MASTER CLASS: ANATOMY, PHYSIOLOGY AND CLINICAL MEDICINE OF THE GASTROINTESTINAL TRACT

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MASTER CLASS: ANATOMY, PHYSIOLOGY AND CLINICAL MEDICINE OF THE GASTROINTESTINAL TRACT Douglas Mader, MS, DVM, Dipl ABVP 1 and Jeanette Wyneken, PhD 2 1 Marathon Veterinary Hospital, 11187 Overseas Hwy, Marathon, FL 33050 USA; 2 Florida Atlantic University, Dept. of Biological Sciences, 777 Glades Rd, Boca Raton, FL 33431 USA Introduction The gastrointestinal (GI) system includes everything from the oral cavity to the excretory orifice. Some references also include organs such as the liver (including the gall bladder) and the pancreas. For this discussion, those digestive glands will be excluded. Overall, the alimentary tract in reptiles is simple and similar to that of mammals. In general, herbivorous and omnivorous animals have longer intestinal tracts than carnivores, and may also have a caecum. Symptoms of GI pathology include, but are not limited to: anorexia, stomatitis, vomiting/regurgitation, diarrhea, constipation and prolapse. Comprehensive discussions on GI anatomy, physiology and diagnostics have been published. 1,3,5,7 Basic Clinical Anatomy Oral Cavity In most species, and particularly snakes, the mouth has two major roles catch the food and transport it to the esophagus. It also serves in aggression (display and bite). Teeth may be homodont or heterodont and are either attached to bony ridges of the jaw (pleurodont) or in sockets (thecodont). Teeth are replaced through out life in many species of lizards and all snakes; however some species with pleurodont teeth, such as chameleons do not replace teeth. Chelonians lack teeth and instead rely on the rhamphothecae to grasp or cut food. The role of the teeth is to capture, grasp, and/or cut food items. Very little mastication, if any, occurs and hence food is swallowed whole or as large particles. The saliva that is produced has little digestive significance; its major role is lubricatory. However, the mouth may receive secretions from other oral glands that produce venom in some venomous snakes and lizards. 103

Esophagus The esophagus is dorsal to the trachea and extends from the pharynx to the stomach. The esophagus of most reptiles has several longitudinal folds that allow for great distensibility to accommodate large food items. In some reptiles, particularly chelonians, the base of the esophagus contains secretory cells that are presumed to be lubrigatory, but their role is poorly studied. In snakes the esophagus is very thin walled but is quite muscular in lizards, turtles, and crocodilians. In marine turtles, keratinized papillae line the esophageal walls; they are well developed and act to trap food as salt water is forcefully expelled. Stomach The stomach in all reptiles is located on the left side of the body and attaches to the left lung (when present) by a gastropulmonary ligament. In snakes, the stomach is fusiform; in most lizards and turtles it is c-shaped and grossly resembles the mammalian stomach. The stomach of crocodilians has two parts, a large fundic portion that receives the esophagus and a smaller pyloric portion that connects proximally to the fundic part by a large orifice and distally to the duodenum. 9 The stomach is rather short in snakes. Its junction with the esophagus is found approximately 75% caudally along the length of the liver. The stomach ends in a muscular sphincter, the pylorus, at the pyloroduodenal junction. The lining of the stomach is glandular and its surface mucosa can be very dynamic shape and thickness. In episodic feeders such as many snakes and some crocodilians, the lining of the stomach may be pale and folded during periods of fasting. After feeding, the mucosa of the stomach and intestine become pink and the epithelial cells elongate, thickening the mucosa and increasing area for absorption. When full the stomach s muscular wall can be stretched thin. Intestines The small intestine may be either straight or be composed of short transverse loops. In snakes, the intestine may have many largely longitudinal folds that allow for expansion and high surface area during digestion. In garter snakes (Thamnophis sirtalis parietalis) that were fed frequently, liver and intestine size was large while snakes fed less frequently showed a marked up- and down regulation of organ size. 11 The small intestine in the lizard and turtle has many loops and convolutions much the same as in mammals. The small intestine terminates at the ileocolic (or ileocæcal) junction which is usually demarked by a narrow sphincter. The digestive efficiency of reptile intestines is much lower than that of mammals, largely because mammals have much greater surface area and to some extent because reptile digestive efficiency is linked to basking or other post feeding thermal regulatory behavior. 10 Digestion in some herbivorous species is aided by fermentation and in some species by the activity of some nematodes. Fermentation is commonly in the large intestine; however, Bjorndal 1 documented fermentation in the small intestine one species of freshwater turtle Pseudemys nelsoni. 104

