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Pathophysiology of Esophageal Motility Disorders in the Dog and Cat
Symposium on Controversial Problems in Clinical Practice
Pathophysiology of Esophageal Motility Disorders in the Dog and Cat Application to Management and Prognosis
Donald R. Strombeck, D.V.M., Ph.D.*
Regurgitation is an important effect of esophageal disease in the dog. This problem makes the animal unacceptable as a pet or as a working dog for several reasons. The most important of these is that it is not possible for the dog to maintain nutritional homeostasis. Few dogs with regurgitation caused by esophageal disease are able to maintain nutritional homeostasis without the need for special feeding or management procedures. A second important reason is that regurgitation is almost as unacceptable as the loss of fecal or urinary continence in a dog that lives in the house. The most common cause of esophageal regurgitation is megaesophagus. Megaesophagus is a congenital or acquired loss of the motor function of the esophagus. The severity of the problem varies greatly, so that in some dogs there is a complete paralysis of the entire esophagus, while in others there is a loss of motility in only a small segment. Recognition of megaesophagus is made by radiographic procedures with or without the use of contrast medium. The problem is usually readily suspected from clinical signs that indicate that the animal is regurgitating rather than vomiting, and radiographic confirmation normally presents few challenges. Although the diagnosis of megaesophagus is easily achieved, there has been a lack of understanding as to what is the proper course of management. There is also some question as to what the prognosis is. An understanding of ·the pathogenesis of megaesophagus is important, so that management programs are not followed that offer no chance for amelioration of the regurgitation. It is also important to accurately predict whether there is any hope for improvement with time. The selection of an effective *Associate Professor of Medicine, School of Veterinary Medicine, University of California, Davis, California
Veterinary Clinics of North America- Vol. 8, No. 2, May 1978
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management program is most important in the dogs with acquired megaesophagus. This problem develops in dogs that are usually firmly established as a member of the family, and attempts will be made to manage the problem as long as possible. It is more important to be able to predict whether there is any chance of improvement in dogs with congenital megaesophagus. The problem is usually recognized before close attachments have been made between the dog and the family, which makes it easier to replace the animal with another. Megaesophagus is not the only manifestation of a loss of esophageal motor function. Other entities are discussed as related motility disorders. Motility disorders of the cat are unusual.
NORMAL STRUCTURE AND FUNCTION OF ESOPHAGUS 6 • 9 • 23 Structure
The entire length of the esophagus in the dog is composed of striated muscle fibers, which are fashioned into two oblique layers. The cervical portion also contains several poorly developed layers of longitudinal striated muscle fibers. Luminal to the muscle layers is the submucosa, and luminal to this layer is a thin layer of smooth muscle called the muscularis mucosa. The innermost layer is the lamina propria, which is covered by a layer of stratified squamous epithelium that faces the lumen. The eat's esophagus consists of longitudinal and circular layers of smooth muscle in the middle and caudal parts. This is similar to the esophagus of man. The transit time of a bolus of food in the esophagus in man and the cat is longer than that in the dog, since striated or skeletal muscle fibers are rapidly contracting, in contrast to smooth muscle fibers. The striated muscles of the canine esophagus are innervated by efferent fibers in the vagus nerve. 2 These fibers arise from lower motor neurons in the nucleus ambiguus, stimulation of which evokes the efferent limb of the esophageal phase of swallowing. Efferent motor fibers from this nucleus are not parasympathetic, even though they are carried in the vagus nerve. Like all other nerve fibers that innervate striated muscles, these fibers terminate on motor end plates in the muscles. The upper motor neurons for the swallowing reflex are located in the central nervous system swallowing center, which is situated in the medial part of the lateral reticular formation. 25 There are connections between this center and that for respiration, since there must be important interactions between these functions. Respiration must be inhibited during deglutition. The central afferent pathway is the tractus solitarius.
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Smooth muscle, on the other hand, is innervated by parasympathetic and sympathetic nerve fibers, which control its motor function. The nuclei for vagal parasympathetic fibers are located in the dorsal motor nucleus of the vagus in the brain stem. 16 They send out long preganglionic fibers, which synapse in the intrinsic plexuses that are located within the layers of smooth muscle. The lower motor neurons in the plexuses send out short postganglionic fibers that innervate the smooth muscle. As was stated earlier, the only smooth muscle in the esophagus of the dog is in the muscularis mucosa, and it contributes little if anything to the peristaltic movement of a bolus of food to the stomach. In contrast, the smooth muscle structure of the esophagus in the cat, being similar to that in man, depends on its intrinsic nervous system for motor function, and it is regulated by the extrinsic parasympathetics for normal coordinated peristalsis. Function
Function of the canine esophagus is controlled entirely by its extrinsic nervous innervation. If both vagi are sectioned in the cervical region of the esophagus, the distal part dilates, retains food, and shows, at .best, feeble simultaneous repetitive contractions following swallowing. 2 Cutting the vagi in the hilar region or cutting some of the multiple esophageal branches to the esophagus produces similar results. Thus, interruption of the efferent fibers paralyzes the esophagus. Denervation also produces the histologic changes of atrophy of striated muscle that occur whenever this type of tissue loses its nerve supply. 22 Paralysis of the esophagus occurs when the nucleus ambiguus is bilaterally destroyed in the dog, but not when the dorsal motor nucleus of the vagus is destroyed. 16 On the other hand, cats that have the latter nucleus destroyed develop paralysis of the esophagus.16 This reinforces the concept that the small amount of smooth muscle in the dog's esophagus does not effectively contribute to peristalsis, while the opposite is true for the caudal esophagus in the cat. If a fistula is created in the lower cervical area of the esophagus to divert a swallowed bolus to the outside, peristalsis will be observed in the esophagus down to the fistula, but none will be evident in the distal part. 20 Therefore, the esophagus relays information centrally that a bolus is approaching, and the reflex response is to continue the peristaltic movement. The amplitude of a primary peristaltic contraction is not reduced if a swallowed bolus is diverted from the esophagus in its thoracic part. 20 The bolus-dependent reinforcement of primary peristalsis is dependent on a central regulating mechanism in the medulla and on sensory information originating in the esophagus, which is being stimulated by the presence of a bolus. This suggests that inflammation of the esophagus could interfere with the reception of this sensory information. In fact, it has been shown that the pro-
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duction of esophagitis in experimental dogs results in severely disordered motor activity. 15 The size of the bolus is also important for the development of the peristaltic wave that will progress through the entire length of the esophagus. Whereas a complete wave of peristalsis is always evident as a bolus of food passes down a normal esophagus, peristaltic waves are often incomplete when a dog swallows a liquid. Secondary Peristalsis. The importance of the reception of afferent information from the esophagus is also illustrated by what is described as secondary peristalsis. Frequently, a large bolus of food becomes lodged in a part of the esophagus and the peristaltic wave that initially propelled its movement passes it and disappears. The bolus would remain there unless a mechanism were present to move it on. The motility that performs this function is called secondary peristalsis. Sensory receptors in the esophagus are stimulated by the lodged bolus and relay information through a reflex, which results in an efferent response that initiates a wave of peristalsis to move the bolus caudally from its lodged position. This peristaltic movement begins in the esophagus cranial to the bolus. 19 As evaluated manometrically, secondary peristalsis is indistinguishable from primary peristalsis. This reflex is one with connections in the central nervous system. 19 In summary, the esophagus in the dog is under complete control of the central nervous system, and it is important to recognize that esophageal motor activity is dependent on afferent activity arising from within the esophagus; hence, it is subject to feedback control.
NORMAL STRUCTURE AND FUNCTION OF GASTROESOPHAGEAL JUNCTION AND SPHINCTERL 6 • 23 • 24 The gastroesophageal sphincter is situated at the caudal end of the esophagus. Its function is to prevent regurgitation of gastric contents into the esophagus, and it can be described as a physiologic, rather than an anatomic, sphincter, since it does not consist of layers of muscles that are increased in mass compared with the structures on either side. In the dog, the gastroesophageal sphincter consists of an outer layer of longitudinal striated muscle fibers that is a continuation of that in the esophagus, and an inner layer of circular smooth muscle that merges with the circular striated muscle of the esophagus adjacent to it. The longitudinal layer merges with the smooth muscle of the stomach about 2 mm below the junction of the gastric mucosa and the esophageal stratified squamous epithelium. The operation of the gastroesophageal sphincter is generally considered to be controlled by both the nervous and endocrine systems.
