Flashcards in PATH: Obstructive and Restrictive Lung Disease Deck (102):
List the obstructive lung diseases.
2) Chronic bronchitis
List the restrictive lung diseases.
1) Pneumoconiosis (Coal Worker's, Silicosis, Asbestosis)
3) Pneumonias (various types)
What are the two divisions of obstructive lung disease?
Acute and Chronic
True or false: most COPD patients are smokers.
True or false: eventually, most smokers develop COPD.
FALSE: only 15% of smokers get COPD
When does symptomatic COPD typically occur?
Middle age (but is dose dependent, so people who smoke more develop COPD earlier)
True or false: men are more likely to have COPD than women.
FALSE: prevalence is approximately equal between sexes
What is emphysema?
abnormal permanent enlargement of airspaces due to destruction of the walls (septa) between them—most commonly due to smoking
Who is at an increased risk for development of COPD (accounting for around 40,000 cases in 2 million Americans)?
Caucasian Americans with alpha-1-antitrypsin deficiency
Emphysema can be regarded as a disease of destructive ________, inadequate ______ control, and insufficient _______ _______.
Emphysema can be regarded as a disease of destructive inflammation, inadequate anti-inflammatory control and insufficient wound repair.
What cytokines are present in the ongoing inflammation of emphysema?
Without alpha-1-antitrypsin, what happens to alveolar wall?
Without this antiprotease, the alveolar wall becomes destroyed (even in the absence of smoking but emphysema is accelerated in smokers with the deficiency)
List genetic polymorphisms that can lead to inadequate repair of elastin and contribute to the development of emphysema.
High levels of:
Poor repair response to:
At what point in a breath is a emphysema patient most likely to have collapsed airways? Why?
At expiration, the loss of elastic tissue reduces radial traction of the small airways and leads to collapse
How does emphysema lead to pulmonary hypertension?
loss of alveolar septal capillaries reduces pulmonary vascular capacitance--making the right heart pump the same amount of blood through a smaller network of vessels ( backing up pressure into the right right)
Emphysema can eventually lead to what disease (progresses from pulmonary HTN)?
Right heart failure (cor pulmonale)
Emphysema due to what is typically centriacinar?
Emphysema due to alpha-1-antitrypsin is typically panacinar
Emphysema due to smoking is typically centered around what structure?
respiratory bronchioles (spares alveoli)
Emphysema due to smoking is more severe in what lobes?
upper (especially apical segments)
Emphysema due to alpha-1-antitrypsin deficiency is more severe in what lobes?
What type of emphysema is typical in young adult male smokers with spontaneous pneumothorax?
distal acinar and associated with massively enlarged subpleural airspaces (bullae) in upper lobes
What two words describe the microscopic pathology of emphysema?
What is the most typical symptom of pure emphysema?
insidious onset of progressive dyspnea
What is the FEV1/FVC ratio for emphysema?
less than 0.7
What is chronic bronchitis?
productive cough for at least 3 months in 2 consecutive years in the absence of a specific diagnosis—mostly due to smoking
What is the pathogenesis of chronic bronchitis?
Toxins→ inflammation and hypersecretion of mucous/ hypertrophy of mucous secreting glands→ Obstruction
The inflammation associated with chronic bronchitis involves infiltration of what cell types?
What leads to the mucous hypersecretion associated with chronic bronchitis?
T cell cytokines like IL-13 and increased transcription of the MUC5AC gene (MUCking up airways)
leads to hypertrophy of submucosal mucous-secreting glands and bronchial goblet cell hyperplasia
Describe the gross pathology of chronic bronchitis.
Bronchial mucosal hyperemia and edema with luminal mucinous or mucopurulent exudate
What will you see under the microscope of lung tissue with acute bronchitis?
-enlargement of submucosal glands
-goblet cell metaplasia in bronchioles
-luminal mucous plugs in bronchioles
-fibrosis in bronchioles
What is the only sign/symptom of chronic bronchitis?
How do you diagnose chronic bronchitis?
How do you treat chronic bronchitis?
