JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

August 2024

D-B04

 

Signalment (JPC #2010741): 6-week-old calf

 

HISTORY: Animal was observed with abdominal distension and sunken eyes shortly before death.

 

HISTOPATHOLOGIC DESCRIPTION: Abomasum (fundus): Diffusely and transmurally, but most prominently within the submucosa, the abomasum is markedly expanded by increased clear space and ectatic lymphatics (edema), dilated blood vessels (congestion), and eosinophilic finely fibrillar material (fibrin). Moderate to high numbers of degenerate and viable neutrophils infiltrate the mucosa and submucosa and extend into the tunica muscularis and serosa. Multifocally within the mucosa there is a loss of differential staining with retention of architecture (coagulative necrosis) and/or replacement of mucosal epithelium by karyorrhectic and cellular debris (lytic necrosis), neutrophils, and hemorrhage. In the deep mucosa, at the level of the gastric glands, are variably sized (up to 300 um), round to oval, well-defined areas of clear space (emphysema). Diffusely throughout the abomasum within small and intermediate sized vessels, the endothelium is discontinuous, fragmented, and necrotic and there is infiltration of the tunica media by numerous degenerate and fewer viable neutrophils, fibrin, and karyorrhectic and cellular debris, which multifocally extend into the tunica externa (vasculitis).

 

MORPHOLOGIC DIAGNOSIS: Abomasum (fundus): Abomasitis, necrohemorrhagic, acute, transmural, diffuse, moderate, with emphysema, marked submucosal edema, and vasculitis, breed unspecified, bovine.

 

ETIOLOGIC DIAGNOSIS: Clostridial abomasitis

 

CAUSE: Clostridium septicum

 

CONDITION: Braxy, bradsot

 

GENERAL DISCUSSION:

• A soil-borne, gram-positive bacillus and common inhabitant of the herbivore intestinal tract
• Causes sporadic acute, severe abomasitis, abomasal ulceration and necrosis, toxemia, and high mortality in lambs and less commonly calves
• Associated with cold weather and occurs more frequently in temperate climates

 

PATHOGENESIS:

• May be associated with ingestion of frozen feeds contaminated with Clostridium (although it is difficult to imagine feed being cold enough, by the time it reaches the abomasum, to cause significant mucosal trauma or hypothermia and necrosis)
• Factors initiating bacterial invasion unknown; local tissue damage allowing for invasion of C. septicum is suspected
• Following invasion, the infection spreads rapidly through connective tissue > suppuration, marked fluid exudation, and gas formation
• Death occurs rapidly due to septicemia and exotoxemia
  1. 4 major toxins (alpha, beta, delta, and gamma) produced; alpha-toxin, a pore-forming cytolysin, is most important (Junior, J Vet Diagn Invest. 2020)

 

TYPICAL CLINICAL FINDINGS:

• Acute anorexia, depression, high fever, diarrhea, abdominal distension (tympany) and pain, followed by recumbency and death
• Death may be sudden without prior illness

 

TYPICAL GROSS FINDINGS:

• Most notable feature is the presence of extensive gelatinous edema and emphysema in the abomasal submucosa
• Blood-tinged fluid within the abdomen and abomasum
• Abomasal serosa congested and covered with fibrin
• Thickened abomasal folds and proximal small intestine, hemorrhagic and necrotic

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Abomasal submucosal edema, emphysema, and diffuse transmural suppurative inflammation
• Areas of coagulative necrosis within submucosa extending into adjacent layers
• Vasculitis, thrombosis, and hemorrhage
• Individual or colonies of gram-positive bacilli 

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:  

• Mycotic abomasitis (Mucor sp., Aspergillus sp., Rhizopus sp.): Necrotizing and hemorrhagic abomasitis with vasculitis and submucosal hemorrhage and edema; fungal hyphae evident with PAS and GMS stains
• Viral abomasitis: Rarely limited to the abomasum; not emphysematous

1. Rinderpest (Morbillivirus, Paramyxoviridae): Syncytia, intranuclear and intracytoplasmic inclusion bodies
2. Malignant catarrhal fever (alcelaphine herpesvirus-1 & ovine herpesvirus-2): Lymphocytic and lymphoblastic vasculitis
3. Infectious bovine rhinotracheitis (bovine herpesvirus 1): Multifocal necrosis in the digestive system with intranuclear inclusion bodies
4. Bovine viral diarrhea virus/mucosal disease (Pestivirus, Flaviviridae): May cause abomasal necrosis, hemorrhage, and thrombosis
5. Bluetongue (Orbivirus, Reoviridae): May cause abomasal necrosis, hemorrhage, and thrombosis

• Bacterial abomasitis:

1. Clostridium novyi (black disease): Similar abomasal lesions with necrotizing hepatitis; usually related to migration of Fasciola hepatica 
2. Clostridium sordellii: Associated with gastritis/abomasitis similar to C. septicum
3. Sarcina-like organisms: Anaerobic gram-positive nonmotile cocci found in rafts & packets; reported in association with abomasal bloat in several calves
   1. Associated with acute fatal acute gastric dilation and gastric emphysema in rhesus macaques (Lee, J Vet Diagn Invest. 2023)
4. Clostridium perfringens type A (enterotoxemia): Similar lesions in neonatal calves in western U.S. with ruminal tympany and abomasitis

