PathologyII Systemspathology

PATHOLOGY OF THE ALIMENTARY SYSTEM

Introduction The digestive system consists of the digestive tract and several glands located outside the tract itself. Animal species differ greatly with regards to the anatomy and physiology of the alimentary system, and although a large variety of gastrointestinal disturbances are important in all, the predominant form of clinical disease varies according to species. In general terms, pathogenic organisms gain entry into the alimentary system by ingestion. Less commonly, they can be coughed up by the lungs and swallowed (ie. Rhodococcus equi), they can make their way through systemic circulation (bacteremia, viremia) or migrate through various regions of the body (parasites). Some defense mechanisms of the alimentary system are: o o o o o o o o o o o o Oral secretions (saliva) Resident flora and fauna Gastric pH Secreted immunoglobulins Vomiting Extra intestinal secretions from the liver and the pancreas Intestinal proteolytic enzymes Submucosal phagocytes and effector cells High rate of epithelial turnover Increased peristalsis Paneth cells (production of antimicrobial peptides) Adaptative immune system From PBVD 2007 Post mortem examination of the gastrointestinal tract During a general post mortem examination, special attention to the gastrointestinal tract should be given in cases of: Sudden death Wasting Hypoproteinemia Vomition Diarrhea Anemia Suspected septicemia Oral cavity 1. Post mortem examination of the oral cavity is of great importance since numerous disease entities

2.

are associated with lesions in this location (particularly in ruminants) To examine the oral cavity properly, the mandibular symphysis is cut and the mandibular rami drawn apart allowing complete exposure of the oral mucosa, the dental arcades, the soft and hard palate, the pharynx, the retropharyngeal lymph nodes, the tonsils and the tongue

Gastrointestinal tract examination 1. The tongue is sectioned and the skeletal muscle assessed for a areas of pallor and/or inflammation 2. The esophagus is to be opened along the entire length and the mucosa assessed for abnormalities 3. The abdominal cavity is opened along the ventral midline and the upper abdominal wall reflected allowing exposure of the abdominal viscera 4. The viscera should be observed carefully for anatomic relationships, displacements, color, strictures, distention, and any other changes 5. The root of the mesentery should be palpated if intestinal volvulus is suspected 6. The root of the mesentery, the vasculature and viscera should be removed so that vessels can be traced along the entire length with the anatomic relationships maintained (especially if infarctive disease is suspected) 7. If the carcass is fresh (< 4 hours dead), the pH of the stomach (or abomasum) should be assessed (pH paper) 8. The stomach should be opened along the greater curvature 9. The intestines should be opened throughout the entire length (antimesenteric side) or at frequent intervals and tissue specimens should be taken from representative areas, including Peyer's patches and mesenteric lymph nodes (fresh and formalin fixed) 10. Intestinal sections need to be opened and sections fixed in neutral buffered formalin as flat as possible 11. The large intestine should be opened and fixed as per small intestine 12. The enteric epithelium is very sensitive to anoxia, and degenerates rapidly after death (within 1020 minutes) making histologic interpretation difficult, so priority should be given to the gastrointestinal system examination in suspected cases of gastrointestinal disease Establishing an accurate etiologic diagnosis in cases of gastrointestinal disease usually requires a combination of diagnostic tests such as histologic examination, bacterial culture, viral isolation, fluorescent antibody testing, fecal flotation, or microscopic examination of mucosal scrapings for parasites

Pathology of the alimentary system Oral cavity Developmental Anomalies Agnathia o Absence of the lower jaw due to failure of development of the 1st branchial arch; seen in lambs Palatoschisis Most common oral developmental anomaly May involve soft palate or both soft and hard palate Affected animals may develop secondary aspiration pneumonia o Pathogenesis Failure of fusion of lateral palatine processes Etiology is unknown, but genetic factors (ie. in Charolais cattle along with arthrogryposis) and maternal ingestion of certain drugs (ie. griseofulvin treatment in queens and mares; steroid administration during pregnancy in primates) and teratogenic plants (ie. lupines, hemlock in ewes and sows) have been associated

