The Gastrointestinal Tract

Chapter 18


The Gastrointestinal Tract



The gastrointestinal (GI) tract is an endoderm-derived structure, consisting of the esophagus, stomach, small intestine, and large intestine. Although the primary purpose of the GI tract is the digestion and absorption of food, it also has important secondary roles, including immune functions, elimination of waste products, and endocrine effects. As such, diseases of the GI tract are a major cause of morbidity and mortality in companion animals and include a wide variety of conditions such as infectious diseases, neoplasia and other mass lesions, motility disorders, congenital disorders, and effects of medications. In this chapter, we will focus on diseases and conditions of the GI tract that can be diagnosed via cytologic examination of various sample types. In addition, we will address sampling techniques, normal findings, and common or important diagnostic dilemmas, and we will also introduce important aspects of histopathology of the GI tract. Because infectious organisms are an important cause of GI disease and will be discussed throughout the chapter, a detailed description of the most common organisms, their location within the GI tract, and additional useful diagnostic testing may be found in Table 18-1.13




Sampling Techniques for the Gastrointestinal Tract


When evaluating a patient for GI disease, it is important to rule out diseases of other organs such as the liver, pancreas, kidneys, and adrenal glands, which may cause secondary GI disease or clinical signs. Once sampling of the GI tract is determined to be appropriate, several methods are used for obtaining cytologic and histologic samples, including ultrasound-guided aspirates or tissue biopsies, endoscopy, laparoscopy, direct sampling during abdominal exploratory surgery, rectal scrapings, and examination of fecal material.



Ultrasound-Guided Sampling


Ultrasonography is commonly used to evaluate the intestinal tract in dogs and cats and is often used to obtain aspirate and tissue biopsy samples. Ultrasonographic evaluation is very helpful in aiding the diagnosis of GI diseases, particularly with infiltrative GI neoplasia; however, it is important to note that overlap exists between the ultrasonographic appearance of neoplastic and nonneoplastic diseases; therefore, ultrasonography is not entirely specific.4 Cytology from aspiration of the wall of the GI tract usually has low yield unless a significant lesion or increased wall thickness is present. Although ultrasound-guided aspirates or biopsies have the advantages of being less invasive and less expensive than obtaining a full-thickness biopsy, full-thickness biopsies remain the gold standard for differentiating certain inflammatory and neoplastic diseases such as intestinal lymphoma versus inflammatory bowel disease.



Endoscopy


Endoscopy is a well-established procedure for examining the GI tract and serves as an important alternative to exploratory surgery for direct examination of the tissues and anatomy. It is minimally invasive and allows visualization and sample collection of the luminal surface of the esophagus, stomach, proximal small intestine, and distal large intestine.5 Access to the remainder of the intestinal tract is limited during an endoscopic procedure. Endoscopic mucosal brushing and endoscopic biopsies are the main sample types that are collected during this procedure and predominantly evaluate the mucosal surface. Although these samples are useful for detecting surface inflammation and occasionally neoplasia, lesions that are deep to the mucosal surface may not be identified.



Laparoscopy and Abdominal Exploration


Laparoscopy is an operative procedure that is performed through a keyhole opening with a rigid endoscope. It allows for visual inspection of the organs and, in specialized settings, may allow for laparoscopy-assisted full-thickness biopsy of the GI tract. Abdominal exploration is a fairly invasive surgical procedure that is often used to obtain full-thickness biopsy samples of the GI tract. Although these procedures are more invasive, full-thickness biopsies in some cases will provide the best opportunity for obtaining a definitive diagnosis. In addition, the generally larger biopsy size obtained via these techniques may allow touch imprints of the tissue to be made prior to placing it in formalin. Cytologic evaluation of touch imprints may sometimes provide a preliminary or definitive diagnosis before histopathology results are available. Although care must be taken to preserve the integrity of the biopsy sample, it is important to gently wipe or blot the blood and serum off of the tissue before making the touch imprints to allow proper adhesion of cells to the slide. It is also possible to make touch imprints of ultrasound-guided or endoscopically obtained tissue biopsies, but the smaller size and greater fragility of these types of samples makes this more difficult.



Fecal Examination


Fecal testing is a common diagnostic procedure in the clinical evaluation of GI disease. Timing of sample collection and preparation is very important. Feces are altered after stool is passed and significant degeneration of cells and some organisms such as Giardia spp. or Tritrichomonas foetus can occur rapidly making identification increasingly difficult with time (Figure 18-1).1 With delayed processing of the fecal sample, some nematode eggs will release larvae, and bacterial overgrowth may occur. A fresh sample that can be processed immediately is best.



