Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity*

Structure and Function

The physiologically normal oral mucosa is smooth, shiny, and pink. It is composed of variably keratinizing, stratified squamous epithelium (mucous membranes). In animals in which the oral mucosa is heavily pigmented (melanosis), assessment of circulatory function (capillary refill time) and color as an indicator of red blood cell concentration (packed cell volume) can be difficult. In these cases, examination of conjunctiva, rectal, and urogenital mucosa can be substituted. The oral cavity is where ingested materials are masticated; mixed with digestive enzymes, such as those in saliva; and passed on through the oropharynx to the esophagus.

Defense Mechanisms

Defense mechanisms of the oral cavity include the stratified epithelial surface that is resistant to trauma and some irritants; taste buds, which reject potentially toxic materials based on taste and tongue feel; an indigenous bacterial flora that occupy attachment sites that would otherwise be available to pathogens; and saliva (Box 7-3). Saliva provides a flushing action so potential pathogens are cleared from the oropharynx and swallowed. Saliva also forms a protective coating of the mucosa and contains antimicrobial lysozyme in the zymogen granules of serous cells and immunoglobulins, especially immunoglobulin A (IgA), in a manner analogous to cryptal enterocytes of the intestine, through the production of a secretory component. Migration through the alimentary tract, including the oral cavity, eliminates neutrophils at the end of their lifespan. In their absence, stomatitis results.

Developmental Anomalies

There are a wide variety of developmental abnormalities in the oral cavity. Some are incompatible with life unless surgically corrected. Only a few of these congenital lesions have a proven hereditary component. Most are idiopathic. Thorough physical examination of neonates must include examination of the oral cavity for these defects.

Palatoschisis, or cleft palate, and cheiloschisis, or cleft lip, are among the most common developmental abnormalities of the oral cavity. Cheiloschisis is sometimes referred to as hare lip because this is a normal feature of the rabbit. It is a failure of fusion of the upper lip along the midline or philtrum. Palatoschisis can be genetic or toxic in origin. It results from a failure of fusion of the lateral palatine processes. It can be caused by steroid administration during pregnancy in primates, including humans. Depending on the size of the defect, which may involve only the soft palate or both the soft and hard palates (Fig. 7-1), the lesion may be surgically correctable. It is a matter of some ethical concern whether to correct such defects without also sterilizing the patient because of the potential for cleft palate to have a genetic cause. Important sequelae to the host from cleft palate are starvation, as the result of the inability of the nursing animal to create a negative pressure in the mouth with a resultant failure to suckle, and aspiration pneumonia, since no effective separation is present between the oral and nasal cavities.

Stomatitis and Gingivitis

Stomatitis and gingivitis refer to inflammation of the mucous membranes of the oral cavity and gingiva, respectively. Because the oral cavity is constantly bombarded with ingested substances that are moved around by the tongue, the final result of a variety of insults to the lining of the oral cavity is a loss of mucosa—erosions, ulcerations, and necrosis. Thus, although inflammation is apparent, clues as to the initiating process may be absent. Lesions may be at different stages and are commonly classified as macules, papules, vesicles, erosions, abscesses, granulomas, and ulcers. These lesions can be caused by infectious agents, particularly viruses; chemical injury; trauma; intoxicants; or autoimmune or systemic disease. They often result in anorexia caused by painful mastication. Hypersalivation (ptyalism) is also apparent, whether from overproduction or a failure to swallow. In the cat, gingivitis is the first and most consistent sign of feline immunodeficiency virus (FIV) infection (immune system failure) associated with a reduction in CD4 lymphocytes, thymic atrophy, and lymph node atrophy.

Vesicular Stomatitides

Although vesicular stomatitis correctly refers to oral vesicles and blisters, the term is generally reserved for those lesions caused by epitheliotropic viruses. The vesicular stomatitides are listed in Table 7-1. Their genesis is from virus-induced epithelial cytolysis attended by fluid accumulation and subsequent rupture of the resultant vesicle. Blistering or vesiculation of the oral epithelium is present early in the course of these diseases. All of these diseases are virus-induced, and all have identical appearances at gross and histopathologic examination. None of these conditions is fatal. They produce great economic loss because of poor weight gain in affected animals and sometimes abortions in gravid females. The exact cause of the abortions is unknown, but it is probably related to the stress induced by the painful oral, cutaneous, and pedal (hoof or foot) lesions. Secondary bacterial invaders, both Gram-negative and Gram-positive, of these lesions can result in endotoxemia. Several diseases, such as foot-and-mouth disease and vesicular exanthema, affect the coronary bands of the digits and interdigital clefts, resulting in lameness. Some of these diseases (foot-and-mouth disease, vesicular exanthema, and swine vesicular disease) are exotic to the United States (US) and thus are reportable to state or federal authorities, or both, if the clinician or pathologist suspects the disease. This requirement is due to the great expense involved in eradicating these diseases from the US and their potential use as agents of agroterrorism. Nontariff export/import barriers designed to prevent the introduction of highly contagious agents, such as foot-and-mouth disease, into animal populations of countries with which we trade are often put in place.

The gross lesions of the vesicular stomatitides are epithelial. Fluid-filled vesicles are present in the oral cavity, lips, rostral palate, and tongue (Fig. 7-2, A). Entry of virus in these cases is most likely oral into areas of temporary loss of mucosa as the result of normal mastication and trauma. The viruses are cytolytic, and the resultant release of virus from cells infects neighboring cells. The lesions enlarge centripetally, forming vesicles. Bullae result from coalescence resulting in erosions and ulcers. These ulcers are typically hyperemic (Fig. 7-2, B). Viremia, often transient, sometimes occurs.

Similar vesicular lesions occur in the nasal mucosa, particularly in pigs with vesicular exanthema and in the proximal epithelium of the alimentary system (esophagus and rumen) of cattle with foot-and-mouth disease. Some animals have conjunctivitis and vesicular dermatitis of the teats and vulva. Microscopically, the lesions of these four diseases (foot-and-mouth disease, vesicular stomatitis, vesicular exanthema, and swine vesicular disease) are similar. Virus-induced, intracellular edema progresses to swelling of the cells of the stratum spinosum, cell lysis and intercellular edema, and resultant vesicles. The epithelium overlying the virus-rich vesicular fluid is thin, and even slight friction can rupture vesicles and bullae, creating an ulcer. Healing of the ulcer progresses from the usual fibrin and/or neutrophil-rich acute stages (scab) to the more chronic stages of granulation.

Lesions and signs of the vesicular stomatitides include vesicles, bullae, and detachment of patches of epithelium with resultant raw ulcers, ptyalism, lameness, fever, and anorexia. Besides the lesions that develop from the initially infected cells, the virus spreads centripetally to adjacent susceptible epithelium, causing repeated episodes of this infectious, lytic cycle. The vesicular stomatitides are tentatively diagnosed based on the clinical signs and lesions resulting from oral and nasal ulceration, conjunctivitis, and ulceration of the genitalia and mammary glands. Lameness is secondary to hoof involvement that is focused at the coronary band. Definitive diagnosis is important and performed at federal laboratories equipped to rapidly respond to suspected outbreaks. Federal quarantine of infected herds is an important control mechanism, followed by eradication, slaughter, and carcass disposal.

Specific Vesicular Diseases

Foot-and-mouth disease is an extremely important disease and disease threat of arteriodactyls worldwide but has not appeared in US livestock since 1929, when it was eradicated after an outbreak in California. Virus spreads rapidly and principally by aerosol. The disease is characterized in its early stages by vesicles in the planum nasale, in the oral cavity, and tongue. The picornavirus of foot-and-mouth disease attaches to susceptible cells via integrins on the cell surface. Fluid from ruptured vesicles spreads to areas of abraded skin, for example, skin of a mammary gland. When coronary bands and hooves are affected, coronary band vesiculation may eventually lead to sloughing of the hoof. Although this disease is not fatal, the pain and accompanying inappetence lead to weight loss. If allowed to heal, the hoof will regrow into a ball-like structure. Young animals with foot-and-mouth disease frequently have a viral myocarditis without other signs. Vaccination is short-lived (6 months) and takes time to become effective in individual animals; thus immediate protection is not provided. Persistent infections occur in water buffalo and infected cattle that have been previously vaccinated.

Vesicular stomatitis is common in calves, pigs, and some wildlife species but does not occur in sheep or goats. It is the only vesicular disease to which horses are susceptible. In northern latitudes, it is generally a warm weather disease, suggesting that insects act as vectors. As the name implies, vesicles in the oral cavity characterize the disease. Clinically the disease is often recognized by inappetence in the affected animal, accompanied by ptyalism.

Vesicular exanthema is a specific disease of pigs that is indistinguishable clinically and pathologically from foot-and-mouth disease. This disease is uniquely American and was believed eradicated from pigs in 1956 through enactment of federal laws requiring the cooking of garbage fed to pigs. The evidence indicates that vesicular exanthema of swine serovars are variants of San Miguel sea lion virus. This latter marine calicivirus occurs in coastal sea lion and fur seal populations from California to Alaska (Web Fig. 7-1).

Swine vesicular disease is indistinguishable from the other vesicular diseases and is exotic to the US. Efforts are underway to develop DNA microarrays to facilitate rapid identification of specific vesicular diseases from a single sample.

Erosive and Ulcerative Stomatitides

Erosions are defined by a loss of part of the thickness of the surface epithelium, whereas ulcers are full-thickness epithelial losses exposing the basement membrane. Thus erosions may progress to ulcers, which in hollow organs may become perforating ulcers. Erosive and ulcerative stomatitis can have a variety of causes. Agents responsible include the viruses of bovine viral diarrhea (BVD) (Fig. 7-3), rinderpest, malignant catarrhal fever (Fig. 7-4), feline calicivirus, and bluetongue, and in equids, nonsteroidal antiinflammatory drugs (NSAIDs). Other causes include uremia (Fig. 7-5); ingested foreign bodies, such as foxtail awns; the feline eosinophilic granuloma complex; and vitamin C deficiency in primates and guinea pigs (Web Fig. 7-2). Often, the oral lesions must be evaluated in the context of the clinical signs, together with histopathologic findings and ancillary testing, to arrive at a definitive diagnosis. Additionally, the vesicular stomatitides can progress to ulceration secondary to abrasion to the point that they cannot be distinguished from the ulcerative stomatitides.

Parapox Stomatitides

The two major diseases in this category, bovine papular stomatitis and contagious ecthyma, are zoonotic. Bovine papular stomatitis is recognized by papules on the nares, muzzle, gingiva, buccal cavity, palate, and tongue (Fig. 7-6). Lesions also occur in the esophagus, rumen, and omasum. Microscopically, acantholysis is responsible for the macule and ballooning degeneration of these cells, which may contain intracytoplasmic eosinophilic parapoxvirus inclusions at a later stage (Fig. 7-7; also see Fig. 1-12). Erosion of the infected cells accompanied by a neutrophilic infiltrate heals readily from the unaffected basal epithelium. The disease is more common in immunosuppressed animals such as those persistently infected with BVD virus. In humans, the disease is called milker’s nodules and is characterized by papules of the hands and arms.

