Respiratory Pathology Flashcards
Which airways have cartilage and glands in their walls?
Bronchi
What is the functions of cartilage and thick connective tissue in bronchi?
Cartilage maintains patency/prevents collapse
Thich connective tissue prevents infection spread into surrounding alveolar parenchyma
What are the consequences of chronic inflammation in the bronchi?
Dilation, increased resistance
What cells are capable of epithelial regenerative capacity in the bronchi?
Mucous, basal and other non-ciliated cells
Which airways have no cartilage or glands in their walls?
Bronchioles
How is airway patency maintained in bronchioles?
Tethering support if interlaveolar septa on bronchiolar wall
What is the consequence of having thin connective tissue in the walls of the bronchioles?
Allows infection to spread to surrounding alveoli
What is the consequence of chronic inflammation of the bronchioles?
Stenosis of lumen
What cells are capable of epithelail regenerative capacity in the bronchioles?
Mucous cells and non-ciliated (Clara) cells
What are the functions of Clara cells in the bronchioles?
Secretory - mucociliary clearance and protection
Rich in cytochrome monooxyegenase enzymes (CYP450) - metabolizes endogenous/xenobiotics, resulting in toxin production
Although resistance of individual small bronchioles is ___,
bronchioles under normal conditions is ___.
Why?
High; low
Total of all bronchiolar cross-sectional areas is much greater than that of the bronchial airways
What is a primary lobule? What is another name for it?
Pulmonary tissue supplies by a terminal bronchiole
“Acinus”
What is a secondary lobule?
Composed of many primary lobules; constitute grossly visible lobules
What are the components of the interalveolar septa?
What is their function?
Epithelial cells (type 1 and 2), capillary endothelium, fibroblasts, macrophages
Function: allows the development of large SA for interface and gas exchange between ventilated gases and perfusing blood
Describe some characteristics of type 1 epithelial cells in the interalveolar septa, including function.
Regenerative capacity?
Squamous
Cover large surface area, barrier - susceptible to damage
Terminally differentiated, metabolically inactive
Describe some characteristics of type 2 epithelial cells in the interalveolar septa, including functions.
Regenerative capacity?
Cuboidal
Produce surfactant/other mediators and are stem cells for repair
Metabolically active, contain CYP450 activities
What is the functon of the capillary endothelium in the interalveolar septa?
Metabolically active cells responsible for metabolizing prostaglandings, angiotensin, histamine
Define bronchitis and bronchiolitis
Inflammation of the bronchi and bronchioles
What are the causes of bronchitis and bronchiolitis?
Infectious: viral, bacterial, fungal, parasitic
Toxic: plant toxins
Hypersensitivity
Functional consequences of bronchitis and bronchiolitis
Increased airway resistance - obstruction, V/Q abnormalities (hypoxemia)
Decrease mucociliary clearance - secondary bacterial infection
Are bronchitis and bronchiolitis reversible?
Yes
Bronchitis and bronchiolitis sequelae
- Resolution and epithelial repair
- Extension to alveoli = pneumonia
- Chronic localized inflammation
Bronchiectasis = bronchi
Bronchiolitis obliterans = bronchioles
- Post-obstructive atelectasis
Definition of bronchiectasis
Dilation of the bronchi beyond normal physiological limits due to destruction of the bronchial wall
Bronchiectasis pathogenesis
Chronic infection - usually bacterial
Neutrophil-mediated destruction of glands and cartilage, fibrosis
Bronchiectasis morphology (grossly)
Dilated airway (saccular or cylindrical)
Thick wall
Luminal exudate (grey, green, or tan; thick, mucoid, or caseous)
Functional significance of bronchiectasis
Increased airway resistance d/t turbulence and luminal obstruction
Poor mucuciliary clearance
Aspiration of infective material into alveoli
Bronchiectasis sequelae
Progression of inflammation - continued damage, pneumonia
(even with abx)
Is bronchiectasis reversible?
No
Definition of bronchiolitis obliterans. Clinical relevance?
Obstruction of the bronchiolar lumen by fibrous connective tissue (no cartilage, tend to collapse and fill)
Usually clinically silent unless widespread
Definition of atelectasis
Collapse of the lung
Classification of atelectasis
- Neonatal - inadequate surfactant
- Acquired - compressive or obstructive
Cause of compressive atelectasis
Fluid, air, mass compresses lung or results in loss of negative pleural pressure
Cause of obstructive atelectasis
Obstructed large airways caused by inflammatory exudate, FB, hemorrhage, intramural masses leads to hypoventilation, pulls all N out of the air, lobules collapse
What is the pathological significance of atelectasis?
Segment of lung is under-ventilated, if wide spread will cause hypoxemia
Atelectasis sequelae
- Reinflation
- Alveolar edema
- Secondary bacterial pneumonia
- Fibrosis and irreverisble collapse
Is atelectasis reversible?
