JPC SYSTEMIC PATHOLOGY
URINARY SYSTEM
January 2024
U-T17 (NP)
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: capillary congestion or thrombosis; 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: swollen, vacuolated cytoplasm with pale nuclei (degeneration); hyaline droplets; or shrunken hypereosinophilic cells with pyknosis (necrosis). 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, glomerular and interstitial capillaries: Fibrin thrombi, diffuse, with glomerular and tubular degeneration, necrosis and proteinosis, Yucatan minipig (Sus scrofa), porcine.
ETIOLOGIC DIAGNOSIS: Renal ricin toxicosis
CAUSE: Ricin
GENERAL DISCUSSION:
- Castor beans (Ricinus communis) contain ricin, a glycoprotein known to cause gastroenteritis, vomiting, diarrhea, and occasionally death
- Ricin is a phytotoxin; highest levels of ricin are found in the seeds
- CDC category B bioterrorism agent
- Affects livestock, poultry, horses, and companion animals
- 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
PATHOGENESIS:
- Classic A-B toxin: Composed of two glycoprotein chains, A (toxic moiety) and B (lectin moiety), linked by a disulfide bond
- Castor bean plant seeds are crushed or broken > toxic compound (A-B toxin) is released > B chain binds to galactosides of cell-surface carbohydrates > endocytosis > A chain moves from Golgi, to cytosol, to endoplasmic reticulum > A chain removes an adenine from 28S subunit of ribosome > inhibits protein synthesis > cell death
- Decreased calcium uptake by sarcoplasmic reticulum in heart and increased sodium-calcium exchange > myocardial necrosis and cardiac hemorrhage > altered cardiac function > hypotension
- Target organ depends on the roue of administration
TYPICAL CLINICAL FINDINGS:
- Most common clinical signs are vomiting, depression, and diarrhea/melena; signs progress to hypotension, increased cardiac output, hypovolemic shock, seizures, and death
- Hepatic enzyme elevation and renal failure
TYPICAL GROSS FINDINGS:
- Necrosis and hemorrhage in the heart, stomach, lungs, liver, kidneys, and pancreas, when given parenterally; hemorrhagic gastroenteritis is most common when ingested
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Kidney: Renal tubular degeneration and necrosis, eosinophilic fluid and debris surrounding glomerular tufts, focal thickening of Bowman’s capsule, and glomerulosclerosis (Roels et. al J Vet Diagn Invest 2010)
- Heart: Myocardial necrosis
- Intestine: Hemorrhagic gastroenteritis
ADDITIONAL DIAGNOSTIC TESTS:
- History and presence of castor beans in the gastrointestinal tract
- Ricinine (a ricin biomarker) can be monitored in urine up to 48 hours after exposure
DIFFERENTIAL DIAGNOSIS:
- For glomerular fibrin thrombi:
- Other plant lectins: Abrin (from the plant Abrus precatorius); Modeccin (from the plant Adenia digitata)
- Snake venom intoxication
- Acute septicemia
COMPARATIVE PATHOLOGY:
- All domestic animal species are susceptible; sensitivity is species dependent, with chickens and frogs being least sensitive and horses most sensitive
- Laboratory rats and mice: Glomerular thrombotic microangiopathy; this is the proposed model for hemolytic uremia syndrome
REFERENCES:
- Albretsen JC, Gwaltney-Brant SM, Khan SA. Evaluation of castor bean toxicosis in dogs: 98 cases. J Am Anim Hosp Assoc. 2000;36(3):229-233.
- Moshiri M, Hamid F, Etemad L. Ricin Toxicity: Clinical and Molecular Aspects. Rep Biochem Mol Biol. 2016 Apr;4(2):60-5.
- Roels S, Coopman V, Vanhaelen P, Cordonnier J. Lethal ricin intoxication in two adult dogs: toxicologic and histopathologic findings. J Vet Diagn Invest. 2010;22(3):466-8.
- 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. St. Louis, MO: Elsevier; 2016:117, 163.