Contagious ecthyma, sore mouth or infectious pustular dermatitis, is a condition of sheep and goats characterized by progression of the stages typical of pox viruses—macules, papules, vesicles, pustules, scabs, and scars in areas of skin abrasions, including the corners of the mouth (Fig. 7-8; also see Fig. 17-43), mouth, udder, teats, coronary bands, and anus. Occasionally, the mucosa of the esophagus and rumen also can be affected. The virus is quite hardy and can survive for 50 to 60 days in the summer and longer in cold weather. At room temperature, scabs containing virus can be infective after 10 years. Eosinophilic cytoplasmic inclusion bodies are visible at microscopic examination of lesions early in the course of disease. The condition in humans is called orf.

Necrotizing Stomatitides

Necrotizing stomatitis occurs in cattle, sheep, and pigs. In cattle, it is sometimes referred to as calf diphtheria (Fig. 7-9). Necrotizing stomatitis is the end-stage of all other forms of stomatitis when they are complicated by infection with Fusobacterium necrophorum, a filamentous-to-rodlike-to-coccoid, Gram-negative anaerobe. Bacterial toxins are responsible for the extensive lesions. Necrotizing stomatitis is characterized by yellow-gray, round foci surrounded by a rim of hyperemic tissue in the oral cavity, larynx, pharynx, or tongue. Well-demarcated foci of coagulation necrosis typify the histologic appearance of necrotizing stomatitis. As might be expected in foci of inflammation, there is a circumferential rim of leukocytes and hyperemia. Clinical signs include swollen cheeks, inappetence, pyrexia, and halitosis. Infection may become systemic if severe, resulting in lesions throughout the alimentary system and associated lymphoid tissue.

Noma is a severe form of oral ischemic necrosis with lesional spirochetes and fusiform bacteria. Although rare, it is seen most often in primates, including humans, and dogs. It is characterized by severe necrotizing gingivitis that can extend into adjacent bone causing osteolysis and sometimes death.

Ulcerative gingivitis (trench mouth), caused by anaerobic spirochetes, affects humans, some nonhuman primates, and rarely, puppies. In addition to Fusobacterium spp., Borrelia vincentii may be causative. Debilitated animals and those with intercurrent infections are at increased risk for these secondary invaders, which may be part of normal oral flora. Similar clinically to necrotizing stomatitis, ulcerative gingivitis is characterized by acute inflammation and necrosis, oral ulceration and pain, halitosis, a fragile oral mucosa, and ptyalism. The morphologic diagnosis is an acute, necrotizing gingivitis. Unlike the case in necrotizing stomatitis, the causative agents are readily identified by tissue smears or by culture.

Eosinophilic Stomatitides

Oral granulomas or ulcers (“rodent ulcers”) occur frequently in cats. Similar lesions occur sporadically in a variety of canine breeds. In cats, they are termed oral eosinophilic granulomas. Although the etiology of this condition is unknown, the histologic appearance of lesions suggests an immune-mediated mechanism, possibly a hypersensitivity reaction to an unknown antigen. Antibodies to intercellular material can often be demonstrated in affected cats. In the majority of cases of both dogs and cats, an increase in circulating eosinophils is present.

In cats, lip lesions are commonly visible near the philtrum and may extend through the adjacent haired skin. Oral lesions may occur anywhere in the mouth, including the gingiva, hard and soft palates, oral and nasal pharynx, tongue, and occasionally draining lymphoid tissues, excluding the tonsils, which do not have afferent lymphatic vessels (Fig. 7-10; also see Fig. 17-21, C). In dogs, eosinophilic granulomas typically are raised, fungating masses on the ventral and lateral lingual epithelium and palate. Collagenolysis (because collagen is acellular, it cannot undergo necrosis) is characteristically central in the lesion. The surrounding inflammatory tissue contains mixed inflammatory cells with increased numbers of eosinophils, mast cells, and multinucleated giant cells (see Web Fig. 3-14). Lesions grouped as the eosinophilic granuloma complex of cats include eosinophilic ulcer, linear (collagenolytic) granulomas, and eosinophilic plaques. The latter two lesions are strictly cutaneous and do not affect the oral cavity. No proven etiologic link has been established between these cutaneous conditions (linear granulomas and eosinophilic plaques) and oral eosinophilic granulomas. The cause of the canine lesions is unknown.

Lymphoplasmacytic Stomatitis

Lymphoplasmacytic stomatitis is an idiopathic condition of the cat named on the basis of the histologic appearance of the lesions (Fig. 7-11). Associations have been hypothesized between this condition and the presence of bacteria or calicivirus associated with feline leukemia virus (FeLV) and/or FIV infection. It is a chronic condition characterized by red, inflamed gums, a fetid breath, and inappetence. The oral mucosa may be hyperplastic and ulcerated. An inefficient immune response may be responsible for the persistence of oral bacteria and the accumulation of lymphocytes and plasma cells.

Chronic Ulcerative Paradental Stomatitis

Chronic ulcerative paradental stomatitis, a condition of dogs also known as ulcerative stomatitis and lymphocytic-plasmacytic stomatitis, is caused by apposition of “kissing ulcers” to dental plaque. The condition is painful with resultant inappetence and anorexia. Affected dogs drool and have halitosis. This condition occurs in older dogs of any breed, but Maltese dogs and cavalier King Charles spaniels are particularly susceptible. The lymphocytic-plasmacytic lesions noted on histologic examination are suggestive of an inflammatory rather than infectious etiology possibly caused by mediators released from the plaque. If untreated, bone resorption may occur.

Oral Mucosal Hyperplasia and Neoplasia

Structure and Function

Molar teeth in general are designed for grinding feedstuffs, whereas incisors in ruminants (mandibular only) are for cropping forage. Canine teeth are designed for tearing flesh. Brachydont teeth consist of a crown, which is the portion above the gingiva (the neck that is slightly constricted), and just below the gingiva are the roots, which are embedded in the bony socket (alveolus) of the jaw. Enamel covers the crown, cementum covers the roots, and both cover the dentin. Besides carnivores, the incisor (lower) teeth of ruminants and porcine teeth, except the canines of the boar, are brachydontic.

Hypsodont teeth have an elongated body, but the neck and roots may form later in life. Cementum covers the tooth, and enamel is beneath the cementum. Beneath the enamel is the dentin. The cementum and enamel invaginate into the dentin, forming the infundibula. Enamel crests result from normal wear, with enamel being the hardest of the layers. The cheek teeth of ruminants and tusks of boars and the teeth of horses are hypsodont.

In simple-toothed animals, such as carnivores, the tooth root is not covered by enamel. Receding gum lines therefore expose the dentin, resulting in pain and invasion by bacteria. Domestic animal species seldom get caries, although buildup of plaque can result in gingival infections and tooth loss.

Malocclusions

Abnormal development and positioning of the teeth may affect dental function. Malocclusion refers to a failure of the upper and lower incisors to oppose properly. This feature is “normal” for some dogs, particularly the brachycephalic breeds. In the extreme, malocclusions can lead to difficulty in the prehension and mastication of food. Malocclusions are named according to the position of the mandible. Protrusion of the lower jaw is termed prognathia, whereas a short lower jaw with resultant protrusion of the upper jaw is termed brachygnathia and sometimes hypognathia (Fig. 7-16). Sometimes these terms are incorrectly used, referring to brachygnathia as superior prognathia and prognathia as superior brachygnathia.

Malocclusions result from abnormal jaw conformation or rarely from abnormal tooth eruption patterns. In some animals, such as rodents and rabbits, the teeth continue to grow throughout the animal’s lifetime. If these animals are not provided with sufficient roughage in their diets, the teeth (both incisors and cheek teeth) overgrow and either “lock” the jaw or because of a lack of occlusal grinding surfaces, prevent the animal from receiving proper nutrition (Web Fig. 7-3).

Anomalies of Tooth Development

In simple-toothed animals and rarely in other animals, agenesis of a tooth or teeth occurs and is generally of no clinical significance (see Fig. 17-35). Supernumerary tooth development is less common than tooth agenesis and is similarly of little clinical significance. Some animals, such as elasmobranches (sharks), continue to produce row on row of teeth as the outermost rows are lost. Dental dysgenesis may be primarily due to dysplasia of the enamel-forming organ or secondary to trauma, infection and hyperthermia, toxicosis, or other metabolic irregularities during odontogenesis.

Dentigerous cysts result from dental dysgenesis, and epithelial-lined, cystic structures in tissue, including the bone of the jaw result. Dentigerous cysts develop from abnormal proliferation of the cell rests of Malassez. They appear as variably sized, sometimes fluctuant swellings of the mandible or maxilla. In the maxilla, they sometimes invade the nasal sinuses. Although rare, dentigerous cysts are often painful, and while not usually neoplastic, they can destroy the jaw. Dentigerous cysts are epithelial-lined and may become impacted with keratin. Rudimentary, malformed teeth may be found within these cysts, and painful fistulas may develop, especially in horses. These draining tracts are seen most often rostral and ventral to the ear (ear tooth). Dentigerous cysts occur less frequently in otherwise normal, mature animals.

Segmental enamel hypoplasia occurs before eruption of the permanent teeth of dogs as a result of hyperthermia and viral infection, most often by canine distemper virus infection. Enamel is fully formed when the teeth erupt; therefore virus infection of ameloblasts must occur during enamel formation, which is before the dog is 6 months of age, if enamel hypoplasia is to occur. Canine distemper virus infection causes necrosis and disorganization of the enamel organ. After the virus is cleared, structure and function of the enamel organ return to normal. Thus segmental enamel hypoplasia results from the lack of enamel formation during the period of virus infection (Fig. 7-17). A similar condition in calves is caused by in utero BVD virus infection.

Chemicals, most notably tetracycline antibiotics ingested during the process of mineralization, can cause yellowish, permanent discoloration (see Fig. 1-58). Congenital porphyria, a defect in red blood cell production, may result in incorporation of porphyrins into dentin, resulting in pink discoloration of the teeth (pink tooth) (Web Fig. 7-4). Both tetracycline and porphyrins fluoresce under ultraviolet light, dramatically demonstrating these lesions.

Fluoride incorporation into the enamel and dentin occurs in fluoride toxicosis, particularly in cattle and sheep. A relationship exists in beef cattle between fluorosis and selenium supplementation, with selenium supplementation being protective in high fluoride areas such as those downwind from aluminum smelters or with high levels of fluoride in ground water. Excessive dietary concentrations of fluorine during odontogenesis (from 6 to 36 months of age) may result in incorporation of the fluoride in the enamel and dentin of the permanent teeth. The result is soft, chalky, discolored enamel, usually yellow, dark brown, or black (Web Fig. 7-5). Occlusal grinding of affected soft teeth against more normal enamel results in rapid dental wear to the extent that severely affected sheep may have almost completely worn down their incisors. One wonders therefore about the cumulative effect of fluoride supplementation in municipal drinking water, vitamins with added fluoride, fluoride-supplemented toothpaste, fluoride treatment of teeth, reconstituted and bottled soft drinks made with fluoridated water, and so forth. It is difficult to calculate the total fluoride load ingested by individuals or what the effects may be of that fluoride supplementation.

