International Congress of the Italian Association of Companion Animal Veterinarians

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1 International Congress of the Italian Association of Companion Animal Veterinarians 2 - May, 201 Rimini, Italy Next Congress : SCIVAC International Congress Ma -, 201 -, Italy Reprinted in IVIS with the permission of the Congress Organizers

2 69 CONGRESSO INTERNAZIONALE MULTISALA SCIVAC RIMINI MAGGIO 2011 Gastrointestinal motility: why it matters Frédéric P. Gaschen Dr med vet, Dr habil, Dipl ACVIM (SAIM), Dipl ECVIM-CA, Louisiana, USA OVERVIEW OF THE ISSUE Motility is often the missing link in the complex equation of gastrointestinal (GI) health in dogs and cats. The prevalence of GI motility disorders in small animals cannot be precisely documented because obtaining a definitive diagnosis is often difficult, sometimes even impossible. However, it is thought that these disorders are of significant clinical importance. Examples of motility disorders include dysphagia, megaesophagus, disorders of gastric emptying, functional intestinal obstruction (ileus), megacolon and constipation. They may reflect secondary involvement of GI motility associated with a variety of diseases located outside the GI tract, including abdominal inflammation, immune-mediated diseases, metabolic diseases, etc. Alternatively, motility disorders may also result from primary GI disorders such as GI inflammation or neoplasia. Abnormal gastric motility may be associated with the potentially devastating gastric dilation-volvulus (GDV) syndrome of dogs. Finally, diseases affecting the autonomous nervous system do impact GI motility as well (e.g. dysautonomia). OBJECTIVES OF THE PRESENTATION To illustrate the importance of digestive motility disorders in canine and feline medicine. To summarize the current state of our knowledge of abnormalities of gastric emptying and intestinal motility and to sum up the treatment modalities available to treat them. PHYSIOLOGY OF GASTRIC EMPTYING AND INTESTINAL MOTILITY GI motility is the end result of a very complex series of events that starts with chewing food and ends with defecation. Smooth muscle activity is tightly regulated by neural impulses from the autonomic nervous system and by a variety of endocrine mechanisms. A very brief summary of these events as they pertain to swallowing and gastric emptying follows. The gastric antrum acts as a pump from which peristaltic waves originate while the gastric body acts as a high compliance reservoir. Contractions only occur when excitatory neurotransmitters such as acetylcholine are released in response to mechano- and chemoreceptors. The mechanical action of the antral pump is divided in 3 phases: (1) propulsion, (2) emptying of fine particles and mixing, and (3) retroplusion of particles > 1 mm and grinding. Gastric motility and emptying are modulated by gastro-gastric reflexes: for instance filling and distention of the gastric reservoir elicits excitatory reflexes stimulating antral contractions. Gastric emptying is inhibited by nutrients entering the small intestine (feedback control) through entero-gastric reflexes and release of intestinal hormones. Cholecystokinin (CCK) is released the duodenal epithelium upon presence of luminal HCl, amino acids and long-chain fatty acids. CCK reaches the stomach via bloodstream, causes relaxation of the gastric reservoir and reinforces enterogastric neural feedback. Other hormones such as glucagon-like peptide 1 (GLP-1) are released from the distal small intestine upon arrival of the chyme, and also exert a negative feedback on gastric emptying. Additionally, the rate of gastric emptying in dogs is modulated by the composition of the diet (e.g. moisture and fat, protein and carbohydrate content) and other factors such as stress and body size. Three physiologic motility patterns are described in the small intestine: peristaltic waves (aboral movement of chyme over long intestinal segments), stationary contractions (intestinal segmentation) and clusters of contraction (mixing and aboral movement of chyme). Diarrhea is usually associated with the occurrence of pathologic giant aboral contractions. In the large bowel frequently occurring colonic motor complexes mix the colonic content and slowly move it aborally. Finally, defecation is usually triggered by giant colonic contractions that occur at intervals of 10 h. DISORDERS OF GASTRIC EMPTYING In human medicine, disorders of gastric motility are clearly defined by the Rome classification III. They include functional dyspepsia, disorders of eructation, and nausea and vomiting with no identifiable cause. The typical symptoms are pain, dyspepsia and heartburn, bloating and early post- 201

