Obstructive & Restrictive Lung Disease, Vascular Disease, Pleura Flashcards
3 types of acquired atelectasis
Resorption
Compression
Contraction
Atelectasis characterized by aiway obstruction with gradual resorption of air reducing lung expansion
Resporption
Atelectasis characterized by fibrotic or other innate restrictive process in the pleura or peripheral lung restricting lung expansion
Contraction atelectasis
Atelectasis characterized by accumulated material in pleural cavityy, squeezing the lung parenchyma
Compression atelectasis
Interstitial fluid in alveolar spaces shows up as pink proteinaceous material on histological slides of lung parenchyma, what condition is this indicative of?
Pulmonary edema
What are some hemodynamic causes of pulmonary edema?
“Pushing out” — Left sided heart failure (MCC), volume overload, pulmonary vein obstruction
“Leaking out” — hypoalbuminemia, nephrotic syndrome, liver dz
Pulmonary edema may also occur due to injury to alveolar wall. What might cause this type of injury?
Bacterial pneumonia
Sepsis
Smoke inhalation
Aspiration
What are 2 important causes of pulmonary edema of which the mechanism is unknown?
Neurogenic (brain injury)
High altitude
2 diseases on the ARDS spectrum
Acute lung injury (ALI) — acute onset, hypoxemia, bilateral infiltrates, no evidence of cardiac failure
Acute respiratory distress syndrome (ARDS) — worsening hypoxemia
Condition that is diagnosed based on presence of histologic manifestations of ARDS
Diffuse Alveolar Damage (DAD)
2 pathogenic mechanisms for infection with ARDS
Either due to inhalation or because something has entered bloodstream (sepsis, bacteremia, etc.) - so it can come from airway or circulation!
Physiologic measurement used to characterized degree of hypoxia in ARDS
PaO2/FiO2 ratio
If <300 it can be characterized as ALI, if it is <200 it can be characterized as ARDS [so ALI is basically mild form of ARDS]
4 characteristics necessary for diagnosis of ARDS
Abrupt onset of symptoms
Hypoxemia (PaO2/FiO2 <200)
Bilateral infiltrates
Non-cardiac in nature
Pathogenic mechanism of ARDS
Acute lung injury —> endothelial activation —> adhesion/extravasation of neutrophils —> accumulation of intraalveolar fluid, formation of hyaline membranes —> resolution of injury
Diffuse alveolar damage (DAD) is characterized by ______ membranes composed of edema + fibrin + cell debris.
What are 2 other characteristics associated with diffuse alveolar damage?
Hyaline
Decreased surfactant —> stiff lungs
Decreased aeration —> ventilation-perfusion mismatch (RBCs not getting close enough to airways due to hyaline!)
4 Stages of progression of ARDS
- Exudative (edema, hyaline membranes, neutrophils)
- Proliferative (fibroblast proliferation, organizing pneumonia, early fibrosis)
- Fibrotic (extensive fibrosis, loss of normal alveolar architecture)
- Either RESOLUTION or FIBROSIS —
Resolution: restoration of normal cell structure/function
Fibrosis: destruction/distortion of normal cell structure
NOTE fibrosis is IRREVERSIBLE
Compare/contrast acute interstitial pnuemonia different from ARDS/DAD?
AIP has same clinical presentation as ARDS
AIP has same histology as ARDS/DAD
Difference is that AIP cannot be attributed to a specific etiology (AIP often presents in middle aged women, usually preceded by a viral illness)
MCC of COPD/Chronic bronchitis
Smoking
Obstructive pulmonary disease characterized by alveolar wall destruction and overinflation
Emphysema
Obstructive pulmonary disease characterized by productive cough and airway inflammation
Chronic bronchitis
Reversible obstructive pulmonary disease characterized by bronchial hyperresponsiveness triggered by allergens, infection, etc.
