P- Restrictive Lung Disease & Pulmonary Vascular Disease Flashcards
In restrictive lung disease, the key abnormality is impaired _______________ due to decreased __________ of alveolar septa, resulting in ________total lung capacity while ________ remains normal or reduced proportionately.
Impaired airway filling due to decreased elasticity (due to fibrosis) of the alveolar septa, resulting in reduced TLC while airflow is normal or reduced proportionately.
What are the two main physiological problems caused by interstitial lung disease fibrosis in the interstitium?
- The septa are stiff and limit the inspiratory volume increasing effort for inspiration
- Fibrosis of the alveolar wall decrease gas exchange by increasing distance from alveoli to capillary
What happens to the DLCO and FEV1/FVC in restrictive lung disease?
DLCO decreases while FEV1/FVC remains normal (because they both decrease proportionately)
What is the clinical presentation of adults respiratory distress syndrome?
What is the clinical course?
- rapidly progressive respiratory failure (24-48hrs)
- hypoxemia - required mechanical ventilation
- dyspnea
Prognosis is poor with 60% mortality.
Survival –> post-ARDS fibrosis leading to chronic pulmonary disease
What are the 4 most common causes that can result in ARDS?
- sepsis
- diffuse pulmonary infections/pneumonia
- gastric aspiration
- severe mechanical trauma with shock (head injuries)
Describe the pathogenesis of ARDS.
- Imbalance between proinflammatory (IL1, IL8, TNF) and anti-inflammatory (IL10, anti-proteases)
- activated macrophages release variety of cytokines that are chemotactic to neutrophils
- activated neutrophils release products that cause acute injury to alveolar capillary endothelial and epithelial lining
- Diffuse Alveolar Damage (DAD) with increased vascular permeability, loss of diffusion, necrosis of type II pneumocytes leading to surfactant loss, sloughing of surface epithelium, leadking of exudate into alveoli, hyaline membranes
What are the characteristic findings of DAD?
- increased vascular permeability
- decreased diffusion capacity
- type II pneumocyte destruction - less surfactant
- sloughing of surface epithelium
- leaking exudate into alveoli
- hyaline membranes
What is the gross morphology of ARDS?
Dark red heavy airless lungs
What is the microscopic appearance of ARDS in the acute stage? Organizing stage?
- DAD- edema, inflammation, fibrin deposition
Acute stage:
- intra-alveolar edema
- hyaline membrane formation
Organizing stage:
- proliferation of type II pneumocytes
- progressive interstitial fibrosis
What is the characteristic CXR appearance for diffuse interstitial lung disease?
Is this the definitive diagnostic standard?
Ground glass shadows
CXR is not the gold standard for diagnosis, the surgical lung biopsy is the gold standard.
However, clinical, radiologic, and histologic features are critical for accurate classification.
REgardless of etiology, end stage interstitial lung disease is always characterized by what histologic feature?
Diffuse interstitial fibrosis with or without honeycombing and cobblestone appearance.
What is the pathogenesis of diffuse interstitial lung disease?
Repeated cycles of lung injury and healing leads to widespread fibrosis and loss of lung function.
- macrophages secrete chemoattractants IL8 to activate neutrophils
- neutrophils release mediators that injure alveolar epithelial cells and connective tissue
- macrophages secrete mediators of wound healing (TGFb) that cause fibrosis
What are the 4 MAJOR categories of interstitial lung disease?
- fibrosing diseases
- smoking-related disorders
- granulomatous disorders
- eosinophilic disorders
What are the 4 major fibrosing interstitial lung diseases?
- Idiopathic pulmonary fibrosis
- Nonspecific interstitial pneumonia (NSIP)
- cryptogenic organizing pneumonia (BOOP)
- Pneumoconioses (silicosis, abestosis, pneumoconiosis)
What are the 2 smoking-related interstitial lung diseases?
- desquamative interstitial pneumonia
2. respiratory bronchiolitis
What are the 2 granulomatous disorders that cause interstitial lung disease?
- sarcoidosis
2. hypersensitivity pneumonitis
What are the clinical features of idiopathic pulmonary fibrosis?
Who is generally affected?
What is the prognosis and treatment?
Insidious onset and slow progression of dyspnea, dry cough, hypoxemia, and respiratory failure.
- older population (males>females)
- prognosis 3 years or less
- lung transplant is the only definitive therapy
What is the gross appearance of a lung that has IPF?
General appearance, cut surface, more severe areas, etc
- cobblestone appearance due to retraction of scar tissue along the interlobar septae
- cut surface shows fibrotic, compressed parenchyma
- severe in subpleural, interlobar and and lower lobes
- alternating areas of dilated air spaces and fibrotic scar bands
What is usual interstitial pneumonia? What fibrosing interstitial lung disease is it associated with?