Yes, if reinflated
Definition and classification of pulmonary emphysema
Enlarged gas-filled space in the lung
Can be alveolar or interstitial
Definition of alveolar emphysema
Abnormal enlargement of air spaces distal to terminal bronchioles accompanied by destruction of alveolar walls
Is alveolar emphysema reversible?
No
What is the pathological significance of alveolar emphysema?
- Decreased alveolar and capillary SA
- Loss of radial support of airways = early closure
- Decreased elastic properties, increased compliance and residual lung capacity
- Loss of capillary area = pulmonary hypertension and cor pulmonale (secondary HF)
Definiton of interstitial emphysema
Excess gas in the pulmonary interstitium, occurs in species with extensive interlobular septa (bovine)
Interstitial emphysema pathogenesis
Forced expiration against obstructed airways
Gas dissects into interstitial tissue - interlobular septa, perivascular areas, subpleural tissues
Pathological significance of interstitial emphysema
Compression of lobules decreases ventilation = restrictive lung disease
Interstitial emphysema sequelae
- Resolution
- Progression = mediastinum and subcutis
- Secondary infection of pockets
- Fibrosis and parenchymal loss
Main causes of pulmonary edema
Increased hydrostatic P – L sided HF
Increased permeability – toxins, infectious agents
Definition of pneumonia
Inflammation of the pulmonary gas exchange parenchyma
Causes of pneumonia
Infectious - viral bacterial, fungal, parasitic
Toxic
Immunologic
Mixed - foreign material, HCl and bacteria in aspiration pneumonia
Classification of pneumonia - simple morphologic and modifiers
Simple:
Bronchopneumonia
Interstitial
Focal or multifocal
Mixed pattern
Modifiers:
Duration - acute, subacute, chronic
Distribution - focal, multifocal, locally-extensive, diffuse
Exudate - necrotizing, fibrinopurulent, granulomatous
Causes of bronchopneumonia
Bacteria, aspiration
Pathogenesis of bronchopneumonia
Deposition of causative agent in terminal bronchioles and alveoli - bacteria, foreign material
Early damage in proximal acinar areas with spread into surrounding alveolar parenchyma
Gross morphology of bronchopneumonia
Distribution: cranioventral
May be intercurrent fibrinous pleuritis
May spread to lobular distrubution
Two indicators of chronicity in regards to bronchopneumonia
Fibrosis
Lympadenomegaly
Microscopic morphology of bronchopneumonia
Abundant exudate in alveoli - neutrophils, fibrin, necrotic debris
Lesions initially airway oriented
Pathological significance of bronchopneumonia
Obstructive and restrictive changes - airway obstruction, infiltrates make lung stiffer, exudate and wall thickening decrease diffusion capacity
Pleuritis may contribute to restrictive disease
Is bronchopneumonia reversible?
Yes
Bronchopneumonia sequelae
- Resolution
- Death
- Septicemia
- Chronicity with bronchiolitis obliterans and bronchiectasis +/- pleural adhesions
Pathogenesis of interstitial pneumonia
Primary injury to elements of the interalveolar septum - epithliem, endothelium
Causes of interstitial pneumonia
Infectious - viral, protozoa, some fungi, rarely bacteria
Toxic
Hypersensitivity
Gross morphology of interstitial pneumonia
Distrubtion: often diffuse or locally extensive
Firm, large red with muscle or liver consistency on cut surface
Microscopic morphology of interstitial pneumonia.
What are some markers of subacute and chronic stages?
Early type 1 epithelial necrosis
Subacute = type 2 epithelial hyperplasia, alveolar septal thickening, mononuclear cells
Chronic = fibrosis
Pathological significance of interstitial pneumonia
Thickening and infiltration of alveolar walls marked by increased stiffness and decreased compliance = restrictive
decreased diffusion capacity = hypoxemia
Interstitial pneumonia sequelae
- Resolution = rare
- Death
- Fibrosis of interalveolar septa and progressive restrictive lung disease
Focal or multifocal pneumonia causes
Fungal:
Blastomyces - multifocal to locally extensive granulomatous or pyogran
Histoplasma - granulomatous
Coccidioides - granulomatous and pyogran
Pneumocystitis - interstitial, not granulomatous
Cryptococcus - rare unless immunosuppressed
Pathogenesis of acute viral pneumonia
Viruses replicate in respiratory airway and type 2 alveolar epithelial cells
Induce inflammatory and immune response
Inflammation in parenchyma focused on interalveolar septa
Viral replication is halted before diffuse interstitial pneumonia develops
Ex: canine adenovirus 2
Morphologic features of acute viral pneumonia
Virus induced epithelial injury and replication - rhinitis, tracheitis/bronchitis, bronchiolitis, patchy interstitial pneumonia
Bronchointerstitial pneumonia morphology
Bronchiolitis + patchy interstitial pneumonia
Pathogenesis of chronic viral pneumonia
Often assoc with viruses that replicate in macrophages and/or depress/evade antiviral immunologic defense mechansisms
Virus spreads throughout lung and induces diffuse interstitial pneumonia
Ex: ovine progressive pneumonia, canine distemper virus
Causes of viral pneumonia in dogs
Canine distemper
Canine influenza
Canine adenovrius type 2
Parainfluenza type 2
Canine respiratory coronavirus
Canine herpesvirus 1
Canine distemper respiratory lesions
Rhinitis, pharyngitis, tracheitis, bronchitis, bronchiolitis
Patchy to diffuse interstitial pneumonia or bronchopneumonia with secondary bacteria infection
IN and IC inclusions in epithelial cells and macrophages; syncytial cells
Canine distemper dx at necropsy - what samples should be submitted?