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The closure of the gastroesophageal sphincter prevents the reflux of gastric contents into the esophagus by maintaining a zone of high pressure at all times, except during a swallowing movement. The sphincter relaxes at the onset of a swallowing movement, and this results in a fall in pressure. Sphincter relaxation occurs as long as five seconds before the arrival of the bolus. The striated fibers in the canine gastroesophageal sphincter are responsible for rapid closure of the sphincter, and its smooth muscle fibers function to maintain closure. The sphincter opens and closes as a part of the complex neural activity associated with swallowing, but it can function independently. Vagotomy causes resting gastroesophageal sphincter pressures to be only slightly reduced and greatly reduces the incidence of relaxation and contraction that occurs with swallowing. Relaxation of the sphincter at the onset of swallowing is mediated by vagal nerve fibers. Blockers of cholinergic or adrenergic activity have no effect on the vagally mediated sphincter relaxation, which suggests that a different neurotransmitter is involved. Vagotomy does not cause the smooth muscle to be paralyzed, since it still contains a primitive nervous system that imparts some function, even though it is much less sophisticated than the control exerted by the central nervous system. Extrinsically denervated circular muscle from the sphincter shows intrinsic properties that include an increased resistance to stretch when graded tension is applied. The muscle also shows a decrease in tension when it is stimulated electrically. Since the response is blocked by tetrodotoxin, it is suggested to be nerve mediated, in this case by the intrinsic nervous system. These effects in isolated muscle from the sphincter are different from those of the smooth muscle in structures caudal to the sphincter. The pressure in the gastroesophageal sphincter normally is maintained at 20 to 50 em of water greater than the esophagus or the stomach. The elevated pressure is regulated in part by events that occur in the stomach. Increases in intragastric pressure, whether by food, water, or abdominal compression, cause sphincter pressure to increase and remain greater than intragastric pressure. Electrical stimulation of the central end of one vagus that has been cut causes an increase in pressure in the sphincter. Thus, this response is dependent on normal vagal innervation of the stomach and sphincter and on afferent information from the stomach. It was stated that the sphincter can open and close after all connections with the central nervous system are removed. This function is lost when a circular cuff of muscle is removed from the esophagus just cranial to the sphincter. Thus, function in the sphincter is dependent on events that occur in the esophagus, and its responses are neurally mediated. This control of sphincter function is probably lost when the most caudal parts of the esophagus are diseased.
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Effect of Hormones and Drugs
Hormones and drugs act on the gastroesophageal sphincter and this adds another dimension to the control of its function. 24 • 29 It would seem likely that the hormone gastrin, which mediates gastric hydrochloric acid secretion, should increase pressure in the sphincter and prevent reflux from the stomach filled with food. The infusion of gastrin into dogs shows that the hormone does indeed increase sphincter pressure. However, this response is to pharmacologic concentrations of gastrin, and more recent studies have shown that the response is not observed with physiologic levels of gastrin release. In dogs, feeding does not increase pressure in the gastroesophageal sphincter, despite a normal response of gastrin release. 18 Other data suggest that normal physiological levels of gastrin increase sphincter pressure in other species. It can be concluded that gastrin plays a role in maintaining a high pressure in the gastroesophageal sphincter during secretion of gastric juices and digestion of food, but that it is less important than originally thought. The effects of gastrin on the circular muscle of the sphincter are blocked by atropine and tetrodotoxin, which suggests that the hormone acts through a nerve pathway. Secretin is a competitive inhibitor of the action of gastrin on the gastroesophageal sphincter. Secretin also inhibits the release of gastrin. Some experiments have shown that alkalinization of the stomach can increase sphincter pressure by reciprocal changes in secretion of the two hormones. Thus, it is evident that gastroesophageal pressure is regulated by a number of gastrointestinal tract hormones that compete for receptor sites. Cholecystokinin and glucagon have inhibitory effects similar to that of secretin. Dietary nutrients affect pressure m the gastroesophageal sphincter. Proteins cause the pressure to increase and fatty meals cause the pressure to decrease. Fat in the diet inhibits the gastrinmediated increase in sphincter pressure. Normal anatomical relationships are important for normal function in the sphincter, and they contribute with neural innervation and endocrine regulation to the optimal functioning of the gastroesophageal sphincter. Premedication drugs used prior to administration of anesthetic agents have been found to lower the pressure in the gastroesophageal sphincter and increase the probability of reflux. 13 These drugs include morphine, pethidine, diazepam, and anticholinergics. Metoclopramide and bethanechol, two drugs that increase motility in the sphincter, can cause its pressure to increase. Inflammation
Inflammation of the esophagus has been shown to cause the gastroesophageal sphincter pressure to decrease in the cat. 11 This is a
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potential positive feedback situation where the presence of esophagitis results in decreased sphincter pressure, which increases the possibility of further reflux and perpetuation of the esophagitis.
MEGAESOPHAGUS EPIDEMIOLOGY
Megaesophagus is the most common motor disturbance involving deglutition in the dog. It is the most appropriate term to describe the dilated esophagus, until the time when the etiologies and the pathogenesis of all cases of esophageal paralysis are understood. Megaesophagus is reported to primarily affect pups, and some studies have shown that it can be genetically determined. 10 • 26 An eight-year survey of cases of megaesophagus at the University of Pennsylvania Veterinary Hospital revealed that two-thirds of their cases developed clinical signs by 10 weeks of age and only 20 per cent developed signs after one year of age. 14 Over an eight-year period at the Veterinary Medical Teaching Hospital (VMTH), University of California, Davis, 55 per cent of 125 dogs with megaesophagus were one year of age or less when signs began. Ten per cent of the dogs were one to two years of age and 25 per cent were distributed equally over ages of from two to seven years. Ten per cent were in a seven to 15 year age group. Thus, a considerable number of adult dogs develop the problem. One published report on megaesophagus describes most of the dogs as being over one year of age. 17 Megaesophagus must be considered in the differential diagnosis of animals of any age that are presented with signs of regurgitation. Incidence by Breed
The incidence of megaesophagus is greater in certain breeds of dogs. The incidence in Great Danes at Pennsylvania was eight times greater than would be expected, and at the VMTH in Davis, the incidence was 10 times greater than what should be found if there is no breed predeliction. In the two studies, the incidence of megaesophagus in German shepherds was twice the anticipated rate. This same predeliction prevailed in Irish setters. Previous reports are cited as identifying the Great Dane and German shepherd as having a higher incidence of megaesophagus. Certain strains· of wirehaired fox terriers have also been reported to have a form of the problem that is inherited. The incidence of megaesophagus was greater than anticipated in female dogs at Pennsylvania, but at the VMTH in Davis, there was an equal number of males and females affected in a population of equal numbers of males and females. In summary, more German shepherds are identified as having
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megaesophagus because of the popularity of the breed, but the Great Dane breed has a greater problem since the anticipated incidence of the disease is up to 10 times greater than normally expected, a rate that is much higher than that in the German shepherd. The overall incidence of megaesophagus at both hospitals was two to three out of every 1000 patients. This rate is anticipated to be higher than in the overall population, since a number of the cases at institutions are referrals. PATHOGENESIS OF MEGAESOPHAGUS
Achalasia The term achalasia was one of the most popular in the past to describe what is now collectively called megaesophagus. It was believed that the problem developed because the gastroesophageal sphincter failed to open, and accumulation of food in the caudal esophagus caused it to dilate. This theory was used to describe the pathogenesis of achalasia in man, and veterinarians considered the problem in dogs to be similar. The current belief is that megaesophagus does not develop for this reason. 7 • 12 • 14 • 31 • 32 The problems in dogs and man cannot be compared, since the anatomy of the middle and caudal thirds of the canine esophagus is completely different from that in man. In the dog, the muscles that are responsible for peristalsis are striated throughout the entire length of the esophagus, while in man, the lower third is all smooth muscle and the middle third is mixed striated and smooth. An important abnormality found in achalasia in humans is degeneration of neurons in the intrinsic nervous system, which is found within the smooth muscle of the esophagus. Thus, the changes found in the body of the dilated canine esophagus, consisting of paralyzed striated muscle fibers, cannot be compared with those that occur in the paralyzed smooth muscle of the esophagus in human beings. Only a small layer of smooth muscle is found in the muscularis mucosa in the dog, and it does not contribute to the peristaltic propulsion of a bolus through the esophagus. The numbers of neurons in the intrinsic plexuses is not reduced in this layer of smooth muscle in dogs with megaesophagus. 4 It is likely that achalasia of the gastroesophageal sphincter could produce megaesophagus in the esophagus made up of striated muscle as readily as in that fashioned from smooth muscle. Dilations that develop from strictures usually remain following correction of the stricture. Only recently has function been evaluated in the gastroesophageal sphincter in cases of canine megaesophagus. There has been only one study reported in which the gastroesophageal sphincter was evaluated by both cineradiography and
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manometric procedures in dogs with megaesophagt:s. 7 The finding was that function in the sphincter was normal. All the dogs in this study had normal esophageal function in the most caudal part of the thoracic esophagus. All the pathology was confined to the cranial and middle parts of the thoracic esophagus. Videofluoroscopic studies in cases of megaesophagus at the VMTH in Davis have not revealed achalasia to be present. Dogs with megaesophagus that involves the entire esophagus and extends to the gastroesophageal sphincter do not show passage of food through the sphincter until the esophagus is tilted into a more vertical position. Gravity moves the food, and the gastroesophageal sphincter offers no resistance to its passage. Studies on normal animals indicate that the information of a bolus of food approaching the sphincter is necessary for it to open properly. It was indicated earlier that removal of the segment of thoracic esophagus adjacent to the sphincter results in a loss of sphincter function. This suggests that sphincter function is not likely to be normal when megaesophagus extends to the sphincter. Thus, the radiologist will not see the sphincter opening and closing when there is an abnormal segment of the esophagus directly adjacent to it. However, if the most caudal segment of the esophagus is normal, the reflex is intact. The only means of definitively determining if an area of increased resistance exists in the gastroesophageal sphincter is by conducting manometric measurements. Radiography cannot answer this question. Increased pressure in the gastroesophageal sphincter in man with achalasia is suggested to be in part produced by circulating gastrin. The intrinsically denervated smooth muscle in achalasia is supersensitive to gastrin. However, it has not been shown that the circular layer of smooth muscle in the dog's sphincter loses its intrinsic innervation, nor that a higher than normal pressure zone exists in the sphincter. 4 • 7 The parasympathetics only regulate function in the gastroesophageal sphincter. With extrinsic denervation, the resting pressure decreases, but the sphincter can still open and close, thus, offering no resistance to the passage of a bolus. 1 Therefore, a lesion in the extrinsic parasympathetic pathway should not produce achalasia that can lead to megaesophagus in the dog. Loss of Motor Function
