Lungs Inflammatory - Pathology

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For an overview of respiratory infections see Respiratory system - inflammation

Pneumonia - Introduction and Classification

Acute fibrinous pneumonia (Image sourced from Bristol Biomed Image Archive with permission)

• Pneumonia
  • Inflammation that takes place in the alveoli and their walls
  • Can be grouped either according to
    • Nature of the inflammatory process
    • Aetiological agent
    • Pattern of the lesion

• Patterns of lung inflammation vary depending on the aetiology, route and method of exposure and multiple host factors including age, general health, and immune status
  • There are five general patterns of pneumonia:
    • Bronchopneumonia
    • Bronchointerstitial pneumonia
    • Lobar pneumonia
    • Interstitial pneumonia
    • Embolic pneumonia

Bronchopneumonia

Chronic bronchopneumonia (Image sourced from Bristol Biomed Image Archive with permission)

• Originates and extends from terminal bronchioles
• Acute inflammatory exudate initially fills alveolar spaces radiating from the bronchioles causing areas of solidification of lung tissue termed consolidation
• In bronchopneumonia this consolidation is oriented around terminal bronchioles
• Most commonly occurs in cranioventral lung lobes and correlates with aerogenous portal of entry and gravitation of infectious droplets
• Most common form of pneumonia seen in domestic animals and the most common causes are bacterial and mycoplasma infections or aspiration
• Gross pathology:
  • Affected parts are firmer (consolidated) than surrounding non-affected tissue
  • Colour varies from red to pink to grey depending upon the stage of infection
  • Extent of the lesion varies with the aetiological agent and the lobulation/septation of the species
• Micro pathology:
  • Early cases centred upon the bronchiolar alveolar junction with exudation, which extends into neighbouring alveoli
  • Exudate contains many neutrophils, macrophages and oedema
  • Alveolar capillaries are hyperaemic
  • Some haemorrhages in severe cases - later stages contain more cells than fluid
• Spread of the inflammation within the lung is usually by extension from lobule to lobule along the airways, or by necrosis of alveoli and septa in the case of toxin-producing bacteria
• Sequel to bronchopneumonia:
  • Mild catarrhal inflammation resolves in 7 days and the lung is back to normal within 3 weeks
  • More severe inflammation becomes chronic with fibrosis or bronchiectasis
  • Abscess formation with pyogenic bacteria
  • Pleuritis in severe fibrinous pneumonia with adhesions
  • Death in fulminating cases due to hypoxaemia and toxaemia

• Suppurative bronchopneumonia
  • Purulent or mucopurulent exudate in airways
  • Generally confined to individual nodules, more obvious in species with prominent lobulation
  • Sometimes referred to as lobular pneumonia
  • Lung colour changes from red to grey to white with time
  • Good exapmle are enzootic pneumonias of cattle, sheep and pigs
• Fibrinous pneumonia
  • Predominantly fibrous exudate
  • Exudate moves through pulmonary tissue to involve whole lung lobe
  • Sometimes referred to as lobar pneumonia (below)
  • Generally more severe than suppurative pneumonias
  • Externally - severe congestion and haemorrhage, intense red colour with fibrinous plaques
  • May develop into sequestra of necrotic tissue encapsulated by connective tissue
  • Microscopically - massive exudation of plasma proteins into bronchioles and alveoli
  • Rarely resolves completely, leaves scars - pulmonary fibrosis and pleural adhesions

Bronchointerstitial pneumonia

• May be considred as a variation of bronchopneumonia
• A hybrid of bronchopneumonia and interstitial pneumonia in which the interstitial inflammation (inflammation of alveolar walls) is restricted to alveoli in the vicinity of terminal bronchioles from which the infections spread
• Like broncho-pneumonia it is most common in cranioventral lobes
• Inhaled mycoplasmas and some viruses
• Initial inflammatory reaction occurring in the bronchioles, but its main expression being an interstitial lymphocytic proliferation, often to the extent of forming complete lymphoid follicles around the airways - a cell-mediated response to chronic persistent antigenic challenge