It is the histologic pattern found in idiopathic pulmonary fibrosis, asbestosis, rheumatoid lung disease.
.
1. patchy interstitial fibrosis with temporal heterogeneity and varying intensity
2. cystic spaces (honeycomb lung)
3. variable interstitial lymphocytic infiltrates
How does the prognosis differ between Nonspecific Interstitial pneumonia (NSIP) and Idiopathic Pulmonary Fibrosis (IPF)?
NSIP is diffuse and treatable with a 90% 5 year survival.
IPF (with UIP) has a 20% survival
What is the pathology of NSIP?
temporally uniform interstitial inflammation and fibrosis
What is the clinical presentation of someone with NSIP?
45-55 years old with dyspnea and cough for several months
All other interstitial lung disorders have been ruled out.
Describe the microscopic features of cryptogenic organizing pneumonia.
What is the gold standard for diagnosis?
What is treatment?
Common response to infectious or inflammatory injury to the lungs:
** temporally uniform polyploid masses of myxoid fibroblastic tissue in peripheral airways and alveoli
Diagnosis: lung biopsy
Treatment: steroids for a long period of time
What are the 4 most common exposures that cause pneumoconioses?
- coal dust
- silica
- asbestos
- beryllium
The development of pneumoconiosis depends on the amount of dust retained in the lungs which depends on what 4 variables of the particle?
- size
- shape
- solubility
- reactivity
In addition to characteristics of the dust in pneumoconiosis (like size, shape solubility and reactivity) what else determines the amount of dust retained in the lungs?
- dust concentration
- duration of exposure
- effectiveness of clearance mechanisms
What are the 3 types of coal workers’ pneumoconiosis?
How many years of exposure is necessary before manifestation?
It takes 10 years of exposure to coal dust to manifest.
- asymptomatic anthracosis
- simple CWP
- complicated CWP/progressive massive fibrosis
Who is likely to get asymptomatic anthracosis?
What is the microscopic appearance?
It is carbon-induced pulmonary lesions in urban dwellers and smokers.
Microscopically:
carbon pigment is engulfed by marcrophages and accumulate in the connective tissue (usually in upper lobes)
Describe Simple CWP microscopically.
What lobe is more likely to be affected.
It is coal dust macules (less than 1cm) which are clusters of carbon-laden marcophages and nodules with small amounts of collagen fibers
Usually in the upper lobe
Who generally gets complicated CWP/progressive massive fibrosis?
What is seen grossly?
People that had simple CWP that has taken years to progress increasing pulmonary dysfunction
Grossly you see blackend scar larger than 2cm
What is seen microscopically in complicated CWP/progressive massive fibrosis?
dense collagen and carbon pigment
How do simple pneumoconiosis and complicated CWP differ in terms of progression?
Simple- nonprogressive after the removal of the stimuli
PMF - can appear long after the removal of the exposure and the lesion enlargens with time
Who is at greatest risk for developing silicosis?
Rock miners, sandblasters, pottery workers
What are the 2 forms of silica and which is more toxic?
Amorphous and crystalline. Crystalline is more toxic
Describe silicotic nodules.
Where are they located, what is their structure?
How do they look grossly and microscopically?
They are multiple discrete hard pale blue/green nodules in the upper lobe of the lung
Central necrosis my be present as a sign of superimposed TB.
Microscopically:
sharply demarcted by concentric hyalinized collagen with dust laden macrophages in the periphery
What are the clinical features of silicosis?
- asymptomatic- normal PFTs
- shortness of breath
- increased TB susceptiblity
- Caplan’s syndrome- silicosis AND rhematoid lung disease
What benign pleural lesions, benign parenychymal lesions and neoplasms are associated with asbestos?
Benign pleural:
- pleural plaque
- pleural effusion
Benign parenchymal:
1. interstitial fibrosis/asbestosis
Neoplasms:
- bronchogenic carcinoma
- mesothelioma
- laryngeal carcinoma
What are the 2 types of asbestos? Which is more prevalent? Which is more pathogenic?
- Amphibole- stiff and more pathogenic
2. Serpentine chrysotile- flexible and more prevalent
What is the pattern of fibrosis seen with asbestosis?
What are unique characteristics morphologically?
UIP in the lower lobes and subpleura
Morphology:
- asbestos bodies - gold brown (iron) rods with translucent centers
- Pleural plaques- dense collagen in parietal pleura and diaphragm
What are the morphologic forms seen in desquamative interstitial pneumonia (DIP)?
What are the clinical features of someone who has this?
diffuse accumulation of pigmented macrophages (iron) in alveolar spaces with mild interstitial fibrosis.
Insidious onset of dyspnea/cough in chronic smokers.