Lesions Caused by Attrition and Abnormal Wear

Loss of normal dental structure and function often results from rapid and irregular and/or abnormal wear of occlusal surfaces in many species of domestic animals. In those species with hypsodont teeth, attention to the dentition as the animal ages is often a major factor in overall body conditioning and health (Fig. 7-18). Aggressive treatment of occlusal surface irregularity by filing of high points in the dental arcade (floating) can notably prolong an animal’s life. Rock chewing or other compulsive oral behaviors in dogs may result in accelerated dental wear. Similarly, cribbing in horses and herbivorous animals grazing on sandy soils can cause premature dental wear. In all species, exposure of dentin or the pulp canal may lead to dental infection with serious consequences.

Miscellaneous Dental Lesions

Infundibular Impaction

Impaction of the infundibulum, also known as infundibular necrosis or infundibular caries, may cause serious dental disease in ruminants and more rarely in horses. Incomplete infundibular cementum formation before the tooth erupts likely predisposes to infundibular impaction. The pathogenic mechanism is comparable to dental caries in simple-toothed animals, which is uncommon in domestic animals. Feed material is ground into the infundibulum, where bacteria metabolize it to form acid, which causes demineralization. Bacterial enzymes digest the organic matrix of enamel and dentin. As a result of this destruction, the pulp cavity becomes exposed and infected, resulting in pulpitis and endodontitis. Dental abscesses and fistulous tracks may develop and rupture into the paranasal sinuses. The inflamed infundibular cavities often continue to become impacted with feed, creating a vicious cycle.

Periodontal Disease

More than 200 species of bacteria and fungi have been associated with dental plaque (a film of an organic matrix, food particles, and bacteria on the tooth surface). This plaque often becomes mineralized (tartar or dental calculus). The mineralized material contributes to atrophy and inflammation of the gingival mucosa and supporting stroma by acting as a nidus for additional plaque accumulation. Bacteria resident in films on the tooth surface produce acids and enzymes that may damage their enamel substrate (cavities) and also destroy the subjacent gingival tissue and periodontal ligament (periodontal disease).

The initial site for destructive inflammation is in the gingival crevice–forming pockets where bacteria lodge. With time, this inflammation spreads distally along the tooth, resulting in gingival-epithelial attachment only on the root of the tooth, deep in the alveolar socket. Progression of inflammation may destroy the connective tissue of the periodontal ligament, resulting in loosening of the tooth. The infection can spread causing alveolar osteomyelitis and pulpitis and can result in apical abscesses and bacteremia. There is significant oral pain, reluctance to masticate, and halitosis. Periodontal disease is common in carnivores and humans. Mildly abrasive diets and brushing of the teeth of pet carnivores, combined with regular dental examination, is preventive as it is in humans.

Dental Neoplasia

Proliferative, cystic, or neoplastic diseases of the dental arcade can originate from cell rests that form from the dental lamina or the enamel organ (the cell rests of Malassez). Dental neoplasms usually arise close to the teeth, either deeply in the jaw or from the oral epithelium. There is a relatively precise method of naming dental neoplasms based on the tissue or cell of origin and the extent of differentiation and odontogenesis present within the neoplastic tissue. The histologic appearance of these neoplasms is complex; pathologists with considerable experience in differentiating these uncommon neoplasms should be consulted when a precise diagnosis is indicated.

Odontomas are hamartomas originating in the enamel organ and are usually seen in puppies and foals (Fig. 7-19). They usually contain well-recognizable dentin and enamel, as well as ameloblasts, odontoblasts, and dental pulp.

Ameloblastoma is a term applied to epithelial neoplasms of enamel organ origin. Several subtypes, distinguished histologically, are ameloblastic fibroma, ameloblastic odontoma, calcifying epithelial odontogenic tumor, peripheral odontogenic fibroma, and other rare tooth neoplasms. Ameloblastoma appears randomly in the dental arcade, usually in adult dogs. They are often osteolytic and thus are locally invasive. Histologic examination by an expert is often necessary to distinguish ameloblastoma from acanthomatous epulis (acanthomatous ameloblastoma) and squamous cell carcinoma.

Structure and Function

The palatine tonsils are pharyngeal lymphoid structures covered by stratified squamous epithelium. Their function is uncertain, although it is likely they serve in lymphocyte production and antibody formation (see Chapter 13). In carnivores, they are found in crypts or recesses at the dorsolateral aspect of the caudal oropharynx. In pigs, they are flat and recognized by tiny pores in the surface epithelium of the caudal soft palate. Equids, ruminants, and pigs have lingual tonsils in addition to palatine tonsils.

Portals of Entry

Tonsils do not possess afferent lymphatic vessels and do not serve as lymph filters. Therefore only primary (or direct) or hematogenous infections occur (tonsillitis) (Fig. 7-20), as well as primary neoplasms of either the lymphoid (lymphoma) (Fig. 7-21) or epithelial (squamous cell carcinoma) (Fig. 7-22) components. In many viremias of mammals, such as pseudorabies of pigs, virus may be isolated from the tonsils.

Structure and Function

Most salivary glands are discrete aggregates of compound tubuloalveolar tissue. Saliva is a mixture of serous and mucoid secretions. Saliva lubricates the mouth and esophagus and moistens ingesta. Saliva also dissolves water-soluble components of food so the taste buds can function. The mucus in saliva binds to masticated food and creates a bolus that is more easily swallowed. Salivary mucus also coats the epithelium of the mouth, preventing mechanical damage to the tissue. Saliva, through its flushing action, reduces bacterial populations. Saliva contains a lysozyme that lyses bacteria. Carbohydrate digestion begins in the oral cavity as a result of the presence of α-amylase, which changes starch into maltose. There are very small quantities of this enzyme in carnivores and cattle. Saliva also is an effective buffer, especially in ruminants, whose forestomachs have no glands. In carnivores, evaporation of saliva is a major mechanism of thermoregulation.

Portal of Entry

Salivary glands are generally affected by blood-borne pathogens, direct penetration by foreign objects, obstruction of the excretory ducts, or bite wounds. In humans, ascending infections from the salivary ducts occur, but there is no evidence that this occurs in domestic animals. The serous portions of the salivary glands are radiosensitive.

Response to Injury

Injury to the salivary gland is accompanied by incomplete regeneration, principally from ductular epithelium. There are often atrophy, fibrosis, and squamous metaplasia of secretory epithelium, sometimes resulting in blockage of ducts.

Inflammatory Diseases

Sialoadenitis, inflammation of a salivary gland, is relatively rare in veterinary medicine. Although diagnosis of systemic diseases is not made by examining the salivary gland, rabies and canine distemper are two very important diseases that cause inflammation of the salivary glands. Saliva is a particularly important medium of spread, by bite wounds, of the rhabdovirus that causes rabies. There are focal necrosis, mononuclear cell inflammation, and sometimes inclusions (Negri bodies) in the nuclei of ganglion cells. In the rat, a coronavirus termed sialodacryoadenitis virus is responsible for inflammation of the salivary gland and some adnexal ocular glands. Salmonella typhisuis has caused suppurative parotid sialoadenitis in pigs.

Gross lesions of sialoadenitis are subtle and include swelling and edema. Sialoadenitis can be accompanied by pain on palpation. Abscesses occasionally occur sometimes secondary to the migration of foreign bodies (grass awns) and are especially noticeable when they occur in the retrobulbar zygomatic gland where they may cause ocular protrusion (proptosis).

Miscellaneous Diseases or Conditions

Changes in the salivary glands are uncommon in domestic animal species. A ranula is a cystic saliva-filled distention of the duct of the sublingual or submaxillary salivary gland that occurs on the floor of the mouth alongside the tongue (Fig. 7-23). It is thus epithelial lined. The cause is generally unknown, although some cases are due to sialoliths. A salivary mucocele, in contrast, is a pseudocyst not lined by epithelium but filled with saliva. The cause of this lesion is also unknown, but it may occur secondary to traumatic rupture of the duct of a sublingual salivary gland with resultant leakage and encapsulation of saliva by reactive connective tissue.

Sialoliths are rare in domestic animal species. When they do occur, they are considered to be caused by inflammation of the salivary gland with sloughed cells or inflammatory exudate forming a nidus for mineral accretion (Fig. 7-24). Thus they are one cause of ranula formation.

Neoplasia

Salivary gland neoplasms, both benign and malignant, are uncommon but occur in all species (Fig. 7-25). They are composed of glandular or ductular elements or a combination of epithelial and mesenchymal components similar to those in mixed mammary neoplasms. A grossly appearing similar condition, salivary gland infarction, occurs infrequently in cats and rarely in dogs. The cause of the infarction is unknown. The gross appearance of firmness and swelling of an infarcted gland must be distinguished microscopically from neoplasia (Web Fig. 7-6). In salivary gland infarction, there are discrete foci of parenchymal necrosis with peripheral hemorrhage and inflammatory cells. Attempted incomplete regeneration of the gland from ductal epithelium can be mistaken for neoplasia unless one is familiar with the former condition.

Structure and Function

The tongue is necessary for prehension, mastication, and swallowing of feedstuffs and water. The epithelial covering of the tongue is stratified squamous with various degrees of keratinization dorsally, but ventrally the epithelium is not keratinized and the tongue attaches to the floor of the oral cavity by a frenulum. Keratinized papillae are most prominent in ruminants and cats. There are various types of papillae, some with secondary lamellae. Vallate papillae, for example, are on the dorsal surface of the tongue near its root and are flat structures completely surrounded by a cleft. Some surface macroscopic papillae contain taste buds. The tongue is a highly vascular (functioning in heat loss in many animals, especially carnivores that have no sweat glands) and sensitive organ containing a variety of serous and mucus glands and sensory cells (taste buds). The muscular part of the tongue is striated in randomly arranged bundles. A cordlike structure enclosed in dense collagen extending lengthwise near the ventral central surface of the tongue of carnivores is called the lyssa. Porcine and equine tongues have a similar structure. The lyssa appears to be a structure without a function. Historically, the lyssa was removed as “prevention” for rabies. Lyssa bodies are synonymous with Negri bodies, and rabies used to be called lyssa. Adipose tissue becomes more abundant in the caudal part of the tongue in most species.

Developmental Anomalies

Congenital diseases of the tongue include epithelial defects such as fissures, epitheliogenesis imperfecta, macroglossia and microglossia, bifid tongue, and hair growing from the tongue (choristoma) (Web Fig. 7-7). Lethal glossopharyngeal defect, or bird tongue of dogs, is characterized by a pointed tongue that cannot wrap around a nipple and create the negative pressure required for nursing and without intervention, starvation results. Ventral ankyloglossia, fusion of the tongue to the floor of the oral cavity, has been reported in related Anatolian shepherd dogs. The cause of these congenital lesions is not known, but they sometimes occur in association with other defects. As in the case of other congenital defects, ingestion of unknown teratogenic substances by the dam during gestation is an etiologic possibility, as is mutation of T-box genes.