Lobar pneumonia

• May be considred as a variation of bronchopneumonia and can be described as an aggressive fulminating bronchopneumonia
• Entire lung lobes or major parts of lung lobes are uniformly consolidated
• The consolidation is not obviously oriented around terminal bronchioles
• Although it can and often is caused by infectious agents that reach alveoli by descending through terminal bronchioles, the rapid spread of the agent throughout the lung parenchyma obliterates any bronchiolar orientation
• A good example is lobar pneumonia observed following Pasteurella (Mannheimia) haemolytica infection in cattle
• These lesions are often extensions of bronchopneumonia therefore again tend to have a cranioventral distribution
• Seen in aspiration of foreign fluids or gastric contents
• In dogs and cats, this is the common appearance of pneumonia because of the lack of complete lobulation and septation
• Gross pathology:
  • Affected area dark red and there may be pleural exudation
  • Haemorrhages and perhaps tissue necrosis
• Micro pathology:
  • Necrotic foci involving all tissue within affected area, with a surrounding rim of leukocytes (often undergoing necrosis), inside of which bacterial colonies may be seen
  • Gut contents in aspiration
• Sequel: commonly death, in survival fibrosis of the affected areas, pleuritis

Interstitial pneumonia

Interstitial pneumonia (Image sourced from Bristol Biomed Image Archive with permission)

• Lung inflammation that occurs primarily in alveolar walls rather than in alveolar spaces
• Can be widely distributed but is often most severe in caudal lung lobes
• Diffuse or patchy damage to alveolar septa, may be acute or chronic
• Lesions in most cases result from blood-borne insult and are more likely to involve the dorsocaudal regions, although the damage is often diffuse
• No concentrated inflammatory response in the airway, only secondary to damage of alveolar walls
• As part of systemic infection
  • Canine distemper (in alveolar macrophages as inclusions)
  • Salmonellosis
  • Toxoplasmosis (in alveolar wall)

• Acute interstitial pneumonia is characterised by exudation into the alveolar lumen and in cattle is associated with interstitial emphysema

Examples:

Acute bovine pulmonary emphysema and oedema (ABPEE)

Fog fever (Image sourced from Bristol Biomed Image Archive with permission)

Fog fever (Image sourced from Bristol Biomed Image Archive with permission)

Tracheal haemorrhages in fog fever (Image sourced from Bristol Biomed Image Archive with permission)

• Synonym: fog fever
• Usually seen in adult beef cattle in the autumn as an outbreak
• Associated with a change in pasture (from dry to lush, green)
• Severe respiratory distress with laboured breathing and grunting on expiration
• Can result in diffuse fibrosing alveolitis
• Gross appearance is that of enlarged wet lungs, the interlobular septa are markedly widenedith oedema and emphysema
• Underlying pathogenesis is ingestion of L-tryptophan in the pasture which is metabolised to 3-methylindole -> bloodstream -> lungs -> metabolised into a compound toxic to Type 1 pneumonocytes and non-ciliated bronchiolar epithelium
• Their loss allows massive flooding of the alveoli with a protein-rich fluid
• The sequence of events in the lung is as follows:
  • Alveolar flooding with a protein-rich fluid due to the necrosis of Type 1 epithelium
  • As the incoming air dries this fluid, fibrinous 'hyaline membranes' form
  • Proliferation of the more resistant cuboidal Type 2 epithelium which line the alveoli, called 'epithelialisation'
  • Then either there is
    • Digestion of the hyaline membranes by macrophages which when completed, allows some of the proliferated Type 2 epithelium to differentiate into Type 1 and reconstitute the functional respiratory unit - a normal alveolus
  • Or
    • Organisation of the fibrin into fibrous tissue in the lumen - destroying the alveolus or proliferation of fibrous tissue in the alveolar wall with retention of the epithelialised appearance to the alveolus
• Sequel
  • Residual scarring if animal survives initial onslaught
  • In chronic exposures there may be extensive fibroplasia

• Ingestion of sweet potatoes ifested with Fusarium solani mould or pasture contaminated with stinkweed or purple mint, rapeseed and kale also cause pulmonary oedema, emphysema and interstitial pneumonia

Paraquat poisoning (Image sourced from Bristol Biomed Image Archive with permission)

Paraquat poisoning

• In dogs and cats
• Free radical release causes damage to air-blood barrier
• Depending on the dose, the lesions range from acute lesions (oedema, haemorrhage, hyaline membranes) -> chronic (fibroplasia of alveolar septae, replacement of alveolar cells with type II cells)
• Additional extrapulmonary lesions to note following paraquat intoxication are necrosis of the adrenal zona glomerulosa and renal tubular epithelium

Diffuse alveolitis

Diffuse fibrosing alveolitis (Image sourced from Bristol Biomed Image Archive with permission)

• Chronic disease of adult cattle occuring sporadically
• Probably caused by repeated subclinical incidents of fog fever or farmer's lung
• Farmer's Lung
  • Extrinsic allergic alveolitis
  • Hypersensitivity of ingested or inhaled moulds
  • May occur as an outbreak or sporadically in adult cattle