Several collection techniques are used for either the luminal contents or the surface mucosa of the rectum. Defecated feces and feces obtained during a digital rectal examination or with a fecal loop represent the rectal lumen, whereas rectal lavage or rectal scrape samples are representative of the mucosal surface. If defecated feces are used, it is critical that they be fresh and not heavily contaminated with debris. Additional fecal diagnostics include fecal flotation, fecal sedimentation, and the Baermann technique; consultation of a veterinary parasitology text is recommended for additional information about these techniques.


When sampling the feces or rectal mucosa, lubricant gel should be used sparingly or avoided entirely, since the lubricant material could complicate evaluation of the cytologic specimen. Cytologically, lubricant has the appearance of thick extracellular magenta aggregates of material that may obscure the cells and organisms within the sample (Figure 18-2).




Direct Smears of Fecal Material


Direct smears from a luminal sample are made by spreading a small amount of feces thinly and evenly across the slide. The sample should not be heat-fixed; it is unnecessary and could cause significant damage to cells and organisms.1 After air-drying, the slide may be stained with a standard Romanowsky-type stain (e.g. Wright stain, Giemsa stain, rapid stains) and evaluated like any cytologic sample. If using a rapid stain (i.e., Diff-Quik), it is recommended to have a separate “dirty” staining station for fecal and ear cytology so as not to contaminate the station where “clean” cytology and hematology samples are stained.




Rectal Scraping


To obtain a sample by rectal scraping, the rectum is cleaned of feces, use of lubricant gel is minimized or avoided, and a rigid instrument such as a conjunctival scraper or chemistry spatula is used to obtain the specimen (Box 18-1 and Figure 18-3). The sample should be obtained cranially enough to reach the rectum, avoiding sampling of the anal mucosa; pressure should be applied firmly enough to sample the mucosa, rather than just the surface material, while being careful not to perforate the rectal wall. Slides are prepared, dried, and stained in a manner similar to the process for a fecal smear.





Esophagus



Normal Esophagus


The esophagus consists of a mucosal epithelium, submucosa, and a muscular wall. The esophageal mucosa is lined by nonkeratinizing stratified squamous epithelium. Submucosal mucous glands are present throughout the esophagus in the dog and are located only at the pharyngeal–esophageal junction in the cat.6


Cells from multiple layers of the squamous epithelium may be identified in cytologic specimens (Figure 18-4). Progressing from superficial to deep, superficial squamous cells are angular with a pyknotic to absent nucleus, intermediate cells are somewhat angular with a larger nucleus, and deep intermediate and parabasal cells have a smaller volume of more deeply basophilic cytoplasm with rounded borders.7 Cytology of normal esophageal brushings and washings consists of predominantly intermediate squamous cells with occasional superficial squamous cells. Cells from the deeper layers, including deep intermediate cells, parabasal cells, and rarely submucosal glandular epithelial cells, may also be seen cytologically, depending on the aggressiveness of the sampling technique, but this finding is typically an indicator of disease.8 Oropharyngeal contamination may be seen in normal or abnormal esophageal samples and may consist of a mixed bacterial population including Simonsiella, and, rarely, respiratory epithelial cells. Simonsiella is a Gram-negative large (6-8 micrometers [µm] long and 2-3 µm wide) rod-shaped bacteria that contains segmented groups of cells aligned face-to-face in juxtaposition, giving it a barcode-like or stacked-disk appearance.




Esophageal Inflammation


Esophagitis occurs with injury to the esophageal mucosa due to a variety of underlying causes, including foreign bodies, infectious etiologies, and mucosal irritants (Box 18-2). Although esophagitis often has an erosive or ulcerative component, lack of a discernible superficial lesion at endoscopy does not rule out underlying esophagitis.



In addition to ingestion of substances damaging to the esophageal mucosa, an important cause of esophagitis with mucosal injury is reflux esophagitis. This condition, which is most common in the distal esophagus, is the effect of gastric acid, pepsin, and possibly bile salts and pancreatic enzymes on the esophageal mucosa.9 Reflux of these substances into the esophagus may occur with relaxation of the lower esophageal sphincter under anesthesia, a hiatal hernia, or chronic vomiting.10 In addition to esophageal inflammation, a possible sequela of gastroesophageal reflux is metaplasia of the distal esophageal stratified squamous epithelium to a more acid-friendly simple columnar epithelium with interspersed goblet cells (Figure 18-5). This lesion has been reported in dogs and cats; grossly or endoscopically, these may range from a region of hyperemia to a polypoid mass, which could be mistaken for neoplasia (Table 18-2).11 In humans, this condition is known as Barrett esophagus, and the lesion may progress and transform into a distal esophageal adenocarcinoma.




