36 Pathology 4: Interstitial Lung Diseases Flashcards
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
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
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)
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
- Forms one of the largest interfaces between the human organism and the environment
- 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
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
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
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
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
- Idiopathic interstitial pneumonia (IP)
- Inorganic dust diseases
- Pneumoconioses
- Coal workers pneumoconiosis
- Asbestosis
- Silicosis
- Many others
- Pneumoconioses
- Organic dust diseases
- Hypersensitivity pneumonitis
- Drugs and radiation diseases
- Drugs and radiation-induced diseases
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
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
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”)
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”)
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
- Lack the ability to limit the repair and move on to excessive scar formation
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
- Macrophages that have a permanent position in a tissue
- 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
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