diagnosis and treatment of gastric motility disorders

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DIAGNOSIS AND TREATMENT OF GASTRIC MOTILITY DISORDERS

ic.ad se:retion. Drug Res 41:954-957, 1991 Address reprint requests to

Jean A Hall, DVM, PhD, and Robert J. Washabau, VMD, PhD

Dawn Merton Boothe, DVM, PhD Texas A&M University College of Veterinary Medicine ~~~- Physiology and Pharmacology College Station, TX 77843-4466

Gastric motility serves three basic functions: storage of ingesta, mixing and dispersion of food particles, and timely expulsion of gastric contents into the duodenum. Disorders of gastric motility result from diseases that either directly or indirectly disrupt these functions. In general, naturally occurring disease states are associated with delay of gastric emptying; acceleration of gastric emptying is less frequently observed.

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Delayed gastric emptying most often results in gastric distension, retention of food, and vomiting. 24• 29 • 78• 81 A gastric motility disorder should be considered when there is a history of chronic vomiting. Vomiting may or may not be associated with feeding. Typically, vomiting of undigested or partially digested food is observed 8 to 10 hours after feeding, at a time when the stomach should be empty of ingested solids. The character of the vomitus is dependent on time lapse since the last meal, degree of gastric trituration, amount of gastric secretions, and extent of hydrolytic digestion. Other signs of a gastric motility disorder may include anorexia, belching, polydipsia, pica, and weight loss. Ani-

From the Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon (JAH), and the Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (RJW)

VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 29 • NUMBER 2 • MARCH 1999

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mals may occasionally assume a position of relief known as the "praying posture" to relieve gastric pain. The physical examination may be normal or may reveal findings associated with the underlying disease process. Abdominal distension may be present, increased bowel sounds may be noted with abdominal auscultation, or nonspecific pain may be evoked on abdominal palpation. Palpable abdominal masses are most consistent with intestinal or other visceral neoplasia, foreign bodies, and intussusceptions. Neuromuscular abnormalities may also be observed in dogs with severe electrolyte or metabolic derangements secondary to chronic vomiting. Laboratory Findings

Laboratory findings are somewhat dependent on the underlying cause. Dogs with persistent vomiting often exhibit dehydration, electrolyte abnormalities, and acid-base disturbances. Gastric outflow obstruction may result in the net loss of hydrogen, chloride, potassium, and sodium ions. Hypokalemia is the most common electrolyte abnormality, resulting from potassium losses in vomitus and renal excretion and from reduced dietary intake. Paradoxical aciduria is observed in some dogs when vomiting occurs secondary to gastric outflow obstruction.

times, it: is difficult to diagnose a1 emptying times are markedly pi:'OIQ Small radiopaque markers sud ene spheres (BIPSs) can also be 111 dogs and cats. 24• 25• 31 BIPSs are ac Prescription Diet d/ d [Hill's Pet ] quantities to meet 25% of the anim four abdominal radiographs are tal next 12 to 24 hours. 25 The percenJaa is calculated and compared with 8 provided in the manufacturer's p BIPS gastric emptying data has sam tation of data obtained from barn.. studies are more useful in dOCUIDII tional obstruction. If available, radioisotope II1elb! gastric emptying. 13• 37• 73 TechnetiUDl' because it is safe, simple to use • radionuclide can be repeated withol Two radionuclide markers can be II solid and liquid emptying to be a&l! The expense and limited availabil widespreap .,epplication in dogs aDil

Tests Used to Evaluate Gastric Motility

Endoscopy and Exploratory l..apl

Methods that are available for evaluating gastric emptying include radioisotope scanning, serial sampling of gastric contents by intubation, ultrasonography, computed tomography, electrophysiology, and manometry. Radiographic techniques are the most available means for diagnosing gastric motility disorders in veterinary practice. Liquid barium sulfate can be used to detect gross abnormalities of gastric emptying. Unfortunately, these contrast studies provide inadequate assessment of the emptying of a typical heterogeneous meal, because solids and liquids empty differently as do large and small particles as well as lipids and carbohydrate solutions. 34• 41 • 49 Delayed gastric emptying may be suspected if liquid barium sulfate remains in the stomach for more than 4 hours in dogs or more than 30 minutes in cats. 55 Barium mixed with food is believed to be a better contrast agent for the study of distal gastric motor function. When solid meals are mixed with barium granules or a barium suspension, however, the barium can dissociate from the food and redistribute into the liquid phase of the gastric contents. 38 The gastric emptying time of ground kibble (8 g/kg) mixed with barium sulfate suspension (5-7 mL/kg) in mature healthy Beagles was reported to range from 5 to 10 hours. 53 In a similar study performed in mixed-breed dogs, total gastric emptying time ranged from 7 to 15 hours. 10 Because of the wide range in reported normal emptying