The large intestine is usually pink in color however it may be darkly pigmented (in many chameleons and some turtles). It tends to have a much larger capacity in herbivorous species than in carnivores and omnivores (summarized by Bjorndal 1 ). A cæcum is absent in most snakes but present pythons. Crocodilians appear the lack a cæcum. 9 Most lizards and chelonians have a cæcum, although it tends to be larger in herbivorous and omnivorous species than in carnivores. The large intestine functions in reclaiming water, absorbing calcium ions, and degrading complex carbohydrates. In some herbivorous chelonians and lizards microbial fermentation occurs in the large intestine. 1 Urea and/or uric acid transfer into the intestine by retrograde movement of urine into the intestine in reptiles. Intestinal microbes in the reptile colon appear to degrade urea and uric acid. While nitrogen assimilation levels are much lower in reptiles than in birds and mammals, nitrogen reclaimed in the colon is co-opted for amino acid synthesis. 10 The food transit times through reptilian GI systems are variable and are usually measured in days to weeks. In addition to thermoregulatory behavior, several mechanisms influence transit times and digestive efficiency. For example, in species that ferment digesta in the hind gut, antiperistalsis may increase transit time and allow functional flexibility how different foods are transported through the gut. 1 The large intestine terminates at the anus that opens into the cloaca. The cloaca is a short, largebore tube. As in birds, the reptilian cloaca is formed of three chambers or regions that may vary in their morphologic distinctness with species. The feces are discharged into the anterior chamber, the coprodeum. The urodeum receives the urogenital ducts. The largest chamber is the posterior proctodeum acts as a general collecting area for digestive and excretory wastes. Although not part of the GI system, the clitoris in females or the male intromittent organs reside in the proctodeum; male and female herps may have scent glands that also open here as well. GI Diagnostics History Anorexia, vomiting, regurgitation, stomatitis, constipation, diarrhea and intestinal prolapse are all seen in herp patients. A common thread in all of these conditions is abnormality in husbandry and nutrition. It is imperative that a comprehensive history is collected prior to starting any physical examination. Important questions include: type of housing, type and density of cage mates, environmental temperatures and humidity, food-type (if prey is fed live or dead), amount and frequency fed, how is food stored, cleaning and disinfection practices, lighting type and photoperiod, and watering practices. 105