The abnormality in megaesophagus is a loss of motor function. A defect in any part of the neural pathway that is necessary for normal esophageal function or in the muscle and myoneural junction will cause a loss of function. Megaesophagus can be produced in the experimental dog by cutting the vagus nerves or by bilateral destruction of the nucleus ambiguus. 16 The motor unit consists of the cranial lower motor neurons in the nucleus ambiguus, the efferent nerve
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fibers in the vagus, the myoneural junction, and the striated muscle fibers. A defect in one part would cause paralysis of the esophagus. A defective motor unit would also result in denervation atrophy, but histologic studies on the muscle in a megaesophagus usually produce normal results, and the changes that are found are usually secondary. Loss of function in the motor unit will also cause denervation potentials to appear on electromyograms, 28 but such recordings at all levels of the esophagus in a small group of dogs with megaesophagus were normal. 32 In the same study, stimulation of the vagus nerves resulted in contraction of the esophagus, a response that would not be possible if a lesion was present in the motor unit. Thus, the esophageal motor unit is normal in megaesophagus, and this indicates that the cranial lower motor neurons in the nucleus ambiguus are normal. Serial sections of the brain stem from one dog with megaesophagus were reported to have a reduced number of cell bodies in the nucleus ambiguus. 5 Unpublished data have been cited to indicate that this is not the situation, but that the number of neurons in the nucleus ambiguus is normal in dogs with megaesophagus. 21 Another study on the effects of vagal stimulation in dogs with megaesophagus produced data that suggested the problem is mainly a neural rather than a muscular defect, but no suggestions were made as to the site of the lesion. 12 A study reported on two dogs suggests that the lesion is the same in pups born with megaesophagus as in dogs that acquire it as an adult. 32 These same observations have since been made on a larger number of animals. The presence of a normal motor unit indicates that the lesion is in either the cranial upper motor neurons or in the receptors or afferent limb of the swallowing reflex. The afferent limb of the reflex consists of nerve fibers that travel in the brain in the tractus solitarius to the nucleus of this tract. Synaptic fibers connect the nucleus of tractus solitarius with the swallowing center, which is located in the medial part of the lateral reticular formation. 25 This center contains the cranial upper motor neurons, and it sends fibers to the respiratory inhibitory centers and to the cranial lower motor neurons in the nucleus ambiguus, which is the beginning of the motor unit. There is evidence that some of the respiratory reflexes mediated by afferent fibers in the vagus are abnormal in some dogs with megaesophagus. 32 This is consistent with the clinical evidence for impairment of respiratory reflexes that is suggested by the high frequency of aspiration pneumonia in dogs with megaesophagus. The pathogenesis of the lesion in megaesophagus is completely unknown. There is evidence for its genetic transmission. Karyotyping has not revealed any chromosomal abnormality in pups with the problem.30 A wide variety of motility disorders have been associated with other types of acquired problems, which have included such diverse
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things as neoplastic and infectious diseases, pharmaceutical agents, or general anesthesias. The relationship between these problems and the development of megaesophagus is unknown. It is possible that a group of neurons in the swallowing reflex is more sensitive to the effects of toxins, drugs, or anesthesias than others in the brain.
RELATED MOTILITY DISORDERS
Megaesophagus is not the most accurate term to describe motility disturbances of the esophagus, since a loss of motor function can occur without the devdopment of megaesophagus. These problems are difficult to diagnose unless it is possible to conduct a motility study of the esophagus with radiographic procedures using positive contrast medium and fluoroscopic control. It is often difficult to determine whether motility is normal or abnormal, and whether the abnormal motility is contributing to a dog's clinical signs. Incoordination of Motor Function
One type of abnormality that can be seen consists of a loss of much of the normal peristaltic activity of the esophagus, and contractions that are evident consist of random and incoordinated movements. This type of motility generally produces marked signs of regurgitation, anorexia, and in many cases, esophageal colic. Part of the animal's anorexia is suggested to be the result of painful spasms of the esophagus when a bolus is swallowed. This type of problem produces a more immediate regurgitation than megaesophagus, even if the motility is confined to the caudal half of the esophagus. An esophagitis can cause esophageal dysphagia where incoordination of motor function is the main feature. This has been shown in the experimental dog/ 5 as well as having been recognized clinically. This undoubtedly occurs much more frequently than it is recognized. Few small animals with acute signs of vomiting or regurgitation are evaluated for an esophagitis by endoscopy, or for the loss of coordinated esophageal function by fluoroscopy during a swallow of contrast medium. Most of these animals recover, and consequently, function in the esophagus is never investigated. In general, animals with radiographically determined incoordination of motility without megaesophagus can improve with time and nonspecific treatment. Clinical improvement is accompanied by radiographic signs of improvement. The motility disorder associated with an esophagitis may be caused by damage to either the sensory receptors in the esophagus or to the peripheral part of the motor unit. It is also possible that in some cases, both problems are caused by ingestion of some toxin, and the motility disorder is a manifestation of central effects of the toxin.
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Motility Deficit A second variety of motility disorder in which megaesophagus is not apparent exists in the dog with radiographic evidence of little or no motility of any type in a normal appearing esophagus. Surprisingly, these animals do not show as severe signs of regurgitation as the dog with random spasms of the esophagus. In some cases there are few, if any, clinical signs. This problem often develops with an inflammatory process in the esophagus. It has also been associated with local esophagitis that causes stricture formation. In contrast to the dog that shows few clinical signs with an esophagus that appears to be hypomotile, some dogs will acquire a motility deficit in a section of esophagus that is only a few centimeters long, and, surprisingly, show severe signs of regurgitation. Such a motility defect may be so subtle that it is difficult to recognize using radiographic procedures. This illustrates that it is not possible to correlate the degree of clinical signs with the severity of radiographic abnormalities. Some of these motility disturbances over a short segment of esophagus are the sequel to damage by a foreign body. Megaesophagus involving one small region of the esophagus is sometimes seen to contract and develop a wave of peristalsis that moves the contents to the stomach. Obviously, the esophagus is not paralyzed, and this problem may represent another example of a defect in the upper motor neurons or the afferent pathway of the swallowing reflex.
EVALUATION OF MOTOR DISTURBANCES Motor disturbances of deglutition are suspected and seldom overlooked if an accurate and complete history is obtained. Obvious signs that the owner will observe are both oral and nasal regurgitation of food, multiple swallowing movements, and hesitation in the initiation of swallows. Many dogs with esophageal motility disturbances may be presented with coughing, dyspnea, gagging, esophageal colic, and hypersalivation as either the primary signs or as the only signs. The differential diagnosis should include esophageal problems whenever any of these signs is evident. The diagnosis of a motor disturbance of the esophagus can only be confirmed by radiographic procedures. Contrast studies should be conducted with the swallowing of both liquids and solid food. Some problems are not properly identified with liquid contrast, since liquids do not stimulate the progressive wave of peristalsis that is produced by a bolus of food. Endoscopy may be of value in dogs with megaesophagus, but it is of no value in evaluating a motility disturbance.
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MANAGEMENT AND PROGNOSIS There is no specific medical treatment for motility disorders of the esophagus. Any concurrent problems that are found should be treated. If a motility disturbance without megaesophagus is recognized, it can be managed with nonspecific treatment, and up to six weeks should be allowed before a final evaluation of recovery is made. Dogs with megaesophagus are not helped with either nonspecific therapy or surgery. It has been reported tlwt me~aesophagus can be a reversible problem. Improvement may occur to a limited extent with the congenital form. Young animals do not normally achieve complete function of the esophagus until they mature. The maturation of swallowing function has been evaluated in growing pups that were normal and ones born with megaesophagus. 8 Manometric measurements show that the motility function of the esophagus continues to mature in many pups with megaesophagus, as well as in normal pups, so that as an adult they may be clinically improved. Thus, improvement is possible, but the problem is not reversible. Any evaluation on the improvement of megaesophagus should also be based on radiographic studies employing fluoroscopy. There is no evidence that the acquired megaesophagus recovers any part of its normal function. Surgery Recommendations for surgical treatment of megaesophagus are based on the theory that an achalasia exists in the gastroesophageal sphincter, and as a consequence, myotomy has been performed. In one report from Pennsylvania, 40 per cent of dogs with megaesophagus underwent surgery. Since the results were poorer than in those that were not treated surgically, the surgery is no longer recommended. From 1967 to 1975, 18 per cent of the cases of megaesophagus at the VMTH in Davis were treated surgically, the results of which have not been evaluated. All cases of megaesophagus that are treated surgically are also managed postsurgically by placing the dog's food at an elevated position, so that the dog must eat in a semivertical position. If any improvement follows, it is not possible to attribute the results to successful surgery. It is more likely that the postsurgical management procedures are responsible for the improvement. · There is no rationale for performing a myotomy unless radiographic studies reveal a stricture at the gastroesophageal junction. As indicated earlier, it has been shown that a higher than normal pressure zone is not a feature of the gastroesophageal sphincter in dogs with megaesophagus. 7 Thus, myotomies should not be done. Complications of myotomies on this sphincter have included herniation of the stomach into the esophagus and gastroesophageal reflux.