Asthma
Diagnostic criteria for chronic bronchitis
Persistent cough with sputum production for 3 months out of 2 consecutive years
Predominant pathophysiologic mechanism in chronic bronchitis
Mucous gland hyperplasia —> damage to airway epithelium
3 primary complications of chronic bronchitis
Squamous metaplasia —> dysplasia —> carcinoma
Bronchiectasis
Death from respiratory infection
Clinical presentation of emphysema on CXR and PFTs
CXR: Enlarged lungs, flattened diaphragm, and increased AP diameter
PFTs: FEV1/FVC reduced
Characteristic patient presentation of chronic bronchitis
“Blue bloaters”
Overweight and cyanotic
Elevated hemoglobin
Peripheral edema
Rhonchi and wheezing
Characteristic patient presentation of emphysema
“Pink puffers”
Older and thin
Severe dyspnea
Quiet chest
X-ray: hyperinflation with flattened diaphragms
Pathogenic mechanism of alpha-1 antitrypsin deficiency
Deficiency in alpha 1 antitrypsin (trapped in liver, causes liver damage) leaves neutrophil elastase uninhibited, which causes lung damage
What type of emphysema is present in alpha1 antitrypsin deficiency?
Predominantly basilar panacinar emphysema
[differentiate from COPD which is centrilobular, centriacinar, or proximal acinar]
Genetic mechanism of alpha 1 antitrypsin deficiency
Deficiency encoded by Pi (proteinase inhibitor) gene on Chr14; Z allele is associated with decreased circulating enzyme
Homozygous PiZZ individuals have markedly decreased a1-AT, with a majority developing panacinar emphysema
[Serum testing for a1-AT is the primary means of dx]
4 primary complications of emphysema
Respiratory failure
Coronary artery disease
Right heart failure (cor pulmonale)
Pneumothorax with lung collapse
3 components of asthma
Recurrent airway obstruction with a reversible component
Airway hyperresponsiveness
Airway inflammation
What are the 2 types of asthma?
Atopic (extrinsic) — 2/3 of all pts
Non-atopic (intrinsic) — 1/3 of all pts
Describe atopic asthma in terms of demographics and diagnostic features
Atopic asthma represents 2/3 of all asthma patients; may affect any age but typically presents in childhood
There is usually family hx of asthma
Characterized by elevated IgE levels (type I hypersensitivity) — eosinophils, mast cells, lymphocytes
Triggers may include a variety of allergens
Describe non-atopic asthma in terms of demographics and diagnostic features
Non-atopic asthma represents 1/3 of all asthma pts, often older pts
Typically normal IgE levels — T lymphocytes and neutrophils
Triggers may include cold, exercise, infection
Immune mechanism of atopic asthma using pollen as example
Pollen Ag recognized by dendritic cell, which signals to Th2 CD4+ cell
Th2 cell overreacts (hyperreactive phenomenon characteristic of asthma), and tells B cell lineage to form IgE antibodies at high levels
Mast cells attracted by IgE, eosinophils recruited and the next time the immune system recognizes pollen, mediators react very strongly producing asthmatic symptoms
What mediators are responsible for the symptoms seen in asthma?
Bronchoconstriction is d/t Leukotrienes C4-D4-E4, histamine, prostaglandin D2, ACh
Mucus secretion and increased vascular permeability d/t leukotriens C4-D4-E4
Recruitment of inflammatory cells due to interleukins
What are the consequences if asthma goes uncontrolled for long periods of time?
Progressive structural changes to airways with characteristic histologic findings = fibrosis, smooth muscle hyperplasia, increased goblet cells and submucosal glands
Changes may be IRREVERSIBLE! There will also be a decreased response to therapeutic agents like bronchodilators and corticosteroids
Unremitting, possibly fatal asthma attack resulting from bronchial occlusion by thick mucus
Status asthmaticus
Characteristic histologic findings associated with status asthmaticus
Coiled mucus plugs: “Curshchmann spirals”
Eosinophils and breakdown product — Charcot Leyden crystals
Other conditions and genetic factors associated with atopic asthma
Associated with seasonal allergies and eczema
May be linked to various alleles controlling factors like IgE, cytokines (IL-4), adrenergic receptors, etc.