What are the morphological characteristics of Respiratory Bronchiolitis-associated interstitial lung disease?
Patchy bronchocentric distribution of iron filled macrophages and interstitial fibrosis.
What is the treatment for smoking related interstitial diseases (desquamative interstitial pneumonia and respiratory bronchiolitis-associated ILD)?
Cessation of smoking
Steroids
What type of interstitial lung disease is sarcoidosis? What structures are majorly affected?
What are secondary structures that are affected?
Granulomatous disease of the lung and mediastinal lymph nodes.
skin, heart, spleen, liver, CNS(VII- facial paralysis)
bone marrow, eyes
What is the main morphological feature of sarcoidosis?
- Non-caseating granulomas (giant cells, histiocytes, with very few or NO surrounding lymphocytes(naked)).
The granulomas are in lung parenchyma, lymphatics, and bronchioles
- Schaumann Bodies- laminated concretions of calcium/proteins
- Asteroid bodies- eosinophilic stellate inclusions with giant cells
How is diagnosis of sarcoidosis made?
It is a diagnosis of exclusion- rule out mycobacterial , fungal, berylliosis
What are clinical features of sarcoidosis?
Who is likely to get it?
It affects younger adults ( whites
women > men
Patients can have bilateral hilar lymphadenopathy, lung involvement, skin, heart, liver, spleen, CN7, bone marrow, eyes involvement
Characterized by progressive chronicity or periods of activity interspersed with remission
What are the most important lab values for determining sarcoidosis?
- ACE elevation
- hypercalcemia
- decreased CD4 lymphocytes
What are the major forms of hypersensitivity pneumonitis?
They are all hypersensitivity reactions (III or IV) to inhaled organic dust antigens
- Farmer’s lung- actinomycetes in warm hay
- Pigeon Breeders- excreta or feathers of birds
- humidifier/air conditioner lung- bacteria in heated water reservoirs
What is the microscopic findings of hypersensitivity pneumonitis?
- patchy lymphocytic infiltrate (peribronchial)
- mild fibrosis
- interstitial non-caseating granulomas
- honeycomb lung
What are the 5 major eosinophilic diseases associated with interstitial lung disease?
- acute eosinophilic pneumonia with respiratory failure
- simple pulm. eosinophilia (Loffler’s)
- tropical
- secondary
- idiopathic chronic eosinophilic pneumonia
What is the definition of pulmonary hypertension?
Mean pulmonary blood pressure reaches 1/4 (normal is 1/8) of systemic level
What are the four most common causes of pulmonary hypertension?
- COPD or ILD - loss of capillaries = increased vascular resistance
- recurrent PE - reduction in functional cross sectional area of pulmonary vascular bed
- heart disease with mitral stenosis/LtoR shunts
- idiopathic- seen in young women
What is the pathogenesis of secondary pulmonary hypertension?
- increased blood flow leads to endothelial or vascular smooth muscle dysfunction
- vasodilator production is decreased (NO and prostacyclin) and vasoconstrictors (endothelin) are increased
- GFs and cytokines induce the migration of vascular smooth muscle cells increasing pulmonary vascular resistance
What is the suspected cause of primary hypertension?
TFG-b pathway abnormality
Bone morphogenetic protein receptor type 2 (BMPR2) is a cell surface protein that binds cytokines and inhibits proliferation of smooth muscle which can lead to vascular thickening.
What are the common morphological features of pulmonary hypertension?
Small/medium vessels: medial hypertrophy and intimal proliferation
Larger vessels : atheroma formation
All have plexiform lesions - capillaries form and fill the lumen of the arteries
What triad is associated with diffuse alveolar hemorrhage syndromes?
- hemoptysis
- anemia
- diffuse pulmonary infiltrates
What are the 3 major diffuse alveolar hemorrhage syndromes?
- Goodpasture’s
- Idiopathic pulmonary hemosiderosis
- Wegener’s granulomatosis
What are the pathological lung findings of Goodpasture syndrome?
What other organ is typically involved?
In the lung there is intra-alveolar hemorrhage with the presence of hemosiderin (free or in macrophages.
There is also glomerulonephritis associated with Goodpasture
What is the pathology of idopathic pulmonary hemosiderosis?
Who is generally affected?
What is the prognosis?
It presents similarly to Goodpasture (alveolar hemorrhage with hemosiderin) but there is no renal involvement or immunoglobin deposition.
It mainly affects children- mild course with full remission
What is Wegener’s granulomatosis? What organs are affectd?
What factor is crucial for diagnosis?
It is systemic necrotizing vasculitis that especially involves the upper and lower respiratory tract and the kideys (glomerulonephritis).
Lungs have inflammation and fibrinoid necrosis and parenchymal granulomatous inflammation.
C-anca
