36 Pathology 4: Interstitial Lung Diseases Flashcards Preview

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Flashcards in 36 Pathology 4: Interstitial Lung Diseases Deck (28)
1

Pulmonary architecture:
Lung compartments

  • Airspaces 
  • Interstitium 
  • Bronchovascular bundles 
  • Airways 
  • Pleura

  • Airspaces
    • Distal airspace
    • Mostly the alveoli
  • Interstitium
    • Mostly alveolar septa an dinterlobular septa
  • Bronchovascular bundles
    • Vessels
  • Airways
    • Large airways: bronchi
    • Small airways: bronchioles
  • Pleura
    • Anatomically not part of the lung, but can be involved in lung disease

2

Pulmonary architecture

  • The pulmonary interstitium 
  • In the healthy lung, alveolar septa are...
  • The basement membranes of epithelium and vascular endothelium
  • The interstitium is the primary site of...

  • The pulmonary interstitium
    • Forms a three-dimensional scaffold that imparts structural integrity to the lung
  • In the healthy lung, alveolar septa are...
    • Very delicate 
    • Composed of a single layer of flattened pneumocytes, a capillary, and a very small amount of extracellular matrix
  • The basement membranes of epithelium and vascular endothelium
    • In thin portions of the alveolar septum are fused (allows easy gas diffusion)
    • In the thicker portions are separated by an interstitial space containing some extracellular matrix, fibroblasts-like interstitial cells and some smooth muscle cells
  • The interstitium is the primary site of...
    • Injury in the interstitial lung diseases

3

Pulmonary architecture:
The main supply routes of the lung

  • Pulmonary arteries 
  • Airways
  • Bronchial arteries 
  • Pulmonary veins 
  • Lymphatics

  • Pulmonary arteries
    • Run in the bronchovascular bundles in the center of the lung lobules (centrilobular)
  • Airways
    • Run in the bronchovascular bundles in the center of the lobules (centrilobular)
  • Bronchial arteries
    • Run with the airways they supply (centrilobular)
  • Pulmonary veins
    • Form in the lobules and then run to the nearest interlobular septum, and from there to the nearest interlobar septum or the pleural surface (septal)
  • Lymphatics
    • Follow both the routes of veins and arteries (centrilobular and septal)

4

Pulmonary architecture:
Two other noteworthy properties of the lungs

  • Surface area
  • Exposure to blood

  • The lungs' large surface area 
    • Forms one of the largest interfaces between the human organism and the environment
      • The other two being skin and the gastrointestinal tract
    • However, this interface is the one most difficult to protect from noxious stimuli (and often even voluntarily exposed to noxious stimuli)
    • Hence, lung disease is very common, and probably not infrequently subclinical
  • The lungs are the only organs that encounter the entire cardiac output of blood
    • They are theoretically exposed to hematogenous factors derived from all other tissues in the body
    • It is therefore not surprising that the lungs are often involved in disease that occur elsewhere in the body
      • Ranging from metastatic disease in cancer patients to lung fibrosis in patient with systemic connective tissue diseases such as rheumatoid arthritis

5

Pulmonary response to injury

  • Three most important reaction patterns to injury
  • Airspace organization
  • Hallmark feature of interstitial pneumonias
  • Consequence of inflammation
  • Whenvever airspace organization is the predominant findings,...
  • Since the lung compartments are intimately associated, one often sees...

  • Three most important reaction patterns to injury
    • Airspace organization
    • Inflammatory infiltrates
    • Fibrosis
  • Airspace organization
    • Involves primarily the airspaces
    • Classical example: organizing pneumonia
  • Hallmark feature of interstitial pneumonias
    • Inflammatory infiltrates which primarily involve the interstitium
  • Consequence of inflammation
    • Fibrosis
    • The degree of fibrosis, or scarring, depends on...
      • The degree and duration of the inflammatory process
      • The extent of tissue destruction by the inflammatory process
  • Whenvever airspace organization is the predominant findings,...
    • The disease is usually not considered an "interstitial lung disease"
  • Since the lung compartments are intimately associated, one often sees...
    • Some "airspace" disease in "interstitial" lung disease
    • Some "interstitial" inflammation in "airspace" disease