Cheiloschisis o Hare lip failure of fusion of upper lip along philtrum Epitheliogenesis imperfecta o Causes widespread defects in the cutaneous epithelium and in the epithelial linings of the oral cavity and the tongue Epidermolysis bullosa o Hereditary skin disease in dogs and sheep that can also involve the lips and oral mucosa Stomatitis and Gingivitis o o o o Inflammation of oral and mucous membranes (stomatitis) and gingival (gingivitis) The oral cavity is constantly exposed to potential insults erosions, ulcerations, or necrosis may develop as a result Causes infectious agents (viruses), chemical injury, trauma, intoxicants, autoimmune disease, systemic disease Common clinical signs include ptyalism, anorexia

A) Vesicular Stomatitides o Characterized by the formation of vesicles (accumulation of serous fluid within the epithelium or between the epithelium and lamina propria) o Can be infectious or non-infectious Infectious Feline calicivirus Mainly a respiratory infection but can cause lingual and oropharyngeal ulcers that start as vesicles Vesicular Stomatitides in production animals Foot and Mouth Disease (FMD) Vesicular Stomatitis (VS) Vesicular Exanthema of Swine (VES) Swine Vesicular Disease (SVD) Picornavirus (Aphtovirus) Rhabdovirus (Vesiculovirus) Calicivirus Picornavirus (Enterovirus) Ruminants, pigs Ruminants, pigs, horses Pigs Pigs

All virally induced; very similar clinical/gross/histologic appearances o Early vesicles/blisters on oral mucosa small clear, fluid-filled vesicles on lips, buccal mucosa, margins of tongue coalesce to form bullaebullae rupture ulcers o Lesions may arise on coronary bands, interdigital skin, teats, vulva; may develop conjunctivitis o Histologically start as intracellular edema ballooning degeneration of stratum spinosum necrosis; cell lysis intercellular edema Fuid/hemorrhage/neutrophil-rich vesicles ulceration fibrinous/fibrinopurulent exudation Nonfatal, but of economic concern poor weight gains, abortions (stress of discomfort of lesions?)

May result in secondary endotoxemia, lameness (foot lesions) Diagnosis depends on gross/histologic lesions, species affected, serology, and virus isolation FMD, VES and SVD are exotic to the US and thus are reportable to state or federal authorities Foot and Mouth Disease o One of the most contagious animal diseases, with important economic losses o Low mortality rate in adult animals, but often high mortality in young due to myocarditis o Vesicles or blisters on the tongue, dental pad, gums, cheek, hard and soft palate, lips, nostrils, muzzle, coronary bands, teats, udder, snout of pigs, corium and interdigital spaces o Post-mortem lesions on rumen pillars, and in the myocardium particularly of young animals tiger heart o Lesions can be more severe in pigs than in cattle Vesicular Stomatitis o Common in calves, does not affect goats, sheep o Insects may act as vectors o Morbidity rate variable, up to 90% in a herd; low mortality rate o Limited to the epithelial tissues of the mouth, teats and feet Vesicular Exanthema o Disease of pigs; indistinguishable clinically and pathologically from FMD o Closely related to San Miguel sea lion virus Swine Vesicular Disease o Indistinguishable from other swine vesicular diseases Notification of authorities State and federal veterinarians should be informed immediately of any suspected vesicular disease. Non-infectious Pemphigus vulgaris o Autoimmune disease mediated by autoantibodies to the desmosome protein desmoglein 3 o Characterized by acantholysis Bullous pemphigoid o Autoimmune disease characterized by subepithelial clefting and no acantholysis B) Erosive/Ulcerative Stomatitides Mechanisms Viral damage to the epithelium Compromised circulation to subepithelial connective tissue resulting in infarction of the epithelium May reflect ulceration of vesicular stomatitides Agents responsible include: o Viruses Bovine viral diarrhea virus (BVD), Rinderpest, Malignant catarrhal fever (MCF), Feline Calicivirus, Equine Viral Rhinopneumonitis, Bluetongue Other causes: Uremia Feline Eosinophilic Granuloma Vitamin C deficiency in primates and Guinea Pigs