Cytologic findings with esophagitis are typically nonspecific with the presence of neutrophils amid the squamous epithelial cells. The presence of eosinophils in esophageal cytology may occur with neoplastic, parasitic, or fungal disease; with reflux esophagitis; as a part of eosinophilic gastroenteritis; or with eosinophilic esophagitis (Figure 18-6). Eosinophilic esophagitis has been reported in dogs, may be associated with allergic skin disease, and is a diagnosis of exclusion after eliminating the aforementioned causes of eosinophils within an esophageal sample.12



Pyogranulomatous esophagitis may occur with pythiosis in dogs (see “Gastric Inflammation”). Spirocerca lupi infection causes a masslike granulomatous lesion in the distal esophagus of dogs because of the presence of adult nematodes in the esophageal submucosa. Typically, a single mass is present in the caudal thoracic portion of the esophagus, occasionally with surface ulceration or protrusion of adult worms into the esophageal lumen. An association exists between spirocercosis and the development of esophageal fibrosarcoma or osteosarcoma.



Esophageal Neoplasia


Primary esophageal neoplasia, which is rare in dogs and cats, includes squamous cell carcinoma and smooth muscle tumors, with rare reports of adenocarcinoma, neuroendocrine carcinoma, primary extraskeletal osteosarcoma, or plasma cell neoplasia.13,14 Fibrosarcoma and osteosarcoma associated with Spirocerca lupi infection is discussed above (see “Esophageal Inflammation”). Rarely, esophageal involvement of canine oral papillomavirus infection may occur.9


Squamous cell carcinoma arising from the esophageal mucosal epithelium most commonly occurs in the middle third of the esophagus and is typically an ulcerated plaque with circumferential esophageal thickening.13 Cytologically, this tumor resembles squamous cell carcinoma elsewhere in the body and often will have superimposed inflammation or evidence of superficial infection. Esophageal adenocarcinoma is rare but may arise from the submucosal esophageal glands or from regions of glandular metaplasia, as with reflux esophagitis. Leiomyomas in the esophagus are more common in dogs and are most commonly found in the outer muscular layer of the distal esophagus at the gastroesophageal junction.14



Stomach



Normal Stomach


The stomach in dogs and cats is glandular, and, from proximal to distal, contains cardiac, fundic, and pyloric regions and consists of the mucosa, muscularis mucosae, submucosa, and smooth muscle wall. The largest portion of the stomach is the fundus, which consists of a surface columnar foveolar epithelium with subjacent glandular cells, including parietal cells and chief cells, which secrete hydrochloric acid and pepsinogen, respectively (Figure 18-7). The pyloric region consists of a similar surface epithelium with predominantly mucous glands in the deeper mucosa (see Figure 18-7).



Normal gastric cytology usually consists of small, to rarely large, sheets of surface epithelium that has a characteristic honeycomb appearance (Figure 18-8). These columnar cells have round to oval basally oriented nuclei with an abundant amount of finely vacuolated cytoplasm.7 Parietal and chief cells may be seen in gastric cytology samples collected from brushing techniques that access the deeper mucosal tissue (see Figure 18-7). Parietal cells have abundant granular eosinophilic to vacuolated cytoplasm, whereas chief cells have many well-staining basophilic cytoplasmic granules.7,8 Particularly in the pyloric region, mucus-secreting cells may be identified in cytologic samples (see Figure 18-7).



Helicobacter spp. are spiral bacteria that are commonly identified in samples of the gastric surface of dogs and cats, often in close association with surface mucus (Figure 18-9). The possible clinical significance of finding Helicobacter organisms in the stomach is discussed below (see “Gastric Inflammation”). Gastric samples may be easily contaminated by food material, or material from the oral cavity and esophagus, which is indicated by the presence of Simonsiella organisms and squamous epithelial cells. Ciliated columnar respiratory epithelium may be noted if the patient swallowed sputum, whereas red blood cells (RBCs) may be identified with traumatic sample collection and blood contamination.




Gastric Inflammation


Gastritis is a nonspecific finding that may occur with a variety of causes (Box 18-3).15 The majority of gastritis cases in dogs and cats are likely a component of inflammatory bowel disease (IBD), which may have predominantly lymphoplasmacytic, eosinophilic or granulomatous inflammation, although the presence of inflammation is not specific for IBD. Normal endoscopic appearance of the gastric mucosa does not rule out underlying inflammation.




Neutrophilic Inflammation


Neutrophilic inflammation in gastric samples may occur with a variety of lesions but is seen most often with gastric ulcers; for a more complete list of common causes, see Table 18-3. Ulcers in the stomach or proximal small intestine may occur as a result of mechanical or chemical irritation, drug administration, or hormone secretion (i.e., gastrin hypersecretion or histamine release). Ulceration with nonsteroidal anti-inflammatory drug (NSAID) administration is secondary to compromise of mucosal protective mechanisms, whereas with excess exogenous or endogenous corticosteroids, mucosal perfusion is reduced.9 Uremic gastropathy is not typically an inflammatory lesion histologically but may cause gastric congestion, hemorrhage, and edema, possibly with ulceration, necrosis, and mineralization of the mucosa.9