• Hypersensitivity diseases often cause an lymphocytic interstitial pneumonia

• Chronic interstitial pneumonia progresses to fibrosis
  • Sometimes called pneumonitis

Embolic pneumonia

• Lung inflammation caused by haematogenous spread of infections into the lung
• No orientation around airways and can be in any lung region but most often affects caudal lobes
• The inflammation is oriented around blood vessels, usually venules or alveolar capillaries in which septic emboli localise

Granulomatous pneumonia

Granulomatous mycotic pneumonia (Image sourced from Bristol Biomed Image Archive with permission)

• Variable number and distribution of caseous or non-caseous granulomas throughout the lung
• Must be distinguished from neoplasms
• Calcification may occur
• Caused by agents resistant to phagocytosis, mostly fungi, Mycobacterium bovis, Rhodococcus equi, foreign material, FIP
• Micro: centre of necrotic tissue surrounded by macrophages, connective tissue and lymphocytes

Verminous pneumonia

Parasitic pneumonia (Image sourced from Bristol Biomed Image Archive with permission)

• Lesions in the lung may be due to:
  • Parasites passing through the lung as part of their migration e.g. Ascaris suum in the pig, aberrant migration in the case of flukes;
  • Parasites for which the lung is the target tissue e.g. Dictyocaulus viviparus
• Lesions can vary from interstitial to chronic bronchitis to granulomatous pneumonia
• May be infiltrate of eosinophils in pulmonary interstitium and bronchoalveolar spaces
• Atelectasis and emphysema may result due to obstruction

Stages of pneumonia

Acute exudative pneumonia (Image sourced from Bristol Biomed Image Archive with permission)

Acute exudative pneumonia (Image sourced from Bristol Biomed Image Archive with permission)

• Regardless of the pattern, all pneumonias pass through three stages:
  • Exudative phase
    • In this initial stage inflammatory exudate pours into alveolar spaces and alveolar capillaries are congested
    • Type I alveolar epithelial cells are highly sensitive to injury and cannot proliferate in response to injury
    • Necrosis and sloughing of injured type I cells, denuding alveolar spaces of lining epithelium
    • Neutrophils begin to enter alveolar spaces distended with inflammatory oedema
  • Proliferative phase
    • Type II alveolar cells (less sensitive to and can proliferate in response to injury) begin to proliferate within 24 hours and eventually line the alveolar walls denuded of type I cells ***By 6 days cuboidal type II cells can completely line the alveoli
    • Proliferation of type II cells marks the shift from the exudative to the proliferative stage of pneumonia, also heralded by decreased blood flow in alveolar capillaries
    • Because the original squamous type I cells have been replaced by cuboidal type II cells, the microscopic appearance of pneumonic lungs at about 1 week has been described as “alveolar epithelialization”, “alveolar adenomatosis”, or “bronchiolisation of alveoli”
  • Repair phase
    • Resolution of pneumonia is accomplished by transformation of type II cells to type I cells

Pulmonary abscesses

Multiple pulmonary abscesses (Image sourced from Bristol Biomed Image Archive with permission)

• Commonly found post mortem
• Can be a consequence of:

1. Septic emboli lodging in the pulmonary vessels
2. Extension from severe focal suppurative bronchopneumonia
3. Aspiration of foreign material (see aspiration pneumonia)
4. Direct penetration

• The pattern of abscessation can suggest the aetiology i.e. multiple widespread abscesses suggest a haematogenous origin; isolated cranioventral abscesses usually arise from suppurative pneumonia.