C) Papular/Proliferative Stomatitides Caused by Parapoxviruses (both zoonotic) Viral infection of epithelial cells results in cell swelling and hyperplasia Bovine Papular Stomatitis o Papules on nares, muzzle, gingiva, buccal cavity, palate, tongue, esophagus, rumen and omasum o Microscopically, there is ballooning degeneration of the stratum spinosum epithelial cells may contain eosinophilic intracytoplasmic parapoxvirus inclusions o May cause papules on hands/arms in humans Contagious Ecthyma o Condition of sheep and goats (Scabby mouth) o Characterized by macules, papules, vesicles, pustules, scabs, scars, nodules in areas of skin abrasions corners of mouth, mouth, udder, teats, coronary bands, anus, esophagus, rumen o Epithelial cells may contain eosinophilic intracytoplasmic viral inclusions D) Necrotizing/Deep Stomatitides Occur in cattle, sheep, pigs Occur when epithelial trauma permits invasion of opportunistically pathogenic normal flora into deeper tissues of the oral cavity involving muscle, fascia, bone, and/or regional lymph nodes Calf Diphtheria (Oral necrobacillosis) o End-stage of any form of stomatitis complicated by infection with Fusobacterium necrophorum (Gram-negative anaerobe)produces necrotizing toxins o Characterized by yellow-grey round foci surrounded by rim of hyperemic tissue in oral cavity, larynx, pharynx raised core of necrotic material easily separated from underlying tissue o There is focal coagulation necrosis surrounded by granulation tissue o Clinical signs swollen cheeks, anorexia, fever, fetid breath Ulcerative Gingivitis (Vincents Gingivitis, Trench mouth) o Fusospirochetal disease that affects some primates, and rarely puppies o Acute inflammation, necrosis painful gums, fetid odor, friability and hemorrhage, hypersalivation Punched-out crater-like ulcers in interdental gingiva, gingival margin, formation of gray pseudomembranes o Caused by two bacteria Borrellia vincentii, Fusobacterium spp. o Related to underlying nutritional deficiencies, debilitating conditions, psychogenic factors Noma (Cancrum Oris) o Acute gangrenous stomatitis in primates, and dogs o Spirochetes and fusiform bacteria, possibly other oral bacteria o More severe that oral necrobacillosis gangrenous perforation of cheeks, lysis of bone, death o Spirochetes demonstrated via Warthin-Starry stain (silver stain) E) Other Stomatitides Oral Eosinophilic Granuloma o Grouped with the eosinophilic granuloma complex (linear granulomas and eosinophilic plaques of the skin) o Characterized by the presence of a focal granuloma or ulcer within the oral cavity of cats, young dogs

Cats upper lips (near commissure); may develop in gingiva, palate, pharynx, tongue, regional lymph nodes Canine eosinophilic granuloma is rare young male Siberian Huskies, Cavalier King Charles Spaniel May occur as an irregularly-shaped ulcer with a firm, indurated base, or as a firm yellow-white granulomatous plaque Affected animals can have peripheral eosinophilia Cause unknown, suspected immune-mediated mechanism hypersensitivity reaction? Histologically, the lesions are characterized by the presence of multiple eosinophilic granulomas around a central foci of collagenolysis

Lymphoplasmacytic Stomatitis o Chronic idiopathic condition of cats characterized by inflamed gingiva, inappetence, fetid breath o Oral mucosa may be hyperplastic and ulcerated o Has been associated with other infectious diseases (feline leukemia virus, feline immunodeficiency virus) Chronic ulcerative paradental stomatitis o Condition of dogs also known as ulcerative stomatitis and lymphocytic-plasmacytic stomatitis o More common in older dogs and in Malteses and Cavalier King Charles Spaniels Hyperplastic and Neoplastic Lesions In dogs, the most common oral masses are not neoplasms but proliferative lesions known as gingival hypertrophy/hyperplasia and fibromatous epulis of the periodontal ligament. If we exclude these lesions, 75-90% of oral tumors in dogs are malignancies: melanomas, squamous cell carcinomas, osteosarcomas or fibrosarcomas. In cats, at least 75% of the neoplasms are squamous cell carcinomas and most of the rest are fibrosarcomas. Hyperplastic Lesions Gingival Hyperplasia o Overgrowth of gingival tissues; may become severe enough to bury incisors o There is nodular proliferation of gingiva accompanied by epithelial hyperplasia and, often, by osseous metaplasia o Most common in brachycephalic dog breeds (present in 30% of Boxers > 5years) o Grossly indistinguishable from fibromatous epulis of the periodontal ligament Fibromatous epulis of the periodontal ligament Characterized by proliferation of primitive mesenchymal tissue resembling periodontal ligament, accompanied by proliferation of odontogenic epithelium and some islands of primitive dental matrix Neoplastic Lesions Oral Melanoma Most common malignant neoplasm of the oral cavity in dogs, rare in other species 90% of canine oral melanomas are malignant (~70% metastasize to regional lymph nodes and 67% to distant sites) Pigmented and nonpigmented (amelanotic) tumors Can begin as a black macule, develops into a rapidly growing, firm mass; may be smooth/domeshaped or ulcerated Interior may appear grey-white, dark brown or black (depending on pigmentation) Microscopically Composed of melanocytes (neural crest origin)