3 prandial satiety. These signs are subjective and their interpretation can be difficult. These limitations have led to difficulty in timely recognition of disorders of gastric motility in dogs and cats. Etiology Primary and secondary disorders of gastric emptying have been recognized. In small animals, most cases are likely due to problems originating in the gastrointestinal tract or in other organs, while primary functional disorders are rare. Slower gastric emptying occurs in dogs following circumcostal gastropexy performed after GDV. Gastric motility is impaired in the fasting and postprandial phases in these dogs. However, it has not been established whether this abnormal motility is the cause of GDV or a consequence of surgical treatment. Some rare cases of pyloric stenosis have been reported in young Siamese cats. The associated delayed gastric emptying was successfully treated by pyloroplasty or pyloromyotomy. The diagnosis of duodenogastric reflux (DGR) in dogs has been the subject of much controversy since this reflux may occur as a physiological event. Moreover, during the initial phase of vomiting, giant contractions of the duodenum occur and are followed by a relaxation of the pylorus which allows the reflux of duodenal chyme in the stomach. Therefore, most instances of vomiting are accompanied by some degree of DGR. However, a syndrome characterized by bilious vomiting, often before the morning meal, has been observed in apparently healthy dogs. Secondary abnormalities of gastric emptying are due to a wide variety of diseases that may affect gastric motility. Many gastrointestinal disorders can cause secondary disorders of gastric motility. Mechanical obstruction is a common cause of delayed gastric emptying. Chronic hypertrophic pyloric antropathy may delay or inhibit gastric emptying. The disease may be due to thickening of the antral mucosa, muscularis, or a combination of both. Young (brachycephalic breeds) or middle-aged males (miniature breeds) are more frequently affected. Recently, an association between the disease and upper respiratory tract stenosis was shown in brachycephalic dogs. Treatment is surgical (pyloroplasty), particularly when the disease is associated with delayed gastric emptying. Gastric or intestinal inflammation is a common cause of gastric motility changes. Therefore it is hardly surprising that parasites, gastric ulcers, food reactions and inflammatory bowel disease (IBD) are often accompanied by abnormal gastrointestinal motility. Acute canine pancreatitis is commonly associated with decreased gastric and intestinal motility. This can significantly complicate treatment and is probably caused by extension of the inflammatory process to stomach and duodenum which are in close proximity of the pancreas. Diabetes mellitus is the most common cause of impaired gastric emptying in humans. This complication of chronic diabetes is rarely observed in dogs and cats. However, hypoadrenocorticism is often accompanied by a decreased gastric motility. Moreover, abnormal small intestinal and colonic motility have been shown in dogs with ablation of 66% of renal mass and chronic renal disease, while gastric emptying seemed normal. However, it is possible that a larger reduction of functional renal mass as is observed in clinical cases (>75%) may have negative effects on gastric motility. Finally, drugs such as opioid analgesics and anticholinergics may interfere with GI neurotransmitters and be at the origin of impaired motor function Clinical signs The most common clinical sign is vomiting of more or less digested food, especially when it occurs long after food intake (e.g. > h), when the stomach should be empty. Sometimes projectile vomiting may occur in the absence of a prodromal phase (nausea, salivation). The animal may be bloated and have pain on cranial abdominal palpation and/or signs of colic. Decreased appetite or anorexia, signs of nausea, increased belching, allotriophagia, or polydipsia may also be observed. Hematemesis suggests the presence of neoplasia obstructing the pylorus, gastric ulcer, or erosive resp. ulcerative gastritis. Diagnostic approach Clinical examination and ancillary tests are designed primarily to detect any underlying disorders (such as obstructive processes that would require gastroscopy or gastrostomy). Presence of food in the stomach after prolonged fasting (eg more than hours) suggests delayed gastric emptying. In the absence of obstruction, CBC, blood chemistry, urinalysis, and medical imaging are valuable aids. The various methods available to investigate gastric emptying have been recently reviewed. They aim at evaluating the gastric emptying and/or intestinal transit time of solid food, and include scintigraphy, radiographic contrast studies (barium meals, barium impregnated polyethylene spheres or BIPS), abdominal ultrasound, and gastric emptying breath test ( 13 C-octanoid acid). All these methods are non-invasive, but all have potential pitfalls. Some require special equipment that can only be found at referral centers. Additionally, some techniques can only be performed after the animals have been manually or chemically restrained, a potential source of stress which may interfere with gastric motility. Radionuclide scintigraphy is recognized as the current gold standard. Radiographic studies are easily accessible in clinical veterinary practice. Liquid barium has been widely used to assess GI transit times and is adequate to evaluate liquid phase gastric emptying. The dose of barium suspension is 6 ml/kg in dogs and 10 ml/kg in cats and should be administered when the stomach is empty. Barium sulfate should be present in the duodenum by 15 minutes in the dog and by 5 minutes in the cat. The stomach should be free of barium after 1 to 4 hours in the dog and after 20 minutes in the cat. However, assessment of gastric emptying of liquids is an insensitive method, with the exception of mechanical obstructions due to foreign bodies or other space-occupying lesions obstructing the gastric or intestinal lumen. Mixing barium with food may better evaluate the solid phase of gastric emptying, however barium can easily separate from the test meal and cause the study to be unreliable. Barium- 202

