JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

August 2023

P-B02

 

Signalment (JPC #1879041): Cow

 

HISTORY: This cow was one of many from a herd with respiratory distress.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Interlobular septa are diffusely expanded up to 20 times normal by abundant eosinophilic beaded fibrillar material (fibrin), clear space (edema), eosinophilic cellular and basophilic karyorrhectic debris (necrosis), large numbers of degenerate and fewer viable neutrophils, and fewer macrophages. Interlobular septa, blood vessels, and bronchioles are diffusely surrounded by abundant lymphocytes and plasma cells (lymphoid hyperplasia). Adjacent alveolar lumina are filled with eosinophilic homogenous material (edema fluid), fibrin, viable and degenerate neutrophils, lymphocytes, plasma cells, macrophages, and abundant necrotic debris. Multifocally, alveolar septa are either discontinuous and replaced by fibrin and necrotic debris (septal necrosis) or are expanded by lymphocytes, histiocytes, and edema. Occasionally, blood vessel walls are variably expanded or replaced by abundant necrotic debris, fibrin, and previously described inflammatory cells (necrotizing vasculitis). Multifocally, few contiguous and coalescent alveolar lumina are expanded by clear space (emphysema). Bronchial and bronchiolar lumina are multifocally filled with an exudate composed of edema, fibrin, neutrophils, lymphocytes, and histiocytes.  

 

MORPHOLOGIC DIAGNOSIS: Lung: Pleuropneumonia, fibrinosuppurative and necrotizing, chronic-active, diffuse, severe, with marked interlobular, alveolar, and interstitial edema, lymphoid hyperplasia, and necrotizing vasculitis, breed unspecified, bovine.

 

ETIOLOGIC DIAGNOSIS: Mycoplasmal pneumonia

 

CAUSE: Mycoplasma mycoides subsp. mycoides (small colony type) (MmmSC)

 

CONDITION: Contagious bovine pleuropneumonia (CBPP)

 

GENERAL DISCUSSION: 

• Mycoplasma spp.: A “mollicute”, the smallest self-replicating organisms; Gram-negative; lack a true cell wall; nonmotile; obligate parasites
• Mycoplasma mycoides subsp. mycoides (small colony type)

• One of the most pathogenic mycoplasma species
• OIE-notifiable disease; eradicated from North America and Australia; endemic in parts of Africa, Asia, eastern Europe
• Affects domestic cattle; also reported in bison, yak, and domestic buffalo
• Sporadic disease is more common in endemic countries practicing vaccination
• Different from M. mycoides subsp. mycoides (large colony type) (now reclassified as M. mycoides subsp. capri)

 

PATHOGENESIS:

• Pathogenic mechanisms are poorly understood; pathogenicity seems to be determined by intrinsic metabolic or catabolic pathway functions (i.e. production of H2O2), or by the mycoplasmal outer surface (contains capsular polysaccharide galactin, bacterial membrane protein LppQ)
• Infected aerosolized droplets (respiratory or urine) > inhalation > colonization of bronchioles/alveoli > attaches to ciliated epithelium via surface neuraminic acid receptors > immobilization of cilia
• Galactin (capsular polysaccharide) has direct cytopathic effect allowing for invasion of blood and lymphatic vessels > targets endothelial cells > vasculitis, contraction of blood vessels, thrombosis > necrosis, sequestration, pulmonary edema
• Superantigen: Mycoplasmas adhere intimately to lymphocytes > lymphoplasmacytic proliferation, inactivation, immunosuppression
• Massive inflammatory reaction in the lungs is principal cause of pathology; likely due to inappropriate activation of alveolar macrophages, excessive TNF-α production, excessive neutrophil recruitment with subsequent release of inflammatory mediators
• Chronic carrier state may develop due to harboring of live organisms in sequestered areas of necrotic tissue in the lung
• Transplacental infection possible

 

TYPICAL CLINICAL FINDINGS:

• Variable morbidity and high mortality rates; higher in naïve herds, adult animals, or in presence of other disease and/or stressors
• Incubation often takes 3 weeks – 6 months; can be more rapid
• Acutely affected animals have fever, anorexia, mucoid nasal discharge, cough, dyspnea, decreased milk production
• Hyperacutely affected animals may have sudden death
• Chronically infected animals may be subclinical or intermittent fever, coughing, cachexia
• Calves less than six months old often develop polyarthritis (carpus and tarsus)
• Pregnant cows may abort  

 

TYPICAL GROSS FINDINGS:

• Lesions are usually unilateral, often restricted to the caudal lung lobes, with extensive fibrin deposition and abundant straw-colored odorless fluid in the thoracic cavity, especially in acute cases 
• The lung parenchyma does not collapse, and the cut surface is marbled with prominent interlobular septa
• Sequestra may be present, especially in chronic cases: masses of necrotic lung parenchyma separated from viable lung tissue by purulent exudate, usually encased in a fibrous capsule
• Fibrinonecrotic pneumonia with severe serofibrinous pleuritis and pleural adhesions

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Serofibrinous or suppurative exudate in bronchioles, alveoli
• Areas of coagulative necrosis
• Fibrin thrombi, vasculitis, infarction, non-suppurative arteritis, thrombosis of pulmonary arteries, veins, and lymphatics
• Lymphoid hyperplasia
• Marked thickening of interlobular septa by fibrin, edema, and inflammation; fibrinous pleural effusion, fibrinous pleuritis, pericarditis, peritonitis, polysynovitis; multiple renal cortical infarctions

 

ULTRASTRUCTURAL FINDINGS:

• Mycoplasmas are pleomorphic bacteria that lack cell walls, membrane bound organelles, fimbria, and flagella
• Large numbers of mycoplasma attach to and destroy cilia
• Cilia are distorted, broken, and lost with basal body degeneration
• Ballooning and blebbing of epithelial cell plasma membranes is typical

 

ADDITIONAL DIAGNOSTIC TESTS: 

• Culture of organism on specialized media
• Immunohistochemistry and PCR for rapid diagnosis
• Mmm antigen can be detected in bronchiolar/alveolar epithelial cells, lung phagocytic cells, in walls of blood vessels/lymphatics, tertiary lymphoid follicles, lymph nodes, glomerular endothelial cells, renal tubules (Teodoro, Vet Pathol 2020)

 

DIFFERENTIAL DIAGNOSIS:

• Bacterial bronchopneumonia: common and economically important disease of cattle; caused by gram-negative bacteria in the Pasteurellaceae family:

• Mannheimia haemolytica (P-B12):  Most important respiratory pathogen in cattle, rapid spread, lungs typically bilaterally affected; leukotoxin induces lysis of ruminant leukocytes and platelets; vasculitis is less prominent than CBPP 
• Histophilus somni (N-B03):  Suppurative and fibrinous bronchopneumonia; coagulative necrosis with streaming necrotic leukocytes
• Pasteurella multocida: Capsular serotype A:3 is the most commonly isolated from cases of pneumonia; less-well studied in cattle pneumonia than M. haemolytica and H. somni