Epithelioid and spindle-shaped melanocytes in varying proportions

Squamous Cell Carcinoma (SCC) 60% of oral neoplasia in the aged cat, less common in dogs, rare in other species Occur most commonly on ventrolateral tongue (more common in cats), tonsil and gingiva (more common in dogs) Locally invasive 5-10% of gingival SCCs metastasize to regional LNs, 3% to distant sites Up to 98% of tonsillar SCCs metastasize to regional LNs, 63% to distant sites Variable gross appearance (flat to proliferative) Microscopically irregular cords/masses of stratified squamous epithelial cells invade submucosa and adjacent muscle o The quantity of keratin depends on maturity of neoplastic cells (numerous keratin pearls in well-differentiated tumors; poorly differentiated tumors have few keratinized cells) o Characterized by presence of desmosomes (intercellular bridges) between adjacent tumor cells Fibrosarcoma Most common in the cat (20% of oral neoplasms), less frequent in dogs, rare in other species Most common on maxillary gingiva and palate, anterior mandible Locally invasive and osteolytic Microscopically proliferartion of mesenchymal cells (fibroblasts) with variable amounts of collagen * A tumor requiring special mention is a distinctive histologically low grade but behaviorally aggressive fibrosarcoma in the mouth of relatively young, large dogs. Most occur on the hard palate and are initially mistaken for reactive fibrosis or exuberant granulation tissue following inflammatory disease. Fibrosarcomas infiltrate extensively and a high proportion recurs after surgery. Distant metastases occur in 10-20% of cases at the time of diagnosis Canine Oral Papillomatosis Papovavirus-induced tumor; usually self-limiting (regress spontaneously); long-lasting immunity Dogs < 1 year old (can occur in older dogs) Masses are papilliform or cauliflower-like, may be quite florid; generally white and friable Occur in mouth, tongue, palate, epiglottis, larynx, may be multiple Microscopically acanthotic, hyperplastic, stratified squamous epithelium creating folds and fronds; cells of stratum spinosum enlarge greatly, with vesicular cytoplasm, ballooning degeneration; may contain intranuclear inclusion bodies Other oral tumors include mast cell tumors, benign plasmacytomas and granular tumors TEETH Malocclusion o Failure of upper and lower dental arcades to interdigitate properly; normal in some breeds (brachycephalic dogs) If severe dysphagia Named according to position of mandible: Prognathialengthening of the mandible Brachygnathia superiorshortness of the maxillae differentiate from prognathia Brachygnathia inferiorshortness of the mandibles (undershot jaw). Common in ruminants and horses (parrot mouth). May lead to problems

in prehension and mastication May result in overgrowth of continuously growing teeth and locking of jaw; may not provide an appropriate grinding surface for mastication and promote inanition May result from poor jaw conformation, abnormal tooth eruption patterns May occur as an acquired disease in species with continuously growing teeth due to lack of appropriate dietary roughage/grinding surface