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Special Feeding Practices The only successful management of motor disturbances of the esophagus involves the use of special feeding practices. As a first attempt, the client should initiate feeding diets of different consistencies and food particle size. In general, diets that are a semiliquid gruel are usually swallowed the most readily, since a feeble wave of peristaltic activity can more readily move a liquid bolus, with less resistance to its flow over a long distance, than a solid bolus. Also, with the aid of gravity, a liquid bolus will move through a paralyzed section of esophagus more readily than a bolus of solid food. This is the basis for feeding a liquid gruel from an elevated position. Some animals cannot maintain nutritional homeostasis with the use of this procedure, and the owner is trained to pass a stomach tube through which the animal is fed. In some dogs with a motility disturbance of the most cranial part of the cervical esophagus, chunks of food are swallowed easier than a soft or semiliquid diet. During client education, it is emphasized that the best management program for each patient may differ from that which is recommended for most animals with the problem, and that a number of different trials will reveal which management will be the most successful.
ESOPHAGEAL MOTILITY DISORDERS IN THE CAT Motor disturbances are seen in the esophagus of cats. The incidence is less than one case per 1000 cats seen at Davis. Based on anatomic similarities, megaesophagus in cats can be compared to achalasia in man. Both species have smooth muscle in all the muscle layers of the distal one-half to one-third of the esophagus. Histologic studies of sections of the feline megaesophagus have shown that there is a normal number of ganglia cells of the intrinsic plexuses. 3 Thus, the problem differs from that in man. It has been suggested to be an inherited defect. 3 The site of the lesion has not been identified. One study reported on a series of cats with esophageal dysfunction that was associated with abnormal gastric retention of food. 27 The clinical signs of persistent vomiting were corrected with a pyloromyotomy, and subsequently normal esophageal function returned. The cats had a reversible megaesophagus. It has been shown that esophagitis, which would be produced by chronic vomition, causes a loss of gastroesophageal sphincter competence.U Furthermore, esophagitis causes deranged esophageal motility. 15 It is not unusual to see a loss of normal peristalsis with some evidence for megaesophagus when the esophageal mucosa has been chemically or mechanically traumatized. The study reported on the cats indicates that esophageal function has a good chance of returning when the vomiting problem is controlled.
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REFERENCES I. Arimori, M., Code, C. F., Schlegel, J. F., et a!.: Electrical activity of the canine esophagus and gastroesophageal sphincter. Am. J. Dig. Dis., 15:191-208, 1970. 2. Carveth, S. W., Schlegel, J. F., Code, C. F., et a!.: Esophageal motility after vagotomy, phrenicotomy, myotomy, and myomectomy in dogs. Surg. Gynecol. Obstet., 114:31-42, 1962. 3. Clifford, D. H.: Myenteric ganglial cells of the esophagus in cats with achalasia of the esophagus. Am. J. Vet. Res., 34: 1333-1336, 1973. 4. Clifford, D. H., and Gyorkey, F.: Myenteric ganglial cells in dogs with and without achalasia of the esophagus. J. Am. Vet. Med. Assoc., 150:205-211, 1967. 5. Clifford, D. H., Pirsch, J. G., and Mauldin, M. L.: Comparison of motor nuclei of the vagus nerve in dogs with and without esophageal achalasia. Proc. Soc. Exp. Bioi. Med., 142:878-882, 1973. 6. Code, C. F., and Schlegel, J. F.: Motor action of the esophagus and its sphincters. In Code, C. F. (ed.): Handbook of Physiology. Washington, D. C., American Physiological Society, 1968. Vol. 4, Section 6 - Alimentary Canal, pp. 1821-1839. 7. Diamant, N., Szczepanski, M., and Mui, H.: Manometric characteristics of idiopathic megaesophagus in the dog: an unsuitable animal model for achalasia in man. Gastroenterology, 65:216-223, 1973. 8. Diamant, N., Szczepanski, M., and Mui, H.: Idiopathic megaesophagus in the dog: reasons for spontaneous improvement and a possible method of medical therapy. Can. Vet. J., 15:66-71, 1974. 9. Doty, R. W.: Neural organization of deglutition. In Code, C. F. (ed.): Handbook of Physiology. Washington, D. C., American Physiological Society, 1968. Vol. 4, Section 6 - Alimentary Canal, pp. 1861-1902. 10. Earlam, R. J., Zollman, P. E., and Ellis, F. H.: Congenital oesophageal achalasia in the dog. Thorax,22:466-472, 1967. II. Eastwood, G. L., Castell, D. 0., and Higgs, R. H.: Experimental esophagitis in cats impairs lower esophageal sphincter pressure. Gastroenterology, 69:146-153, 1975. 12. Gray, G. W.: Acute experiments on neuroeffector function in canine esophageal achalasia. Am. J. Vet. Res., 35:1075-1081, 1974. 13. Hall, A. W., Moosa, A. R., Clark, J., et a!.: The effects of premedication drugs on the lower oesophageal high pressure zone and reflux status of Rhesus monkeys and man. Gut, 16:347-352, 1975. 14. Harvey, C. E., O'Brien, J. A., Durie, V. R., et a!.: Megaesophagus in the dog: a clinical survey of 79 cases. J. Am. Vet. Med. Assoc., 165:443-446, 1974. 15. Henderson, R. D., Mugashe, F., Jeejeebhoy, K. N., eta!.: The role of bile and acid in the production of esophagitis and the motor defect of esophagitis. Ann. Thorac. ?urg., 14:465-473, 1972. 16. Higgs, B., Kerr, F. W. F., and Ellis, F. H.: The experimental production of esophageal achalasia by electrolytic lesions in the medulla. J. Thorac. Cardiovasc. Surg., 50:613-625, 1965. 17. Hofmeyr, C. F. B.: An evaluation of cardioplasty for achalasia of the oesophagus in the dog. J. Small Anim. Pract., 7:281-301, 1966. 18. Hollenbeck, J. I., Maher, J. W., Wickbom, G., et a!.: The effect of feeding on the canine lower esophageal sphincter. J. Surg. Res., 18:497-499, 1975. 19. Janssens, J., Valembois, P., Hellemans, J., et a!.: Studies on the necessity of a bolus for the progression of secondary peristalsis in the canine esophagus. Gastroenterology, 67:245-251, 1974. 20. Janssens, J., Valembois, P., Vantrappen, G., et a!.: Is the primary peristaltic contraction of the canine esophagus bolus-dependent? Gastroenterology, 65:750-756, 1973. 21. Leipold, H.: Unpublished observations cited by Guffy, M. M., in Esophageal Disorders. In Ettinger, S. J. (ed.): Veterinary Internal Medicine. Philadelphia, W. B. Saunders Co., 1975. 22. Lynch, V. P., Schlegel, J. F., and Ellis, F. H.: Autotransplantation of the canine esophagus. Surg. Gynecol. Obstet., 138:396-400, 1974. 23. Miller, M. E., Christensen, G. C., and Evans, H. E.: Anatomy of the Dog. Philadelphia, W. B. Saunders Co., 1964.