Physical Examination The physical exam (PE) should be as performed for any evaluation, but particular interest should be directed toward the alimentary tract. Mucous membranes can be difficult to evaluate as many herps have pigmented membranes. Light grey to black coloration may be found and this is normal. Blanching and CRT may be impossible in these animals. The dentition should be evaluated and any missing teeth noted. Animals with pleurodont dentition (e.g., iguanas) will replace damaged or lost teeth. Reptiles with acrodont dentition (e.g. Chameleons) do not replace damaged teeth, and finding such can be a potential problem area and needs further investigation. As part of a thorough examination, the oral cavity needs to be examined for evidence of stomatitis or other pathology. This necessitates opening the mouth, which is not always easy in stronger patients. If needed, chemical restraint may be employed. Palpation of the GI tract varies with species. Snakes are relatively simple, especially in the smaller, thin animals. Larger, heavy bodied animals may not be possible to adequately palpate. Access to the internal organs of most chelonians is limited to the area immediately adjacent to the pre-femoral regions. Again, in some animals, this can be challenging without sedation. Smaller lizards and crocodilians are generally palpable, but the difficulty increases with size. Some animals will inflate with air in a defensive behavior making internal palpation impossible. Additionally, the presence of abdominal ribs and/or ossified scales may limit the information gained from palpation. The cloaca often presents the best window for evaluation of the mucous membrane color. Simple eversion of the vent or insertion of an otoscope cone allows examination of this area. GI Evaluation As with any medical evaluation, a standard data base is fundamental to evaluation of GI disease. In the authors experience a standard CBC/chem analysis is essential. Unfortunately, there are no pathognomonic laboratory profiles for GI disease. Findings range broadly from leukopenia to leukocytosis, and anemia to polycythemia. Nevertheless, laboratory documentation is necessary for establishing differentials and forming a therapeutic plan, as well as a providing baseline data for comparison during treatment progression. Fecal analysis, both direct (saline and iodine stained) and floatation should be performed. If feces are unavailable, a sample should be collected directly from the colon via a saline wash. Microbial cultures do have benefit but should be tailored and targeted for specific pathogens. Random combo cultures of the oral cavity and cloaca are uninformative as a rule. 106

Survey radiographs are an essential part of the standard data base. Although difficult to see in many reptiles, the normal GI tract is often hidden by scales, bones and, in chelonians, the shell. That stated, abnormalities in the GI tract, such as foreign bodies, masses, abscesses, ileus, gas and other pathologies are often readily apparent, thus warranting the acquisition of at least a two view study. Advanced diagnostics may be necessary to help identify more difficult problems. As expected, these tests are more involved/invasive, require more specialized equipment and advanced training in many cases. Initially, contrast can be added to the survey radiographs in the next step in diagnostics. Barium is readily administered but should not be given to dehydrated patients. Patients MUST be properly warmed to their preferred optimum temperature (POT). Animals that are hypothermic will have delayed emptying times, with delays as long as 25 days being reported. Barium should not be used if plans include endoscopy. Barium will interfere with visualization of the GI tract and can damage endoscopes. Endoscopy is often the gold standard when diagnostics are needed in the alimentary tract. Endoscopy allows direct visualization of the affected region, will permit diagnostic sampling as needed, and can be curative in the case of foreign body retrieval. Depending on the size of the patient, both rigid and flexible scopes can be used. Although infrequently used, MRI and CT imaging can also be employed in GI diagnostics. 3-D imaging and organ reconstruction and permit virtual endoscopy of patients. However, cost and availability make these modalities less available to most practitioners. Common GI Pathology Bacterial Disease The GI tracts of all reptiles are colonized by bacteria. There have been several studies looking at normal flora in both wild and captive specimens. Not surprisingly, higher numbers of bacteria are more prevalent in captive animals likely due to husbandry and stress issues. Many microbes found in the GI tract of herps can be considered anywhere from pathogens to normal to opportunists depending on the situation. While random cultures of the oral cavity and cloaca traditionally have been performed, they are generally a futile exercise that results in no more than a waste of the client s money. Bacteria cultured from an infected oral cavity are almost always secondary to some inciting cause. Husbandry issues (temperature, humidity, improper cage furniture) are often at the heart of the problem, with trauma an intimate second. Nonetheless, bacteria isolated from a stomatitis lesion do not lack significance; treatment should be based on its culture and sensitivity data. 107