Developmental Anomalies Tooth agenesis (anodontia) and supernumerary teeth (polyodontia) Common anomalies, of little clinical importance Dentigerous Cysts Rare condition; may be asymptomatic or lead to painful and destructive diseases of the jaw Cysts lined by stratified squamous epithelium, often filled with keratin, may contain fragments of poorly-developed teeth Horse (ear tooth) may give rise to a painful fistulous lesion (rostal and ventral to ear) Pathogenesis Abnormal tooth development formation of epithelium-lined cystic structures in bone or soft tissues of jaw Arise from proliferation of the epithelial cell rests of the enamel organ (cell rests of Malassez) Segmental Enamel Hypoplasia Segmental thinning/lack of dental enamel Pathogenesis Occurs in any systemic disturbance that interferes with the function of ameloblasts at a critical period of enamel formation (ie. distemper infection in dogs during odontogenesis , BVD in cattle) Segmental lack of enamel relates to period of virus activity; enamel formation returns after recover from infection Excess fluoride is toxic to ameloblasts and odontoblasts hypoplasia or weaknesses in enamel and dentine may cause pitting, ridging, and brown mottling of teeth due to oxidation of poorly mineralized matrix Enamel Discoloration Incorporation of pigmented chemical agents into teeth during mineralization o Pediatric tetracycline useyellow discoloration of permanent teeth if administered during the process of mineralization o Congenital porphyria pink discoloration of permanent teeth (incorporation of porphyrins to dentin) Fluoride Toxicosis Usually seen in cattle, sheep Brown discoloration (oxidation of poorly mineralized matrix) Often present with rapid early dental attrition Pathogenesis Excessive fluoride deposition into enamel and dentin due to fluoride toxicosis during odontogenesis (6-36 months) Miscellaneous Lesions Dental Attrition and Abnormal Wear o Usually relate to normal or abnormal wear on teeth due to grinding action o Ruminants dental attrition is a normal age-related change

o Horses abnormal/irregular wear due to poor masticatory function, defective enamel, abnormal oral conformation serious dental malformation o Dogs habitual rock-chewing or abnormal mastication erosion of crown enamel o Exposure of dentin/pulp canal can lead to dental infection Feline External Resorptive Neck Lesions o May cause clinical signs related to painful mastication o Lesions are usually marked by red granulation tissue at the overlying gingival margin o Characterized by odontoclastic resorption of dental tissues; may occur in root, but more commonly occurs in neck area o Major cause of spontaneous tooth loss or extraction in cats o Unknown cause Infundibular Impaction o Impaction of the infundibulum, infundibular necrosis and caries cause serious disease in ruminants and horses and can progress into pulpitis and endodontitis o Comparable to pathogenic mechanism of dental caries in simple-toothed species o Incomplete cementum formation in infundibulum before dental eruption feed material may become impacted in infundibulum bacteria metabolize it acid demineralizes tooth o Bacterial enzymes may also degrade organic dentin/enamel matrix pulp cavity is penetrated pulpitis, periodontitis, dental abscess, fistula formation Periodontal Disease Dental plaque/calculus (tartar) o Plaque is a non-mineralized composite mass of bacteria, food particles and other tissue cells adhered to the tooth surface o When mineralized (calcium and phosphate) it is referred as calculus or tartar o Plaque predisposes to caries and periodonitisgingivitis Periodontitis and periodontal disease o Refers to the regression of the gum line with inflammation of the gingival sulcus and alveolus, with resorption of the alveolar bone and periodontal ligament o Inflammation invades connective tissues of periodontal ligament suspensory apparatus is destroyed tooth is loosened o Alveolar osteomyelitis and pulpitis abscess formation, bacteremia, pain, halitosis Dental Neoplasia Tumors of odontogenic origin in domestic animals are rare and there is a precise method of naming them based on the tissue or cell of origin, the extent of differentiation and odontogenesis present Tumors of dental tissues other than fibromatous epulis of periodontal ligament origin and canine acanthomatous ameloblastoma are rare

Fibromatous epulis of periodontal ligament origin (fibromatous epulis) ( see hyperplastic lesions) Common, benign tumor composed primarily of periodontal ligament-type stroma Local excision is curative Canine acanthomatous ameloblastoma (previously referred as acanthomatous epulis) Aggressive infiltrative tumor of odontogenic epithelium without odontogenic mesenchyme No metastatic potential however recurrence is common This tumor often recurs as squamous cell carcinoma Other

Ameloblastoma, amyloid producing odontogenic tumor, ameloblastic fibroma, odontomas, feline inductive odontogenic tumor, cementoma, cementifying fibroma

TONSILS Pharyngeal lymphoid structures lined by stratified squamous epithelium; do not contain afferent lymphatics, do not act as lymph filters Primary bacterial infection tonsillitis Primary lymphoid neoplasms lymphosarcoma Primary epithelial squamous cell carcinoma