Infectious causes of pneumonia

.	VIRAL	BACTERIAL	FUNGAL	PARASITIC
Dogs	Canine distemper	usually secondary	Blastomyces dermatitidis	Angiostrongylus vasorum
.	Infectious canine tracheitis	bronchopneumonia: Bordetella bronchiseptica, Staphylococci, Streptococci, Coliforms	Histoplasma capsulatum	Toxoplasma gondii
.	Herpes virus	.	.	.
Cats	Feline calicivirus	bronchopneumonia: Pasteurella sp., Streptococcus spp.	.	Aelurostrongylus abstrusus
.	.	Feline chlamydiosis	.	.
Horses	Equine rhinopneumonitis	Strangles	Pneumocystis carinii	Parascaris equorum
.	Equine influenza	Glanders	.	.
.	Equine viral arteritis	Rhodococcus equi	.	.
Cattle	Parainfluenza- 3	Necrotic Laryngitis	.	Dictyocaulus viviparus
.	.	Pneumonic pasteurellosis	.	.
.	.	Contagious bovine pleuropneumonia	.	.
.	.	Enzootic pneumonia of calves	.	.
.	.	Acute exudative pneumonia	.	.
.	.	Mycoplasmal pneumonia	.	.
.	.	Mycobacterium bovis - tuberculosis	.	.
.	.	bronchopneumonia: Pasteurella sp., Corynebacterium pyogenes	.	.
Sheep	Maedi Visna	bronchopneumonia: Corynebacterium pyogenes	.	Muellerius capillaris
.	Parainfluenza- 3	Enzootic pneumonia of lambs	.	.
.	Sheep Pulmonary Adenomatosis	Pseudomonas (Malleomyces) pseudomallei	.	.
Pigs	Inclusion body rhinitis	Enzootic pneumonia of pigs	.	Ascaris suum
.	Swine influenza	Actinobacillus pleuropneumoniae	.	.
.	Porcine reproductive and respiratory syndrome	Necrotic Laryngitis	.	.
.	Postweaning multisystemic wasting syndrome	Pasteurella multocida	.	.
.	Porcine respiratory coronavirus	Contagious porcine pleuropneumonia	.	.
.	.	Glasser's disease	.	.
.	.	Bordetella bronchiseptica	.	.
.	.	bronchopneumonia: Pasteurella spp., Corynebacterium pyogenes, also Streptococcus spp., Tuberculosis	.	.

Other forms of pneumonia

Aspiration pneumonia

Acute necrotising pneumonia (Image sourced from Bristol Biomed Image Archive with permission)

Aspiration pneumonia (Image sourced from Bristol Biomed Image Archive with permission)

• Response of the lungs to aspirated foreign material will depend on the nature of the material (e.g. food), the bacterial load and the distribution of the material within the lungs
• Mild bronchopneumonia can develop into a severe necrotising pneumonia and in very severe cases can progress to gangrenous pneumonia (below)
• In Cattle
  • Associated with poor husbandry
  • Regurgitated ruminal content
  • Cranio-ventral distribution
  • Respiratory insufficiency secondary to congenital cardiac disease
• In Horses
  • Most commonly in right ventral lung lobe (most rostral secondary bronchus leads to right accessory lobe)
  • Risk factors:
    • Oesophageal obstruction
    • Spontaneous reflux (GI obstruction, equine grass sickness)
    • Dysphagia
    • Iatrogenic
      • Nasogastric tube in the wrong place
• In Dogs
  • Most commonly vomited/regurgitated material or contrast medium introduced into airways
  • In severe acute cases may die from septic shock
  • In chronic cases -> bronchopneumonia
  • Common sequel to myasthenia gravis, megaoesophagus or persistent right aortic arch

Gangrenous pneumonia

Gangrenous pneumonia (Image sourced from Bristol Biomed Image Archive with permission)

• Can occur following severe infections in which tissue becomes necrotic and is then invaded by putrefactive saprophytes, however this is rare.
• The usual cause is administration of medicines (intended for the oesophagus!) or as a sequel to aspiration pneumonia
• The dead tissue undergoes liquefactive necrosis forming a cavity which is surrounded by intense hyperaemia and inflammation

Lipid pneumonia

Lipid pneumonia (Image sourced from Bristol Biomed Image Archive with permission)

• Associated with inhalation of oil, paraffin, etc.
• Reaction dominated by macrophages which fill the alveoli and interstitial thickening (mononuclear cells and fibrosis)
• Tends to acumulate in ventral regions bilterally
• Occurs subclinically in cats, sometimes dogs, unrelated to aspiration
• Gross lesion:
  • Multifocal, firm, white nodules
• Microscopic lesions:
  • Macrophages full of lipid forming foam within alveoli
  • Interstitial lymphocyte and plasma cell infiltration, fibrosis

Uraemic pneumonia

• Severe uraemia causes increased permeability of the blood-air barrier and therefore can cause pulmonary oedema
• In addition to the oedema, there may also be degeneration and calcification of smooth muscle and connective tissue fibres
• Lungs do not collapse on opening the thorax in severe cases

Fetal pneumonia

• Especially foals and farm species
• Due to aspiration of amniotic fluid contaminated with meconium and bacteria
  • Secondary to fetal distress
  • Microscopic lesions of bronchopneumonia
  • Involves all lobes (versus postnatal bronchopneumonia)
• Haematogenous spread
  • Causes interstitial pneumonia
  • Often caused by Listeria monocytogenes, Salmonella spp. or Chlamydia psittaci
• In viral abortions
  • Cause bronchointerstitial pneumonia
  • E.g.: IBR, PI-3 and equine viral rhinopneumonitis