6

Pulmonary response to injury

  • The earliest common manifestation of most of the interstitial diseases 
  • The initial stimuli for this damage 
  • The accumulation of inflammatory and immune effector cells within the alveolar walls and spaces
  • Neutrophil recruitment can be caused by...
  • Alveolar macrophages
  • In diseases such as sarcoidosis, cell-mediated immune reactions result in...
  • What's responsible for the slowly progressive pulmonary fibrosis
  • The alveolar macrophage plays a central role in the development of...
  • Loss of homeostatic matrix regulation with concomitant alterations in synthesis and degradation results in...

  • The earliest common manifestation of most of the interstitial diseases
    • Damage to the alveolar structure
  • The initial stimuli for this damage
    • Heterogeneous
    • Some of these stimuli, such as oxygen-derived free radicals and some chemicals, are directly toxic to endothelial cells, epithelial cells, or both
  • The accumulation of inflammatory and immune effector cells within the alveolar walls and spaces
    • Distorts the normal alveolar structures
    • The inflammatory cells release mediators that injure parenchymal cells and stimulate fibrosis
  • Neutrophil recruitment can be caused by...
    • Complement activation in some disorders
  • Alveolar macrophages
    • Increase in number in all interstitial diseases
    • Release chemotactic factors for neutrophils (e.g., IL-8, leukotriene B4)
  • In diseases such as sarcoidosis, cell-mediated immune reactions result in...
    • The accumulation of monocytes and T lymphocytes and in the formation of granulomas
  • What's responsible for the slowly progressive pulmonary fibrosis
    • The interactions among lymphocytes and macrophages
    • The release of lymphokines and monokines
  • The alveolar macrophage plays a central role in the development of...
    • Fibrosis
    • Not only the infiltrating inflammatory cells, but also local (resident) cells become stimulated and release soluble factors that promote fibroblast activation, proliferation, and matrix production
  • Loss of homeostatic matrix regulation with concomitant alterations in synthesis and degradation results in...
    • The disproportionate deposition of lung connective tissue

7

Classification of the interstitial lung diseases

  • Interstitial lung diseases 
    • General
    • Affect...
    • The result of the inflammation and fibrosis
  • In the late stages of pulmonary fibrosis,...
  • In most of the diseases, the process is...
  • The radiographic and gross anatomic diagnosis
  • Classification of interstitial lung diseases

  • Interstitial lung diseases
    • A heterogeneous group of non-neoplastic disorders resulting from damage predominantly to the pulmonary interstitium by varying patterns of inflammation and fibrosis
    • Frequently affect not only the interstitium, but also the airspaces, airways, and pulmonary vessels
    • The result of the inflammation and fibrosis is a marked decrease in pulmonary compliance, significant reduction in oxygen exchange (diffusing capacity), pulmonary hypertension, right heart dilatation and failure (cor pulmonale), and death
  • In the late stages of pulmonary fibrosis,...
    • The lung is remodeled into extensive scar tissue
  • In most of the diseases, the process is...
    • Uneven throughout the pulmonary parenchyma, with some less-involved airways (especially respiratory bronchioles) stretched wide by scar contraction
  • The radiographic and gross anatomic diagnosis
    • "Honeycomb lung" or "honeycomb change"
  • Classification of interstitial lung diseases
    • Not every interstitial lung disease is idiopathic, but many (nonidiopathic) interstitial lung diseases are commonly described using the same terminology

8

Classification of the interstitial lung diseases

  • Etiological classifications
  • Unknown etiology diseases
  • Inorganic dust diseases
  • Organic dust diseases
  • Drugs and radiation diseases