-Short-acting, Inhaled Bronchodilators:
-Long-acting, Inhaled anti-cholinergics
What is Bronchiectasis?
permanent dilation of bronchi due to destruction of muscle and elastic tissue by chronic or recurrent necrotizing infections
What three diseases can lead to the bronchial obstruction and chronic persistent infection that causes bronchiectasis?
1) Cystic Fibrosis
2) Immunodeficiency States
3) Kartagener syndrome
What is Kartagener syndrome?
rare AR disease causing ciliary impairment
What can lead to localized bronchiectasis?
bronchial tumor or necrotizing pneumonia
Describe the gross pathology of bronchiectasis.
Dilated bronchi (especially when close to visceral pleural surface); more pronounced in lower lobes
Describe the microscopic pathology of bronchiectasis.
scarred, dilated bronchi with intense acute and chronic inflammation
What type of sputum is coughed up with bronchiectasis?
copious purulent sputum
How do you diagnose bronchiectasis?
How do you treat bronchiectasis?
What is the definition of asthma?
chronic episodic obstructive airway disease due to reversible bronchoconstriction resulting from hyper-reactivity to various stimuli
What type of inflammation occurs in asthma?
What is involved with the early acute phase of Th2 type inflammation?
What is involved with the late acute phase of Th2 type inflammation (4-8 hours after attack and lasting 24 hours max)?
Leukotrienes C4, D4, E4
Describe the gross pathology of asthma.
Hyperinflated lungs +/- foci of atelectasis
Bronchial mucous plugs due to hypersecretion
Describe the microscopic pathology of asthma.
Bronchial luminal mucous and lots of neutrophils, the 3 C's, eosinophils, and submucosal edema (with mixed inflammatory infiltrate)
What are the 3 C's?
1) Curschmann's spirals
2) Charcot-Leyden crystals
3) Creola bodies
What are Curschmann's spirals?
small whorled mucous strands twisted in a common direction with a dense refractile coiled or braided core.
What are Charcot-Leyden crystals?
tiny crystals which are bipyramidal on longitudinal section and hexagonal on cross-section
What are Creola Bodies?
fragments of degenerated, sloughed respiratory epithelium
Describe the 6 changes that occur with airway remodeling.
1) Basement membrane thickening (2.5X larger)
2) Submucosal glandular hypertrophy/hyperplasia
3) Muscular wall hypertrophy and hyperplasia
4) Goblet cell metaplasia (and presence in bronchioles)
5) Bronchial epithelial hyperplasia
6) Submucosal thickening with fibrous tissue
How do you diagnose asthma?
History and Physical; spirometry
How do you treat asthma?
agonists; inhaled corticosteroids, antibody to IgE
What is pneumoconioses?
fibrosing restrictive lung diseases caused by inhalation of organic or inorganic particulates or chemical fumes
What is coal worker's pneumoconioses?
broad spectrum lung disease due to inhalation of coal dust ranging from asymptomatic non-fibrotic coal dust macules or fibrotic coal nodules to debilitating progressive massive pulmonary fibrosis
Black lung disease begins as what?
Anthracosis: Ingestion of carbon particles by alveolar macrophages
How does black lung disease progress from anthracosis?
inflammasome activation and IL-1 (due to non-carbon material in coal) can lead to fibrosis
What is the only way to definitively diagnose black lung?
lung exam by a pathologist
How can you treat black lung disease?
What is silicosis?
slowly progressive nodular fibrosing lung disease due to inhalation of silicon dioxide in stone (especially quarts) or coal released by processes that powderize some of it (ex. sandblasting)
What is the pathogenesis of silicosis?
Ingestion of silica by alveolar macrophages→ release of TNF, IL-1, ROS, TGF-beta, fibronectin→ chronic inflammation
Describe the gross pathology of silicosis.
discrete palpable grey-tan nodules +/- anthracotic pigment
Describe the microscopic pathology of silicosis.
nodules of concentrically arranged hyalinized collagen
What interesting, yet non-specific feature of silicosis can be seen under the microscope?
weakly birefringent particles are visible under polarized light
What is asbestosis?
slowly progressive pulmonary interstitial fibrosis due to inhalation of asbestos fibers
Asbestosis is associated with what conditions?