Treatment of GI bacterial diseases in reptiles is similar to than that for mammals. Systemic and oral medications are both effective. In general, if the mouth works, use it. The most important treatment note the patient MUST be warmed to its POT. Viral Diseases As with bacteria, isolation of viruses from the GI tract of an ill reptile is not necessarily diagnostic of viral disease. Viral pathogens do cause disease, however, their confirmation at causative agents often is lacking both from because the necessary investigation was omitted and/or of confirmatory tests were lacking. Inclusion body disease (IBD) of boid snakes, Adenovirus, Dependovirus, and Herpesvirus have all been associated with GI disease in herps. Diagnosis of viral diseases can be accomplished (depending on the pathogen) via serology, viral isolation, electron microscopy, PCR testing and in some cases, histopathology. Treatment for viral disease is often symptomatic: thermal support, fluids, nutritional supplementation and antibiotics as needed for secondary infections. Anecdotal reports suggest that some antivirals, such as Acyclovir, may have some value in treating affected animals. Fungal Diseases Most fungal diseases, or mycoses, in reptiles are cutaneous rather than systemic or enteric. As with all other potential reptile pathogens, fungal infections can almost always be linked to poor husbandry. Culpability is often placed on wet bedding, excessive humidity, poor water quality (for aquatic species) and similar conditions. However, the underlying cause of fungal disease is usually some form of immunesuppression, secondary to some management related cause. Although not common, fungal overgrowth can be noted with prolonged or inappropriate use of antibiotics. Several publications list the various fungal agents associated with disease conditions. 8 Fungal organisms have been isolated from the oral cavity (including the lips and teeth), through the stomach, intestinal tract and into the cloaca. Diagnosis is made through standard techniques such as cytology (impression smears, washes), culture and biopsy with histopathology. Treatment of fungal disease is best based on isolation and identification of the fungus (sensitivities should be requested when collecting fungal cultures). Often fungal infections are associated with granulomatous responses, and effective treatment necessitates surgical debulking or excision in combination with systemic chemotherapeutics to maximize success. 108

Limited pharmacokinetic studies have been performed with antifungal medications. Reptile formularies list common antifungals and established doses. Enteric Parasites Although not as frequently seen as a few years ago, enteric parasitism is still one of the more common causes for morbidity in herps. With the advances in captive propagation and the decline in procurement of wild caught herps (and the concurrent reduction of intermediate hosts), the diagnosis of exotic parasitism is less common. Symptoms and signs of parasitism range the gamut from anorexia to vomiting/regurgitation to diarrhea to constipation. All wild herps harbor a normal population of parasites, just as they have a normal flora of bacteria, fungi, etc. The key is determining whether or not the finding of a particular parasite is a true disease threat or a normal finding. Parasites that reside herps as the natural hosts can become problematic in captivity due to overcrowding, stress, unsanitary conditions and biologic concentration. For instance, Oxyurids (pinworms) are a normal inhabitant in the GI tract of many herbivores and are an essential part of the digestive process. These worms have a direct life cycle, and in poor conditions, can intensify in such numbers that, at high densities, they can cause intestinal impactions. Coccidia, such as Isospora amphiboluri, is a common finding in Bearded Dragons (Pagona vitticeps). Controversy exists as to whether or not the coccidia found in Bearded Dragons represents Coccidiasis (infection with coccidians, but NOT disease) or Coccidiosis (infection with coccidians WITH associated disease). 4 It is common to find Coccidia shed in feces of normal, apparently healthy dragons. The question is whether or not to treat presuming that the finding of any coccidian has potential for causing morbity. Treatment of coccidian parasites has been problematic, but a recent report suggests that Ponazuril may show some promise. 2 Trematodes and Cestodes are less commonly found in captive herps, but remain a concern in wild and some zoo collections. These parasites are associated with disease but also are correlated with poor husbandry conditions and stress as previously discussed. Praziquantal is the current drug of choice for treatment of these parasites. 4 Cryptosporidiosis, caused by C. serpentis and C. saurophilus has been reported to cause pathology in several species. Anorexia, regurgitation, gastric hypertrophy are common in snakes. In E. macularis, C. saurophilus colonizes the intestinal tract rather than the stomach. Diagnosis is via gastric wash, biopsy, IFA and PCR. Currently there is no definitive treatment for Cryptosporidiosis. Prevention through strict quarantine protocols is the best method to keep this pathogen out of a colony. 109