  • Etiological classifications
    • Infection
    • Inorganic dust exposure
    • Organic dust exposure
    • Idiopathic
    • Drug-induced
  • Unknown etiology diseases
    • Idiopathic interstitial pneumonia (IP)
      • Usual interstitial pneumonia (UIP)
      • Non-specific IP (NSIP)
      • Desquamative IP (DIP)
      • Lymphoid IP (LIP)
      • Cryptogenic organizing pneumonia (COP)
      • Acute interstitial pneumonia (AIP)
      • Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)
    • Systemic disease associated
      • Includes connective tissue/autoimmune diseases
      • Many of the entities seen in this setting have radiographic and histologic findings resembling or identical to the idiopathic IPs listed above
    • Sarcoidosis
    • Pulmonary Langerhans cell histiocytosis
    • Lymphangioleiomyomatosis
    • Chronic eosinophilic pneumonia
  • Inorganic dust diseases
    • Pneumoconioses
      • Coal workers pneumoconiosis
      • Asbestosis
      • Silicosis
      • Many others
  • Organic dust diseases
    • Hypersensitivity pneumonitis
  • Drugs and radiation diseases
    • Drugs and radiation-induced diseases

9

Usual interstitial pneumonia and idiopathic pulmonary fibrosis

  • Usual interstitial pneumonia (UIP)
  • Idiopathic pulmonary fibrosis (IPF)
  • IPF vs. UIP 

  • Usual interstitial pneumonia (UIP)
    • A diffuse fibrosing lung disease that shows the histologic features "usually" seen in this entity
    • Any disease that histologically looks like UIP
  • Idiopathic pulmonary fibrosis (IPF)
    • A chronic fibrosing lung disease in older people with no apparent cause
    • Histologic findings are those of UIP
  • IPF vs. UIP
    • IPF is a clinical term
    • UIP is a patholgy term
    • Every IPF has the histopathologic features of UIP, but not every UIP is IPF
    • Ex. UIP can be the histologic findings in lung involvement by connective tissue disease or lung disease related to asbestos exposure (asbestosis), organic dust exposure (hypersensitivity pneumonitis) or drug toxicities

10

Usual interstitial pneumonia and idiopathic pulmonary fibrosis

  • IPF is characterized by...
  • Prognosis

  • IPF is characterized by...
    • Marked interstitial fibrosis
    • An insidious onset with slow but inexorable progression
    • A poor prognosis with most patients dying of their disease
  • Prognosis
    • Poor
    • Median survival without lung transplant is between 3 and 5 years
    • Median survival of a lung transplant recipient is also only about 5 years

11

Usual interstitial pneumonia and idiopathic pulmonary fibrosis

  • The key histologic features of the UIP pattern 
  • Fibrosis 
  • Fibroblastic focus/foci
  • Main constituents of scar tissue or fibrosis
  • Diagnostic feature of UIP

  • The key histologic features of the UIP pattern
    • Architectural distortion
    • Fibrosis with honeycomb change
    • Fibroblastic foci
    • Patchy distribution
  • Fibrosis
    • Starts in the periphery of a lung lobule (the small secondary lung lobule, not the whole lobe)
    • Advances to the center of the lobule
  • Fibroblastic focus/foci
    • At the interface between fibrosis and uninvolved lung
    • An area in which the fibrosis is actively happening and advancing
    • Have the appearance of an "immature" fibrosis
      • They look rather loose and do not contain many collagen fibers
  • Main constituents of scar tissue or fibrosis
    • Collagen fibers
    • Stain red with the pathologists' routine Hematoxylin & Eosin stain
      • Fibrotic biopsies overall look very "red" or "pink" under the microscope
  • Diagnostic feature of UIP
    • Spared areas of lung that looks rather normal ("usual")

12

Usual interstitial pneumonia and idiopathic pulmonary fibrosis

  • Geographic heterogeneity
  • Temporal heterogeneity
  • To make the diagnosis of UIP ona lung biopsy, the pathologist needs to see...
  • Interdisciplinary discussion among pulmonologist, radiologist and pathologist
  • What causes IPF

  • Geographic heterogeneity: coexistence of...
    • Remodeled/scarred lung
    • Near normal, spared
  • Temporal heterogeneity: coexistence of...
    • Mature scar tissue with dense collagen
    • Immature fibrosis characterized by fibroblastic foci
  • To make the diagnosis of UIP ona lung biopsy, the pathologist needs to see...
    • Fibrosis of the lung with distortion of lung architecture (often accompanied by honeycomb change)
    • Geographic heterogeneity
    • Temporal heterogeneity
  • Interdisciplinary discussion among pulmonologist, radiologist and pathologist
    • Usually the best way to place patients into a diagnostic category if the diagnosis is unclear
  • What causes IPF
    • Unknown (hence "idiopathic")