Environmental factors impacting asthma
Disease of industrialized societies — pollution, lack of allergen exposure at early age
Early infection
Samter’s triad includes what specific type of asthma? What are the other 2 disease associations?
- Aspirin-sensitive asthma
- Nasal polyps
- Recurrent rhinitis
Pathologic mechanism of aspirin sensitive asthma
When COX enzymes inhibited by aspirin or other NSAID, arachidonic acid is shunted into 5-lipoxygenase pathway which results in some production of leukotrienes C4-D4-E4, which are responsible for bronchoconstriction, mucus secretion, and increased vessel permeability resulting in asthmatic symptoms
End stage process of multiple chronic respiratory conditions (infection, obstruction, ABPA, CF, etc.) charcterized by a necrotizing inflammatory response
Bronchiectasis
What condition is defined by dysfunction of dynein arm of microtubules resulting in characteristic triad of respiratory symptoms as well as male infertility?
Kartagener’s syndrome: Primary Ciliary Dyskinesia
Triad of sx associated with Kartagener’s syndrome: Primary Ciliary Dyskinesia
Sinusitis
Bronchiectasis
Situs inversus
Difference in ciliary ultrastructure between PCD and CF
PCD has abnormal ciliary ultrastructure
CF has normal ciliary ultrastructure; damage of cilia occurs secondary to other disease processes
Difference in etiology of male infertility in CF vs. PCD
CF — congenital bilateral absence of vas deferens
PCD — immotile sperm (this disease results in abnormal cilia AND flagella!)
[can also differentiate from Young’s syndrome male infertility which results from retained sperm in epididymis]
What is ABPA?
Allergic bronchopulmonary aspergillosis: exaggerated hypersensitivity response to aspergillus infection overlying chronic lung disease (asthma or cystic fibrosis)
ABPA results in increased ____ on serum testing, as well as positive _____ test. There is thick mucus in bronchi as well as ________ characteristic of aspergillus infection. It is associated with _______ in advanced disease
IgE; skin; fungal hyphae; bronchiectasis
Histologic findings with ABPA
Silver stain demonstrates aggregates of fungal hyphae characteristic of Aspergillus spp. (characteristic septations of hyphae and narrow angle branching)
5 categories of restrictive lung disease
Fibrosing: idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, connective tissue disease-associated, pneumoconiosis, drug reactions, radiation pneumonitis
Granulomatous: sarcoidosis, hypersensitivity pneumonitis
Eosinophilic
Smoking related: desquamative interstitial pneumonia, respiratory bronchiolitis-associated ILD
Other: Langerhans cell histiocytosis, pulmonary alveolar proteinosis, lymphoid interstitial pneumonia
Factors involved in pathogenesis of idiopathic pulmonary fibrosis
Environmental factors — industrialized societies, smoking
Genetic factors
Age — typically 50+
Clinical findings of idiopathic pulmonary fibrosis
Dyspnea
Crackles on exam = “Velcro-like”
Restrictive pattern on PFT’s — decrease in DLco, FVC
Basilar infiltrates - progression to “honeycomb” lung
Classic findings on what test is required for diagnosis of idiopathic pulmonary fibrosis?
High-resolution CT scan OR pulmonary biopsy
[biopsy shows usual interstitial pneumonia (UIP) characterized by normal and fibrotic areas, fibroblast foci, peripheral honeycombing]
T/F: Honeycomb fibrosis is specific to interstitial pulmonary fibrosis
False, it is just the end-stage of IPF
Prognosis of idiopathic pulmonary fibrosis
It is progressive, most pts expire from respiratory disease 3-5 years after diagnosis
Potential therapies: lung transplant, medication to arrest fibrosis (tyrosine kinase inhibitors, TGF-beta inhibitors)
Idiopathic lung condition with unique histology consisting of uniform infiltrates and fibrosis, no heterogeneity, no fibroblast foci, no granulomata, and it has an overall better prognosis than UIP
Non-specific interstitial pneumonia (NSIP)
[note that NSIP is NOT non-specific because it has unique histology]
Respiratory condition that presents with pneumonia-like consolidation in 5-6th decades and exists as a diagnosis of exclusion when there is no infection, drug or toxin, or relation to CT disorders
Cryptogenic Organizing Pneumonia (COP)
[formerly BOOP — bronchiolitis-obliterans-organizing pneumonia]
Histologic findings and prognosis associated with cryptogenic organizing pneumonia
Fibroblast (Masson bodies) — organizing plugs of CT
Good prognosis - pts tend to have full recovery with oral steroids
What autoimmune diseases can manifest as ILD (UIP, NSIP, organizing pneumonia, bronchioloitis)?
