JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-T04 

 

Signalment (JPC# 920336): Adult female rhesus macaque

 

HISTORY: Received a calculated inhaled dose of 36.5 mg/kg aerosolized ricin and developed signs of acute respiratory distress shortly before death at 48 hours post exposure

 

HISTOPATHOLOGIC DESCRIPTION: Lung: In 95% of the lung parenchyma, expanding the perivascular and peribronchial connective tissue and pleura and compressing the adjacent pulmonary parenchyma there is diffuse, marked edema admixed with abundant fibrin and multifocal neutrophils, macrophages, and lymphocytes. Alveolar lumina are diffusely expanded by edema fluid and abundant beaded, eosinophilic material (fibrin) admixed with few to moderate numbers of neutrophils and macrophages. The alveolar, bronchiolar, and bronchial epithelium is segmentally to diffusely necrotic and often lost with replacement by variably polymerized fibrin, edema, hemorrhage, and scant cellular and karyorrhectic debris, which also expands remaining alveolar septa. Lymphatic vessels are multifocally ectatic (edema). Blood vessel walls are edematous, often contain small amounts of fibrin, and endothelial cells are multifocally hypertrophic. Incidentally, there are also multifocal areas of black granular pigment accumulation within macrophages (anthracosilicosis). 

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, bronchointerstitial, fibrinonecrotizing, acute, diffuse, with abundant intra-alveolar, perivascular, and peribronchiolar fibrin and edema, Rhesus monkey (Macaca mulatta), nonhuman primate.

 

ETIOLOGIC DIAGNOSIS: Pulmonary ricin toxicosis

 

CAUSE: Ricin

 

GENERAL DISCUSSION:

• Ricin is derived from the castor bean plant, Ricinus communis
• The toxin is present in all parts of the plant, but is most highly concentrated in the seeds
• One of the most potent and lethal toxins known to man
• Category B bioterrorism agent 
• Has anticancer properties

 

PATHOGENESIS: 

• Ricin is type 2 ribosome-inactivating protein (RIP)
• Type 2 RIPs have an A chain (glycosidase) covalently linked to a B chain (lectin)
• RTB helps toxin enter the cytoplasm à translocation via Golgi to ribosomal subunits à RTA depurinates large ribosomal subunits à inhibition of protein synthesis & cell death  
• Edema is associated with changes in endothelial cell dynamics: direct toxicity, opening of endothelial gaps, and leukocyte-mediated injury.  
• Host Lewis X glycans (which normally interact with selectins on endothelial cells, platelets, and leukocytes) confer sensitivity to ricin (Stadlmann 2017).

 

TYPICAL CLINICAL FINDINGS: 

Inhalation

• Cough, fever, dehydration, rapidly progressive dyspnea leading to respiratory failure and death
• Signs develop within 8-24 hours, and death within 2 days

 

Ingestion

• Vomiting
• Watery to hemorrhagic diarrhea

 

TYPICAL GROSS FINDINGS:  

• Firm, rubbery lungs that are mottled red and purple and do not collapse (rib impressions) 
• Serous or serosanguinous fluid and fibrin strands within the thoracic cavity and overlying the visceral pleural surfaces
• Frothy fluid within the trachea and mainstem bronchi
• Mediastinal lymph nodes enlarged and edematous
• Pericardial sac distended with serous or serosanguinous fluid

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Severe, diffuse, necrotizing bronchiolitis and alveolitis with fibrinopurulent bronchointerstitial pneumonia, edema, and tracheobronchial lymphadenitis
• A few animals may have adrenocortical necrosis

 

ADDITIONAL DIAGNOSTIC TESTS:  

 

DIFFERENTIAL DIAGNOSIS:  

• Acute respiratory distress syndrome (ARDS): Usually has prominent hyaline membranes, as well as alveolar edema.
• Toxins: 

• Oxygen (P-T02): In animals exposed to 95-100% oxygen, diffuse pulmonary damage develops and is usually fatal after 3 to 4 days; there is extensive damage to type I pneumocytes and capillary endothelium; hyaline membranes formed by cellular debris and proteinaceous exudate are a characteristic sign of pulmonary oxygen toxicity

 

COMPARATIVE PATHOLOGY: 

• Common species affected by ricin toxicity are horses and dogs, more often via ingestion (instead of inhalation as in an experimental setting); a case series looking at two dogs reported uncontrollable vomiting and hemorrhagic diarrhea as the initial clinical presentation (24-48 hours after ingestion) (Roels, J Vet Diagn Invest 2007)
• Macroscopic lesions (no images): Hemorrhagic, ulcerative gastroenteritis, and parenchymal congestion
• Light microscopy: Renal tubular degeneration and necrosis; congestion, hemorrhage, disruption of villi, necrotic crypts; lymphoid depletion in the spleen and lymph nodes  

 

REFERENCES:

1. Bhaskaran M, Didier PJ, Sivasubramani SK, Doyle LA, Holley J, Roy CJ.  Pathology of lethal and sublethal doses of aerosolized ricin in rhesus macaques.   Tox Pathol. 2014; 42: 573-581.
2. Mouser P, Filigenzi MS, Puschner B, Johnson V, Miller MA, Hooser SB. Fatal ricin toxicosis in a puppy confirmed by liquid chromatography/mass spectrometry when using ricinine as a marker. Jour Vet Diagn Invest. 2007;19:216-20.
3. Roels S, Coopman V, Vanhaelen P, Cordonnier J.  Lethal ricin intoxication in two adult dogs. Jour Vet Diagn Invest. 2010 May;22(3):466-8.
4. Stadlmann J, Taubenschmid J, Wenzel D, et al. Comparative glycoproteomics of stem cells identifies new players in ricin toxicity. Nature. 2017;549(7673):538-542.
5. Wilhelmsen CL, Pitt MLM. Lesions of acute inhaled lethal ricin intoxication in Rhesus monkeys. Vet Pathol. 1996;33:296-302.

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