Systemic Disease: Primary Involvement of the Tongue

Disease agents that principally target the tongue are relatively rare. The exception to this rule is Actinobacillus lignieresii, a gram-negative bacillus that is a normal inhabitant of the oral cavity. It is an opportunistic invader of damaged lingual tissue, principally in bovids and occasionally in equids and small ruminants. The granulomas resulting from infection contain centrally located actinobacilli rimmed by radiating amorphic, eosinophilic, and clublike structures composed of immunoglobulin molecules from lesion plasmacytes (Fig. 7-26). Mixed mononuclear inflammatory cells, including multinucleated Langhans’ giant cells, often surround these foci (Splendore-Hoeppli phenomenon), and infection may drain and cause similar inflammation in submaxillary and retropharyngeal lymph nodes. The amount of fibrous tissue present depends on the duration of the inflammation and the swelling. Inflammation and fibrosis cause increased firmness of the tongue and linguamegaly, or “wooden tongue” (Fig. 7-27). Horses are rarely affected by Actinobacillus lignieresii infections, but when they are, lesions are cutaneous or lymph node abscesses, mastitis, and occasional glossitis.

Systemic Disease: Secondary Involvement of the Tongue

Thrush is a Candida albicans (yeast) infection of intact mucous membranes of the tongue and esophagus (Fig. 7-28). It occurs principally in ungulates but has also been seen in carnivores. Thrush is not a primary disease but often indicates an underlying debility, particularly in young animals. It occurs as a result of antibiotic treatment that kills normal flora, increased serum glucose concentrations as a result of diabetes mellitus, a high-sugar diet, or intravenous glucose therapy. The availability of iron is a limiting factor for the indigenous bacteria, which compete with yeast for mucosal colonization. Immunodeficiency states also contribute to the development of thrush. All of these scenarios provide tissue conditions suitable for the proliferation of yeast forms. Rarely, systemic infection may result. Factors predisposing to systemic infections include multiple antibiotic usage, indwelling catheters, and endotracheal tubes. This infection presents as a gray-green pseudomembrane that is easily scraped off the intact underlying mucosal surface (Fig. 7-29).

Often, lingual lesions are manifestations of systemic diseases, such as BVD, foot-and-mouth disease, multisystemic amyloidosis, and uremia (Fig. 7-30; also see Fig. 11-27). These diseases are discussed in more detail in this and other chapters of this book.

Hyperplastic and Neoplastic Conditions

Epithelial hyperplasia of the lateral edges of the tongue is common in piglets before nursing, when the fringelike epithelium is rubbed off (Web Fig. 7-8).

Lingual (glossal) neoplasms are rare but when they occur are generally of epithelial origin. Squamous cell carcinomas are most common (Fig. 7-31; also see Fig. 6-10), but papillomas (Fig. 7-32), rhabdomyomas, rhabdomyosarcomas, fibrosarcomas, melanomas, and granular cell tumors have all been reported in domestic animals.

Parasites

Parasites of the tongue are uncommon, with the exception of those that reside in muscles such as Sarcocystis spp. in most species and Trichinella spiralis in pigs and occasionally in carnivorous wildlife such as polar bears. Gongylonema spp. can be present in the lingual mucosa of pigs and ruminants and are of no clinical significance.

Structure and Function

The esophagus extends from the aboral end of the oropharynx, passes through the mediastinum and the diaphragmatic hiatus, and ends at the stomach. The esophagus is lined by nonkeratinizing stratified squamous epithelium in carnivores and is keratinized in pigs, horses, and ruminants. Keratinization is greatest in ruminants, less in horses, and least in pigs. Longitudinal and oblique mucosal folds are present to varying degrees. Transverse, herringbone-like folds are present in the cat.

The tunica muscularis is completely striated in ruminants and dogs. In the horse, the distal third of the esophagus contains smooth muscle. The pig is similar to the horse, except that the middle third of the esophagus contains a mixture of smooth and striated muscle. In cats, opossums, and primates, the distal two-thirds of the esophagus is composed of smooth muscle. The smooth muscle is arranged as an inner circular layer and an outer longitudinal layer.

Mixed mucinous glands are present in the tunica submucosa of pigs and dogs. In pigs, the glands are most abundant in the cranial half of the esophagus, and in dogs, they are present throughout. Glands are present in cats, horses, and ruminants only at the junction of the esophagus and pharynx.

It is important to remember that unlike the rest of the tubular digestive tract, the esophagus is unique in that it lacks a serosa in all but the abdominal portion. This means that there is no serosa to leak serum and fibrin to seal a puncture wound from a perforation of a foreign body or a surgical incision. Likewise, sutures are not likely to seal an incision. Combine this with the strong muscular peristaltic contractions that characterize this organ and it is easy to understand why esophageal surgery is not often performed and is even less often successful. For the same anatomic reasons, perforating foreign bodies of the esophagus do not seal themselves off.

Esophageal innervation is from the vagus nerves. Esophageal smooth muscle contains myenteric ganglia. Striated muscle is innervated by motor end-plates via efferent fibers of the hypoglossal nerve along with contributory neurofibers from cranial nerves 5, 9, and 10, which control voluntary lingual function.

Portals of Entry

Materials from the oral cavity pass via the esophagus to the stomach or rumen, including caustic chemicals. Penetration or obstruction by foreign objects is the most common portal of entry into the mediastinum (Fig. 7-33). Some parasites spend part or all of their life cycles in the esophagus. Iatrogenic puncture of the esophagus is a not uncommon sequela to passage of stomach tubes. Gastric reflux is an additional portal of entry into the esophagus.

Developmental Anomalies

Esophageal motility disorders are termed achalasia. In this condition, the sequential contractility of the esophagus is defective and the lower cricopharyngeal sphincter fails to function properly. Achalasia results in difficulty in swallowing and may be responsible for regurgitation and weight loss.

Cricopharyngeal achalasia is a congenital, possibly neurogenic, disorder of the upper esophageal (cricopharyngeal) sphincter. It occurs in young, small breed dogs, particularly terriers, cocker spaniels, and miniature poodles. Postweaning dysphagia and regurgitation after a meal of solid food is characteristic of this functional disorder. Liquids are generally swallowed without incidence. Gagging or choking behavior of the patient after swallowing is a good indicator in the appropriately aged dog of this condition.

Acquired canine achalasia is extremely uncommon. In this condition, there is often a visible abnormality of the musculature of deglutition (cricopharyngeus). There does not appear to be a characteristic change in the affected musculature. Esophageal myotomy of the appropriate cricopharyngeal sphincter muscle is palliative for these idiopathic conditions.

Megaesophagus

Megaesophagus or esophageal ectasia is dilation of the esophagus because of insufficient, absent, or uncoordinated peristalsis in the mid and cervical esophagus. It has been described in dogs, cats, cows, ferrets, horses, and new world camelids. Causes include innervation or denervation disorders and partial physical obstructions and stenosis, secondary to inflammatory diseases of esophageal musculature or persistence of the right aortic arch. Many cases are idiopathic.

Congenital megaesophagus is usually due to partial blockage of the lumen of the esophagus by a persistent right fourth aortic arch. Because of the persistence of the arch, a vascular ring forms around the esophagus and trachea, preventing full dilation of the esophagus. The ring is formed by the aorta, pulmonary artery, and ductus arteriosus. This form of megaesophagus is unique in that the esophageal obstruction, and thus dilation, occurs cranial to the heart because of the location of the obstructing vascular ring (Fig. 7-34; also see Fig. 10-64). Persistent right aortic arch is likely hereditary in German shepherds, Irish setters, and greyhounds. All other forms of megaesophagus result in dilation cranial to the stomach.

Congenital megaesophagus also occurs as an idiopathic denervation of the esophagus, most notably in great Danes, Irish setters, miniature schnauzers, Labrador retrievers, wire hair fox terriers, shar-peis, Newfoundlands, Siamese cats, and in some cases of vagal indigestion, in cattle. Some cases of myasthenia gravis (see later discussion) are congenital and may be of genetic origin.

Acquired megaesophagus (esophageal achalasia) is the result of failure of relaxation of the distal esophageal (cardiac) sphincter of the stomach. The obstruction and thus dilation occurs cranial to the stomach (Fig. 7-35). Although the gross appearance of acquired megaesophagus in animals is similar to that of humans, the cause of the condition in animals does not involve the cardiac sphincter. Causes are idiopathic or secondary to polymyositis (inflammation of the esophageal muscle), myasthenia gravis (a congenital or autoimmune disease directed against acetylcholine receptors of the neuromuscular junction), hypothyroidism (which can result in muscle atrophy and denervation disease), congenital myopathy, lead and thallium poisoning (via effect on innervation), peripheral neuropathies, vagal indigestion, esophagitis, and recurrent gastric dilation. Increased risk in dogs is seen in German shepherds, golden retrievers, and Irish setters.

Megaesophagus is recognized clinically by regurgitation after ingestion of solid food. Thus congenital megaesophagus is often recognized at weaning. Often, animals are thin and may have aspiration pneumonia. Radiographically, the esophagus is dilated anterior to the lesion and retains radiopaque dyes (Web Fig. 7-9). Dilation may vary from diffuse to locally extensive, depending on its cause. Putrid ingesta are sometimes found in the dilated, atonic portions of the esophagus. Although degenerate nerve fibers are occasionally found within vagus nerves, megaesophagus can occur without detectable histologic lesions.

Hiatal Hernia

Protrusion of the abdominal esophagus and cardia of the stomach through the diaphragm into the thoracic cavity is termed a hiatal hernia. This inversion is generally into the esophageal lumen and is self-reducing. Sometimes a gastroesophageal intussusception results.

Eosinophilic Esophagitis

Eosinophilic esophagitis is an emerging disease in humans; in a single dog, clinical signs include regurgitation, dysphagia, and cough, accompanying a diffusely affected, friable, hyperemic, ulcerated esophageal mucosa visible by endoscopy. Inflammation is dominated by granulocytes—half of which are eosinophils. Diagnosis is by elimination of other causes of inflammatory esophagitis. Seventy percent of humans and the single dog described had concurrent allergic skin disease.

Esophageal Parasites

With notable exceptions, parasitic diseases of the esophagus are generally of no clinical importance. The more common parasites of the esophagus are Gongylonema spp., which affect ruminants, pigs, horses, primates, and occasionally rodents. These nematodes reside in the esophageal mucosa and are characteristically thin, red, and serpentine. They can be 10 to 15 cm in length and are easily visible (Fig. 7-36). The intermediate hosts are cockroaches and dung beetles.