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24. Misiewicz, ]. J.: Symposium on gastroesophageal reflux and its complications. Section 4, Pharmacology and therapeutics. Gut, 14:243-246, 1973. 25. Nakayama, S., Neya, T., Watanable, K., et a!.: Effects of electrical stimulation and local destruction of the medulla oblongata on swallowing movements in dogs. Rendic. Gastroenterol., 6:6--11, 197 4. 26. Osborne, C. A., Clifford, D. H., and Jessen, C.: Hereditary esophageal achalasia in dogs.]. Am. Vet. Med. Assoc., 151:572-581, 1967. 27. Pearson, H., Gaskell, C.]., Gibbs, C., eta!.: Pyloric and oesophageal dysfunction in the cat.]. Small Anim. Pract., 15:487-501, 1974. 28. Pelemans, W., VanTrappen, G., Hellemans, J., et a!.: Denervation potentials in the canine esophagus. In Proceedings of the Fourth International Symposium on Gastrointestinal Motility. Vancouver, Mitchell Press, 1974. 29. Pope, C. E.: Pathophysiology and diagnosis of reflux esophagitis. Gastroenterology, 70:445-454, 1976. 30. Smith, A.: Unpublished cases from the Veterinary Medical Teaching Hospital, Davis, California. 31. Sokolovsky, V.: Achalasia and paralysis of the canine esophagus.]. Am. Vet. Med. Assoc., 160:943-955, 1972. 32. Strombeck, D. 'R., and Troya, L.: Evaluation of lower motor neuron function in two dogs with megaesophagus. J. Am. Vet. Med. Assoc., 169:411-414, 1976. Department of Medicine University of California School of Veterinary Medicine Davis, California 95616
Pathophysiology of Esophageal Motility Disorders in the Dog and Cat Application to Management and Prognosis
Donald R. Strombeck, D.V.M., Ph.D.*
Regurgitation is an important effect of esophageal disease in the dog. This problem makes the animal unacceptable as a pet or as a working dog for several reasons. The most important of these is that it is not possible for the dog to maintain nutritional homeostasis. Few dogs with regurgitation caused by esophageal disease are able to maintain nutritional homeostasis without the need for special feeding or management procedures. A second important reason is that regurgitation is almost as unacceptable as the loss of fecal or urinary continence in a dog that lives in the house. The most common cause of esophageal regurgitation is megaesophagus. Megaesophagus is a congenital or acquired loss of the motor function of the esophagus. The severity of the problem varies greatly, so that in some dogs there is a complete paralysis of the entire esophagus, while in others there is a loss of motility in only a small segment. Recognition of megaesophagus is made by radiographic procedures with or without the use of contrast medium. The problem is usually readily suspected from clinical signs that indicate that the animal is regurgitating rather than vomiting, and radiographic confirmation normally presents few challenges. Although the diagnosis of megaesophagus is easily achieved, there has been a lack of understanding as to what is the proper course of management. There is also some question as to what the prognosis is. An understanding of ·the pathogenesis of megaesophagus is important, so that management programs are not followed that offer no chance for amelioration of the regurgitation. It is also important to accurately predict whether there is any hope for improvement with time. The selection of an effective *Associate Professor of Medicine, School of Veterinary Medicine, University of California, Davis, California
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management program is most important in the dogs with acquired megaesophagus. This problem develops in dogs that are usually firmly established as a member of the family, and attempts will be made to manage the problem as long as possible. It is more important to be able to predict whether there is any chance of improvement in dogs with congenital megaesophagus. The problem is usually recognized before close attachments have been made between the dog and the family, which makes it easier to replace the animal with another. Megaesophagus is not the only manifestation of a loss of esophageal motor function. Other entities are discussed as related motility disorders. Motility disorders of the cat are unusual.
NORMAL STRUCTURE AND FUNCTION OF ESOPHAGUS 6 • 9 • 23 Structure
The entire length of the esophagus in the dog is composed of striated muscle fibers, which are fashioned into two oblique layers. The cervical portion also contains several poorly developed layers of longitudinal striated muscle fibers. Luminal to the muscle layers is the submucosa, and luminal to this layer is a thin layer of smooth muscle called the muscularis mucosa. The innermost layer is the lamina propria, which is covered by a layer of stratified squamous epithelium that faces the lumen. The eat's esophagus consists of longitudinal and circular layers of smooth muscle in the middle and caudal parts. This is similar to the esophagus of man. The transit time of a bolus of food in the esophagus in man and the cat is longer than that in the dog, since striated or skeletal muscle fibers are rapidly contracting, in contrast to smooth muscle fibers. The striated muscles of the canine esophagus are innervated by efferent fibers in the vagus nerve. 2 These fibers arise from lower motor neurons in the nucleus ambiguus, stimulation of which evokes the efferent limb of the esophageal phase of swallowing. Efferent motor fibers from this nucleus are not parasympathetic, even though they are carried in the vagus nerve. Like all other nerve fibers that innervate striated muscles, these fibers terminate on motor end plates in the muscles. The upper motor neurons for the swallowing reflex are located in the central nervous system swallowing center, which is situated in the medial part of the lateral reticular formation. 25 There are connections between this center and that for respiration, since there must be important interactions between these functions. Respiration must be inhibited during deglutition. The central afferent pathway is the tractus solitarius.
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Smooth muscle, on the other hand, is innervated by parasympathetic and sympathetic nerve fibers, which control its motor function. The nuclei for vagal parasympathetic fibers are located in the dorsal motor nucleus of the vagus in the brain stem. 16 They send out long preganglionic fibers, which synapse in the intrinsic plexuses that are located within the layers of smooth muscle. The lower motor neurons in the plexuses send out short postganglionic fibers that innervate the smooth muscle. As was stated earlier, the only smooth muscle in the esophagus of the dog is in the muscularis mucosa, and it contributes little if anything to the peristaltic movement of a bolus of food to the stomach. In contrast, the smooth muscle structure of the esophagus in the cat, being similar to that in man, depends on its intrinsic nervous system for motor function, and it is regulated by the extrinsic parasympathetics for normal coordinated peristalsis. Function
Function of the canine esophagus is controlled entirely by its extrinsic nervous innervation. If both vagi are sectioned in the cervical region of the esophagus, the distal part dilates, retains food, and shows, at .best, feeble simultaneous repetitive contractions following swallowing. 2 Cutting the vagi in the hilar region or cutting some of the multiple esophageal branches to the esophagus produces similar results. Thus, interruption of the efferent fibers paralyzes the esophagus. Denervation also produces the histologic changes of atrophy of striated muscle that occur whenever this type of tissue loses its nerve supply. 22 Paralysis of the esophagus occurs when the nucleus ambiguus is bilaterally destroyed in the dog, but not when the dorsal motor nucleus of the vagus is destroyed. 16 On the other hand, cats that have the latter nucleus destroyed develop paralysis of the esophagus.16 This reinforces the concept that the small amount of smooth muscle in the dog's esophagus does not effectively contribute to peristalsis, while the opposite is true for the caudal esophagus in the cat. If a fistula is created in the lower cervical area of the esophagus to divert a swallowed bolus to the outside, peristalsis will be observed in the esophagus down to the fistula, but none will be evident in the distal part. 20 Therefore, the esophagus relays information centrally that a bolus is approaching, and the reflex response is to continue the peristaltic movement. The amplitude of a primary peristaltic contraction is not reduced if a swallowed bolus is diverted from the esophagus in its thoracic part. 20 The bolus-dependent reinforcement of primary peristalsis is dependent on a central regulating mechanism in the medulla and on sensory information originating in the esophagus, which is being stimulated by the presence of a bolus. This suggests that inflammation of the esophagus could interfere with the reception of this sensory information. In fact, it has been shown that the pro-
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duction of esophagitis in experimental dogs results in severely disordered motor activity. 15 The size of the bolus is also important for the development of the peristaltic wave that will progress through the entire length of the esophagus. Whereas a complete wave of peristalsis is always evident as a bolus of food passes down a normal esophagus, peristaltic waves are often incomplete when a dog swallows a liquid. Secondary Peristalsis. The importance of the reception of afferent information from the esophagus is also illustrated by what is described as secondary peristalsis. Frequently, a large bolus of food becomes lodged in a part of the esophagus and the peristaltic wave that initially propelled its movement passes it and disappears. The bolus would remain there unless a mechanism were present to move it on. The motility that performs this function is called secondary peristalsis. Sensory receptors in the esophagus are stimulated by the lodged bolus and relay information through a reflex, which results in an efferent response that initiates a wave of peristalsis to move the bolus caudally from its lodged position. This peristaltic movement begins in the esophagus cranial to the bolus. 19 As evaluated manometrically, secondary peristalsis is indistinguishable from primary peristalsis. This reflex is one with connections in the central nervous system. 19 In summary, the esophagus in the dog is under complete control of the central nervous system, and it is important to recognize that esophageal motor activity is dependent on afferent activity arising from within the esophagus; hence, it is subject to feedback control.
NORMAL STRUCTURE AND FUNCTION OF GASTROESOPHAGEAL JUNCTION AND SPHINCTERL 6 • 23 • 24 The gastroesophageal sphincter is situated at the caudal end of the esophagus. Its function is to prevent regurgitation of gastric contents into the esophagus, and it can be described as a physiologic, rather than an anatomic, sphincter, since it does not consist of layers of muscles that are increased in mass compared with the structures on either side. In the dog, the gastroesophageal sphincter consists of an outer layer of longitudinal striated muscle fibers that is a continuation of that in the esophagus, and an inner layer of circular smooth muscle that merges with the circular striated muscle of the esophagus adjacent to it. The longitudinal layer merges with the smooth muscle of the stomach about 2 mm below the junction of the gastric mucosa and the esophageal stratified squamous epithelium. The operation of the gastroesophageal sphincter is generally considered to be controlled by both the nervous and endocrine systems.
