JPC SYSTEMIC PATHOLOGY
Signalment: 7-month-old female Yucatan minipig
HISTORY: Received a lethal dose of a toxic substance and died in severe respiratory distress 24 hours later
HISTOPATHOLOGIC DESCRIPTION: Kidney: Diffusely, glomeruli have one or more of the following changes: marked capillary congestion or fibrin thrombi; necrosis and mesangiolysis, characterized by pyknotic or karyorrhectic endothelial or mesangial nuclei; proteinosis, characterized by uriniferous spaces filled with homogeneous eosinophilic material; and hypertrophic parietal epithelium. Tubular epithelial cells multifocally have one or more of the following changes: degeneration, characterized by swollen, vacuolated cytoplasm with pale nuclei; hyaline droplets; or necrosis, characterized by shrunken hypereosinophilic cells with pyknosis. Multifocally tubules are mildly ectatic with proteinosis, characterized by tubular lumina that are variably filled with eosinophilic material. Interstitial capillaries are diffusely dilated by congestion and multifocally by fibrin thrombi admixed with necrotic debris. There is occasional deposition of deeply basophilic mineral within glomerular and interstitial capillary basement membranes.
MORPHOLOGIC DIAGNOSIS: Kidney, glomeruli and interstitial capillaries: Fibrin thrombi, numerous, diffuse, with glomerular and tubular degeneration, necrosis and proteinosis, Yucatan minipig (Sus scrofa), porcine.
ETIOLOGIC DIAGNOSIS: Renal ricin toxicosis
- Ricin is a phytotoxin (toxalbumin, ribosome inactivating protein) derived from the castor bean plant, Ricinus communis
- Composed of two glycoprotein chains, A (toxic moiety) and B (lectin moiety), linked by a disulfide bond
- Exposure occurs via ingestion of seeds or improperly detoxified seed products (fertilizer, soil conditioner, animal feed) or experimental/intentional exposure via inhalation or injection
- Parenteral route leads to more severe results than ingestion
- Seeds must be macerated to have an effect, if swallowed whole, the hard seed coat prevents absorption and poisoning
- Causes gastroenteritis, necrosis and hemorrhage in heart, stomach, lungs, liver, kidneys and pancreas
- Used experimentally as an anticancer immunochemotherapeutic
- CDC category B bioterrorism agent
- Ricinus communis also contains RCA120 (a hemagglutinin), and ricinine (an alkaloid)
- Ricin’s B chain avidly binds to galactosides of cell-surface carbohydrates > endocytosis of toxin through uncoated pits > enters cytosol via the Golgi apparatus (presence of B chain facilitates A chain transport into the cytosol) > A chain removes an adenine from 28S subunit of ribosome > inhibits protein synthesis > cell death
- Also causes apoptosis (mechanism not fully understood)
- It has been suggested that liver and kidney damage are the result of vascular disturbances induced by the toxin
TYPICAL CLINICAL FINDINGS:
- Ingestion: Nausea, vomiting, abdominal pain, diarrhea, anuria, mydriasis, vascular collapse and shock
- Inhalation: Respiratory distress, severe dyspnea
- Intramuscular injection: Local pain and systemic signs similar to ingestion
TYPICAL GROSS FINDINGS:
- Ingestion: Ulcers and hemorrhage in gastrointestinal mucosa; lymphoid and hepatic necrosis; nephritis and splenitis
- Parenteral: Hemorrhage and necrosis in the heart, stomach, lungs, liver, kidneys, pancreas, and muscle; splenitis
- Inhalation: Necrotizing pneumonia and severe pulmonary edema
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Ingestion: Gastrointestinal hemorrhage, necrosis and fibrin thrombi in mesenteric lymph nodes, spleen, liver and kidneys
- IM Injection: Muscle and regional lymph node necrosis and moderate involvement in the liver, spleen and kidneys
- Inhalation: Fibrinopurulent pneumonia and pleuritis, diffuse necrosis, peribronchial and vascular edema, purulent tracheitis and mediastinal lymphadenitis
- In 2010 case report of two dogs with ricin intoxication the most prominent histopathologic lesions were: renal tubular degeneration and necrosis, eosinophilic fluid and debris surrounding glomerular tufts, focal thickening of Bowman’s capsule, and glomerulosclerosis
ADDITIONAL DIAGNOSTIC TESTS:
- History and presence of castor beans in the gastrointestinal tract
- ELISA and immunohistochemistry within 24 hours of exposure
- Serum sample for antibody 2 weeks post exposure
- Ricinine can be monitored in urine up to 48 hours after exposure
For glomerular fibrin thrombi:
- Other plant lectins:
- Abrin (from the plant Abrus precatorius)
- Modeccin (from the plant Adenia digitata)
- Snake venom intoxication
- Acute septicemia
- All domestic animal species are susceptible; sensitivity is species dependent, with chickens and frogs being least sensitive and horses most sensitive
- Ricin-induced glomerular thrombotic microangiopathy in rats has been used as a model for toxin-induced hemolytic uremic syndrome
- Similar histologically to glomerular and cutaneous vasculopathy seen in greyhounds, where shiga toxic Coli induced vascular damage suspected as the cause
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- Worbs, S, Kohler, K, Pauly, D, Avondet, M, Schaer, M, Dorner, M, Dorner, B. Ricinus communis Intoxications in Human and Veterianry Medicine—A Summary of Real Cases. 2011;3:1332-1372.