Gasterophilus spp. occur in equids. These fly larvae have interesting life cycles because their eggs are laid on the skin in varying locations. The warmth and moisture from licking activates them. The larvae burrow into the oral mucosa, molt, and then migrate down the esophagus. They occur both in the distal esophagus and stomach, where they attach to the mucosa via oral hooks. They eventually detach, leaving craters at the site of attachment, and pass in the feces.

Hypoderma lineatum is the larvae of the warble fly of ruminants. These parasites eventually migrate to the esophageal adventitia and then to the subcutaneous tissue of the back.

Spirocerca lupi of canids is probably the most pathogenic of the esophageal parasites. These nematodes reach the esophageal submucosa after migrating from the stomach. They penetrate through the gastric mucosa to reach the adventitia of arteries and then migrate in the adventitia to the abdominal aorta and aborally to the caudal aorta where they form a granuloma in the adventitia. From here they migrate to the adjacent esophageal submucosa. A passage forms between the esophageal lumen and the granuloma containing the parasite, allowing discharge of ova into the lumen of the alimentary system and eventually into the feces. Clinical sequelae of infestation include dysphagia, aortic aneurysms, hemothorax, and rarely esophageal fibrosarcomas or osteosarcomas (Fig. 7-37). Occasionally, chronic aortic granulomas will extend into the adjacent thoracic vertebral bodies of chronically affected canids to cause spondylosis deformans adjacent to the aortic granulomas. Spirocerca lupi infestations occur in warmer climates. The intermediate hosts are dung beetles, and the paratenic hosts are chickens, reptiles, and rodents.

Miscellaneous Esophageal Lesions and Conditions

Idiopathic muscular hypertrophy of the distal esophagus is a lesion peculiar to horses and pigs that can be quite spectacular at necropsy (Fig. 7-38) but usually is of no clinical significance. The esophageal musculature can be several centimeters thick, and the lesion can extend along the distal quarter of the esophagus. Rarely this condition plays a role in esophageal impaction. Similarly, dilation of the esophageal glands present throughout the esophagus of aged dogs can be a spectacular gross lesion of no clinical consequence. It is therefore important to carefully evaluate these lesions either at necropsy or during fiberoptic viewing in the live animal to determine whether what appear to be erosions and ulcers are instead mucosal elevations caused by glands filled with mucus. Because the lesions are subepithelial, the overlying mucosa is smooth and shiny. Dilated esophageal glands vary in number and location but are generally only a few millimeters in diameter (Fig. 7-39). They are most numerous in the distal esophagus.

Esophageal erosions and ulcers are relatively common and have a variety of causes. One of the more common causes of esophageal erosions and ulcers is reflux of stomach acid. This reflux of gastric acids causes chemical burning of the distal or aboral esophagus and is commonly called acid reflux esophagitis (Fig. 7-40) or clinically, heartburn in humans. Other causes of esophageal ulcers include improper use of stomach tubes, which cause linear scraping on the crests of the longitudinal folds of the esophageal mucosa (Fig. 7-41), foreign bodies such as bones in dogs and infectious diseases, such as BVD (Fig. 7-42), which cause mucosal injury in other locations as well.

Leukoplakia of the esophagus and stomach is characterized by discrete, flat, white mucosal elevations (epithelial plaques) of no clinical significance and of unknown cause. They are sometimes mistaken for thrush lesions or neoplasia. Unlike thrush lesions, they do not scrape off easily, and their regularity, number, and location distinguish them from neoplasms. Histologically, the stratum basale and prickly cell layers are notably thickened, and the surface cells have pyknotic nuclei and some parakeratosis. In humans, about 5% of these lesions become cancerous. They are present in the oral cavity and esophagus of humans and are believed related to chronic irritation most often associated with smoking or chewing tobacco. Alcohol consumption and restorative dental amalgams may also predispose to leukoplakia.

Choke

Choke is a clinical term referring to esophageal obstruction subsequent to stenoses or blockage. Choke most often occurs in anatomic locations in which the esophagus cannot fully expand. These locations are dorsal to the larynx, cranial to the first rib at the thoracic inlet, the base of the heart, and the diaphragmatic hiatus. Choke occurs most frequently as a result of ingestion of large foreign bodies, such as potatoes, apples, bones (Fig. 7-43), or corn cobs (Fig. 7-44), or medicaments, such as large gelatin-filled capsules or tablets (dry boluses). If these bodies are lodged against the epithelium for longer than 2 days, the interaction often results in circumferential pressure necrosis of the esophageal mucosa (Fig. 7-45), which forms strictures during healing. These strictures then can cause reflex regurgitation after ingestion of food with possible starvation or aspiration pneumonia resulting.

In older horses, poor dentition causes feed to be incompletely masticated, resulting in impaction in the esophagus. Neoplastic or inflammatory lesions of the esophagus or periesophageal tissues also cause obstruction. Persistence of the right aortic arch has already been discussed as a cause of esophageal stenosis and megaesophagus.

Neoplasia

Neoplasms of the esophagus are rare. Bracken fern (Pteridium aquilinum) consumption sometimes in association with papilloma viruses has been associated with squamous cell carcinomas in bovids. The clinical signs are similar to those of other causes of esophageal blockage and include dysphagia, regurgitation, weight loss, and dilation of the esophagus proximal to the mass. Tumors of the esophagus are occasionally palpable but are most often intraluminal rather than mural. Epithelial tumors include papillomas (Fig. 7-46) and squamous cell carcinomas. The latter have wide metastatic potential. Smooth muscle tumors of the esophagus, whether benign or malignant, are also rare but may result in similar clinical signs (Fig. 7-47). Esophageal fibrosarcomas of dogs often develop in areas with Spirocerca lupi infestation. Esophageal lymphoma occurs sporadically in most species (Fig. 7-48).

Structure and Function

The rumen has small papillae that vary by diet up to 1.5 cm in length. Their length, shape, and degree of keratinization are affected by diet, and they are longer with high roughage diets and shorter with more concentrates in the ration. These changes are most obvious in the ventral compartment—the ventral ruminal sac. The reticulum has a honeycomb appearance, and the omasum consists of a series of about 100 longitudinal folds similar to the pages of a book. The nonglandular stratified squamous mucosa of the reticulum, rumen, and omasum can be acutely inflamed when their contents have an acid pH and the abnormal milieu permits bacterial and mycotic overgrowth.

The epithelial lining of the forestomach functions as a protective barrier for the forestomach and for the metabolism of ingesta and the absorption of volatile fatty acids. Because the reticulo-omasal orifice is more dorsal than the floor of the compartments, the reticulum can trap foreign bodies, especially dense metallic ones. These can irritate or penetrate the mucosa (“hardware disease”). Problems with motility and imbalances of rumen flora and fauna are the most frequent abnormalities of forestomach function. Often, the changes in flora and fauna are precipitated by a change in ingested substrate, promoting the growth of particular organisms. These changes alter ruminal pH and thus affect the integrity of the mucosal lining of the compartments of the forestomach or cause the production of excessive gas, resulting in ruminal distention.

Parts of compartment one (C1) and C2 and C3 of the camelid forestomach are lined by mucinous glandular epithelium. Concretions of ingesta are sometimes found within the saccules that contain the glands. The saccules are also the sites of water and other solutes. The nonglandular portions of C1 and C2 are lined by nonkeratinized stratified squamous epithelium without papillae. The forestomach of new world camelids contracts at two to three times the rate of other ruminants (and in reverse order), and with each cycle, the saccules empty and refill. This results in high digestive efficiency across the saccules.

Bloat (Ruminal Tympany)

Ruminal tympany or bloat is by definition an overdistention of the rumen and reticulum by gases produced during fermentation. Mortality of affected animals is approximately 50%. A hereditary predisposition to bloat might exist in cattle because cases are on record of bloat in monozygotic twins. Bloat can be divided into primary tympany and secondary tympany.

Primary tympany is also known as legume bloat, dietary bloat, or frothy bloat. It generally occurs up to 3 days after animals begin a new diet. Certain legumes, such as alfalfa, ladino clover, and grain concentrates, promote the formation of stable foam. The nonvolatile acids of legume and ruminal fermentation lower the rumen pH to between 5 and 6, which is optimal for formation of bloat. Foam mixed with rumen contents physically blocks the cardia, preventing eructation and causing the rumen to distend with the gases of fermentation. Clinical signs include a distended left paralumbar fossa, a distended abdomen (see Fig. 1-27), increased respiratory and heart rates, and late in the disease, decreased ruminal movements. When death occurs, it is attributable to distention of the abdomen, which compresses the diaphragm, moving it cranially (orad), with resultant decreased pleural cavity size and respiratory embarrassment. There is also increased intraabdominal and intrathoracic pressure, resulting in decreased venous return to the heart and ultimately generalized congestion cranial to the thoracic inlet.

The lesions of primary tympany are often difficult to detect if there is an interval between death and postmortem examination because the foam can collapse. Conversely, fermentation can occur after death in a nonbloated animal, resulting in the production of abundant gas. The most reliable postmortem indicator of antemortem bloat is the sharp line of demarcation most evident in the mucosa between the pale, bloodless esophagus distal to the thoracic inlet and the congested proximal esophagus cranially (orad) to it. This line may sometimes form even after death before the blood clots. This division is known as a bloat line (Fig. 7-49).

Secondary tympany is caused by a physical or functional obstruction or stenosis of the esophagus resulting in failure to eructate. Examples of physical causes are esophageal papilloma, lymphoma, esophageal foreign bodies, and enlarged mesenteric or tracheobronchial lymph nodes, usually from lymphoma or tuberculosis. Vagus indigestion or other innervation disorders are examples of functional disorders.

It is questionable if new world camelids bloat.

Foreign Bodies

Foreign bodies can collect or lodge in the rumen. These include trichobezoars (hair balls) and phytobezoars (plant balls). Trichobezoars are sometimes a sequela to a habit of bucket-fed calves sucking on the skin of each other to satisfy their nursing instincts. Trichobezoars can form in utero because of hair circulating in the amniotic fluid and being swallowed by the fetus. Phytobezoars result from an excess of indigestible roughage.

Ingestion of nails and wire, common where straw and hay bales are bound by wire, can result in perforation of the wall of the reticulum with resultant reticulitis, peritonitis, or eventually possible pericarditis (hardware disease) (Fig. 7-50). Often, in areas in the US in which ruminants are at high risk of hardware disease because of farming practices, magnets are placed in rumens to prevent the ingested wires and nails from penetrating the reticular mucosa. Occasionally, ruminants ingest plates from storage batteries and suffer lead poisoning.

Inflammatory Diseases

Inflammation of the rumen, rumenitis, is generally considered synonymous with lactic acidosis. Lactic acidosis is synonymous with grain overload, rumen overload, carbohydrate engorgement, and chemical rumenitis. All ruminants are susceptible. The pathophysiology of lactic acidosis usually involves a sudden dietary change to an easily fermentable feed or a change in the feed volume consumed. The latter scenario is most likely to occur during weather changes, especially among feedlot cattle, when a sudden cooling rainstorm will stimulate food intake of cattle that had previously lost appetite because of high environmental temperatures and humidity.