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The closure of the gastroesophageal sphincter prevents the reflux of gastric contents into the esophagus by maintaining a zone of high pressure at all times, except during a swallowing movement. The sphincter relaxes at the onset of a swallowing movement, and this results in a fall in pressure. Sphincter relaxation occurs as long as five seconds before the arrival of the bolus. The striated fibers in the canine gastroesophageal sphincter are responsible for rapid closure of the sphincter, and its smooth muscle fibers function to maintain closure. The sphincter opens and closes as a part of the complex neural activity associated with swallowing, but it can function independently. Vagotomy causes resting gastroesophageal sphincter pressures to be only slightly reduced and greatly reduces the incidence of relaxation and contraction that occurs with swallowing. Relaxation of the sphincter at the onset of swallowing is mediated by vagal nerve fibers. Blockers of cholinergic or adrenergic activity have no effect on the vagally mediated sphincter relaxation, which suggests that a different neurotransmitter is involved. Vagotomy does not cause the smooth muscle to be paralyzed, since it still contains a primitive nervous system that imparts some function, even though it is much less sophisticated than the control exerted by the central nervous system. Extrinsically denervated circular muscle from the sphincter shows intrinsic properties that include an increased resistance to stretch when graded tension is applied. The muscle also shows a decrease in tension when it is stimulated electrically. Since the response is blocked by tetrodotoxin, it is suggested to be nerve mediated, in this case by the intrinsic nervous system. These effects in isolated muscle from the sphincter are different from those of the smooth muscle in structures caudal to the sphincter. The pressure in the gastroesophageal sphincter normally is maintained at 20 to 50 em of water greater than the esophagus or the stomach. The elevated pressure is regulated in part by events that occur in the stomach. Increases in intragastric pressure, whether by food, water, or abdominal compression, cause sphincter pressure to increase and remain greater than intragastric pressure. Electrical stimulation of the central end of one vagus that has been cut causes an increase in pressure in the sphincter. Thus, this response is dependent on normal vagal innervation of the stomach and sphincter and on afferent information from the stomach. It was stated that the sphincter can open and close after all connections with the central nervous system are removed. This function is lost when a circular cuff of muscle is removed from the esophagus just cranial to the sphincter. Thus, function in the sphincter is dependent on events that occur in the esophagus, and its responses are neurally mediated. This control of sphincter function is probably lost when the most caudal parts of the esophagus are diseased.
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Effect of Hormones and Drugs
Hormones and drugs act on the gastroesophageal sphincter and this adds another dimension to the control of its function. 24 • 29 It would seem likely that the hormone gastrin, which mediates gastric hydrochloric acid secretion, should increase pressure in the sphincter and prevent reflux from the stomach filled with food. The infusion of gastrin into dogs shows that the hormone does indeed increase sphincter pressure. However, this response is to pharmacologic concentrations of gastrin, and more recent studies have shown that the response is not observed with physiologic levels of gastrin release. In dogs, feeding does not increase pressure in the gastroesophageal sphincter, despite a normal response of gastrin release. 18 Other data suggest that normal physiological levels of gastrin increase sphincter pressure in other species. It can be concluded that gastrin plays a role in maintaining a high pressure in the gastroesophageal sphincter during secretion of gastric juices and digestion of food, but that it is less important than originally thought. The effects of gastrin on the circular muscle of the sphincter are blocked by atropine and tetrodotoxin, which suggests that the hormone acts through a nerve pathway. Secretin is a competitive inhibitor of the action of gastrin on the gastroesophageal sphincter. Secretin also inhibits the release of gastrin. Some experiments have shown that alkalinization of the stomach can increase sphincter pressure by reciprocal changes in secretion of the two hormones. Thus, it is evident that gastroesophageal pressure is regulated by a number of gastrointestinal tract hormones that compete for receptor sites. Cholecystokinin and glucagon have inhibitory effects similar to that of secretin. Dietary nutrients affect pressure m the gastroesophageal sphincter. Proteins cause the pressure to increase and fatty meals cause the pressure to decrease. Fat in the diet inhibits the gastrinmediated increase in sphincter pressure. Normal anatomical relationships are important for normal function in the sphincter, and they contribute with neural innervation and endocrine regulation to the optimal functioning of the gastroesophageal sphincter. Premedication drugs used prior to administration of anesthetic agents have been found to lower the pressure in the gastroesophageal sphincter and increase the probability of reflux. 13 These drugs include morphine, pethidine, diazepam, and anticholinergics. Metoclopramide and bethanechol, two drugs that increase motility in the sphincter, can cause its pressure to increase. Inflammation
Inflammation of the esophagus has been shown to cause the gastroesophageal sphincter pressure to decrease in the cat. 11 This is a
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potential positive feedback situation where the presence of esophagitis results in decreased sphincter pressure, which increases the possibility of further reflux and perpetuation of the esophagitis.
MEGAESOPHAGUS EPIDEMIOLOGY
Megaesophagus is the most common motor disturbance involving deglutition in the dog. It is the most appropriate term to describe the dilated esophagus, until the time when the etiologies and the pathogenesis of all cases of esophageal paralysis are understood. Megaesophagus is reported to primarily affect pups, and some studies have shown that it can be genetically determined. 10 • 26 An eight-year survey of cases of megaesophagus at the University of Pennsylvania Veterinary Hospital revealed that two-thirds of their cases developed clinical signs by 10 weeks of age and only 20 per cent developed signs after one year of age. 14 Over an eight-year period at the Veterinary Medical Teaching Hospital (VMTH), University of California, Davis, 55 per cent of 125 dogs with megaesophagus were one year of age or less when signs began. Ten per cent of the dogs were one to two years of age and 25 per cent were distributed equally over ages of from two to seven years. Ten per cent were in a seven to 15 year age group. Thus, a considerable number of adult dogs develop the problem. One published report on megaesophagus describes most of the dogs as being over one year of age. 17 Megaesophagus must be considered in the differential diagnosis of animals of any age that are presented with signs of regurgitation. Incidence by Breed
The incidence of megaesophagus is greater in certain breeds of dogs. The incidence in Great Danes at Pennsylvania was eight times greater than would be expected, and at the VMTH in Davis, the incidence was 10 times greater than what should be found if there is no breed predeliction. In the two studies, the incidence of megaesophagus in German shepherds was twice the anticipated rate. This same predeliction prevailed in Irish setters. Previous reports are cited as identifying the Great Dane and German shepherd as having a higher incidence of megaesophagus. Certain strains· of wirehaired fox terriers have also been reported to have a form of the problem that is inherited. The incidence of megaesophagus was greater than anticipated in female dogs at Pennsylvania, but at the VMTH in Davis, there was an equal number of males and females affected in a population of equal numbers of males and females. In summary, more German shepherds are identified as having
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megaesophagus because of the popularity of the breed, but the Great Dane breed has a greater problem since the anticipated incidence of the disease is up to 10 times greater than normally expected, a rate that is much higher than that in the German shepherd. The overall incidence of megaesophagus at both hospitals was two to three out of every 1000 patients. This rate is anticipated to be higher than in the overall population, since a number of the cases at institutions are referrals. PATHOGENESIS OF MEGAESOPHAGUS
Achalasia The term achalasia was one of the most popular in the past to describe what is now collectively called megaesophagus. It was believed that the problem developed because the gastroesophageal sphincter failed to open, and accumulation of food in the caudal esophagus caused it to dilate. This theory was used to describe the pathogenesis of achalasia in man, and veterinarians considered the problem in dogs to be similar. The current belief is that megaesophagus does not develop for this reason. 7 • 12 • 14 • 31 • 32 The problems in dogs and man cannot be compared, since the anatomy of the middle and caudal thirds of the canine esophagus is completely different from that in man. In the dog, the muscles that are responsible for peristalsis are striated throughout the entire length of the esophagus, while in man, the lower third is all smooth muscle and the middle third is mixed striated and smooth. An important abnormality found in achalasia in humans is degeneration of neurons in the intrinsic nervous system, which is found within the smooth muscle of the esophagus. Thus, the changes found in the body of the dilated canine esophagus, consisting of paralyzed striated muscle fibers, cannot be compared with those that occur in the paralyzed smooth muscle of the esophagus in human beings. Only a small layer of smooth muscle is found in the muscularis mucosa in the dog, and it does not contribute to the peristaltic propulsion of a bolus through the esophagus. The numbers of neurons in the intrinsic plexuses is not reduced in this layer of smooth muscle in dogs with megaesophagus. 4 It is likely that achalasia of the gastroesophageal sphincter could produce megaesophagus in the esophagus made up of striated muscle as readily as in that fashioned from smooth muscle. Dilations that develop from strictures usually remain following correction of the stricture. Only recently has function been evaluated in the gastroesophageal sphincter in cases of canine megaesophagus. There has been only one study reported in which the gastroesophageal sphincter was evaluated by both cineradiography and
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manometric procedures in dogs with megaesophagt:s. 7 The finding was that function in the sphincter was normal. All the dogs in this study had normal esophageal function in the most caudal part of the thoracic esophagus. All the pathology was confined to the cranial and middle parts of the thoracic esophagus. Videofluoroscopic studies in cases of megaesophagus at the VMTH in Davis have not revealed achalasia to be present. Dogs with megaesophagus that involves the entire esophagus and extends to the gastroesophageal sphincter do not show passage of food through the sphincter until the esophagus is tilted into a more vertical position. Gravity moves the food, and the gastroesophageal sphincter offers no resistance to its passage. Studies on normal animals indicate that the information of a bolus of food approaching the sphincter is necessary for it to open properly. It was indicated earlier that removal of the segment of thoracic esophagus adjacent to the sphincter results in a loss of sphincter function. This suggests that sphincter function is not likely to be normal when megaesophagus extends to the sphincter. Thus, the radiologist will not see the sphincter opening and closing when there is an abnormal segment of the esophagus directly adjacent to it. However, if the most caudal segment of the esophagus is normal, the reflex is intact. The only means of definitively determining if an area of increased resistance exists in the gastroesophageal sphincter is by conducting manometric measurements. Radiography cannot answer this question. Increased pressure in the gastroesophageal sphincter in man with achalasia is suggested to be in part produced by circulating gastrin. The intrinsically denervated smooth muscle in achalasia is supersensitive to gastrin. However, it has not been shown that the circular layer of smooth muscle in the dog's sphincter loses its intrinsic innervation, nor that a higher than normal pressure zone exists in the sphincter. 4 • 7 The parasympathetics only regulate function in the gastroesophageal sphincter. With extrinsic denervation, the resting pressure decreases, but the sphincter can still open and close, thus, offering no resistance to the passage of a bolus. 1 Therefore, a lesion in the extrinsic parasympathetic pathway should not produce achalasia that can lead to megaesophagus in the dog. Loss of Motor Function