SALIVARY GLANDS Inflammatory Diseases Sialoadenitis o Recognized rarely in veterinary medicine o Causes include Rabies Sialodacryoadenitis Virus (Coronavirus) of Rats inflammation of salivary and extraocular glands Salmonella typhisuis parotid sialoadenitis in pigs o Gross lesions may be subtle; history of pain on palpation o Abscesses occur occasionally

Miscellaneous conditions Ranula o o Cystic dilation of salivary duct of the sublingual or submaxillary salivary glands; occurs on floor of mouth adjacent to tongue May be associated with sialolithiasis

Salivary Mucocele o Pseudocyst (not lined by epithelium) and filled with saliva; cause is often unknown, may relate to traumatic rupture of duct of sublingual gland Sialoliths o Rare in domestic species; inflammation of the salivary gland sloughed cells form a nidus for mineral accretion

Salivary Gland Infarction o Occurs infrequently in cats, rarely in dogs o Grossly appears firm, swollen; discrete foci of parenchymal necrosis with peripheral hemorrhage and inflammation Canine necrotizing sialometaplasia o Salivary gland infarction o More common in small breed terriers (Jack Russell terrier) Neoplasia Very rare

10

Composed of glandular or ductular elements or a combination of both epithelial and mesenchymal components (as with mammary tumors) Most are adenocarcinomas with aggressive behavior

TONGUE

Developmental Anomalies Epithelial defects (fissures), epitheliogenesis imperfecta, macroglossia, microglossia, and haired skin growing from tongue

Lethal Glossopharyngeal Defect of Dogs (Bird Tongue) o Abnormality resulting in pointed tongueunable to wrap around a nipple and generate negative pressure to suckle; may result in starvation Infectious Disease Wooden Tongue (Actinobacillus lignieresii) o Presentation Swelling, inflammation, fibrosis of tongue wooden tongue o Pathogenesis Actinobacillus lignieresii a normal oral commensal and opportunistic invader into traumatized lingual muscle in cattle, small ruminants and occasionally horses o Diagnosis Granulomas containing colonies of Gram-negative bacilli, surrounded by a zone of pallisading eosinophilic club-shaped structures composed of immunoglobulin products from host inflammatory cells; rosettes surrounded by granulocytes, macrophages, epithelioid cells, multinucleate Langerhans-type giant cells (Splendore-Hoeppli phenomenon); further surrounded by lymphocytes, plasma cells, and peripheral fibrosis (depending on chronicity) Similar lesions within draining lymph nodes Needs to be differentiated from Actinomyces bovis osteomyelitis Thrush (Candidiasis) Primarily occurs in ungulates, rarely in carnivores o Pathogenesis Infection of intact epithelium of the tongue and in the esophagus by Candida albicans; secondary to primary debility, often in young animals May result from: Prolonged use of antibiotics (dysbacteriosis) Elevated serum glucose concentrations (diabetes mellitus, high-sugar diet, IV glucose therapy) Immunodeficiency o Diagnosis Gray-green pseudomembrane easily scraped off intact oral mucosa *Lesions on the tongue may reflect various systemic diseases, including BVD, FMD, and uremia Hyperplastic and Neoplastic Conditions Epithelial Hyperplasia o Lateral edges of the tongue; common in piglets before they start nursing Squamous Cell Carcinoma o Most common neoplasm

11

Other Primary Neoplasms o Rhabdomyoma/rhabdomyosarcoma o Fibrosarcomas o Melanomas o Granular Cell Tumors Parasitic Diseases Sarcocystis spp. Common incidental finding in cattle Trichinella spiralis Pigs, occasionally in carnivorous wildlife (polar bears) Gongylonema spp. May be seen in mucosa of pigs and ruminants; no clinical significance

References Pathologic Basis of Veterinary Disease McGavin & Zachary, 4th ed.,2007 Pathology of Domestic Animals, eds. Jubb KVF, Kennedy PC, Palmer NC, 5th ed. Elsevier, Philadelphia, PA, 2007 Tumors in Domestic Animals, ed. Meuten DJ, 4th ed. Iowa State Press, Ames, IA, 2002

12