• Toxin-associated abomasitis (arsenic, thallium, phosphorus, zinc) cause hemorrhage, necrosis, and ulcers throughout gastrointestinal tract

 

COMPARATIVE PATHOLOGY:

C. septicum in other species:

• Clostridial myositis: 
  1. Often seen in many species; caused by several Clostridia species, most commonly C. septicum, C. chauvoei, C. perfringens, C. novyi, and C. sordellii; “Malignant edema” often due to C. septicum and “gas gangrene” often due to C. perfringens: wound infection most common (may also be due to activation of dormant spores, potentially from previously compromised gastrointestinal mucosa, especially in horses); tissue is hemorrhagic with gelatinous exudate in the subcutis/ intramuscular tissue and few bacteria; gas formation is variable (with gas = gas gangrene; absence of gas = malignant edema) (Junior, J Vet Diagn Invest. 2020)
  2. Malignant edema or gas gangrene reported in exotic hoof stock and elephants 
• Gangrenous dermatitis (GD) in poultry: Typically caused by C. septicum, C. perfringens type A, and occasionally C. sordelli; most often seen in young growing chickens and characterized by necrotic areas of skin and severe, underlying, infectious cellulitis; likely due to cutaneous wound coupled with immunosuppression (e.g., avian birnavirus/infectious bursal disease (H-V07), chicken infectious anemia virus, reticuloendotheliosis virus, or avian adenovirus) (Fulton, 2019) 
  1. Other reported causes include Staphylococcus aureus, E. coli, Proteus sp., Enterococcus faecalis, and Bacillus sp. 
• Postpartum gangrenous metritis in goats most commonly caused by C. perfringens, but also C. septicum, C. novyi, or C. chauvoei; death after kidding; dams had hemorrhagic edematous, and necrotic uteri with thrombi with intralesional gram-positive rods (Dorso, J Vet Diagn Invest. 2023)

 

Other Clostridial diseases:

• C. perfringens: Causes many diseases, including hemorrhagic gastrointestinal diseases, muscle infections, and enterotoxemias (D-B02, see also U-B06 Pulpy kidney disease)
  1. Classified into 7 major types (A, B, C, D, E, F, G), based on the production of 6 major lethal toxins
• C. haemolyticum: Bovine bacillary hemoglobinuria / infectious icterohemoglobinuria / redwater; hepatic damage (secondary to fluke migration) → infarction → necrosis (usually solitary site) → hemolysis → death; mottled kidneys with deep red urine in the urinary bladder 
• C. novyi: Big head and Black disease in sheep / infectious necrotic hepatitis; wound infections; multiple areas of hepatic necrosis
• C. chauvoei (M-B01): Blackleg in cattle and sheep
• C. colinum: Ulcerative enteritis / quail disease
• C. spiroforme: Spontaneous or antibiotic-induced enterotoxemia in rabbits
• C. villosum: Subcutaneous abscesses and pyothorax in cats
• C. difficile: Spontaneous or antibiotic-induced enterocolitis in hamsters, rabbits, guinea pigs, swine and horses
• C. sordelli: Wound infections in many species; reported in foals and captive lions
• C. carnis, C. histolyticum: Wound infections in many species
• C. tetani: Tetanus; neurotoxin → muscle spasms, stiff gait, rigid posture, trismus (lockjaw)
• C. botulinum: Botulism; flaccid paralysis → respiratory paralysis
• C. piliforme: Necrotizing hepatitis and enteritis in many species; sole gram-negative Clostridium species

 

REFERENCES:

1. Cooper BJ, Valentine BA. Muscle and Tendon. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:230-233. 
2. Dorso L, Chartier C, Popoff MR, Tesson C, Despres J, Uzal FA. Postpartum clostridial gangrenous metritis in 12 dairy goats in France. J Vet Diagn Invest. 2023;35(3):266-271. 
3. Fulton RM, Boulianne M. Bacterial Diseases. In: Boulianne M ed. Avian Disease Manual. 8^th ed. Madison, WI: Omnipress; 2019: 87-88.
4. Jones MEB, Gasper DJ, Mitchell E. Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:133. 
5. Junior CAO, Silva ROS, Lobato FCF, Navarro MA, Uzal FA. Gas gangrene in mammals: a review. J Vet Diagn Invest. 2020;32(2):175-183.
6. Landolfi JA, Terrell SP. Proboscidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:427. 
7. Lee LM, et al. Sarcina sp. as a presumptive cause of fatal acute gastric dilation and gastric emphysema in rhesus macaques. J Vet Diagn Invest. 2023 Nov;35(6):698-703. 
8. Shivaprasad HL, Barnes HJ. Chapter 14: Integumentary System. In: Abdul-Aziz T, Fletcher OJ, Barns HJ, eds. Avian Histopathology. 4th ed. Madison, WI: Omnipress; 2016: 620.
9. Spagnoli ST, Gelberg HB. Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:434. 
10. Stanton JB, Zachary JF. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:234-235. 
11. Uzal FA, Plattner BL, Hostetter JM. Alimentary System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:53-54. 
12. Valentine BA. Skeletal Muscle. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1010, 1016.

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