JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
August 2021
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 karryorhectic and cellular debris (lytic necrosis), neutrophils, and hemorrhage.  In the deep mucosa, at the level of the gastric glands, are variably sized (up to 300um), 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 karryorhectic 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 acute, severe abomasitis, abomasal ulceration and necrosis, toxemia, and high mortality in lambs and less commonly calves; sporadic
• Associated with cold weather and occurs more frequently in temperate climates

PATHOGENESIS:

• Factors initiating bacterial invasion unknown; local tissue damage allowing for invasion of 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
• septicum produces four toxins that cause severe tissue damage, increase capillary permeability and cause myonecrosis and facilitate spread of the infection
  • Alpha toxin: Pore-forming cytolysin; not the same as perfringens alpha toxin
  • Beta toxin: Deoxyribonuclease; leukocidal
  • Delta toxin: Hemolysin; also known as septicolysin; pore-forming toxin that acts synergistically with alpha toxin
  • Gamma toxin: Hyaluronidase; connective tissue damage

TYPICAL CLINICAL FINDINGS:

• Acute onset of 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
• Submucosa expanded by gelatinous edema and emphysema

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Abomasal submucosal edema, emphysema, and diffuse transmural suppurative inflammation
• Suppurative infiltrate with areas of coagulative necrosis within submucosa extending into adjacent layers
• Vasculitis, thrombosis, and hemorrhage
• Gram-positive bacilli

ADDITIONAL DIAGNOSIS TESTS:

• Fluorescent antibody test, culture, PCR

DIFFERENTIAL DIAGNOSIS: 

• Abomasitis:
• Mycotic abomasitis (Mucor , 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
• Rinderpest (Morbillivirus, Paramyxoviridae): Syncytia, intranuclear and intracytoplasmic inclusion bodies
• Malignant catarrhal fever (alcelaphine herpesvirus-1 & ovine herpesvirus-2): Lymphocytic and lymphoblastic vasculitis
• Infectious bovine rhinotracheitis (bovine herpesvirus 1): Multifocal necrosis in the digestive system with intranuclear inclusion bodies
• Bovine viral diarrhea virus/mucosal disease (Pestivirus, Flaviviridae): May cause abomasal necrosis, hemorrhage, and thrombosis
• Bluetongue (Orbivirus, Reoviridae): May cause abomasal necrosis, hemorrhage, and thrombosis
• Bacterial abomasitis:
• Clostridium novyi (black disease): Similar abomasal lesions with necrotizing hepatitis; usually related to migration of Fasciola hepatica
• Clostridium sordellii: Associated with gastritis/abomasitis similar to septicum
• Sarcina-like organisms: Anaerobic gram-positive nonmotile cocci found in rafts & packets; reported in association with abomasal bloat in several calves
• 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 (“Malignant edema”/”Gas gangrene”): Wound infections and septicemia with septicum and other clostridial organisms primarily in ruminants, horses and swine; tissue is hemorrhagic with gelatinous exudate in the subcutis and intramuscular connective tissue; gas formation is variable
• Necrotizing gastritis in a New Zealand white rabbit
• Gangrenous dermatitis (GD) in poultry: Typically caused by septicum, C. perfringens type A, and occasionally C. sordelli
• Other Clostridial diseases:
  • C. perfringens: Enterotoxemia
    • Classified into 5 major types (A, B, C, D, and E), based on the production of 4 major lethal toxins; 2 more types recently added (see D-B02):
      • Type A produces alpha toxin
      • Type B produces alpha toxin, beta toxin, and epsilon toxin
      • Type C produces alpha toxin and beta toxin
      • Type D produces alpha toxin and epsilon toxin
      • Type E produces alpha toxin and iota toxin

• 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: 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. Garcia JP, Moore J, Loukopoulos P, Diab SS, Uzal FA. Necrotizing gastritis associated with Clostridium septicum in a rabbit. J Vet Diagn Invest. 2014;26(5):669-673.
2. Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery, and peritoneal cavity. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 6^th St. Louis, MO: Elsevier Mosby; 2017:362.
3. Gornatti-Churria CD, Crispo M, Shivaprasad HL, Uzal A. Gangrenous dermatitis in chickens and turkeys. J Vet Diagn Invest. 2018;30(2):188-196.
4. Oliveira Jr. CA, Silva ROS, Lobato FCF, Navarro MA, Uzal FA. Gas gangrene in mammals: a review. J Vet Diagn Invest. 2020;32(2):175-83.
5. Popoff, MR. Toxins of histotoxic clostridia: Clostridium chauvoei, Clostridium septicum, Clostridium novyi, and Clostridium sordellii. In: Uzal, FA., eds. Clostridial Diseases of Animals. Ames, IA: Wiley-Blackwell, 2016:23–43.
6. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:53.

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