TABLE 18-3


Causes of Gastric Inflammation











































































Type of Inflammation Disease Process Potential Causes
Neutrophilic Mechanical ulceration Gastric foreign body, hairball
  Chemical gastritis Ingestion of irritating plants or chemicals
  Gastric or gastrointestinal (GI) ulcers Hypersecretion of acid (liver disease, gastrin-secreting tumor)
Histamine release (mast cell tumor, medications and hormones)
Drug therapy (nonsteroidal anti-inflammatory drugs [NSAIDs], corticosteroids)
Sepsis, burns, hypoadrenocorticism, surgery
Lymphoplasmacytic Inflammatory bowel disease  
  Hyperplastic or hypertrophic conditions Chronic hypertrophic gastropathy of Drentsche Patrijshond and Basenji dogs
Chronic hypertrophic pyloric gastropathy
Pyloric stenosis
Benign gastric polyps
  Atrophic conditions Chronic atrophic gastritis of Norwegian Lundehund dogs
  Healing gastric ulcers  
  Helicobacter infection  
  Parasite infestation Physaloptera and Gnathostoma in dogs and cats
Ollulanus and Cylicospirura in cats
  Secondary to other conditions Neoplasia
Eosinophilic Inflammatory bowel disease  
  Allergy or hypersensitivity disorders  
  Neoplasia Mast cell tumor, T-cell lymphoma
  Infectious agents Pythiosis, Toxocara canis larval migration
  Miscellaneous Feline hypereosinophilic syndrome
Canine idiopathic eosinophilic gastrointestinal masses
Scirrhous eosinophilic gastritis
Feline gastrointestinal eosinophilic sclerosing fibroplasia
Granulomatous Inflammatory bowel disease  
  Infectious etiologies Mycobacteriosis, histoplasmosis, pythiosis


Lymphoplasmacytic Inflammation


Lymphoplasmacytic gastritis is the most common histopathologic finding in abnormal gastric biopsies in dogs and has a variety of causes and disease associations, including IBD, hyperplastic, hypertrophic, or atrophic conditions, and others (Figure 18-10).16 For a more complete list of potential causes, see Table 18-3.



Several hyperplastic or hypertrophic gastric conditions occur in dogs (see Table 18-3). In addition to a lymphoplasmacytic inflammatory component, these conditions often have a component of mucosal epithelial proliferation, with or without thickening or muscular hypertrophy of the stomach wall; therefore, increased mucosal epithelium may be noted cytologically in these conditions. As a result of their gross or endoscopic appearance as a diffuse or regional masslike thickening of portions of the stomach, these hyperplastic and hypertrophic lesions may be confused with gastric adenocarcinoma (see Table 18-2).13 For this reason, it is important to consider these benign conditions when increased mucosal epithelium is seen in cytology specimens.


Helicobacter spp. are highly prevalent spiral bacteria found in the stomach of dogs and cats; however, it is controversial whether a causal association exists between the presence of Helicobacter and the presence of gastritis in these species (see Figure 18-9 and Table 18-1). In cats, an association seems to exist between Helicobacter and lymphoid follicle formation or epithelial proliferation in the stomach, and possible associations have been made between Helicobacter infection and gastric mucosal-associated lymphoid tissue (MALT) lymphoma.17,18 Helicobacter may be present in higher numbers and easier to identify in cytologic specimens than in histologic samples because of their presence in the surface mucus, which is readily sampled for cytologic evaluation.



Eosinophilic Inflammation


Eosinophilic inflammation in stomach samples may occur as a component of IBD or with other diseases typically associated with eosinophils (see Table 18-3). Other conditions with a predominance of eosinophils include idiopathic eosinophilic GI masses, scirrhous eosinophilic gastritis, and feline GI eosinophilic sclerosing fibroplasia; an important feature of these diseases is their tendency to form a thickened or masslike region in the stomach, giving the impression of neoplasia (see Table 18-2). The term idiopathic eosinophilic gastrointestinal masses (IEGM) refers to a condition in dogs, with a predisposition in Rottweiler dogs, in which one or multiple mass lesions consisting of eosinophilic inflammation are present in the GI tract, with intervening eosinophil-free regions.19 Scirrhous eosinophilic gastritis in dogs is a thickening of the gastric wall with granulation tissue and eosinophils.13 Feline gastrointestinal eosinophilic sclerosing fibroplasia is a masslike lesion, most commonly at the pyloric sphincter but also common at the ileocecocolic junction, and it may also involve the mesenteric lymph nodes. Cytologically, this lesion has either increased eosinophils, alone or in combination with large spindle cells amid pink, extracellular matrix, with neutrophils and intracellular and extracellular rod-shaped or coccoid bacteria with fewer lymphocytes, plasma cells, and mast cells (Figure 18-11).20


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Aug 6, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on The Gastrointestinal Tract

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