13

Usual interstitial pneumonia and idiopathic pulmonary fibrosis

  • Risk factors associated with IPF 
  • Some patients with familial disease have been found to carry certain mutations in...
  • Some of these mutations have also been identified in individuals with...
  • It is unclear whether...
  • What induces a fibrotic environment
  • The fibroblastic focus may represent...
  • While similar injuries may occur in people without IPF, IPF patients may...

  • Risk factors associated with IPF
    • Cigarette smoking
    • Environmental pollutants
    • Chronic microaspiration
  • Some patients with familial disease have been found to carry certain mutations in...
    • Surfactant proteins
    • Gel-forming mucin
    • Telomerase
  • Some of these mutations have also been identified in individuals with...
    • Sporadic IPF, suggesting there may be a genetic predisposition in some patients
  • It is unclear whether...
    • Inflammation is the primary problem in this disease that in the long run results in fibrosis
    • The fibrosis occurs in the absence of much inflammation due to aberrant epithelial cell and fibroblast responses to some nonspecific lung injury
  • What induces a fibrotic environment
    • Multiple microinjuries to alveolar epithelial cells (for example a "cracking" open of the alveolar lining caused by a stretch injury)
    • Growth factors secreted by the injured epithelial cells activate and recruit fibroblasts
  • The fibroblastic focus may represent...
    • Repair at the initial site of such injury
  • While similar injuries may occur in people without IPF, IPF patients may...
    • Lack the ability to limit the repair and move on to excessive scar formation
      involving the whole lung

14

Lung involvement by sarcoidosis

  • Sarcoidosis
  • Macroscopically,...
  • Histological hallmarks
  • Histiocytes
  • Epitheliod histiocytes

  • Sarcoidosis
    • A systemic disease of unknown cause characterized by non-necrotizing granulomatous inflammation in various tissues and organs
    • The lung is one of the organs commonly involved in sarcoidosis (in about 90%), often together with the mediastinal lymph nodes
  • Macroscopically,...
    • There are no focal lesions
    • At times, the coalescence of granulomas produces small nodules
  • Histological hallmarks
    • Classic non-necrotizing granulomas
    • Composed of an aggregate of tightly clustered epithelioid histiocytes with
      multinucleated giant cells
      • Epithelioid histiocytes: histiocytes that look similar to an epithelial cell
  • Histiocytes
    • Macrophages that have a permanent position in a tissue
      • Macrophage: a monocyte once it leaves the blood stream
    • Derived from the monocyte system, so their progenitors are in the bone marrow
    • Primary goal: clean up
  • Epitheliod histiocytes
    • Histiocytes that look similar to an epithelial cell
    • Normal macrophages/histiocytes transform under IL-1 and TNF-α influence into these bigger, more round macrophages with abundant cytoplasm
    • Sometimes coalesce and form multinucleated giant cells

15

Lung involvement by sarcoidosis

  • Scar formation
  • The granulomas in sarcoidosis
  • Two additional microscopic features of the granulomas that are sometimes seen in sarcoidosis

  • Scar formation
    • With chronicity dense fibrous scars surround the granulomas of sarcoidosis
    • This scar formation can progress (and the granulomatous inflammation subside) so that in late stages of sarcoidosis only scars are left behind, and one may be lucky to find a single giant cell
  • The granulomas in sarcoidosis
    • Consistently arranged along lymphovascular routes in the lung
    • Main locations: lymphovascular routes are along the bronchovascular bundles and along the septa and pleura
      • Occasionally find granulomas in alveolar septa as well
    • The relative frequency of granulomas in the bronchial submucosa accounts for the high diagnostic yield of bronchoscopic biopsies
  • Two additional microscopic features of the granulomas that are sometimes seen in sarcoidosis
    • Neither one of them are pathognomonic of sarcoidosis
    • "Schaumann bodies" are laminated concretions composed of calcium and proteins
    • "Asteroid bodies" are stellate inclusions containing degraded cytoskeletal protein enclosed within multinucleated giant cells