Ruminal microflora is generally rich in cellulolytic gram-negative bacteria necessary for the digestion of hay. A sudden change to a highly fermentable, carbohydrate-rich feed promotes the growth of Gram-positive bacteria, Streptococcus bovis, and Lactobacillus spp. The lactic acid produced by the fermentation of ingested carbohydrates decreases the ruminal pH below 5 (normal = 5.5 to 7.5). This acidic pH eliminates normal ruminal flora and fauna and damages ruminal mucosa. Increased concentrations of dissociated fatty acids lead to ruminal atony. When death occurs, it is due to dehydration secondary to the increased osmotic effect of ruminal solutes (organic acids), causing movement of fluids across the damaged ruminal mucosa into the rumen, acidosis (from absorption of lactate from the rumen), and circulatory collapse. Mortality among animals with lactic acidosis ranges from 25% to 90% and usually occurs within 24 hours.

At necropsy, the ruminal and intestinal contents are watery and acidic. Often, abundant grain is found in the rumen. The mucosa of the ruminal papillae is brown and friable and detaches easily, especially from the ventral ruminal sac. Caution must be exercised in interpreting this latter finding as a lesion because the ruminal mucosa often detaches easily in animals that have been dead for even a few hours at high environmental temperatures. Hydropic change and coagulative necrosis of the ruminal epithelium followed by an influx of neutrophils are common microscopic lesions. Animals surviving lactic acidosis develop stellate scars that are visible because of their color difference from the unaffected surrounding ruminal mucosa. Scars are pale; unaffected mucosa may be light to dark brown to black, depending on the original diet.

New world camelids appear to be more sensitive than ruminants to high carbohydrate diets. While their compartments do not have papillae, widespread ulceration of the squamous mucosa occurs in cases of lactic acidosis. New world camelids retain feed in their stomach longer than ruminants, possibly increasing fermentation and acid production. They rely on emptying of fluid to preserve milieu. High energy feeds may quickly impede motility promoting a drop in pH.

Bacterial rumenitis generally occurs secondary to lactic acidosis or mechanical injury to the ruminal mucosa. Bacteria that colonize the damaged ruminal wall can be transported into the portal circulation and to the liver, resulting in multiple abscesses. Arcanobacterium (Actinomyces) pyogenes is a common cause of bacterial abscesses in the liver. Fusobacterium necrophorum, also transported from the rumen to the liver, results in necrobacillosis, which has distinctive liver lesions.

Mycotic infections of the rumen also occur secondary to the damage to the ruminal mucosa caused by lactic acidosis and mechanical injury. Mycotic rumenitis also results from the administration of antibiotics, usually in calves but also in adult cattle, which reduce the numbers of normal flora and allow fungi to proliferate. In cases of mycotic rumenitis, lesions are generally circular and well delineated and are caused principally by infarction from thrombosis secondary to fungal vasculitis (Fig. 7-51). Offending fungi include Aspergillus, Mucor, Rhizopus, Absidia, and Mortierella spp. These fungi can spread to the placenta hematogenously and cause mycotic placentitis, which leads to abortions.

Ruminal candidiasis occurs as an incidental finding at necropsy. There is usually an underlying debilitating condition, glucose therapy, milk-replacer overload (sour rumen), or an antibiotic-induced kill-off of resident flora and fauna. Ruminal candidiasis is seldom diagnosed in a live animal.

Miscellaneous Diseases or Conditions

Ruminal papillae vary in length, becoming longer with high-roughage diets (Fig. 7-52). Such diets also can cause the papilla to become tongue- or leaf-shaped. Animals consuming diets with less than 10% roughage can develop ruminal parakeratosis. These rumens have hard, brown, often clumped, papillae. This lesion has little to no clinical consequence.

Ruminal papillomas are papilloma virus-induced in some cases, but in certain countries, bracken fern has been implicated as a cofactor in these forestomach neoplasms (Fig. 7-53).

Vagal indigestion results in a functional outflow problem from the forestomach. Damage to the vagus nerve can occur anywhere along its length and can result in functional pyloric stenosis and omasal dilation. Causes of vagal indigestion include damage to the vagus nerve due to traumatic reticuloperitonitis, liver abscesses with secondary peritonitis, volvulus of the abomasum, and bronchopneumonia. Mechanical obstruction of the forestomach or abomasal outflow can be due to abomasal lymphoma or papillomas or from blockage after ingestion of indigestible or foreign materials. Diet and dwarfism are sometimes associated with vagus indigestion. Many cases are idiopathic. Clinical signs include ruminoreticular distention. The presence of abomasal distention depends on the precise location of the damage to the vagus nerve. Vagal indigestion is divided into the following four types, based on the anatomic location of the functional obstruction.

Ruminal Parasitism

Paramphistomiasis is a fluke infestation of the ruminant forestomach in warmer latitudes around the world. These trematodes are in the genera Paramphistomum, Calicophoron, and Cotylophoron. They are similar in size and appearance to ruminal papillae (Fig. 7-54). Although the presence of adult organisms in the forestomach is usually of no clinical significance, heavy infestations of larvae in the proximal small intestine, before migration to the rumen and reticulum, can cause hypoproteinemia, anemia, and death. Larvae burrow deeply into and sometimes through the wall of the small intestine and can be found in the peritoneal cavity. The intermediate host is a snail. Cercariae encyst on aquatic vegetation and are eaten by the ruminant.

Structure and Function

The gastric mucosa of simple-stomached animals contains numerous folds or rugae that are flattened when the stomach is distended. Foveolas or gastric pits communicate with the lumen of the stomach and transport gastric cell secretions. The glandular stomach functions in the enzymatic and hydrolytic digestion of ingested food substances. The epithelial covering is one cell thick, and the cell types include columnar mucus and bicarbonate-secreting surface epithelial cells, mucous neck cells arranged in tubuloalveolar glands, acid-secreting parietal cells, pepsinogen-secreting chief cells, and neuroendocrine (enterochromaffin, argentaffin) cells that secrete gastrin, enteroglucagon, and somatostatin (Fig. 7-55). The neuroendocrine cells do not communicate with the gastric lumen. The mucous neck cells are the precursor cells for all the other epithelial types in the stomach and are responsible for the replacement of surface epithelial cells as they are lost, either at the end of their normal lifespan or from some type of insult.

Multiple submucosal lymphoid patches are present in monogastric animals. In ruminants, a single lymphoid patch is present at the fold separating the omasum and abomasum.

In some species, such as the horse and rat, the cranial or orad part of the stomach (nonglandular part or pars nonglandularis) is lined by stratified squamous epithelium, whereas the distal portion (pars glandularis) is lined by glandular epithelium. In the horse, the dividing line between the two is called the margo plicatus. The pars nonglandularis in the pig is a small square to rectangular area of stratified squamous epithelium surrounding the esophageal opening.

Defense Mechanisms

The gastric mucosal barrier is significant in preventing autodigestion and bacterial overgrowth. There is, however, a resident flora that is difficult to grow on artificial media. Microorganismal overgrowth is prevented under normal physiologic conditions by abomasal or gastric motility, prostaglandin E₂ (PGE₂), a protective layer of mucus and bicarbonate, secretory IgA, transforming growth factor-α (TGF-α), epidermal growth factor, an extremely acid luminal pH, and an effective pyloric sphincter that prevents regurgitation into the stomach or abomasum of duodenal, hepatic, and pancreatic secretions. An intact epithelial layer and adequate blood flow also prevent acid-induced damage.

Gastric Dilation and Volvulus

Simple gastric dilation occurs in a variety of animals and in humans (Fig. 7-56). In dogs, particularly in the large, deep-chested breeds, the acute gastric dilation and volvulus syndrome occurs. This lesion is life-threatening and should not be confused with simple gastric dilation that is common in young puppies after overeating. Predisposing factors to acute gastric dilation include a source of distending gas, fluid, or feed; obstruction of the cardia that prevents eructation and emesis; and obstruction of the pylorus that prevents passage of gastric contents into the small intestine. The source of gas is not well understood. Theories include gas production by Clostridium perfringens, spores of which are present in the feed, carbon dioxide (CO₂) from physiologic mechanisms of digestion, or simple aerophagia.

The result of repeated episodes of gastric dilation is stretching and relaxation of the gastrohepatic ligament. Recurrent dilation, combined with overfeeding, postprandial exercise, and perhaps a hereditary predisposition, results in gastric rotation. Gastric rotation is recognized by splenic displacement and a twisted esophagus and results in vascular compression and decreased venous drainage and hypoxemia (Figs. 7-57 and 7-58). The stomach generally is rotated clockwise on the ventrodorsal axis when the abdomen is viewed from the ventral surface. Rotation is 180 to 360 degrees. The combination of gastric hypoxemia, acid-base imbalance, obstruction of the pylorus and cardia, and increased intragastric pressure leads to antiperistaltic waves followed by atony, cardiovascular ischemia, arrhythmias, and shock. Decreased portal venous return leads to pancreatic ischemia and release of myocardial depressant factor, cardiac collapse, and death.

Epidemiologic evidence suggests that dry dog foods that list oils or fats among the first four ingredients increase the risk of the gastric dilation and volvulus syndrome. Gastric dilation and volvulus is sometimes associated with gastric eversion or intussusception into the distal esophagus. This latter condition can also occur independently of gastric dilation and volvulus.

Abomasal Displacement

Normally, the abomasum lies over the xiphoid process at the abdominal ventral midline. Abomasal displacement is usually to the left side, although right-sided displacements also occur (Fig. 7-59). Left-sided displacement of the abomasum is a generally nonfatal entity seen in high-producing dairy cattle during the 6 weeks after parturition. Strenuous activity can predispose nonpregnant cows to displacement. In the postcalving period, abomasal atony can occur as a result of heavy grain feeding (volatile fatty acids decrease motility) and hypocalcemia. Meanwhile, the gravid uterus may have displaced the rumen and abomasum cranially and to the left, rupturing the attachment of the greater omentum to the abomasum. The abomasum then occupies the cranial left quadrant of the abdomen and displaces the rumen medially. This change leads to partial obstruction of abomasal outflow. Metabolic alkalosis contributes to rumen atony and impaired movement of ingesta. The associated hypochloremia is a result of hydrogen chloride (HCl) secretion and is common along with hypokalemia. Abomasal ulcers and peritoneal adhesions can result in cases of chronic displacement.

Fifteen percent of abomasal displacements are right-sided. The abomasum can be overdistended, displaced dorsally, and rotated on its mesenteric axis, and 20% of these cases develop abomasal volvulus. Right-sided displacements occur in postparturient dairy cows and in calves.

Clinical features of displaced abomasums, whether right-sided or left-sided, include anorexia, cachexia, dehydration, lack of feces, ketonuria, and a characteristic high-pitched ping subsequent to percussion over the abomasum. Idiopathic abomasal volvulus occurs occasionally in ruminants and calves (Web Fig. 7-10).