Rheumatoid arthritis
Systemic sclerosis
Lupus erythematosus
[note that if ILD occurs as a manifestation of these conditions, they are not diagnosed as pure diseases, but the prognosis is linked to treatment of the underlying condition]
Of the interstitial lung diseases, which ones are considered granulomatous diseases?
Sarcoidosis
Hypersensitivity pneumonia
Systemic disease manifesting non-caseating (non-necrotizing) granulomata that presents as incidental abnormal radiograph, or with c/o dyspnea
Sarcoidosis
Clinical presentation of sarcoidosis
In addition to incidental radiograph findings or dyspnea, pts also tend to have:
Elevated serum ACE levels
Pts also tend to be <40 y/o, 10-fold predominance in african americans, commonly involves the lungs (also LNs or anywhere around the body)
[etiology is likely immune-related; possible genetic predisposition]
Characteristic granuloma inclusions seen in sarcoidosis
Asteroid body
Schaumann bodies
[in addition to other granulomata findings like histiocytes, multinucleated giant cells, some lymphocytes, fibrotic sclerotic stroma, tight formation]
The stages of sarcoidosis do not occur in order. 20% of patients have progressive lung disease. Death may occur via involvement of what systems?
Pulmonary, cardiac, or neurologic
Respiratory condition caused by immune reaction to inhaled antigen resulting in airway-centered granulomata with associated lymphocytes
Hypersensitivity pneumonitis
Diagnosis of hypersensitivity pneumonitis requires a detailed history. What are some environmental exposures that might trigger this disease?
Pigeon breeder’s lung — protein from bird feces
Farmer’s lung — actinomycetic spores in hay
Hot tub lung — reaction to mycobacterium avium complex (MAC)
Disease affecting smokers in 4-5th decades with restrictive lung disease presentation and shows characteristic “stuffed” alveolar spaces full of macrophages on histology
Desquamative interstitial pneumonia (DSIP)
Treatment and prognosis of desquamative interstitial pneumonia (DSIP)
Treatment: stop smoking, corticosteroids
Good prognosis: >95% survival at 5 years
Disease that exists as part of a spectrum with DSIP, but less symptomatic and earlier presentation (3rd-4th decades) and has dose-dependent relationship to smoking; radiographic abnormalities prompt biopsy for diagnosis
Respiratory brionchiolitis interstitial lung disease (RB-ILD)
Histologic findings associated with RB-ILD
Macrophages present to lesser extent
“Peribronchiolar” metaplasia (abnormally located ciliated cells)
May have fibrosis in advanced cases
T/F: RB-ILD is often reversible with smoking cessation if caught early
True
Lung disease found in young smokers and characterized by stellate lung lesions, progressive scarring leads to cysts and peripheral cysts may rupture and present with pneumothorax
Langerhans Cell Histiocytosis (LCH)
Histologic findings associated with Langerhans Cell Histiocytosis (LCH)
Eosinophils
Langerhans cells (immature dendritic cells) — S-100 and CD1a positive!!!
Varying fibrosis and cysts
What is the best way to reverse Langerhans Cell Histiocytosis?
Smoking cessation!