16

Lung involvement by sarcoidosis

  • Histopathologic features of sarcoidosis
  • Possible causes of sarcoidosis

  • Histopathologic features of sarcoidosis
    • Granulomatous inflammation with well formed non-necrotizing granulomas in
    • Lymphangitic distribution
  • Possible causes of sarcoidosis
    • Exposure to certain microorganisms (especially mycobacteria and propionibacteria)
    • Certain dusts (Beryllium exposure results in a histologically similar lung disease)
    • Altered cytokine and T cell responses

17

Silicosis

  • General
  • Frequency
  • Presentation
  • Risk factors
  • Acute silicosis

  • General
    • A lung disease caused by inhalation of crystalline silicon dioxide (silica)
  • Frequency
    • The most prevalent chronic occupational disease in the world
  • Presentation
    • Usually presents after decades of exposure as a slowly progressing, nodular, fibrosing pneumoconiosis
  • Risk factors
    • Workers in a large number of occupations are at risk, especially sandblasters and many mine workers
    • Less commonly, heavy exposure over months to a few years can result in acute silicosis
  • Acute silicosis
    • A lesion characterized by the generalized accumulation of a lipoproteinaceous material within alveoli
    • Histologically indistinguishable from pulmonary alveolar Proteinosis

18

Silicosis

  • Forms
  • Process
  • Animals exposed to silica demonstrate...

  • Forms
    • Both crystalline and amorphous forms
    • Crystalline forms (including quartz, crystobalite, and tridymite) are much more fibrogenic
      • Reveals the importance of the physical form and surface properties in pathogenesis
      • Of these, quartz is most commonly implicated in silicosis
  • Process
    • After inhalation, the particles interact with epithelial cells and macrophages
    • Although lung macrophages that ingest the silica particles may ultimately succumb to its toxic effects, silica causes activation and release of mediators by viable macrophages
      • Such mediators include IL-1, tumor necrosis factor (TNF), fibronectin, lipid
        mediators, oxygen-derived free radicals, and fibrogenic cytokines
  • Animals exposed to silica demonstrate...
    • A steady recruitment of macrophages and lymphocytes to the alveoli and interstitium, which further amplify the pathologic process
    • Anti-TNF monoclonal antibodies can block lung collagen accumulation in mice that are given silica intratracheally
    • TNF seems to be an important mediator in inflammatory diseases

19

Silicosis

  • Histopathologically, silicosis is characterized by discrete nodules in the upper zones of the lungs
    • Early vs. later stages
    • Other findings
    • Eggshell calcification
  • Progressive massive fibrosis (PMF)
  • Often, patients exposed to silica (“free” silicon dioxide = SiO2) are also exposed to...
  • Asbestos 
  • Main points about silicosis

  • Histopathologically, silicosis is characterized by discrete nodules in the upper zones of the lungs
    • Early vs. later stages
      • In early stages these nodules are tiny and barely palpable
      • As the disease progresses, these nodules may coalesce into hard, collagenous scars
    • Other findings
      • Some nodules may undergo central degeneration and cavitation
      • Acid-fast bacteria in those nodules may be due to superimposed tuberculosis
      • Fibrotic lesions may also occur in the hilar lymph nodes and pleura
    • Eggshell calcification
      • Sometimes, thin sheets of calcification occur in the lymph nodes
      • These are seen radiographically as calcium surrounding a zone lacking calcification
  • Progressive massive fibrosis (PMF)
    • If the disease continues to progress, expansion and coalescence of lesions produce PMF
    • Examination of silicotic nodules by polarization microscopy reveals very faint birefringent silica particles
  • Often, patients exposed to silica (“free” silicon dioxide = SiO2) are also exposed to...
    • Silicates (“combined” silicon dioxide = SiO2 that is bound to other minerals, for example magnesium or aluminum)
    • When one views a silicosis case under the microscope, one sees not only the dim silica particles but also the slightly larger and much brighter silicate crystals.
  • Asbestos
    • A silicate (there are many different asbestos silicates) with striking health effects
  • Main points about silicosis
    • Exposure to silica (silicon dioxide = SiO2)
    • Upper lobe predominant single or confluent nodules