associated with pleural plaques, lung cancers, and mesotheliomas
What is a strange feature of the epidemiology of asbestosis?
has a long latency so expected to peak in 2024
How does asbestosis occur?
amphibole type asbestos passes through tissue by gravity (have pointed ends that cannot be broken by macrophages and iron-coated ends that elicit a fibrosing tissue reaponse)
Describe the gross pathology of asbestosis.
interstitial pulmonary fibrosis (mostly at basal lower lobes), visceral pleural fibrosis, and well-circumscribed round/oval tan/white fibrous plaques on lower parietal pleura and domes of diaphragm
Describe the microscopic pathology of asbestosis.
interstitial fibrosis and ferruginous bodies of fibers
What is sarcoidosis?
non-caseating granulomatous multi-system inflammatory disease of unknown cause
Where is sarcoidosis most common (body-wise)?
most common in lung, lymph node, eye, and skin
What is the most likely cause of sarcoidosis?
Unknown—but most likely immunologic stimuli→ Th1 CD4 lymphocyte response
What is the role of IL-8 in sarcoidosis?
acts early as a chemo-attractant of neutrophils
Which interleukins promote the Th1 immune response of CD4 lymphocytes?
IL-12, IL-18, IL-27
Which interleukins mediate the transition to fibrosing inflammation? How?
IL-4 (it is a chemoattractant to fibroblasts)
Describe the gross pathology of sarcoidosis.
small tan non-necrotic granulomas in lymphangitic distribution along bronchovascular bundles and in bilateral hilar LN +/- interstitial fibrosis in lungs
Describe the microscopic pathology of sarcoidosis.
tight naked granulomas with giant cells (with asteroid bodies and Schaumann bodies) and epitheloid macrophages
What is an asteroid body?
stellate eosinophilic aggregates of cytoskeletal proteins within vacuoles
What is a Schaumann body?
laminated basophilic concretion of calcified proteins
25% of patients with sarcoidosis have what accompanying sign?
skin nodules (granulomas) or erythema nodosum
What is the differential diagnosis if you see reticulonodular pulmonary infiltrates and bilateral hilar lymphadenopahty on x-ray?
True of false: non-infectious interstitial lung disease is usually chronic.
What is Usual Interstitial Pneumonia?
prototype chronic, slowly progressive, fibrosing inflammatory disease of the lungs involving predominantly the septa between air spaces
Describe the gross pathology of UIP.
fibrosis with large discrete scars worse in periphery and in lower lobes(lung is firmer and greyer)→ honey comb lung
Describe the microscopic pathology of UIP.
non-uniform patchy interstitial inflammation repair response and fibrosis with temporal heterogeneity
What is the hallmark of UIP?
fibroblast foci of immature fibrosis bulging into alveoli
What is temporal heterogeneity?
simulatneous presence of early, intermediate and late fibrosing lesions
What is the radiology diagnosis of UIP?
asymmetric bilateral irregular reticular(nodular) obacities at the bases and periphery with +/- a little ground-glass, traction bronchiectasis, honeycomb change
What is COP?
cryptogenic organizing pneumonia (bronchiolitis obliterans--organizing pneumonia) is a rare subacute fibrosing lung disease
COP is usually caused by what?
necrotizing infection (not cryptogenic)
What is the pathological hallmark of COP?
Masson bodies= plugs of fibrosing granulation tissue in alveoli and ducts
What do you see in a radiograph of COP?
bilateral opacities less dense than acute bacterial pneumonia or tumor→ ground glass and possibly air bronchograms
How can you treat COP and NSIP?
What is NSIP?
non-specific interstitial pneumonia (but it IS specific)
What are the two types of NSIP?
Cellular (more inflammatory than fibrotic)
Fibrotic (more fibrotic than inflammatory)
What can you see in a radiograph of NSIP?
bilateral ground glass opacities
When does radiation pneumonitis occur?
1-2 months after radiation
What is the microscopic pathology of radiation pneumonitis?
Type two pneumocyte hyperplasia
Blood vessel injury
Residual hemosiderin (later)
Interstitial lymphocytes (later)
Active fibroblasts (later)
Interstitial fibrosis (later)