Respiratory disease characterized by impairment of surfactant metabolism due to defect of GM-CSF resulting in accumulation of surfactant proteins throughout alveoli and airspaces
Pulmonary alveolar proteinosis
Pulmonary alveolar proteinosis may be autoimmune (>90%), secondary to other disease, or hereditary (very rare). It can be treated with ______
Subcutaneous GM-CSF
Histologic and bronchioloalveolar lavage findings with pulmonary alveolar proteinosis
Histology: proteinaceous collections in alveolar spaces (appears similar to pulmonary edema on histology, need history to make dx)
Fluid from bronchioalveolar lavage shows copious milky fluid
Reaction by the lungs to inhaled mineral or organic dust - often due to occupational exposure or air pollution (exaggerated response in some individuals indicates possible genetic component)
Pneumoconiosis
Aggravating factors of pneumoconiosis
Worse if exposure is high and repetitive, size of particles is small (means they can reach alveoli), and impaired ciliary clearance d/t smoking
Coal worker’s pneumoconiosis is a disease due to inhaled coal dust, with a spectrum of disease including what 3 components?
Anthracosis
Coal macules/nodules
Progressive massive fibrosis
[most pts will not have progressive dz]
What is silicosis?
Disease resulting from inhaled silicon dioxide — occurs in mining/quarry work, concrete repair, demolition, etc.
Insidious in onset, can occur after exposure is no longer present
May progress to massive pulmonary fibrosis and has 2x risk of developing cancer (as opposed to CWP)
Histologic and radiographic findings characteristic of silicosis
Histology: dense collagenous nodules
Radiographic: eggshell calcifications (calcified hilar LNs)
Interstitial and pleural disease resulting from inhalation of asbestos fibers in which risk correlates with exposure (insulation, shipyards, paper mills, oil or chemical refinery)
Asbestosis
Disease manifestations of asbestosis
Pleura — fibrosis/fibrous plaques, effusions, mesothelioma
Lung — interstitial fibrosis, carcinoma
Possibly extrapulmonary neoplasms
2 types of asbestos fibers and which one is most dangerous
Serpentine
Amphibole — most dangerous, able to be inhaled deeper into lungs
Characteristic histologic finding associated with asbestosis
Asbestos bodies (consist of central filament, asbestos itself, and macrophage debris)
Pleural plaque formation (known as “candlewax drippings”) manifests on histology as hyalinized collagen
Pulmonary emboli may be defined as obstruction of pulmonary vessels by what structures?
Blood clot (“true” thromboembolism)
Bone marrow/fat
Cancer (tumor embolus)
Septic emboli
Air
Foreign material
Parasites (dorofilaria)
In what patient populations might you see talc embolism?
IV drug users
Describe appearance of pulmonary infarcts
Wedge shaped lesions
Begin as hemorrhagic, then fibrosis sets in (red—> white infarct)
Define pulmonary hypertension
Pulmonary artery pressure (PAP) greater than 25 mmHg
Histologic findings associated with pulmonary HTN
Plexiform lesion — very characteristic!
Medial hypertrophy (smooth muscle in small arteries is good indicator)
3 pulmonary hemorrhage syndromes
Goodpasture syndrome
Polyangiitis with granulomatosis (Wegener’s)
Idiopathic pulmonary hemosiderosis
What does Goodpasture syndrome show on immunofluorescence?
Linear pattern of deposition d/t anti-basement membrane Abs
Pulmonary hemorrhage syndrome typically found in male smokers in their teens/20s, characterized by heavy red-brown lungs with necrosis, hemorrhage, and hemosiderin-laden macrophages, as well as linear deposits of Ig along basement membrane; clinical features include hemoptysis, focal pulmonary consolidation, renal failure, and possibly death d/t uremia
Goodpasture syndrome
Pulmonary hemorrhage syndrome d/t autoimmune dz associated with hemoptysis, capillaritis, and scattered, poorly formed granulomas unlike those seen in sarcoidosis
Polyangiitis with granulomatosis
Pulmonary hemorrhage syndrome associated with intermittent, diffuse alveolar hemorrhage of which the cause and pathogenesis is unknown; it is most often seen in young children, with insidious onset of productive cough, hemoptysis, and anemia, plus diffuse pulmonary infiltration
Idiopathic pulmonary hemosiderosis