20

Coal worker pneumoconiosis (CWP)

  • Coal worker pneumoconiosis
  • The spectrum of lung findings in coal workers 
  • Like silicosis, CWP preferentially involves...
  • Excluding lung cancer
  • Things to remember about CWP

  • Coal worker pneumoconiosis
    • A lung disease caused by the inhalation of coal dust
  • The spectrum of lung findings in coal workers
    • Asymptomatic anthracosis
    • Simple CWP with little to no pulmonary dysfunction
    • Complicated CWP, or progressive massive fibrosis (PMF), in which lung function is compromised
  • Like silicosis, CWP preferentially involves...
    • The upper lung zones
  • Excluding lung cancer
    • Often they are smokers
    • Even if biopsy of one nodule shows only fibrosis, one can never exclude with certainty that another nodule represents lung cancer
  • Things to remember about CWP
    • The difference between simple CWP and complicated CWP (progressive massive fibrosis) is the size of the conglomerate fibrotic masses
    • Upper lung zone predominant disease

21

Coal worker pneumoconiosis (CWP)

  • Histopathologically, the most innocuous coal-induced pulmonary lesion in CWP
  • Process
  • Fibrosis at this stage 
  • Simple CWP
  • Complicated CWP (or progressive massive fibrosis, PMF) 
  • People in the mines are often not only exposed to pure coal dust but also to...

  • Histopathologically, the most innocuous coal-induced pulmonary lesion in CWP
    • Coal dust macules
    • Consists of carbon-laden macrophages embedded in a delicate network of collagen fibers
  • Process
    • Inhaled carbon pigment is engulfed by alveolar or interstitial macrophages, which then accumulate in the connective tissue along the lymphatics, including the pleural lymphatics
  • Fibrosis at this stage
    • Minimal
  • Simple CWP
    • Coal macules (1 to 2 mm in diameter) and somewhat larger coal dust nodules
    • Located primarily adjacent to respiratory bronchioles, the site of initial dust
      accumulation
    • Coal macules do not grow after coal dust exposure ceases, though patients will cough up black dust for years afterwards
  • Complicated CWP (or progressive massive fibrosis, PMF)
    • Occurs on a background of simple CWP 
    • Generally requires many years to develop
    • Defined by the size of the nodules (> 2 cm)
    • There are usually multiple nodules
    • Microscopically, the lesions consist of dense collagen and carbon pigment
    • Sometimes the center of a big nodule is necrotic, resulting most likely from local ischemia
  • People in the mines are often not only exposed to pure coal dust but also to...
    • Silica or silicates
    • Therefore, it is common to see silicotic nodules and birefringent crystals in patients with CWP

22

Asbestosis

  • Asbestosis 
  • Asbestos 
  • Occupational exposure to asbestos is linked to...
  • What dictates whether asbestos causes disease
  • Two distinct geometric forms of asbestos
  • Asbestos fibers that remain in the lung 
  • Amphiboles

  • Asbestosis
    • A lung disease caused by the inhalation of asbestos
  • Asbestos
    • A family of fibrous minerals, hydrated silicates of sodium, iron, calcium, and
      magnesium
  • Occupational exposure to asbestos is linked to...
    • Localized fibrous plaques or, rarely, diffuse pleural fibrosis (benign)
    • Pleural effusions (benign)
    • Parenchymal interstitial fibrosis (asbestosis) (benign)
    • Lung carcinoma (malignant)
    • Mesothelioma (malignant)
    • Laryngeal and other extrapulmonary neoplasms, including colon carcinomas, and perhaps malignant lymphomas (malignant)
  • What dictates whether asbestos causes disease
    • Fiber burden, size, shape, and solubility of the different forms of asbestos
  • Two distinct geometric forms of asbestos
    • Serpentine (curly and flexible fibers)
    • Amphibole (straight, stiff, and brittle fibers)
  • Asbestos fibers that remain in the lung
    • Long (mean length about 35 micrometer)
    • Slender (around 2 to 5 micrometer)
    • They can...
      • Cause local fibrosis just like the other silicates
      • Get carried through lymphatics to the pleura where we think they cause mesothelioma
  • Amphiboles
    • Less prevalent
    • The most fibrogenic and pathogenic

