36 Pathology 4: Interstitial Lung Diseases Flashcards Preview

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

Pulmonary architecture:
Lung compartments

  • Airspaces
  • Interstitium
  • Bronchovascular bundles
  • Airways
  • Pleura
A
  • 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
Q

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…
A
  • 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
Q

Pulmonary architecture:
The main supply routes of the lung

  • Pulmonary arteries
  • Airways
  • Bronchial arteries
  • Pulmonary veins
  • Lymphatics
A
  • 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
Q

Pulmonary architecture:
Two other noteworthy properties of the lungs

  • Surface area
  • Exposure to blood
A
  • 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
Q

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…
A
  • 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
Q

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…
A
  • 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
Q

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
A
  • 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
Q

Classification of the interstitial lung diseases

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

Usual interstitial pneumonia and idiopathic pulmonary fibrosis

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

Usual interstitial pneumonia and idiopathic pulmonary fibrosis

  • IPF is characterized by…
  • Prognosis
A
  • 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
Q

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
A
  • 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
Q

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
A
  • 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
Q

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…
A
  • 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
Q

Lung involvement by sarcoidosis

  • Sarcoidosis
  • Macroscopically,…
  • Histological hallmarks
  • Histiocytes
  • Epitheliod histiocytes
A
  • 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
Q

Lung involvement by sarcoidosis

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

Lung involvement by sarcoidosis

  • Histopathologic features of sarcoidosis
  • Possible causes of sarcoidosis
A
  • 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
Q

Silicosis

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

Silicosis

  • Forms
  • Process
  • Animals exposed to silica demonstrate…
A
  • 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
Q

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
A
  • 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
Q

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
A
  • 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
Q

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…
A
  • 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
Q

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
A
  • 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
Q

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…
A
  • 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
Q

Asbestosis

  • Histopathologically, asbestosis is marked by…
  • Asbestos bodies
  • Ferruginous bodies
  • Fibrosis in asbestosis
A
  • 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
Q

Asbestosis

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

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
A
  • 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
Q

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
A
  • 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
Q

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
A
  • 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):