4 impregnated polyethylene spheres (BIPS TM ) have been used for evaluation of GI transit times in dogs and cats. They come in various sizes (from 1.5 to 5 mm diameter) and can easily be used in practice. However, correlation between gastric emptying of BIPS and the gold standard radioscintigraphy has been disappointing in dogs and in cats. This probably reflects the fact that BIPS > 2 mm are only emptied after all solid food has left the stomach during the interdigestive MMC. Treatment Immediate treatment of any obstructive disease is imperative (surgery, gastroscopy). Therapy of functional, nonobstructive disorders of gastric motility is based on two main pillars: dietary modification and judicious use of prokinetic drugs. Proper diagnosis and treatment of any underlying disease that might affect gastric motility is an essential premise. Dietary modifications designed to facilitate gastric emptying are based on our knowledge of digestive physiology. First, gastric emptying of liquid food is faster than that of solid foods. Also, diets with high caloric density tend to remain longer in the stomach. In addition, gastric emptying of fat is slower than that of proteins, which is slower than that of carbohydrates. Consequently, feeding liquid or semiliquid diet of low caloric density low in fat and protein should maximize gastric emptying. Finally, increased meal frequency and decreasing meal size are also useful. Dietary treatment of bilious vomiting (DGR) consists in feeding the dogs a light meal late at night. Use of prokinetic drugs may be beneficial in nonobstructive disorders of gastric emptying. Serotonergic drugs (cisapride, metoclopramide) act on 5-hydroxytryptamine (5-HT) receptors of different types. Metoclopramide (MCP) is often used as an anti-emetic for its inhibitory effects on dopamine receptors in the CRTZ of the medulla oblongata. In addition, MCP acts on 5-HT3 receptors (antagonist) and 5-HT4 (agonist). These effects stimulate contraction of smooth muscle cells of the stomach and intestine. In addition, the MCP increases the tone of the lower esophageal sphincter (LES). Cisapride (CSP) is a serotonergic drug that was withdrawn from the pharmaceutical market but is available as a generic from compounding pharmacies. The principal mode of action of CSP is its ability to bind to 203

5 5-HT4 receptors, and stimulate smooth muscle contractions. Erythromycin (EMC) is a macrolide antibiotic. At reduced doses, it exerts gastrokinetic effects similar to motilin. EMC triggers MMC type III, a motility pattern responsible for cleaning the stomach during the interdigestive phase. The administration of EMC stimulates gastric emptying without any attention to particle size. This early release of gastric contents can lead to dumping of insufficiently processed food in the small intestine. Furthermore, in cats, EMC increases the LES pressure. Acetylcholinesterase inhibitors increase the concentration of acetylcholine in the synaptic cleft between postganglionic myenteric neurons and smooth muscle cells of the stomach and intestine. They stimulate the activity of GI smooth muscle. Ranitidine and nizatidine are two inhibitors of histamine receptor type 2. Although they are mostly used to decrease gastric acidity, their prokinetic effect is not negligible. All other H2 antagonists lack this prokinetic effect. REFERENCES Can be obtained from the author upon request (fgaschen@lsu.edu) Address for correspondence: Frédéric P. Gaschen Louisiana State University School of Veterinary Medicine Baton Rouge, Louisiana, USA 204