23

Asbestosis

  • The occurrence of asbestosis, like the other pneumoconioses, depends on...
  • The initial injury occurs...
  • Macrophages
  • Chronic deposition of fibers and persistent release of mediators eventually lead to...
  • In contrast to other inorganic dusts, asbestos can also act as...
  • Some of the oncogenic effects of asbestos are mediated by...
  • For example, the adsorption of carcinogens in tobacco smoke onto asbestos fibers may well be important in the remarkable synergy between...

  • The occurrence of asbestosis, like the other pneumoconioses, depends on...
    • The interaction of inhaled fibers with lung macrophages and other parenchymal cells.
  • The initial injury occurs...
    • At bifurcations of small airways and ducts, where the asbestos fibers land and penetrate
  • Macrophages
    • Both alveolar and interstitial
    • Attempt to ingest and clear the fibers
    • Are activated to release chemotactic factors and fibrogenic mediators that amplify the response
  • Chronic deposition of fibers and persistent release of mediators eventually lead to...
    • Generalized interstitial pulmonary inflammation and interstitial fibrosis
  • In contrast to other inorganic dusts, asbestos can also act as...
    • A tumor promoter
  • Some of the oncogenic effects of asbestos are mediated by...
    • Reactive free radicals generated by asbestos fibers
    • Toxic chemicals can adsorb onto the asbestos fibers contributing to the oncogenicity of the fibers
  • For example, the adsorption of carcinogens in tobacco smoke onto asbestos fibers may well be important in the remarkable synergy between...
    • Tobacco smoking and the development of lung carcinoma in asbestos workers

24

Asbestosis

  • Histopathologically, asbestosis is marked by...
  • Asbestos bodies 
  • Ferruginous bodies
  • Fibrosis in asbestosis

  • Histopathologically, asbestosis is marked by...
    • Diffuse pulmonary interstitial fibrosis, which is sometimes indistinguishable from diffuse interstitial fibrosis resulting from other causes, except for the presence of asbestos bodies
  • Asbestos bodies
    • Appear as golden brown, fusiform or beaded rods with a translucent center
    • Consist of asbestos fibers coated with an iron-containing proteinaceous material
    • Arise when macrophages attempt to phagocytose asbestos fibers
      • The iron is presumably derived from phagocyte ferritin
  • Ferruginous bodies
    • Other inorganic particulates may become coated with similar iron protein complexes
    • Sometimes one cannot tell for sure whether a body is an asbestos body or not
  • Fibrosis in asbestosis
    • Fibrosis around respiratory bronchioles and alveolar ducts and extends to involve adjacent alveolar sacs and alveoli
    • The fibrous tissue distorts the native architecture, creating enlarged airspaces enclosed within thick fibrous walls
    • Eventually, the affected regions become honeycombed

25

Asbestosis

  • Asbestosis vs. UIP
  • In contrast to CWP and silicosis, asbestosis...
  • Pulmonary hypertension
  • Pleural plaques
  • Things to remember about asbestosis

  • Asbestosis vs. UIP
    • The pattern of fibrosis is similar to that seen in UIP, with fibroblastic foci and varying degrees of fibrosis
    • The only difference is the presence of asbestos bodies
  • In contrast to CWP and silicosis, asbestosis...
    • Begins in the lower lobes and subpleurally (just like idiopathic UIP = IPF)
    • The middle and upper lobes of the lungs become affected as fibrosis progresses
  • Pulmonary hypertension
    • Caused by the scarring trapping and narrowing pulmonary arteries and arterioles
  • Pleural plaques
    • The most common manifestation of asbestos exposure
    • Well-circumscribed plaques of dense collagen often containing calcium
    • Usually do not contain asbestos bodies
    • If you see plaques in a patient, there is a very high probability that the patient
      was exposed to asbestos
    • But the presence of plaques does not mean that the patient is at higher risk for mesothelioma or lung cancer than another exposed patient without plaques
  • Things to remember about asbestosis
    • Amphibole asbestos fibers are the most dangerous
    • Asbestosis is lower lobe predominant
    • Asbestosis can look like UIP/IPF, exposure history and asbestos body counts on slides are important

