers for more severe                                     Chronic cough
esophageal disturbances during chest pain . However, the re-                                     Stridor
                                                                                                 Lateral neck pain
sults of prolonged ambulatory esophageal motility studies
                                                                                                 Dental erosion
confirm that this relationship is infrequent . 47, 48 In addition,
amelioration of chest pain does not predictably correlate
with reduction of amplitude by either pharmacotherapy 52 or
surgical myotomy . 53 Results of more recent studies suggest
that the motility changes may represent an epiphenomenon              ulcers . Direct evidence for aspiration is more difficult to
of a chronic pain syndrome rather than the direct cause of            identify in adults, resting primarily on the presence of fat-
the complaints .41, 48                                                filled macrophages in sputum, 62 radioactivity in the lungs
   Other potential causes of esophageal chest pain include            after the tracer is placed in the stomach overnight, 63 and
the excitation of temperature receptors and luminal disten-           high esophageal or hypopharyngeal acid reflux recorded by
tion . The ingestion of hot or cold liquids can produce severe        24-hour pH monitoring with dual probes .64, 65 There is better
chest pain . It was previously believed that this was related to      evidence from both animal and human studies that a neural
esophageal spasm, but studies have shown that cold-induced            reflex is the pathophysiologic basis for these symptoms .
pain produces esophageal aperistalsis and dilatation, which           Acid perfusion into the distal esophagus increases airway
suggests that the cause of esophageal chest pain may be               resistance in all subjects, but the changes are most marked
activation of stretch receptors by acute distention .54 Such          in patients with asthma and heartburn .66 Dogs do not pro-
distention and pain are experienced with acute food impac-            duce this response after bilateral vagotomy 67 ; nor do humans
tion, the drinking of carbonated beverages (in some pa-               after atropine . 66 These findings suggest bronchial constriction
tients), and dysfunction of the belch reflex . 55 Another possi-      that is vagally mediated .
bility is that chest pain is caused by proximal distention of            Abnormal amounts of acid reflux recorded by prolonged
the esophagus by abnormal distal contractions or by im-               esophageal pH monitoring have been identified in 35% to
paired LES functioning and emptying .56 In addition, esopha-          80% of asthmatic adults . 68 Symptoms that suggest reflux-
geal chest pain in susceptible patients can be reproduced             induced asthma include the onset of wheezing at a late age
with smaller volumes of esophageal balloon distention than            without a history of allergies or asthma ; nocturnal cough or
the volumes that produce pain in asymptomatic patients .57            wheezing ; asthma worsened after meals, exercise, or the su-
Thus, altered pain perception may contribute to these pa-             pine position ; and asthma that is exacerbated by broncho-
tients' reactions to pain stimuli . Anxiolytics and antidepres-       dilators or that is steroid dependent . Patients who experience
sants can raise pain thresholds as well as improve mood               reflux with symptoms strongly suggestive of aspiration usu-
states . This may explain the mechanism by which these                ally have nocturnal cough and heartburn, recurrent pneu-
medications improve esophageal chest pain in the absence of           monias, unexplained fevers, and associated esophageal
manometric changes .58,59                                             motility disorders . 69 Ear, nose, and throat complaints associ-
                                                                      ated with gastroesophageal reflux include postnasal drip,
                                                                      voice changes, hoarseness, sore throat, persistent cough, otal-
RESPIRATORY ; EAR, NOSE, AND                                          gia, halitosis, dental erosion, and excessive salivation 70' 71
THROAT ; AND CARDIAC SYMPTOMS                                         Up to 25% of patients with gastroesophageal reflux disease
                                                                      complain of only head and neck symptoms . 72 Examination
Extraesophageal symptoms of esophageal diseases are sum-              of the vocal cords may help in suspected acid-related prob-
marized in Table 6-5 . Although these symptoms may be                 lems . Some patients have redness, hyperemia, and edema of
caused by esophageal motility disorders, they are most fre-           the vocal cords and arytenoids . In more severe cases, vocal
quently associated with gastroesophageal reflux disease .             cord ulcers, granulomas, and even laryngeal cancer, all sec-
However, the classic reflux symptoms of heartburn and re-             ondary to gastroesophageal reflux disease, have been re-
gurgitation often are mild or absent .                                ported . Normal results of a laryngeal examination, however,
   The mechanism by which gastroesophageal reflux can                 are not incompatible with acid reflux-related extraesophageal
cause chronic cough and other extraesophageal symptoms is             symptoms .70 Further evidence for the connection between
probably twofold : (1) by intermittent recurrent microaspira-         esophageal stimulation and vagal reflexes can be fours"
tion of gastric contents and (2) by a vagally mediated neural         the syndrome of "swallow syncope ." In this di"'
reflex . In animal studies, the instillation of small amounts of      lowing or pharyngeal esophageal stimu,'
acid in the trachea60 or on the vocal cords 61 can produce            profound, even lethal bradycardia, presumt
marked changes in airway resistance as well as vocal cord             gal mechanism .71