JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

October 2024

D-T14 (NP)

 

Signalment (JPC #2548607): 3-month-old mixed breed beef heifer

 

HISTORY: This heifer was one of several calves and cows that were acutely ill. Several died in the last four months. This calf died enroute to the laboratory. A bottle of monosodium methanearsonate herbicide with a pinhole leak had been dripping into a meal supplement in a storage shed.

 

HISTOPATHOLOGIC DESCRIPTION: Rumen: Diffusely there is a lack of normal ruminal papillar architecture with blunting, collapse, and loss of papillae. The mucosal epithelium is eroded, ulcerated, and multifocally separated from the lamina propria and replaced by eosinophilic cellular and karyorrhectic debris (necrosis), keratin debris, fibrin, hemorrhage, edema, numerous viable and degenerate neutrophils, fewer lymphocytes and plasma cells, and few small colonies of coccobacilli. Multifocally within the lamina propria, most severely underlying areas of ulceration, there is necrotic debris, viable and degenerate neutrophils, edema, and fibrin. Edema and neutrophils extend transmurally through all layers of the rumen to the serosa.

 

MORPHOLOGIC DIAGNOSIS: Rumen: Rumenitis, necrohemorrhagic and neutrophilic, acute, diffuse, severe, with transmural congestion and edema, mixed breed, bovine.

 

ETIOLOGIC DIAGNOSIS: Rumenal arsenic toxicosis

 

CAUSE: Organic arsenic (trivalent)

 

GENERAL DISCUSSION:

• Sources include insecticides, herbicides, wood preservatives, smelter exhaust, insulation materials, paint pigments, feed additives, some medications, and as a byproduct of some mining activities; persistent in the environment
• Poisoning usually occurs by accidental exposure to herbicides and pesticides via:
  • Ingestion (more toxic): Most often occurs when animals acquire access to pasture recently contaminated with herbicides containing sodium arsenite, lead arsenate, and arsenic pentoxide; less often, poisoning occurs with Paris green (cupric acetoarsenite, an insecticide) or through contaminated water or pasture from smelter exhaust (ore often contains arsenic) 
  • Percutaneous (less toxic): Most often occurs with the use of sodium arsenite sprays or dips; absorption is increased if the animals are hot at dipping and kept hot afterward and/or if not dried quickly; absorption is rapid through wounds and hyperemic skin
• Toxicity varies considerably depending on the chemical structure of the arsenic compound, and syndromes differ according to chronicity and whether the arsenic is organic or inorganic: 
  • Organic compounds (aliphatic or phenylarsonic): Most commonly a feed additive; generally less toxic; almost exclusively cause neurotoxicity
  • Inorganic compounds (trivalent or pentavalent): Most commonly an herbicide or pesticide; main effects are in GI tract, liver, and kidneys; cause enteric disease with renal and hepatic manifestations +/- neurologic signs; large doses result in rapid death 
• Excreted in urine, bile, milk, hair, nails, and exfoliated epidermal cells 

 

PATHOGENESIS:

• Inorganic arsenic compounds: 
  • Inhibit cellular respiration by binding to sulfhydryl enzymes (the main mechanism of action), especially lipoic acid and alpha-keto oxidases (tricarboxylic acid cycle), and inactivating them, which disrupts cellular metabolism; tissues of high oxidative energy and/or rapidly dividing cells are most affected (i.e. intestinal epithelium, kidney, liver, skin, brain and lung)
  • The lesions in arsenical poisoning are often associated with vascular injury due to effects on capillary integrity
  • In the skin, arsenic is a low-grade corrosive that produces irritant contact dermatitis; its presence also increases skin susceptibility to UV damage 
• Organic arsenic compounds: Act by an unknown mechanism to produce demyelination and axonal degeneration

 

TYPICAL CLINICAL FINDINGS:

• Inorganic arsenic compounds: 
  • Contact dermatitis: Erythema, indolent/non-healing ulcers; usually on mouth, lips, other mucocutaneous junctions, and feet 
  • Clinical pathology findings related to kidney (azotemia, proteinuria, renal tubular casts, etc) and liver (increased ALT)
  • Symptoms based on timeline:
    • Peracute: Sudden death due to circulatory collapse within minutes to less than 24 hours 
    • Acute: Abdominal distress, nervous depression, circulatory weakness 1-2 days after poisoning, followed by terminal diarrhea and convulsions 
    • Subacute: Tremors, incoordination, +/- hemorrhagic and diffuse diarrhea
    • Chronic: Unthriftiness, capricious appetite, loss of vigor, abortion, brick-red mucous membranes and muzzle, dry seborrheic/alopecic coat 
• Organic arsenic compounds: 
  • Neurologic signs (dependent on specific compound), mostly in swine; see comparative pathology section

 

TYPICAL GROSS FINDINGS:

• Abomasum is most severely affected in both acute and chronic poisonings
  • Peracute: No lesions to minimal gastric edema
  • Acute: Intense gastrointestinal mucosal congestion (“rose-red inflammation”), especially in the stomach or abomasum; prominent submucosal edema (especially in abomasal plicae); +/- ulceration and epithelial sloughing with accumulation of luminal fluid and detritus, and petechial hemorrhage 
  • Subacute: Pale, swollen kidneys; pale, soft, orange liver; petechiae of the intestinal serosa and mucosa
  • Chronic: Mild gastrointestinal congestion, edema, and ulceration with prominent fatty changes in the heart, liver, and kidneys 
• Hemorrhagic typhlocolitis in ruminants (seen with arsenic, other heavy metals, or oak/acorn poisoning)
• No gross lesions within the central or peripheral nervous system.
• Contact dermatitis – congestion, ulceration 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Dermatitis – congestion, necrosis, ulceration
• Inorganic acute toxicity 
  • Gastric and intestinal mucosal and submucosal congestion, edema, hemorrhage and ulceration
  • Multifocal hepatic and renal proximal tubular necrosis and edema
  • +/- mesenteric and ruminal lymph node and spleen lymphocytolysis
• Inorganic chronic toxicity: 
  • Mild gastrointestinal congestion, edema, and ulceration
  • Renal tubular necrosis, degeneration, fibrosis and fatty changes
  • Liver degeneration and fatty changes 
• Organic arsenicals: Moderate, diffuse cerebral edema and petechiae with vascular necrosis; demyelination and degeneration of peripheral nerves and spinal cord (the spinocerebellar tracts and dorsal funiculi are predominantly affected and usually in a chronological order of cervical, then thoracic, and lastly lumbar).

 

ADDITIONAL DIAGNOSTIC TESTS:

• Detection of chemical residues in tissues or body fluids
  • Acute exposure: Urine, vomitus, feces, milk, liver, intestine and kidney
  • Chronic exposure: Skin, hair, and nervous tissue (organic arsenicals)
• Analysis of suspected baits, feed, plants, or soil

 

DIFFERENTIAL DIAGNOSIS:

• Differential diagnosis for acute inorganic poisoning (gastroenteritis and central nervous system signs):
  • Lead toxicosis: Central nervous system signs predominate; gastrointestinal involvement is inconsistent
  • Malignant catarrhal fever (bovine gammaherpesvirus): Ocular and buccal lesions 
  • Mucosal disease (bovine pestivirus): Buccal and nasal mucosa lesions
  • Mercury toxicity in pigs and cattle: Central nervous system and gastrointestinal signs, edematous kidneys; laminar cortical necrosis in cattle
  • Plants: Brackens and mustards
  • Salmonellosis: Button ulcers; paratyphoid nodules; diagnose via culture
• Differential diagnosis for chronic inorganic arsenical poisoning (diarrhea and weight loss):
  • Inanition
  • Parasitism: Ostertagiasis, trichostrongylosis, and oesophagostomiasis
• Differential diagnosis for organic arsenical poisoning (afebrile neurologic signs):
  • Organic mercury poisoning
  • Salt poisoning
  • Industrial organophosphate contamination of swine feed
  • Selenium toxicosis of swine feed: Focal symmetrical encephalomalacia

            

COMPARATIVE PATHOLOGY:

• Humans, dogs, rats, mice, swine, and ruminants are affected by arsenic toxicosis 
• In humans chronic exposure occurs with environmental (water contamination) and industrial settings and is associated with visceral and cutaneous malignancies, Bowen’s disease, palmar and solar hyperkeratosis, and cutaneous pigmentary disturbances 
• Organic arsenical poisoning in pigs is predominately neurologic; organoarsenical phenylarsonic acid derivatives are used as feed additive for growth promoting and control of enteric diseases (i.e. swine dysentery) but have a low margin of safety; there are two main syndromes: 
  • Arsanilic acid poisoning – acute onset of cutaneous erythema, hyperesthesia, ataxia, blindness, vestibular disturbances, and terminally, muscular weakness; no gross neural lesions; microscopically, mild edema of the white matter; degeneration of nerves, including optic neuropathy
  • 3-nitro poisoning – repeated clonic seizures following exercise with progression to paraplegia, but no blindness; microscopically, Wallerian-like degeneration with fragmentation and loss of axons, destruction of myelin sheaths, and glial proliferation in the spinal cord, most intense in the dorsal proprioceptive and spinocerebellar tracts in the cervical spinal cord and progresses to the lateral and ventral funiculi of the lumbar spinal cord; mild optic and peripheral neuropathy

Rainbow trout (osteichthyes)- Nephrocalcinosis can be induced experimentally with arsenic toxicity.

 

REFERENCES:

1. Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:327-328.
2. Cianciolo RE, Mohr FC. Urinary System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:424. 
3. Frasca SJ, Wolf JC, Kinsel MJ, Camus AC, Lombardini ED. Osteichthyes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:955. 
4. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:570.
5. Miller AD, Porter, BF. Nervous System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:939.
6. 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; 2022:447. 
7. Sula MM, Lane LV. The Urinary System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:734-735.
8. Uzal FA, Platter BL, Hostetter JM. Alimentary System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:51, 52, 57, 100, 114.
9. Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1158.

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