Gastric Dilation and Rupture

Gastric dilation occurs in horses as a result of the ingestion of fermentable feeds or grain, a situation analogous to grain overload with lactic acidosis in cattle. Acute gastric dilation and rupture in equids occurs most frequently as a terminal event in intestinal obstruction and displacement. Because gastric dilation and rupture can occur after death, the diagnostic challenge is to determine if the rupture occurred antemortem or postmortem. The only reliable indicator of the time of rupture, in relation to the death of the animal, is the presence of hemorrhage and evidence of inflammation, such as fibrin strands, along the margins of the rupture (usually the greater curvature) because such inflammatory responses occur only in live animals (Figs. 7-60 and 7-61).

In Northern Europe, acute gastric dilation occurs in horses on pasture as part of the syndrome called grass sickness or dysautonomia. The esophagus and stomach are often dilated and atonic. Although serologic evidence suggests an association of grass sickness with Clostridium perfringens type A enterotoxin, noninflammatory degeneration of associated autonomic ganglia have also been described. This condition can be experimentally produced in the horse with whole blood from affected animals, suggesting that a soluble toxin may be the cause.

Chronic gastric dilation is also associated with ingestion of poorly digestible substances. Habitual cribbing and aerophagia may also be contributory.

Dysautonomia also occurs in pet carnivores secondary to ganglionic death in cranial nerves, spinal nerves, and autonomic nerves. Associated ganglionic peptides are reduced in an amount consistent with the functional aberrations. Ganglioneuritis creates a similar syndrome to dysautonomia in a variety of species and is infrequently diagnosed. GI signs of dysautonomia include xerostomia, decreased anal tone, vomiting, and regurgitation. See Chapter 14 for a description of the histologic lesions.

Chronic abomasal and/or ruminal dilation may occur in cows with overeating disease, dystocia, exhaustion, poor quality or frozen feedstuffs, abomasal ulcers with or without abomasal lymphoma, and vagal indigestion. A sequela of abomasitis may be a mycotic infection similar to that which occurs in the rumen (Fig. 7-62).

In monkeys, an increased frequency of acute gastric dilation often occurs during weekends, when there may be changes in feeding behavior secondary to unfamiliar keepers. Studies have implicated Clostridium perfringens overgrowth secondary to an increase in fermentable feed consumption in the pathogenesis of gastric dilation in primates.

Chronic gastric dilation in canids is usually secondary to gastric ulcer, mural gastric lymphomas, uremia affecting gastric structure and function, pyloric stenosis or obstruction, acute gastric dilation, intervertebral disc disease, or vagotomy. Chronic gastric dilation is characterized by reduced feed intake, diminished gastric motility, and increased gastric gas accumulation sometimes resulting in abdominal distention similar to that of bloat.

Abomasal Dilation and Tympany

Abomasal dilation and tympany is a syndrome of young cattle that occurs most commonly in dairy breeds with a history of one or more of the following: only a single milk feeding per day, cold milk or milk replacer, lack of free choice water, inconsistency of feeding time, dosing with high energy oral electrolyte solutions, and sometimes, failure of passive transfer of immunity. The pathophysiology is presumed to be abomasal fermentation of high energy ingesta by gas-producing bacteria. Hyperglycemia and a resultant glycosuria are present. Hemorrhage, edema, necrosis, and sometimes emphysema of the abomasum and other compartments of the forestomach are found at necropsy.

Impaction

Impaction of the monogastric stomach and abomasum has a variety of causes. Intrathoracic lesions, such as pneumonia, pleuritis, lymphadenopathy, and lymphoma of mediastinal lymph nodes, can infiltrate and damage the vagal nerves, resulting in a problem with abomasal/gastric motility and emptying. Roughage, hairballs, and other foreign materials also cause impaction. Gastric trichobezoars and phytobezoars of monogastric animals are similar to those that occur in the rumen (Web Fig. 7-11).

Abomasal emptying defect is principally a condition of Suffolk sheep 2 to 6 years of age. It is characterized by an impacted, dilated abomasum. Clinical signs include anorexia, weight loss, and increased ruminal chloride levels. The latter feature is believed to be secondary to abomasal reflux. Scattered chromatolysis and neuronal necrosis in the celiac and mesenteric ganglia are consistent changes from a neurotoxicosis. The process is likely mediated by excitotoxins, although viruses have not been ruled out. Clusters of affected animals in a single flock are suggestive of an environmental cause. Inflammation is minimal. Abomasal emptying defect may be a form of acquired dysautonomia.

Inflammatory Diseases

Inflammation of the simple stomach or abomasum is designated as gastritis and abomasitis, respectively, and must be differentiated from simple hyperemia and petechiae, which are often nonspecific agonal lesions. Gastritis is often associated clinically with vomiting, dehydration, and metabolic acidosis. Hemorrhage, edema, increased amounts of mucus, abscesses, granulomas, foreign body penetration, parasites, inflammatory cells of various types, erosions, ulcerations, and necrosis characterize the changes in the mucosal surface and subsequent inflammatory reaction.

Clostridium septicum is a cause of hemorrhagic abomasitis with submucosal emphysema of sheep and cattle, a disease known as braxy. Although this disease is most common in the United Kingdom and Europe, it occurs in North America as well. Generally, the disease follows ingestion of frozen feeds contaminated with the causative Clostridium spp. The lesions are produced by the exotoxin of the bacteria, and death therefore is due to an exotoxemia.

Sarcina-like organisms have been reported in association with abomasal bloat in several calves. Sarcinas are anaerobic, gram-positive, nonmotile cocci found in rafts or packets. They are suspected gastric pathogens in a variety of animal species. The lesions are similar to braxy.

In many septicemias of pigs, bacterial emboli lodge in the vessels of the gastric submucosa and cause thrombosis, resulting in hyperemia, hemorrhage, infarction, and ulceration. This occurs in salmonellosis, swine dysentery, Glasser’s disease, and colibacillosis. Certain intoxicants such as vomitoxin produced by Fusarium spp. can cause similar lesions (Fig. 7-63).

A deep mycosis that causes a granulomatous gastritis is due to Histoplasma capsulatum (see intestinal diseases of carnivores). Very rarely, Mycobacterium tuberculosis causes granulomatous gastritis in a variety of species. In granulomatous gastritis, epigastric discomfort after eating (postprandial), emesis, progressive cachexia, weakness, vomiting of blood (hematemesis), and pyloric obstruction caused by the space-occupying inflammatory reaction occur. In both histoplasmosis and tuberculosis, regional (gastric, splenic, and hepatic) lymph nodes may be affected. Nodular or diffusely thickened gastric and lymphoid lesions contain predominately macrophages. Mononuclear inflammatory cells, fibroblasts, granulocytes (including eosinophils), and multinucleate giant cells are also present. Often the causative organisms can be demonstrated within the granulomatous inflammation, but special stains, such as acid-fast for mycobacteria and periodic acid–Schiff (PAS) reaction, or Gomori’s methenamine silver stain may be necessary to demonstrate fungi.

Eosinophilic gastritis is uncommon in all species of domestic animals but has been reported in pet carnivores and humans. In general, the etiologic basis for this condition is poorly understood. The three types of gastritis characterized by an influx of eosinophils are as follows:

The gross lesions of eosinophilic gastritis are rather nonspecific and consist of diffuse or nodular mural thickenings. Microscopic lesions are characterized by infiltrates of eosinophils in the mucosa and the submucosa and are seen extensively through the muscularis of the stomach. Similar lesions are sometimes present in segments of the small intestine and colon. In the dog, there is sometimes necroproliferative eosinophilic perivasculitis and eosinophilic lymphadenopathy. In the scirrhous form, the eosinophilic infiltrate is followed by transmural fibroplasia and scarring.

Hypertrophic or Hyperplastic Enteritides

Hypertrophic gastritis, characterized by thickened rugae, is the result of hyperplasia of the gastric glands. This effect is believed to be a response to chronic retention of gastric fluid and reflux of intestinal bile. Similar mucosal glandular changes are seen in immune-mediated lymphoplasmacytic gastritis of dogs. Hypertrophic gastritis has also been described in primates, horses, pigs, and rodents. The nematode Nochtia nocti causes this lesion in the stomachs of monkeys. Equine hypertrophic gastritis is a focal lesion or more diffuse lesion associated with the nematodes, Habronema spp. and Trichostrongylus axei, respectively.

Chronic giant hypertrophic gastropathy of dogs affects the basenji, beagle, boxer, and bull terrier breeds, among others. The disease is similar to Ménétrier’s disease in humans. Clinical signs include weight loss, diarrhea, vomiting, and hypoproteinemia. The chronic gastritis results in increased mucosal permeability to serum proteins with subsequent protein-losing gastropathy. Unlike normal gastric mucosal folds, in giant hypertrophic gastropathy, the mucosa does not flatten with distention of the organ (Fig. 7-64). Microscopically, the mucosa is hypertrophic and hyperplastic. The incorporation of folds of submucosa and muscularis mucosa is variable, as is the presence of inflammatory cells, principally lymphocytes and plasma cells. The cause of this condition is unknown.

An ulcer is a mucosal defect in which the entire epithelial thickness, down to or through the basement membrane, has been lost. Penetration through the remaining tissue layers to the peritoneal cavity is termed a perforating ulcer. Partial-thickness epithelial loss is termed an erosion. Chronic ulcers differ from acute ulcers by the presence of an indurated rim caused by fibrosis and attempts at epithelial regeneration. The identification of gastric ulcers is not challenging, either at necropsy or by endoscopy. They are sharply bordered cavities, often coated with exudate. Thrombosis of blood vessels is sometimes adjacent to ulcers in ruminants with mycotic vasculitis secondary to ruminal lactic acidosis. Thus it is an infarct.

The pathogenesis of most gastric and duodenal ulcers in humans has been demonstrated to be a result of infection with a helical bacterium, Helicobacter pylori. The same bacterium has been epidemiologically linked to gastric adenocarcinoma. Helicobacter mustelae acts similarly in ferrets. Although similar, gastric Helicobacter-like organisms (GHLOs) are readily demonstrated in dogs and cats, their relationship with ulcer formation or neoplasia is not established. It appears that the stomachs of as many animals without gastritis or ulcers are as heavily colonized by these bacteria as are those animals with ulcers (Fig. 7-65). More than 90% of cats are infected with two Helicobacter spp. Helicobacter felis can be cultured in vitro, but the noncultivatable Helicobacter heilmannii is the more frequent. Pathologic and clinical outcomes appear to depend on a number of bacterial virulence factors as well as on the host response to these agents. Investigations suggest there may be a link between the presence of Helicobacter and other diseases, including coronary and neurologic disease.

Theories abound as to the causes of most gastric ulcers in animals. None have been proved. There may be a heritable component to ulcer susceptibility. The conditions necessary for ulcer development boil down to an imbalance between acid secretion and mucosal protection. This imbalance occurs as a result of the following:

All of these mechanisms allow pepsin and hydrochloric acid into the submucosa.