Endoscopic examination of tl lesions associated with gastric oudl bodies, ulcers, neoplasms, and inflal ric stenosis, for example, may appi pyloric sphincter. Endoscopy IDil) biopsy, brush cytology, fluid colle (e.g., foreign body retrieval, percula tube placement) procedures. Exploratory surgery is indicate extramural lesion is suspected of : The stomach and other viscera sllOII and full-thickness biopsies should 1

REGULATION OF GASTRIC a.1

Disorders of gastric motility (! common link for a number of disl inherent properties of gastric smool by neurohumoral input ultimately these control mechanisms do not 1

GASTRIC MOTILITY DISORDERS

ion of relief known as the "praying

be normal or may reveal findings R process. Abdominal distension nds ma\· be noted with abdominal r be e'\:oked on abdominal palpaBklSt consistent with intestinal or lies. and intussusceptions. NeuroDbserYed in dogs with severe elec~- to chronic vomiting.

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allen exhibit dehydration, electro.-bances. Gastric outflow obstrucchloride, potassium, and t mmmon electrolyte abnormality, -.us and renal excretion and from ICidmia is observed in some dogs .aric outflow obstruction.

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., aluating gastric emptying include ~ ol gastric contents by intubation, ... electrophysiology, and manom-.st available means for diagnos~- practice. d lo detect gross abnormalities of ~ rontrast studies provide inaderl a typical heterogeneous meal, ~tly as do large and small llydr.lte solutions. 34• 41 • 49 Delayed · liquid barium sulfate remains in D dogs or more than 30 minutes !d lobe a better contrast agent for lion. When solid meals are mixed pension. however, the barium can IJale into the liquid phase of the S time of ground kibble (8 g/kg) l (>-7 mL/kg) in mature healthy ; lo 10 hours. 53 In a similar study ;astric emptying time ranged from nge in reported normal emptying

379

times, it is difficult to diagnose an emptying disorder unless gastric emptying times are markedly prolonged. Small radiopaque markers such as barium-impregnated polyethylene spheres (BIPSs) can also be used to quantify gastric emptying in dogs and cats. 24• 25• 31 BIPSs are administered in food (usually Hill's Prescription Diet d/ d [Hill's Pet Nutrition, Topeka, KS] in sufficient quantities to meet 25% of the animal's daily caloric needs), and two to four abdominal radiographs are taken at convenient intervals over the next 12 to 24 hours. 25 The percentage of BIPSs that have left the stomach is calculated and compared with the standard gastric emptying curves provided in the manufacturer's packaging brochure. Interpretation of BIPS gastric emptying data has some of the same limitations as interpretation of data obtained from barium studies. BIPS and barium emptying studies are more useful in documenting mechanical rather than functional obstruction. If available, radioisotope methods are the best means of evaluating gastric emptying. 13• 37• 73 Technetium 99m is the isotope used most widely because it is safe, simple to use and nonabsorbable; studies using this radionuclide can be repeated without interference from previous studies. Two radionuclide markers can be tracked simultaneously, which allows 52 solid and liquid emptying to be assessed during the same test period. The expense and limited availability of this method have limited its widespread application in dogs and cats. _ ='"""'"

Endoscopy and Exploratory Laparotomy

Endoscopic examination of the stomach is useful in identifying lesions associated with gastric outflow obstruction, for example, foreign bodies, ulcers, neoplasms, and inflammatory or obstructive lesions. Pyloric stenosis, for example, may appear as a grossly thickened and closed pyloric sphincter. Endoscopy may also be used for diagnostic (e.g., biopsy, brush cytology, fluid collection and analysis) and therapeutic (e.g., foreign body retrieval, percutaneous endoscopic gastrostomy (PEG) tube placement) procedures. Exploratory surgery is indicated as a diagnostic procedure when an extramural lesion is suspected of causing gastric outflow obstruction. The stomach and other viscera should be palpated for infiltrative lesions, and full-thickness biopsies should be taken for definitive diagnosis. REGULATION OF GASTRIC EMPTYING

Disorders of gastric motility control mechanisms may be the final common link for a number of disease processes affecting motility. The inherent properties of gastric smooth muscle cells and their modification by neurohumoral input ultimately control gastric motility. Disorders of these control mechanisms do not constitute disease entities per se but