• Mycoplasma bovis:  
  • MmmSC and M. bovis result in similar gross pulmonary lesions
    • M. bovis causes caseonecrotic bronchopneumonia with multiple well-delineated necrotic foci filled with caseous material, linear necrotic lesions in interlobular septa, extensive fibrosis, necrotic sequestra, and acute fibrinous to chronic fibrosing pleuritis
    • M. bovis does not cause the extensive fibrinous exudates in interlobular septa and pleural surfaces as with MmmSC  
      • M. bovis induces apoptosis of bovine lymphocytes, suppresses the proliferative response of lymphocytes to mitogens, and impairs neutrophil activation
    • Ears: Predominant pathogen isolated from the middle ear of calves with otitis media; causes suppurative to caseous exudate and often extensive osteolysis 
    • Mammary glands: An important cause of infectious mastitis in cows; highly transmissible; mild to severe fibrinosuppurative to caseonecrotic inflammation  
    • Joints: Arthritis and tenosynovitis characterized by fibrinous to caseous exudate accompanied by fibrosis; periarticular involvement foci of caseous necrosis, linear necrotic lesions and extensive fibrosis; pneumonia is found in nearly all calves with M. bovis arthritis
    • Other: Subcutaneous decubital abscesses, meningitis (complication of otitis media-interna), cardiac disease (isolated reports of myocarditis and endocarditis)   
    • M. bovis causes particularly severe disease in farmed bison, with high morbidity and mortality
    • AIP is caused by ingestion of plants containing L-tryptophan or other pneumotoxins that are converted to 3-methylindole  
    • Histologic lesions include alveolar and interstitial edema and emphysema with formation of hyaline membranes

 

COMPARATIVE PATHOLOGY:

Mycoplasma spp. in other species:

• Goats: Three mycoplasmas are associated with respiratory infections in goats:
  • M. mycoides ssp. capri (Mmc): 
    • Ubiquitous pathogen in small ruminants causing mastitis, arthritis, keratitis, pneumonia and septicemia and also found as a saprophyte in the ear canal
    • The designation M. mycoides ssp. mycoides large colony type has been discarded and bacteria of this type are now considered a serovar of Mmc
    • Recent report of Mmc causing arthritis, pleuropneumonia, and meningitis in dairy goat kids demonstrated that general mycoplasma PCR fails to detect Mmc (Johnson, J Vet Diagn Invest 2019)
  • M. capricolum ssp. capripneumoniae 
    • Considered the only etiologic agent of typical contagious caprine pleuropneumonia (CCPP)
    • Gross lesions are similar to those of bovine disease 
    • Histologically: Severe fibrinous pleuropneumonia, but distention of the interlobular septa and formation of pulmonary sequestra less obvious than in bovine disease
    • Also affects nondomestic caprids (ibex), gazelles, Tibetan antelope, etc…
  • M. capricolum capricolum: Fibrinopurulent polyarthritis in kids
• Sheep: M. ovipneumoniae isolated with P. multocida in enzootic ovine pneumonia
• Swine:  
  • M. hyopneumoniae (P-B03): Enzootic pneumonia
  • M. hyorhinis: Arthritis and polyserositis
• Deer: M. bovis: Pneumonia 
• Bison: M. bovis: Pneumonia, polyarthritis, fibrinosuppurative pleuritis, and disseminated microabscesses 
• Chickens and turkeys:  
  • M. synoviae: Tenosynovitis, arthritis, and sinusitis
  • M. gallisepticum: Sinusitis
• Rats and mice:   
  • M. pulmonis (P-B01): Pneumonia 
  • M. arthritidis: Arthritis
• Humans: M. pneumonia: Primary atypical pneumonia

 

References:

1. 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, 542-546, 551-554, 563-564, 579, 590.
2. Di Teodoro G, Marruchella G, Di Provvido A, et al. Contagious Bovine Pleuropneumonia: A Comprehensive Overview. Vet Pathol. 2020; 57(4):476-489.
3. Johnson G, Fales WH, Shoemake BM, et al. An outbreak of Mycoplasma mycoides subspecies capri arthritis in young goats: a case study. J Vet Diagn Invest. 2019; 31(3): 453-457.
4. Jones MEB, Gasper DJ, Mitchell E. Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Terio KA, McAloose D, St. Leger J, Eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:134.
5. Lopez A, Martinson SA. Respiratory system. In: Zachary JF ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier Inc; 2022:612,613-614.
6. Stanton JB, Zachary JF. Mechanisms of microbial infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier Inc; 2022:.214-215.

 

 

 

 

 

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