Severe gastric hyperacidity and gastric ulcers is sometimes associated with the presence of islet cell tumors producing gastrin. Some of these gastrin-producing tumors arise in the duodenum, but the majority originate in the pancreas. These neoplasms release histamine into the bloodstream, which binds to receptors on parietal cells of the stomach, increasing HCl secretion. The gastric ulceration produced associated with these tumors is known as Zollinger-Ellison syndrome.

In dogs, gastric ulceration causes vomiting, inappetence, abdominal pain, and anemia secondary to gastric bleeding (Fig. 7-66). Melena (digested blood in feces) may also be present if the ulceration persists, and significant amounts of blood are lost to the GI system. Gastric ulcers in dogs and cats are generally idiopathic but can occur in those animals with mast cell tumors that stimulate gastric HCl secretion through histamine release and its effect on the surrounding blood vessels or other neoplasia that infiltrate and weaken the gastric wall.

Ulcers are idiopathic in foals. Foals with gastric ulcers may have abdominal pain, bruxism (grinding of the teeth), ptyalism, and gastric reflux and may lie in dorsal recumbency. Gastric ulcers associated with administration of NSAIDs are common in horses and to a lesser extent in other species (Fig. 7-67). Equine gastric ulcer syndrome occurs in 40% to 90% of competitive and performance horses, with the most severe ulcers occurring in those animals that are worked the hardest. More than one-third of horses used less strenuously develop mild ulcers.

Cattle with abomasal ulcers have partial or complete anorexia, decreased milk production, palpable discomfort on pressure applied to the right xiphoid area, and melena. In any species, the vomiting of coffee grounds–like material (hematemesis) or passage of melena is highly suggestive of gastric ulcer disease. Abomasal ulcers of ruminants vary in significance from subclinical to fatal (Figs. 7-68 and 7-69). In calves, ulcers are associated with dietary changes or mechanical irritation of the abomasum by roughage. Dietary changes involve substitution of roughage for milk or milk replacer, together with the associated stress. In dairy cattle, ulcers are associated with heavy grain feeding (lactic acidosis) at the time of parturition, displacement of the abomasum, BVD, impaction, torsion, and gastric lymphoma. Because cattle have an effective omentum that seals abomasal ulcers, they may live for a long time unless a large perforation occurs, resulting in septic peritonitis.

In pigs, gastric ulcers are common and occur in penned pigs fed finely ground grain. These ulcers always are limited to the stratified squamous epithelium of the esophageal portion of the gastric mucosa that surrounds the cardia (Fig. 7-70). Death can result from exsanguination into the gastric lumen. Evidence suggests that a high-carbohydrate diet is not sufficient alone to produce erosions and ulcers but rather that the appropriate diet in combination with fermentative commensal bacteria, such as Lactobacillus and Bacillus spp., produces lesions. Lesions progress from parakeratosis to hyperkeratosis through keratolysis to erosive gastritis or perforation of the stomach

Miscellaneous Diseases and Conditions

Uremic gastritis occurs most frequently in carnivores as a result of chronic renal disease (Fig. 7-71; also see Fig. 1-54, Fig. 11-28, and Fig. 11-29). In ungulates, it is a rare event and is usually secondary to obstructive kidney disease (postrenal uremia). Uremic gastritis is characterized by mineralization of the glands, vessels, and lamina propria of the gastric mucosa and sometimes results in ulcer formation.

Amyloidosis occasionally is present in the stomach concomitant with systemic amyloid infiltrates. Generalized amyloid A (AA) amyloidosis with gastric deposits of amyloid has been reported in bats, Siamese and Abyssinian cats, goats, rhesus monkeys, sheep, and Siberian tigers.

Pyloric stenosis can be anatomic or physiologic because of an inability of the pyloric sphincter to function properly. This condition may be congenital or acquired. This lesion occurs most often in dogs (particularly brachycephalic breeds), Siamese cats, horses, and humans. Congenital pyloric stenoses may be hereditary, at least in humans. Pyloric stenosis is often first recognized in recently weaned animals by projectile vomiting, retention of gastric contents, gastromegaly, and the presence of strong gastric peristaltic waves (Web Fig. 7-12). Pyloric muscular hypertrophy, variable submucosal edema, vascular ectasia, and degeneration of myenteric ganglion cells (dysautonomia) may be identified histologically in some cases. Functional pyloric stenosis can be a feature of vagus indigestion of ruminants. In general, the many causes of pyloric stenosis are not well understood.

Giant hypertrophic pyloric gastropathy, not to be confused with giant hypertrophic gastropathy of basenjis and other dogs, is an idiopathic condition seen most often in older small breed dogs. To the uninitiated, the gross and microscopic features of this pyloric lesion strongly imitate those of carcinoma (Fig. 7-72). Microscopically, there is notable foveolar and glandular hyperplasia with variable hypertrophy of pyloric smooth muscle, small mucosal erosions, and ulcerations. There is usually a lymphoplasmacytic infiltrate of variable degree in the lamina propria.

Parasites

Neoplasia

Gastric neoplasia, although uncommon, manifests in different ways in domestic animals. Leiomyoma and more rarely leiomyosarcoma arise from the tunica muscularis (Fig. 7-78). Lymphoma can be primary, metastatic, or multicentric in origin (Figs. 7-79 and 7-80; also see Fig. 13-85). In cattle, lymphoma is often caused by the bovine leukemia virus and has a predilection for the abomasum and the right atrium and uterus (Fig. 7-81). Squamous cell carcinoma of the stratified squamous (esophageal) portion of the stomach is relatively common in the horse (Fig. 7-82). Glandular neoplasms, adenomas, and adenocarcinomas occur in all species but are seen most often in dogs and cats. Dogs and rarely cats occasionally develop gastric mast cell tumors.

1. Coiling the intestine in the abdomen.

2. Numerous intestinal folds that contain villi that notably increase the number of cells contacting the ingesta (Fig. 7-84).

3. Each enterocyte has a microvillous border, further increasing the surface area available for digestive and absorptive processes.

Structure and Function

The intestinal mucosa is composed of three layers—a single-cell-thick layer of epithelial cells lining the intestinal lumen, mesenchymal cells of the lamina propria, and the muscularis mucosa. Damage to any of these structures can result in digestive dysfunction and resultant diarrhea.

These cells function as a selectively permeable barrier allowing nutrient, electrolyte, and water absorption, while excluding pathogens, toxins, and other antigens. An understanding of these cell types and their functional roles in digestion and absorption is important in understanding the mechanisms of intestinal disease. Similarly, an understanding of the biology of these cell types is important in predicting clinical outcomes and designing therapeutic strategies for treating intestinal disease.

Defense Mechanisms

Defense mechanisms of the intestinal tract are diverse. They include indigenous (nonpathogenic) bacterial flora, intestinal and extraintestinal secretions, gastric acidity, intestinal motility, epithelial cell turnover, bile salts, immunologic mechanisms, and although a secondary mechanism, the Kupffer cells of the liver.

Secretions of the oral cavity, saliva, and intestine, called mucins, inhibit the adherence of organisms to the mucosa of the alimentary system. In addition to physically trapping pathogens, intestinal mucus serves to cover glycolipid and glycoprotein receptors on the surface of enterocytes (unstirred layer), thus preventing pathogen attachment and damage by toxins. Mucins are viscous, thus aid in protecting the epithelium from the shear forces of particulates driven against them by peristaltic waves. Because they are extensively glycosylated, mucins can cross-link and trap bacteria, making them more amenable to clearance by passage through the alimentary system.

Normal gastric acidity kills many organisms before they have the chance to reach the small intestine. Very young animals are achlorhydric, thus they may be more susceptible to some organisms such as pathogenic Escherichia coli. Helical bacteria in the stomach are the single greatest cause of gastric ulcers in humans. Although similar organisms occur in the stomachs of domestic animals, particularly carnivores, their role in gastritis of animals is less certain. Normal gastric acidity apparently does not kill all potentially pathogenic bacteria (helical bacteria) in the stomach and proximal small intestine of domestic animals.

Indigenous (nonpathogenic) bacterial flora (microbiota) competitively bind to putative attachment sites on the enterocytes, thus preempting pathogen attachment. These prokaryotic symbionts co-evolved with their hosts and are an integral part of homeostatic mechanisms. Killing of these bacteria through the use of antibiotics sometimes allows pathogens to colonize the intestine and produce disease. Thus gnotobiotic animals are more susceptible to infection. The microbiome enhances the host’s genome in contributing to normal physiology and disease resistance and susceptibility. Bacteria in the intestine outnumber the total somatic and germ cells of the body by approximately a factor of ten. Probiotics are “friendly bacteria” that are sometimes used therapeutically or prophylactically in a variety of products and nutraceuticals. These “friendly bacteria” also compete for substrate with pathogens, alter the microenvironmental pH making the growth of competitive bacteria difficult, and produce short chain fatty acids and inhibitory growth substances (bacteriocins) that are toxic to other bacteria. Colicins are bacteriocins produced by E. coli. Bacterial growth is also inhibited by lactoferrin and peroxidase from the pancreas and lysozyme and defensins from Paneth cells. Transferrin in serum and lactoferrin produced by enterocytes and neutrophils at sites of infection serve to sequester iron that is necessary for bacterial growth.

Intestinal peristalsis is protective in that loss of motility may lead to bacterial overgrowth in the intestine and increased susceptibility of enterocytes to toxins that are not moved out of the gut. Diarrhea can be in part a defense mechanism that rids the body of bacteria and toxins. Conversely, some bacteria secrete toxins that impair intestinal motility thus allowing pathogens a greater opportunity to attach to enterocytes.

Epithelial cells of the intestine have the greatest turnover rate of any fixed cell population in the body. In effect, this means that pathogens with a life cycle that exceeds that of the enterocytes will likely not be successful because their host cell will slough before the pathogen can reproduce. In addition, experimental evidence indicates that enterocyte microvilli form unilaminar vesicles containing digestive enzymes such as catalase and alkaline phosphatase on their surface. These vesicles are shed into the intestinal lumen where they may interact with the pathogen(s), thus preventing contact of pathogens with enterocytes since these vesicles are passed in the feces.

Bile salts inhibit the growth of many organisms. Kupffer cells of the liver act as a secondary line of defense. Because all the blood from the intestine enters the portal vein and percolates through the hepatic sinusoids, the Kupffer cells are perfectly positioned to phagocytose bacteria and endotoxins with which they come in contact. In pigs, goats, and cattle (artiodactyls), these functions are performed by intravascular pulmonary macrophages.

Secretory IgA and IgM constitute very important mechanisms of humoral immunity and function largely to prevent attachment of pathogens to intestinal epithelium. Crypt epithelial cells produce the secretory component of IgA. IgA functions through adhesion to M cells that regulates transepithelial movement of antigens while masking certain other antigens (Fig. 7-88).

Although in its infancy, research indicates that genetic polymorphisms of the host, including human leukocyte antigen (HLA), likely play a role in disease susceptibility and resistance.

Diarrhea