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may provide the mechanisms by which various disease processes produce similar symptoms of nausea, vomiting, and altered motility. 33• 75• 83 Smooth muscle cells in the distal stomach have slow fluctuations in membrane potential. Extracellular recordings from the gastric serosal surface show that these changes in membrane potential produce the gastric slow waves. The dominant slow waves originate from a group of cells called the "gastric pacemaker" located in the midstomach along the greater curvature. These smooth muscle cells have the highest frequency of spontaneous depolarization, and their slow waves propagate distally (approximately 5 per minute) through the longitudinal muscle layer to the pylorus. Action potentials, which only occur during a specific phase of the slow-wave cycle, are associated with contractions. During the fasting state, a cyclically recurring series of electrical events called the "migrating motility complex" (MMC) occurs every 90 to 120 minutes. 14 This cycle is composed of three phases followed by a transition from phase III back to phase I again. The time period from feeding to appearance of the fasting motility pattern ranges from 6 to 16 hours in normal dogsY· 39 The digestive pattern ends with a series of strong peristaltic contractions involving most of the stomach. This series is followed by a phase of motor quiescence which lasts approximately 60 to 110 minutes. Gastric contractions then reappear, gradually increase in frequency, and culminate in a 10- to 25-minute phase of intense peristaltic contractions. Quiescence returns, and the cycle repeats until the animal feeds again. Phase I is a period of quiescence, phase II is a period of increasing but irregular contractile activity, and phase III is a period of intense regular contractions. During phase III, a contraction occurs with almost every slow-wave cycle (4--5 contractions per minute). The MMC passes from the stomach and small intestine to the colon in approximately 2 hours. At about the time that a phase III front reaches the terminal ileum, another phase III front begins in the stomach. Disorders of gastric motility control mechanisms associated with the fasting state may include slow-wave dysrhythmias (e.g., tachygastria, bradygastria), increased action potentials, decreased action potentials, absence of phase III, decreased occurrence or disruption of phase III, and retrograde propagation of phase III-like activity. 29 Disorders of gastric motility control mechanisms during the fed state have been less well documented in dogs and cats. In summary, because the mechanical activity of the stomach ultimately is linked to gastric slow waves, any disorder that disrupts the normal slow-wave activity has the potential to disrupt coordination of the mechanical activity. Dysrhythmias may therefore be fundamental in the pathophysiology of disorders affecting gastric motility. DISORDERS OF GASTRIC MOTILITY

There are three general types of gastric motility disorders: accelerated gastric emptying, retrograde transit (e.g., enterogastric and gastro-

esophageal reflux), and delayed p tional obstruction). · Accelerated Gastric Emptying

Gastric motility disorders aaa usually iatrogenic in origin. 1'heai syndrome, which may occur seeD~ gastric vagotomy, vagotomy with 1 enterostomy. 36• 40• 50• 52• 59 Prokinetic dl ated gastric emptying. Retrograde Transit

Gastric motility disorders asso vomiting, gastroesophageal refiUX,4 vomiting syndrome. Vomiting is a~ it represents the extreme form of 1 reflux is a less extreme form of ft! emptying may contribute to the llil malities in liquid or solid food e11111 been obser~d in patients with gall Duqdenogastric reflux can be, an epiphenomenon associated wi disorder (abnormal pyloric functio ary to chronic gastritis. Bilious 'ftl pathic disorder associated with d fected dogs tend to vomit smaH a empty stomach after an overnig1 disorders is often made by sympllll Delayed Gastric Emptying:

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Anatomical lesions of the pyl impede gastric emptying because 1 eral, diagnosis of mechanical obaf,t involves survey and contrast radii copy (Fig. 1). Surgical removal ol, is the preferred therapy. Gastroial dicated in treating patients with • Pyloric stenosis or chronic II common cause of gastric outflow Cl dogs are of male gender, YOUIIJ! of small breeds. Histopathologiall circular muscles of the pylorus, b.] or a combination of both muscula

idh '~ disease processes proBiiling.. and altered motility. 33, 75' 83 IIDmach have slow fluctuations in !IIJnlings from the gastric serosal -.embrane potential produce the IIRr waves originate from a group • bated in the midstomach along wmsde cells have the highest fre'- and their slow waves propagate t lbrough the longitudinal muscle lills,. "M~ilich only occur during a ~are associated with contractions. I!ICUJting series of electrical events .,r (MMC) occurs every 90 to 120 ~ phases followed by a transi~ The time period from feeding pallt:tn ranges from 6 to 16 hours lllsn ends with a series of strong at ol the stomach. This series is !IKr which lasts approximately 60 IBl reappear, gradually increase in 5-minute phase of intense peristaland the cycle repeats until the Iaf quiescence, phase II is a period actnity, and phase III is a period liB phase ill, a contraction occurs 1-5 Ollltractions per minute). The t small intestine to the colon in lillie that a phase III front reaches liunt begins in the stomach. iiiDI mechanisms associated with eclysrhythmias (e.g., tachygastria, liills, decreased action potentials, III!Dre or disruption of phase III, ~ activity. 29 Disorders of gas1 the fed state have been less well because the mechanical illked io gastric slow waves, any •w•n·e activity has the potential nical activity. Dysrhythmias may p.ysiology of disorders affecting

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GASTRIC MOTILITY DISORDERS

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esophageal reflux), and delayed gastric emptying (mechanical and functional obstruction). Accelerated Gastric Emptying

Gastric motility disorders associated with accelerated transit are usually iatrogenic in origin. These include the postprandial dumping syndrome, which may occur secondary to partial gastrectomy, proximal gastric vagotomy, vagotomy with pyloroplasty or antrectomy, or gastroenterostomy.36'4o,so,s2,59 Prokinetic drug therapy may also result in accelerated gastric emptying.