Miscellaneous GI Pathology Neoplasia Neoplasia has been reported in the GI tract of all major reptilian orders. The etiopathogenesis of reptilian neoplasia is not understood, but may still have a link to husbandry, poor nutrition, immunosuppression, and contaminant exposures. Clinical signs are non-specific, including anorexia, vomiting/regurgitation, non-specific swellings or masses, obstipation/constipation, prolapse etc. Diagnostics incorporate all the usual procedures, including and not limited to laboratory screening, radiographs, cytology/biopsy and histopathologic analysis. Treatment depends on the clinical presentation, but surgical removal of the mass or debulking with adjunctive therapy is the mainstay. Scattered reports of chemotherapy and radiation therapy have been attempted in limited numbers in reptilian patients. In spite of the small numbers of reports, attempts should be made at therapy using principles developed with small animal patients. GI Foreign Bodies As with other small animal patients, GI foreign bodies (FB) are not. Pica is seen frequently in reptiles and some animals (alligators and some tortoises) normally ingest pebbles as gastroliths in their stomachs as an aid to digestion. The challenges to the clinician are to determine which apparent GI densities are normal, passing through, or are an actual cause for concern. Presenting signs include the usual: anorexia, lethargy, vomiting/regurgitation, constipation, swelling, prolapsed, malodor. Diagnostics such as laboratory screening and survey radiographs are essential. If endoscopy is considered, barium is not recommended. Treatment for GI foreign includes conservative therapy laxatives, endoscopic retrieval and surgery. Coexistent with GI FB is toxemia related to ingested materials. Lead poisoning, associated with lead fishing weights and zinc toxicity from consuming pennies minted after 1982. Chelation therapy, as performed in small animal medicine, has been used successfully in herp patients. LITERATURE CITED 1. Bjorndal K. A. Fermentation in Reptiles and Amphibians. In R. I. Mackie and B. A. White (eds.), Gastrointestinal Ecosystems and Fermentation, pp. 199 230. Chapman and Hall, Inc., New York. 1997. 110

2. Bogoslavsky BA. The use of Ponazuril to treat coccidiosis in either inland Bearded Dragons.proc. Proceedings of the ARAV. New Orleans. Pp 8-10, 2007. 3. Diaz-Figueroa O, Mitchell MA. Gastrointestinal Anatomy and Physiology.. In DR Mader, Reptile Medicine and Surgery. Elsevier. St. Louis. 145-162. 2006. 4. Greiner EC, Mader DR. Parasitology. In DR Mader, Reptile Medicine and Surgery. Elsevier. St. Louis. 343-364. 2006. 5. Guard CL. The reptilian digestive system: general characteristics. In K Schmidt-Nielsen, L Bolis, CR Taylor, PJ Bentley, and CE Stevens (eds.), Comparative Physiology: Primitive Mammals, pp 43 51. Cambridge Univ. Press, Cambridge. 1980. 6. Karasov, WH, DH Solberg, JM. Diamond. What transport adaptations enable mammals to absorb sugars and amino acids faster than reptiles? Am. J. Physiol. Gastrointest. Liver Physiol. 249: G271-G283. 1985. 7. Kardong, KV. Vertebrates: Comparative Anatomy, Function, Evolution. 4 th edition. McGraw-Hill Science, New York. 2005. 8. Pare, JA and ER Jacobson. Mycotic Diseases of Reptiles In. ER Jacobson 527-570, Infectious Diseases and Pathology of Reptiles: Color Atlas and Text. CRC Press, Boca Raton. 2007. 9. Reese, A. M. The Alligator and its Allies. G. P. Putnam's Sons, New York, N.Y. 358pp. 1917. 10. Singer, MA. Do mammals, birds, reptiles and fish have similar nitrogen conserving systems? Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 134(4): 543-558. 2003. 11. Starck, JM, K Beese. Structural flexibility of the small intestine and liver of garter snakes in response to feeding and fasting. The Journal of Experimental Biology 205, 1377-1388. 2002. 111