The abnormality in megaesophagus is a loss of motor function. A defect in any part of the neural pathway that is necessary for normal esophageal function or in the muscle and myoneural junction will cause a loss of function. Megaesophagus can be produced in the experimental dog by cutting the vagus nerves or by bilateral destruction of the nucleus ambiguus. 16 The motor unit consists of the cranial lower motor neurons in the nucleus ambiguus, the efferent nerve
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fibers in the vagus, the myoneural junction, and the striated muscle fibers. A defect in one part would cause paralysis of the esophagus. A defective motor unit would also result in denervation atrophy, but histologic studies on the muscle in a megaesophagus usually produce normal results, and the changes that are found are usually secondary. Loss of function in the motor unit will also cause denervation potentials to appear on electromyograms, 28 but such recordings at all levels of the esophagus in a small group of dogs with megaesophagus were normal. 32 In the same study, stimulation of the vagus nerves resulted in contraction of the esophagus, a response that would not be possible if a lesion was present in the motor unit. Thus, the esophageal motor unit is normal in megaesophagus, and this indicates that the cranial lower motor neurons in the nucleus ambiguus are normal. Serial sections of the brain stem from one dog with megaesophagus were reported to have a reduced number of cell bodies in the nucleus ambiguus. 5 Unpublished data have been cited to indicate that this is not the situation, but that the number of neurons in the nucleus ambiguus is normal in dogs with megaesophagus. 21 Another study on the effects of vagal stimulation in dogs with megaesophagus produced data that suggested the problem is mainly a neural rather than a muscular defect, but no suggestions were made as to the site of the lesion. 12 A study reported on two dogs suggests that the lesion is the same in pups born with megaesophagus as in dogs that acquire it as an adult. 32 These same observations have since been made on a larger number of animals. The presence of a normal motor unit indicates that the lesion is in either the cranial upper motor neurons or in the receptors or afferent limb of the swallowing reflex. The afferent limb of the reflex consists of nerve fibers that travel in the brain in the tractus solitarius to the nucleus of this tract. Synaptic fibers connect the nucleus of tractus solitarius with the swallowing center, which is located in the medial part of the lateral reticular formation. 25 This center contains the cranial upper motor neurons, and it sends fibers to the respiratory inhibitory centers and to the cranial lower motor neurons in the nucleus ambiguus, which is the beginning of the motor unit. There is evidence that some of the respiratory reflexes mediated by afferent fibers in the vagus are abnormal in some dogs with megaesophagus. 32 This is consistent with the clinical evidence for impairment of respiratory reflexes that is suggested by the high frequency of aspiration pneumonia in dogs with megaesophagus. The pathogenesis of the lesion in megaesophagus is completely unknown. There is evidence for its genetic transmission. Karyotyping has not revealed any chromosomal abnormality in pups with the problem.30 A wide variety of motility disorders have been associated with other types of acquired problems, which have included such diverse
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things as neoplastic and infectious diseases, pharmaceutical agents, or general anesthesias. The relationship between these problems and the development of megaesophagus is unknown. It is possible that a group of neurons in the swallowing reflex is more sensitive to the effects of toxins, drugs, or anesthesias than others in the brain.
RELATED MOTILITY DISORDERS
Megaesophagus is not the most accurate term to describe motility disturbances of the esophagus, since a loss of motor function can occur without the devdopment of megaesophagus. These problems are difficult to diagnose unless it is possible to conduct a motility study of the esophagus with radiographic procedures using positive contrast medium and fluoroscopic control. It is often difficult to determine whether motility is normal or abnormal, and whether the abnormal motility is contributing to a dog's clinical signs. Incoordination of Motor Function
One type of abnormality that can be seen consists of a loss of much of the normal peristaltic activity of the esophagus, and contractions that are evident consist of random and incoordinated movements. This type of motility generally produces marked signs of regurgitation, anorexia, and in many cases, esophageal colic. Part of the animal's anorexia is suggested to be the result of painful spasms of the esophagus when a bolus is swallowed. This type of problem produces a more immediate regurgitation than megaesophagus, even if the motility is confined to the caudal half of the esophagus. An esophagitis can cause esophageal dysphagia where incoordination of motor function is the main feature. This has been shown in the experimental dog/ 5 as well as having been recognized clinically. This undoubtedly occurs much more frequently than it is recognized. Few small animals with acute signs of vomiting or regurgitation are evaluated for an esophagitis by endoscopy, or for the loss of coordinated esophageal function by fluoroscopy during a swallow of contrast medium. Most of these animals recover, and consequently, function in the esophagus is never investigated. In general, animals with radiographically determined incoordination of motility without megaesophagus can improve with time and nonspecific treatment. Clinical improvement is accompanied by radiographic signs of improvement. The motility disorder associated with an esophagitis may be caused by damage to either the sensory receptors in the esophagus or to the peripheral part of the motor unit. It is also possible that in some cases, both problems are caused by ingestion of some toxin, and the motility disorder is a manifestation of central effects of the toxin.
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Motility Deficit A second variety of motility disorder in which megaesophagus is not apparent exists in the dog with radiographic evidence of little or no motility of any type in a normal appearing esophagus. Surprisingly, these animals do not show as severe signs of regurgitation as the dog with random spasms of the esophagus. In some cases there are few, if any, clinical signs. This problem often develops with an inflammatory process in the esophagus. It has also been associated with local esophagitis that causes stricture formation. In contrast to the dog that shows few clinical signs with an esophagus that appears to be hypomotile, some dogs will acquire a motility deficit in a section of esophagus that is only a few centimeters long, and, surprisingly, show severe signs of regurgitation. Such a motility defect may be so subtle that it is difficult to recognize using radiographic procedures. This illustrates that it is not possible to correlate the degree of clinical signs with the severity of radiographic abnormalities. Some of these motility disturbances over a short segment of esophagus are the sequel to damage by a foreign body. Megaesophagus involving one small region of the esophagus is sometimes seen to contract and develop a wave of peristalsis that moves the contents to the stomach. Obviously, the esophagus is not paralyzed, and this problem may represent another example of a defect in the upper motor neurons or the afferent pathway of the swallowing reflex.
EVALUATION OF MOTOR DISTURBANCES Motor disturbances of deglutition are suspected and seldom overlooked if an accurate and complete history is obtained. Obvious signs that the owner will observe are both oral and nasal regurgitation of food, multiple swallowing movements, and hesitation in the initiation of swallows. Many dogs with esophageal motility disturbances may be presented with coughing, dyspnea, gagging, esophageal colic, and hypersalivation as either the primary signs or as the only signs. The differential diagnosis should include esophageal problems whenever any of these signs is evident. The diagnosis of a motor disturbance of the esophagus can only be confirmed by radiographic procedures. Contrast studies should be conducted with the swallowing of both liquids and solid food. Some problems are not properly identified with liquid contrast, since liquids do not stimulate the progressive wave of peristalsis that is produced by a bolus of food. Endoscopy may be of value in dogs with megaesophagus, but it is of no value in evaluating a motility disturbance.
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MANAGEMENT AND PROGNOSIS There is no specific medical treatment for motility disorders of the esophagus. Any concurrent problems that are found should be treated. If a motility disturbance without megaesophagus is recognized, it can be managed with nonspecific treatment, and up to six weeks should be allowed before a final evaluation of recovery is made. Dogs with megaesophagus are not helped with either nonspecific therapy or surgery. It has been reported tlwt me~aesophagus can be a reversible problem. Improvement may occur to a limited extent with the congenital form. Young animals do not normally achieve complete function of the esophagus until they mature. The maturation of swallowing function has been evaluated in growing pups that were normal and ones born with megaesophagus. 8 Manometric measurements show that the motility function of the esophagus continues to mature in many pups with megaesophagus, as well as in normal pups, so that as an adult they may be clinically improved. Thus, improvement is possible, but the problem is not reversible. Any evaluation on the improvement of megaesophagus should also be based on radiographic studies employing fluoroscopy. There is no evidence that the acquired megaesophagus recovers any part of its normal function. Surgery Recommendations for surgical treatment of megaesophagus are based on the theory that an achalasia exists in the gastroesophageal sphincter, and as a consequence, myotomy has been performed. In one report from Pennsylvania, 40 per cent of dogs with megaesophagus underwent surgery. Since the results were poorer than in those that were not treated surgically, the surgery is no longer recommended. From 1967 to 1975, 18 per cent of the cases of megaesophagus at the VMTH in Davis were treated surgically, the results of which have not been evaluated. All cases of megaesophagus that are treated surgically are also managed postsurgically by placing the dog's food at an elevated position, so that the dog must eat in a semivertical position. If any improvement follows, it is not possible to attribute the results to successful surgery. It is more likely that the postsurgical management procedures are responsible for the improvement. · There is no rationale for performing a myotomy unless radiographic studies reveal a stricture at the gastroesophageal junction. As indicated earlier, it has been shown that a higher than normal pressure zone is not a feature of the gastroesophageal sphincter in dogs with megaesophagus. 7 Thus, myotomies should not be done. Complications of myotomies on this sphincter have included herniation of the stomach into the esophagus and gastroesophageal reflux.