26

Hypersensitivity pneumonitis (HP)

  • Hypersensitivity pneumonitis ("extrinsic allergic alveolitis")
  • Often, the disease is designated according to...
  • "Farmer's lung"
  • "Bird-fancier's lung"
  • Clinical variability
  • Histopathologic features of hypersensitivity pneumonitis

  • Hypersensitivity pneumonitis (HP) ("extrinsic allergic alveolitis")
    • A diffuse inflammatory lung disease seen in patients exposed to organic dusts
  • Often, the disease is designated according to...
    • The exposure believed to be responsible
  • "Farmer's lung"
    • Patients (often farmers) with HP who are exposed to organic dust from moldy hay or grains
  • "Bird-fancier's lung"
    • Patients with HP who have contact to pet birds at home or breed pigeons 
  • Clinical variability
    • Ranging from subclinical or subtle disease for which the patient does not even see a doctor, to fulminant acute reactions that can lead to death
  • Histopathologic features of hypersensitivity pneumonitis
    • Airway-centered cellular interstitial pneumonia
    • Poorly formed non-necrotizing granulomas

27

Hypersensitivity pneumonitis (HP)

  • Most patients with HP are...
  • Histopathologically, subacute disease is characterized by...
  • Inflammatory response
  • Not everything that histologically is diagnosed as UIP is...
  • Granulomas

  • Most patients with HP are...
    • Biopsied either during the subacute or chronic phase of the disease
  • Histopathologically, subacute disease is characterized by...
    • An airway-centered interstitial inflammation
    • The airway- or bronchocentricity may be explained by the hypothesis that the antigen, to which the patient reacts, is inhaled and enters the lung through the airways
  • Inflammatory response
    • Expected to be in the areas of first contact
    • Later, in longstanding disease, inflammation diffusely involves alveolar septa throughout the lung
    • Even later, when inflammation and injury give result in scarring, inflammation subsides and the lung becomes fibrotic
    • In late stages, the lung can acquire the histopathologic features of UIP
  • Not everything that histologically is diagnosed as UIP is...
    • Idiopathic disease or IPF
  • Granulomas
    • Important feature of HP
    • The morphologic correlate of a type IV hypersensitivity reaction
    • In HP, granulomas are non-necrotizing and often "poorly formed"
    • They do not look like the granulomas of sarcoidosis
      • Typically surrounded by a rim of lymphocytes and a ring of fibrosis
    • Instead are composed of a loose cluster of epithelioid histiocytes without many lymphocytes and without surrounding fibrosis

28

Hypersensitivity pneumonitis (HP)

  • Suggestive of HPIn the right clinical setting (i.e. a potential exposure can be identified),...If you encounter a patient with chronic lung disease, and all you see in a lung biopsy is fibrosis,...
  • HP is caused by...
  • However, the presence of granulomas suggests a role of...
  • Th1-type cytokine network 
  • Th2-like immune responses 

  • Suggestive of HP
    • The coexistence of an airway-centered interstitial pneumonia with poorly formed granulomas
  • In the right clinical setting (i.e. a potential exposure can be identified),...
    • The findings are pretty much diagnostic of HP
  • If you encounter a patient with chronic lung disease, and all you see in a lung biopsy is fibrosis,...
    • It is the presence of the rare poorly formed granuloma that often raises
      the question of HP
  • HP is caused by...
    • Inhalation of an antigen that provokes humoral and cellular immune responses in susceptible individuals (immunologic)
    • Possible deposition of immune complex in the lung that would lead
      to complement activation and inflammation
  • However, the presence of granulomas suggests a role of...
    • T-cell mediated cellular immunity
  • Th1-type cytokine network
    • Appear to play an important role in the development of hypersensitivity pneumonitis
  • Th2-like immune responses
    • May be important to maintain it in the chronic form

Decks in Pulm Class (47):