Lung, brain, thymus, lymph node, spleen, stomach, urinary bladder
Also, PCR respiratory panel
Canine influenza virus respiratory lesions
Lymphocytic or supparative rhinitis
Erosive/hyperplastic tracheitis, bronchitis, bronchiolitis
Tracheal/bronchial gland epithelial cell necrosis/hyperplasia with lymphs, neutrophils
Patchy interstitial pneumonia (bronchopneumonia)
Supparative bronchopneumonia with secondary bacterial to pneumonia
Name two emerging viral respiratory agents in dogs
Canine pneumovirus
Canine bocavirus (parvoviridae)
CAV-2 replication and pneumonia type
Replication in type 2 alveolar epithelial cells
Interstitial pneumonia usually around bronchioles
Canine distemper replication and pneumonia type
Replication in alveolar epithelial cells and macrophages
Interstitial pneumonia
Common to have viral dissemination systemically
Parainfluenza replication and pneumonia type
Infects type 2 alv cells, alv macrophages, bronchial and bronchiolar epithelium = depresses defense mechanisms
Locally extensive interstitial pneumonia
Respiratory syncytial virus replication and pneumonia type
Replication in type 2 alv cells, macrophages, multinucleated syncytial cells
Patchy interstitial pneumonia with diffuse bronchiolitis
Often see terminal interstitial emphysema in dorsocaudal and other lung lobes
Chronic progressive pneumonia (Maedi-Visna) respiratory lesions
Chronic, persistent infection
Interstitial pneumonia with marked interstitial accumulation of lymphocytes and macrophages
Usually see hyperplasia of type 2 epithelial cells, nonciliated bronchiolar epithelial cells, and metaplasia of smooth muscle in interalveolar septa
May be 2ry bacterial bronchopneumonia
Extrapulmonic lesions include encephalitis and arthritis
Pathogenesis of bacterial pneumonia (pneumonic pasteurellosis due to Mannheimia haemolytica)
Colonization of resp tract, depression of defense mechanisms
Exponential growth of M. haemolytica with leukotoxic production
Damage to neutrophils, macrophages, release of endotoxin
Leukotoxin and endotoxin mediated tissue damage accentuated by neutrophil release of toxic molecules
Respiratory lesions associated with pneumonic pasteurellosis
Severe fibrinous bronchopneumonia with fibrinous pleuritis
Cranioventral, neutrophil rich inflammation oriented around terminal bronchioles
Most severe in cranioventral areas
Abundant fibrinous and fibrinopurulent exudate in alveoli and in interlobular septa
May be large areas of parenchymal necrosis surrounded by neutrophils
Pneumonic pasteurellosis sequelae
Death
Chronic bronchopneumia with bronchiolitis obliterans, bronchiectasis, pleural fibrosis
Pathogenesis of bovine toxic interstitial pneumonia
Ingestion of pneumotoxin
Ruminal conversion and/or intestinal absorption
Activation of pneumotoxin by pulmonary CYP450 monooxygenase
Covalent bidning or free-radical damage by metabolites or pulmonary cell death
Pneumotoxins in cattle
L-tryptophane/3-methylindole
Moldy sweet potatoes (4-ipomeanol)
Perilla mint (purple mint)
Stinkwood (Ziera arborescens)
Pulmonary cells most susceptible to toxic injury
Non-ciliated bronchiolar cells
Type 1 alveolar epithelial cells
Capillary endothelial cells
What happens if bovines survive past 24 hours after onset of toxic interstitial pneumonia?
Hyperplasia of type 2 alveolar epithelial cells
Repeat exposures may cause fibrosis
Pulmonary neoplasia is more common in what species?
Cats and dogs
Benign pulmonary epithelial tumors
Adenoma
Papilloma
Malignant pulmonary epithelial tumors
Adenocarcinoma
Carcinoma
Adenosquamous carcinoma
Bronchial gland carcinoma
Most common form of neoplasia in the lung
Metastatic neoplasia
Gross distribution of pulmonary neoplasia and biological behavior of carcinomas
Most common in caudal lung fields - any lobe can be affected
Met local = thorax, lung, lymph node
Distant met = LN, kidney, liver, spleen, bone, brain (nail bed in cats)