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Gastric motility disorders associated with retrograde transit include vomiting, gastroesophageal reflux, duodenogastric reflux, and the bilious vomiting syndrome. Vomiting is a common gastroenterological sign, and it represents the extreme form of retrograde transit. 43 Gastroesophageal reflux is a less extreme form of retrograde transit, and delayed gastric emptying may contribute to the signs of gastroesophageal reflux. Abnormalities in liquid or solid food emptying and in antral contractility have been observed in patients with gastroesophageal reflux. 52, ..,. Duodenogastric reflux can be a normal physiological event57, ss, 69 or an epiphenomenon associated with an undetermined 'gastric motility disorder (abnormal pyloric function); alternatively, it may occur secondary to chronic gastritis. Bilious vomiting syndrome in dogs is an idiopathic disorder associated with duodenogastric reflux of bile. 24' 81 Affected dogs tend to vomit small amounts of bile in the morning on an empty stomach after an overnight fast. Definitive diagnosis of these disorders is often made by symptomatic response to therapy. Delayed Gastric Emptying: Mechanical Obstruction

Anatomical lesions of the pylorus and adjacent duodenal segment impede gastric emptying because of mechanical obstruction. 22, 47 In general, diagnosis of mechanical obstruction is usually straightforward and involves survey and contrast radiography, ultrasonography, or gastroscopy (Fig. 1). Surgical removal of the foreign object or the affected area is the preferred therapy. Gastrointestinal prokinetic agents are contraindicated in treating patients with mechanical obstruction. Pyloric stenosis or chronic hypertrophic pyloric gastropathy is a common cause of gastric outflow obstruction. 6, 24' 47, 68, 74' 76, 81 Most affected dogs are of male gender, young to middle-aged, brachycephalic, or of small breeds. Histopathological changes include hypertrophy of the circular muscles of the pylorus, hyperplasia of the antropyloric mucosa, or a combination of both muscular hypertrophy and mucosal hyperpla-

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Table 1. MECHANISMS, SITES OF ACTIVITY, AND INDICATIONS FOR GASTROINTESTINAL PROKINETIC AGENTS

Agent

Mechanism of Action

Sites of Activity

D 2-dopaminergic antagonist a 2-adrenergic antagonist f3 2-adrenergic antagonist 5-HT4-serotonergic agonist 5-HT3 -serotonergic antagonist Dz-dopaminergic antagonist a 2-adrenergic antagonist J3 2-adrenergic antagonist 5-HT4 -serotonergic agonist 5-m ,-serotonergic antagonist 5-HT3-serotonergic antagonist 5-HT2 -serotonergic agonist Nonserotonergic mechanism Motilin agonist (cat) 5-HTrserotonergic agonist (dog) Acetylcholinesterase inhibitor Mrmuscarinic agonist (?) Acetylcholinesterase inhibitor M3 -muscarinic agonist (?)

Metoclopramide (Reglan; AH Robins)

Domperidone (Motilium; Janssen) Cisapride (Propulsid; Janssen)

Erythromycin (Erythromycin; Mylan) Ranitidine (Zantac; Glaxo) Nizatidine (Axid; Eli Lilly)

Indications

LES, stomach, intestine, CRTZ Stomach Stomach LES, stomach, intestine Stomach, intestine

Vomiting disorders, gastroesophageal reflux, delayed gastric emptying, postoperative ileus, intestinal pseudoobstruction

Stomach, CRTZ Stomach Stomach LES, stomach, intestine Stomach, intestine, emetic center

Vomiting disorders, delayed gastric emptying (?) Gastroesophageal reflux, delayed gastric emptying, postoperative ileus, intestinal pseudo-obstruction, constipation, chemotherapy-induced emesis

Stomach, intestine, CRTZ Colon Canine antrum Stomach, intestine Stomach, intestine

Delayed gastric emptying (liquids > solids)

Stomach, intestine, colon

Delayed gastric emptying, intestinal pseudo-obstruction, constipation

Stomach Stomach, intestine, colon

Delayed gastric emptying, intestinal pseudo-obstruction, constipation

Stomach

LES = lower esophageal sphincter; M = muscarinic; CRTZ = chemoreceptor trigger zone; 5-HT = 5-hydroxytryptamine. JA: Diagnosis and management of gastrointestinal motility disorders in dogs and cats. Compend Conlin Educ Pract Vet 19:721, 1997;

Adapted from Washabau RJ, Hall

with permission.

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