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Special Feeding Practices The only successful management of motor disturbances of the esophagus involves the use of special feeding practices. As a first attempt, the client should initiate feeding diets of different consistencies and food particle size. In general, diets that are a semiliquid gruel are usually swallowed the most readily, since a feeble wave of peristaltic activity can more readily move a liquid bolus, with less resistance to its flow over a long distance, than a solid bolus. Also, with the aid of gravity, a liquid bolus will move through a paralyzed section of esophagus more readily than a bolus of solid food. This is the basis for feeding a liquid gruel from an elevated position. Some animals cannot maintain nutritional homeostasis with the use of this procedure, and the owner is trained to pass a stomach tube through which the animal is fed. In some dogs with a motility disturbance of the most cranial part of the cervical esophagus, chunks of food are swallowed easier than a soft or semiliquid diet. During client education, it is emphasized that the best management program for each patient may differ from that which is recommended for most animals with the problem, and that a number of different trials will reveal which management will be the most successful.
ESOPHAGEAL MOTILITY DISORDERS IN THE CAT Motor disturbances are seen in the esophagus of cats. The incidence is less than one case per 1000 cats seen at Davis. Based on anatomic similarities, megaesophagus in cats can be compared to achalasia in man. Both species have smooth muscle in all the muscle layers of the distal one-half to one-third of the esophagus. Histologic studies of sections of the feline megaesophagus have shown that there is a normal number of ganglia cells of the intrinsic plexuses. 3 Thus, the problem differs from that in man. It has been suggested to be an inherited defect. 3 The site of the lesion has not been identified. One study reported on a series of cats with esophageal dysfunction that was associated with abnormal gastric retention of food. 27 The clinical signs of persistent vomiting were corrected with a pyloromyotomy, and subsequently normal esophageal function returned. The cats had a reversible megaesophagus. It has been shown that esophagitis, which would be produced by chronic vomition, causes a loss of gastroesophageal sphincter competence.U Furthermore, esophagitis causes deranged esophageal motility. 15 It is not unusual to see a loss of normal peristalsis with some evidence for megaesophagus when the esophageal mucosa has been chemically or mechanically traumatized. The study reported on the cats indicates that esophageal function has a good chance of returning when the vomiting problem is controlled.
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REFERENCES I. Arimori, M., Code, C. F., Schlegel, J. F., et a!.: Electrical activity of the canine esophagus and gastroesophageal sphincter. Am. J. Dig. Dis., 15:191-208, 1970. 2. Carveth, S. W., Schlegel, J. F., Code, C. F., et a!.: Esophageal motility after vagotomy, phrenicotomy, myotomy, and myomectomy in dogs. Surg. Gynecol. Obstet., 114:31-42, 1962. 3. Clifford, D. H.: Myenteric ganglial cells of the esophagus in cats with achalasia of the esophagus. Am. J. Vet. Res., 34: 1333-1336, 1973. 4. Clifford, D. H., and Gyorkey, F.: Myenteric ganglial cells in dogs with and without achalasia of the esophagus. J. Am. Vet. Med. Assoc., 150:205-211, 1967. 5. Clifford, D. H., Pirsch, J. G., and Mauldin, M. L.: Comparison of motor nuclei of the vagus nerve in dogs with and without esophageal achalasia. Proc. Soc. Exp. Bioi. Med., 142:878-882, 1973. 6. Code, C. F., and Schlegel, J. F.: Motor action of the esophagus and its sphincters. In Code, C. F. (ed.): Handbook of Physiology. Washington, D. C., American Physiological Society, 1968. Vol. 4, Section 6 - Alimentary Canal, pp. 1821-1839. 7. Diamant, N., Szczepanski, M., and Mui, H.: Manometric characteristics of idiopathic megaesophagus in the dog: an unsuitable animal model for achalasia in man. Gastroenterology, 65:216-223, 1973. 8. Diamant, N., Szczepanski, M., and Mui, H.: Idiopathic megaesophagus in the dog: reasons for spontaneous improvement and a possible method of medical therapy. Can. Vet. J., 15:66-71, 1974. 9. Doty, R. W.: Neural organization of deglutition. In Code, C. F. (ed.): Handbook of Physiology. Washington, D. C., American Physiological Society, 1968. Vol. 4, Section 6 - Alimentary Canal, pp. 1861-1902. 10. Earlam, R. J., Zollman, P. E., and Ellis, F. H.: Congenital oesophageal achalasia in the dog. Thorax,22:466-472, 1967. II. Eastwood, G. L., Castell, D. 0., and Higgs, R. H.: Experimental esophagitis in cats impairs lower esophageal sphincter pressure. Gastroenterology, 69:146-153, 1975. 12. Gray, G. W.: Acute experiments on neuroeffector function in canine esophageal achalasia. Am. J. Vet. Res., 35:1075-1081, 1974. 13. Hall, A. W., Moosa, A. R., Clark, J., et a!.: The effects of premedication drugs on the lower oesophageal high pressure zone and reflux status of Rhesus monkeys and man. Gut, 16:347-352, 1975. 14. Harvey, C. E., O'Brien, J. A., Durie, V. R., et a!.: Megaesophagus in the dog: a clinical survey of 79 cases. J. Am. Vet. Med. Assoc., 165:443-446, 1974. 15. Henderson, R. D., Mugashe, F., Jeejeebhoy, K. N., eta!.: The role of bile and acid in the production of esophagitis and the motor defect of esophagitis. Ann. Thorac. ?urg., 14:465-473, 1972. 16. Higgs, B., Kerr, F. W. F., and Ellis, F. H.: The experimental production of esophageal achalasia by electrolytic lesions in the medulla. J. Thorac. Cardiovasc. Surg., 50:613-625, 1965. 17. Hofmeyr, C. F. B.: An evaluation of cardioplasty for achalasia of the oesophagus in the dog. J. Small Anim. Pract., 7:281-301, 1966. 18. Hollenbeck, J. I., Maher, J. W., Wickbom, G., et a!.: The effect of feeding on the canine lower esophageal sphincter. J. Surg. Res., 18:497-499, 1975. 19. Janssens, J., Valembois, P., Hellemans, J., et a!.: Studies on the necessity of a bolus for the progression of secondary peristalsis in the canine esophagus. Gastroenterology, 67:245-251, 1974. 20. Janssens, J., Valembois, P., Vantrappen, G., et a!.: Is the primary peristaltic contraction of the canine esophagus bolus-dependent? Gastroenterology, 65:750-756, 1973. 21. Leipold, H.: Unpublished observations cited by Guffy, M. M., in Esophageal Disorders. In Ettinger, S. J. (ed.): Veterinary Internal Medicine. Philadelphia, W. B. Saunders Co., 1975. 22. Lynch, V. P., Schlegel, J. F., and Ellis, F. H.: Autotransplantation of the canine esophagus. Surg. Gynecol. Obstet., 138:396-400, 1974. 23. Miller, M. E., Christensen, G. C., and Evans, H. E.: Anatomy of the Dog. Philadelphia, W. B. Saunders Co., 1964.
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24. Misiewicz, ]. J.: Symposium on gastroesophageal reflux and its complications. Section 4, Pharmacology and therapeutics. Gut, 14:243-246, 1973. 25. Nakayama, S., Neya, T., Watanable, K., et a!.: Effects of electrical stimulation and local destruction of the medulla oblongata on swallowing movements in dogs. Rendic. Gastroenterol., 6:6--11, 197 4. 26. Osborne, C. A., Clifford, D. H., and Jessen, C.: Hereditary esophageal achalasia in dogs.]. Am. Vet. Med. Assoc., 151:572-581, 1967. 27. Pearson, H., Gaskell, C.]., Gibbs, C., eta!.: Pyloric and oesophageal dysfunction in the cat.]. Small Anim. Pract., 15:487-501, 1974. 28. Pelemans, W., VanTrappen, G., Hellemans, J., et a!.: Denervation potentials in the canine esophagus. In Proceedings of the Fourth International Symposium on Gastrointestinal Motility. Vancouver, Mitchell Press, 1974. 29. Pope, C. E.: Pathophysiology and diagnosis of reflux esophagitis. Gastroenterology, 70:445-454, 1976. 30. Smith, A.: Unpublished cases from the Veterinary Medical Teaching Hospital, Davis, California. 31. Sokolovsky, V.: Achalasia and paralysis of the canine esophagus.]. Am. Vet. Med. Assoc., 160:943-955, 1972. 32. Strombeck, D. 'R., and Troya, L.: Evaluation of lower motor neuron function in two dogs with megaesophagus. J. Am. Vet. Med. Assoc., 169:411-414, 1976. Department of Medicine University of California School of Veterinary Medicine Davis, California 95616