JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

August 2023

P-B01

 

Signalment (JPC #2317878): Laboratory rat

 

HISTORY: Unknown history

 

HISTOPATHOLOGIC DESCRIPTION: Lungs: Affecting approximately 90% of one lung lobe are multifocal to coalescing nodules of inflammation composed of numerous lymphocytes, plasma cells, macrophages, and fewer neutrophils admixed with scattered fibrin, hemorrhage, and edema that surround bronchi, bronchioles, and associated blood vessels and efface or compress the adjacent alveolar architecture. Respiratory epithelium in bronchioles and bronchi often demonstrates one of the following changes: 1) disorganized and hyperplastic, piling up to seven cell layers thick, 2) ulcerated and replaced with previously described inflammatory cells, or 3) degenerative with loss of cilia and cytoplasmic vacuolation. There is moderate goblet cell hyperplasia. Multifocally, bronchi and bronchioles are expanded up to 4mm with a neutrophilic exudate (bronchiectasis and bronchiolectasis). Bronchiolar associated lymphoid tissue (BALT) in both lung lobes is diffusely markedly hyperplastic characterized by pale germinal centers and increased tingible body macrophages. Adjacent, less affected lung parenchyma is variably atelectic and there are rare foci of alveolar emphysema.  

 

Esophagus: No significant findings.

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, bronchointerstitial, lymphohistiocytic, subacute, diffuse, severe, with marked bronchiectasis and bronchiolectasis, and bronchiolar-associated lymphoid hyperplasia, rat, rodent.

 

ETIOLOGIC DIAGNOSIS: Mycoplasmal pneumonia

 

CAUSE: Mycoplasma pulmonis

 

CONDITION: Murine respiratory mycoplasmosis (MRM)

 

GENERAL DISCUSSION: 

• M. pulmonis, regarded as the only clinically significant Mycoplasma sp. in rodents and has an affinity for the ciliated epithelial cells of the respiratory tract, middle ear, endometrium, and synovium
• M. pulmonis is a Gram-negative bacterium (however they lack a cell wall) of the order Mycoplasmatales 
• Coinfection with other infectious entities is common, including Sendai virus, rat coronavirus, Filobacterium rodentium (formerly “CAR bacillus”), Streptococcus pneumoniae, Corynebacterium kutscheri, Bordetella bronchiseptica, Klebsiella pneumoniae, and Pasteurella pneumotropica, as part of the chronic respiratory disease (CRD) syndrome

 

PATHOGENESIS:

• Modes of transmission: Aerosolization (inefficient), venerally, direct contact, and transplacental (rats)
• Incidence and severity of the disease affected by:

• Strain: LEW develop more severe disease than F344
• Sex: Females develop more severe disease 
• Co-infections (e.g. Sendai virus, Pasturella pneumotropica)
• Ammonia levels: High levels can increase progression of disease

• Inhalation > extension to the lungs (may take as long as six months) > colonization of apical cell membrane of respiratory epithelium, adhering to the ciliated epithelium > interference with mucociliary clearance (ciliostasis) > increased susceptibility to respiratory pathogens > concurrent infections
• Chronic neutrophil chemotaxis in major airways > lysozyme-rich exudates > weakening of bronchiolar walls and distention of airways > bronchiectasis, bronchiolectasis, blockage of airways with exudate > atelectasis
• Mitogenic for B-cells and acts a superantigen, resulting in severe bronchiole associated lymphoid tissue (BALT) hyperplasia 
• Invasion of the middle ear through the Eustachian tube results in chronic otitis media
• Ciliostasis caused by inflammation or by some pathogenic organisms 

 

TYPICAL CLINICAL FINDINGS:

•   Minimal to florid respiratory distress, sniffling, torticollis, infertility, and arthritis
•   Increased respiratory sounds; mucopurulent/porphyrin-containing oculonasal discharge
•   Dyspnea, weight loss, rough hair coat, hunched posture, infertility, vestibular signs

 

TYPICAL GROSS FINDINGS:

• Upper respiratory tract: Catarrhal to mucopurulent exudate in nasal passages, trachea, and tympanic cavities 
•    Lower respiratory tract: Asymmetric cranioventral distribution; mucopurulent exudate within the trachea, bronchi, and bronchioles; elevated often linear foci representing dilated bronchioles containing suppurative exudates; abscessation; and purple/gray (“gray lung”) depressed areas of atelectasis, bronchiolectasis 
•    Enlargement of regional lymph nodes 
•    Uterine horns, ovarian bursa, and oviducts may contain purulent exudate
•    Swelling of tibiotarsus (synovial infection)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Upper respiratory tract:

• Suppurative rhinitis, otitis media and/or middle ear fibrosis, laryngitis, and tracheitis
• Lymphoid hyperplasia
• Respiratory epithelium: Loss and flattening of cilia, epithelial hypertrophy, squamous metaplasia, goblet cell hyperplasia

•    Lower respiratory tract:

• Bronchopneumonia characterized by bronchial and bronchiolar neutrophilic exudate that can progress to bronchiectasis and bronchiolectasis with attenuated epithelium, bronchial/bronchiolar rupture, and abscessation
• Respiratory epithelial hyperplasia and hypertrophy
• Peribronchial, peribronchiolar, and perivascular lymphocyte and plasma cell infiltration and severe BALT hyperplasia is a prominent feature in CRD in rats 

•   Genital tract:

• Endometritis, salpingitis, perioophoritis

 

ULTRASTRUCTURAL FINDINGS:

• M. pulmonis colonizes the surface of ciliated and non-ciliated respiratory epithelial cells; M. pulmonis lacks a cell wall
• Minimal cellular damage except for the distortion and/or loss of cilia and excessive lengthening of microvilli

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:

•   Filobacterium rodentium (P-B16, formerly “Cilia-associated respiratory (CAR) bacillus”) (Gram-negative): Very similar to mycoplasmosis (cannot differentiate histologically); causes bronchiectasis, bronchiolectasis, abscessation, atelectasis, and BALT hyperplasia; also rhinitis, otitis, and tracheitis; Warthin-Starry stain to identify filamentous argyrophilic bacilli; cilia usually still present
•   Corynebacterium kutscheri (P-B05, Gram-positive): Multifocal suppurative pneumonia, often with large areas of abscessation 
•   Streptococcus pneumoniae (P-B07, Gram-positive)  Fibrinopurulent bronchopneumonia, pleuritis, and pericarditis
•   Sendai virus (P-V05, Paramyxovirus, Parainfluenza 1): Usually subclinical; bronchitis, bronchiolitis, and alveolitis with epithelial necrosis  
• Lymphoma: M. pulmonis can induce immature/proliferating lymphocytes in the BALT

 

COMPARATIVE PATHOLOGY:

•   Mice: 

• M. pulmonis: Respiratory and (experimentally induced) genital tract disease; often subclinical; if there are signs, they may include weight loss, dyspnea, “chattering,” otitis resulting in head tilt, circling, or vestibular signs; disease susceptibility depends on strain/isolate of M. pulmonis and strain of mouse; C57BR, B6 and B10 are relatively resistant; microscopic findings: respiratory epithelium squamous metaplasia, epithelial syncytia in nasal epithelium, suppurative rhinitis and pneumonia, and peribronchial lymphoid hyperplasia; however, mice do NOT develop intense BALT hyperplasia or severe bronchiolectasis like in rats; Immunodeficient mice have less severe respiratory disease, but disease is often disseminated with severe polyarthritis, splenitis, pericarditis

• M. neurolyticum: Neurological signs from exotoxin after intercerebral inoculation (“rolling disease”); conjunctivitis in young mice
• M. arthritidis: Polyarthritis in mice and rats with intranasal inoculation, natural disease not reported

•   Ruminants:

• M. mycoides subsp. mycoides small colony type (P-B02): Contagious bovine pleuropneumonia; gross lesions are unilateral and restricted to caudal lobes, characteristic marbled appearance with sequestra and pleural fibrosis; fibrinous bronchopneumonia 
• Mycoplasma capricolum ssp. capripneumoniae: Cause of contagious caprine pleuropneumonia
• M. bovis: Distinctive caseonecrotic bronchopneumonia, otitis media, and arthritis in calves; chronic pneumonia and polyarthritis in feedlot cattle; severe mastitis
• M. agalactiae:  Contagious agalactia in goats and sheep
• M. ovipneumoniae: Associated with ovine enzootic pneumonia
• M. capricolum: Arthritis, mastitis, pneumonia, septicemia in goats
• M. mycoides spp mycoides large colony: Pleuropneumonia, polyarthritis, and septicemia in goat kids and, to a lesser extent, labs

•   Swine:

• M. hyopneumoniae (P-B03): Enzootic pneumonia of swine; grower-finisher pigs; characteristic gross feature is red-tan-gray discoloration, collapse, and rubbery (thymus-like) lobular pattern in cranioventral region
• M. hyorhinis: Polyarthritis and polyserositis 
• M. hyosynoviae: Polyarthritis, but not polyserositis

• Other species: 

• Avian:

•  M. gallisepticum: Chronic respiratory disease in turkeys and chickens, classic triad is air sacculitis, fibrinous perihepatitis, and adhesive pericarditis; infraorbital sinusitis in turkeys; conjunctivitis in finches 
• M. synoviae: Synovitis, sternal bursitis, air sacculitis, and sinusitis in chickens and turkeys
• M. meleagridis: Turkeys; air sacculitis, decreased egg hatchability

• Cats: M. felis and others: Opportunistic pathogen of the conjunctiva of cats, not important as a primary respiratory pathogen
• Dogs: M. cynos: Most pathogenic in dogs, may be part of canine infectious respiratory disease (CIRD) complex; other mycoplasmas are minimally pathogenic
• NHP: M. pneumoniae is a cause of pneumonia    

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH, eds. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley-Blackwell; 2016:63-65, 134-136, 186, 228. 
2. Boulianne M, ed. Avian Disease Manual. 8th ed. Jacksonville, FL: American Association of Avian Pathologists, Inc; 2019:90-97.
3. Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016: 533-535, 551-554, 563-564, 579, 590.
4. Delaney MA, Treuting PM, Rothenburger JL.   Rodentia. In: Terio KA, McAloose D, St Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Academic Press; 2018:510.
5. Lopez A, Martinson SA. Respiratory system, thoracic cavities, mediastinum, and pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 558-559, 562, 581, 588, 612-615. 
6. Lowenstine LJ, Osborn KG. Respiratory system diseases of nonhuman primates. In: Abee CR, Mansfield K, Tardif S, eds. Nonhuman Primates in Biomedical Research. Vol 2. 2^nd Ed. San Diego, CA: Academic Press;2012:457-458. 
7. Schmidt RE, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2^nd ed. Ames, IA: John Wiley and Sons, Inc; 2015:38, 267. 

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