JPC SYSTEMIC PATHOLOGY
Signalment (JPC # 4066069): Tissue from an ox.
HISTOPATHOLOGIC DESCRIPTION: Lung: Diffusely affecting 100% of the section bronchi and bronchioles, are expanded by an exudate composed of viable and degenerate neutrophils, eosinophilic cellular and karyorrhectic debris, alveolar macrophages, sloughed epithelial cells, fibrin, hemorrhage, and edema. Bronchiolar and bronchial epithelium are characterized by one or more of the following changes: epithelial necrosis, attenuation, hyperplasia (up to 8 cell layers thick), and viral syncytial cell formation (with up to 8 nuclei) with cells budding off the epithelium into the lumen. Multifocally, there are 3-6 um, round to oval, brightly eosinophilic intracytoplasmic inclusion bodies in respiratory epithelium and syncytial cells. Alveolar lumina are variably expanded by moderate to abundant amounts of fibrin, edema, hemorrhage, small amounts of necrotic debris, neutrophils, and macrophages, which are admixed with viral syncytial cells. Alveolar septa are moderately expanded by eosinophilic beaded fibrillar material (fibrin), macrophages, fewer neutrophils, syncytial cells, hemorrhage and edema, or replaced with eosinophilic cellular and karyorrhectic debris (septal necrosis). There is type II pneumocyte hyperplasia. Interlobular septa and visceral pleura are moderately expanded by hemorrhage, fibrin, and edema, and in the perivascular connective tissue there are also markedly ectatic lymphatic vessels.
MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, bronchointerstitial, necrotizing, suppurative and histiocytic, subacute, multifocal, moderate, with bronchiolar viral syncytial cells and epithelial eosinophilic intracytoplasmic viral inclusions, breed unspecified, bovine.
ETIOLOGY DIAGNOSIS: Paramyxoviral pneumonia
CAUSE: Bovine Respiratory Syncytial Virus (BRSV)
- Enzootic pneumonia, also known as “calf pneumonia” or “viral pneumonia” is a multifactorial disease that often begins with a respiratory infection with BRSV, PI-3 virus, or one or more viruses (adenovirus, BoHV-1, reovirus, bovine respiratory corona virus, rhinovirus)
- BRSV, a paramyxovirus (pneumovirus), is an important component of the “Bovine Respiratory Disease Complex” and “Acute Undifferentiated Respiratory Disease”, which affects young cattle (<1yr.), and occasionally adults by predisposing animals to secondary bacterial infections (i.e.; Mannheimia haemolytica). BRSV is an essential component of fatal feedlot pneumonia in cattle; BRSV is also capable of independently producing primary respiratory disease
- Antigenically related to human RSV, an important respiratory disease of children
- Colostral antibodies dissipate at 3-4 months; calves born in winter generally have lower titers to BRSV
- Mechanism of injury: dysfunction and death of ciliated cells of the conductive system, and alveolar type II pneumocytes
- Aerosolization and inhalation of viral antigen>> deposition on mucous layer of the conductive system>> penetration of mucous layer and entry to epithelial cells (unknown mechanism)>> **replicates and infects all respiratory epithelial cells; however, ciliated cells are the main target (bronchiolar epithelum)**>> virus attaches to ciliated cells via heparin binding domains on G glycoprotein (attachment protein) which mediates attachment of viral particles to the host cell and F glycoprotein (fusion protein) which induces fusion of infected cells
- Other encoded proteins include matrix proteins (M, M2), nucleocapsid protein (N), phosphoprotein (P), polymerase (L), small hydrophobic protein (SH) and non-structural proteins (NS1,2)
- Less viral antigen is expressed in alveolar type II pneumocytes and macrophages than in bronchiolar epithelium
- Virus may infect and replicate in lung dendritic cells and alveolar macrophages; TLR3 and TLR4 may initiate a cascade of events resulting in lung injury
- BRSV replication is limited to respiratory epithelium; there is no evidence of a viremic phase; syncytia are sites of active viral replication
TYPICAL CLINICAL FINDINGS:
- Clinical signs in cows and calves are similar: high fever, coughing, tachypnea, nasal discharge, and conjunctivitis
- Severe cases may lead to pronounced dyspnea, with open mouth breathing
- Biphasic course: transient pyrexia and mild respiratory disease with temporary improvement for days-weeks; subsequent rapid onset of severe respiratory distress
TYPICAL GROSS FINDINGS:
- Cranio-ventral lobes: consolidation and atelectasis; deep red in color or mottled and rubbery
- Caudal-dorsal lobes: edematous, heavy and firm; failure to collapse
- Variation in the above two patterns occurs regularly
- +/- subpleural and interlobular emphysema with bullae formation
- +/- hypertrophy and edema of bronchial and mediastinal lymph nodes
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- HALLMARKS: Bronchointerstitial pneumonia, characterized by necrotizing bronchiolitis, formation of bronchiolar and alveolar epithelial syncytial, and exudative and proliferative alveolitis
(Acute lesions): 1-8 days post infection
- Bronchioles lined by flattened epithelium with lumen and contain necrotic epithelial cells, neutrophils, and lymphocytes
- Alveoli contain moderate numbers of neutrophils and macrophages
- Thickened alveolar septa with mononuclear cells
- Infrequent hyaline membranes
- Bronchiolar syncytia
- Intracytoplasmic eosinophilic inclusion bodies in syncytia cells, and rarely in bronchiolar and alveolar epithelium
(Subacute lesions): > 8 days post infection
- Represents early repair of the above lesions
- Bronchiolar epithelium becomes hyperplastic and there is disappearance of syncytial cells as viral antigen is cleared
- Type II pneumocyte hyperplasia
- Lymphocytes and plasma cell surround bronchioles and thicken alveolar septa (as early as 10 days post infection)
- Bronchiolitis obliterans (as early as 10 days post infection)
- +/- medial hypertrophy of pulmonary arterioles (which may develop secondary to pulmonary hypertension and bronchiolitis obliterans)
- Virus infects type I and II pneumocytes; viral nucleocapsid material is found in the cytoplasm; the virus is not found in macrophages or neutrophils
ADDITIONAL DIAGNOSTIC TESTS:
- Lung tissue from the lesional cranio-ventral areas of lung most profitable sites for viral detection
- PCR may be more effective for subacute or chronic cases
- Immunofluorescent antibody and ELISA
- Parainfluenza type 3 (PI-3) (paramyxovirus): Very similar histologically with syncytial cells and ICIB
- Infectious bovine rhinotracheitis (Bovine herpesvirus-1): INIB; not ICIB
- Atypical interstitial pneumonia (fog fever): No inclusions, differentiate multinucleated giant cells from syncytial cells at the level of the bronchioles and alveoli
- Fibrinous bacterial bronchopneumonias commonly results in formation of alveolar multinucleated macrophages; presence of bronchiolar multinucleated cells in BRSV will help differentiate
- Sheep/goats/alpine chamois: susceptible to BRSV with similar lesions
- Deer/antelope: Often serologically positive to BRSV
- Mice: pneumonia virus of mice (PMV); Sendai (respirovirus) viral pneumonia
- Human RSV can cause respiratory disease in calves, but there is no evidence that BRSV causes disease in humans
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