Pathology Of Restrictive Lung Diseases Flashcards
PFT values in restrictive diseases
FEV is reduced
FEV1 is reduced
FEV1/FVC ratio is either normal or increased
2 general categories of restrictive lung diseases
1) chest wall disorders w/ normal lungs
- obesity, pleural diseases, neuromuscular disorders
2) disorders of the lung parenchyma w/ normal chest wall
- ARDS
- pneumonconioses, interstital fibrosis
- sarcoidosis
What are the end-stage conditions of restrictive lung diseases?
Respiratory failure, pulmonary HTN and cor pulmonale
causes ventilation- perfusion ratio mismatches and hypoxia
Idiopathic pulmonary fibrosis
Fibrosis category of restrictive lung disease
Unknown etiology that is characterized by patchy, progressive bilateral interstitial fibrosis
Most commonly affects males, but can affect females
Almost always occurs after age 50
- Requires usual interstitial pneumonia pattern to diagnose*
Cellular senescence and IPF
It is hypothesized that repeated injury and defective repair of alveolar epithelium eventually causes germ line mutations that’s leads to a loss of telomerase.
- causes premature cellular senescence and prevents mitosis
Also is hypothesized that exuberant fibroblastic foci is developed, leading to mass fibrosis
IPF morphology
Pleural surfaces of the lung look cobble-stoned and hard
- also possess rubbery white areas of fibrosis, mostly in the lower lobe of the lungs
Histologically shows honeycomb fibrosis
- formed by hyperplastic type 2 pneumocystis and causes alveolar wall collapse
IPF clinical features
Nonproductive (no sputum) coughing w/ progressive dyspnea
Velcrolike crackles (dry rales)
Shows cyanosis, peripheral edema in late stages
Honeycombing on xrays and CTs
Treatments
- NO anti-inflammatory
- anti-fibrotic therapies are good, but only if caught early and most are not
- lung transplant is the only definitive treatment (however this is really high risk)
Pneumoconioses
Lung disorders caused by inhalation of organic/inorganic dusts/particles
Three most common (not in order) are:
1) coal dust * not reactive*
2) silica reactive
3) asbestos reactive
Note: this is especially problematic in cystic fibrosis patients since mucocillary movement is primary mover in getting these particles out
Pathogenesis of pneumoconioses
Dependent on the following characteristics
1) size
- > 5 microns in size = get lodged in upper airways
- <0.5 microns in size = move into the alveoli and come out normally
- 1-5 microns in size = get larger in alveoli and are the MOST dangerous
2) shape
3) reactivity of the particles
Pneumoconioses pathogenesis
Following phagocytosis by macrophages, many particles activate the inflammasome and produce IL-1
- cause fibroblast proliferation and collagen deposition
Coal workers pneumoconiosis
Includes 3 sub types
1) asymptomatic Anthracosis
2) simple coal workers pneumoconiosis
3) complicated CWP or progressive massive fibrosis (PMF)
All 3 produce black lung disease due to carbon pigmented macrophages getting trapped in the vasculature
Symptoms/signs
- usually asymptomatic and benign (until it hits #3)
- in PMF, cause spulmonary HTN, dyspnea, chest pain, peripheral edema and cor pulmonale
Silicosis
THE MOST PREVALENT CHRONIC OCCUPATIONAL DISEASE
Caused by inhalation of silica
- causes activation of inflammasomes and produces increased fibrogenic cytokines
Morphology
- shows tiny and discrete pale/black nodules in upper zones of the lungs only
- lots of collagen fibers surrounding the tissues
Clinical features:
- fine nodules in the upper lung zones and the outlining of the lungs on xrays
- most symptoms are not present until PMF is present
- increased susceptibility to TB* and often shows granulomas
Treatment:
Asbestos
Includes a wide group of crystalline silicate particles
Causes some of the following
1) parenchyma interstital fibrosis
2) localized fibrous plaques
3) pleural effusions
4) lung cancers
5) mesothelioma (malignant lung cancers)
Signs/symptoms
- progressively worsening dyspnea (usually diagnostic 10 yrs after exposure)
- productive cough
- disease usually remains static, but can progress to CHF/cor pulmonale
Asbestosis unique pathogenesis
Functions as both a tumor initator and promoter
- generates reactive free radicals, destroying mesothelium in the distal lungs/lower lobes
- spreads to middle and upper as disease progresses
Also increases absorption of potentially toxic chemicals that may be inhaled
- amplifies toxic chemical effects
Shows honeycombing as well (similar to IPF)
Also can develop calcium plaques on the diaphragm or base of the lungs
morpholgoy shows unique golden brown staining asbestosis bodies
Asbestosis and cancer relationship
Risk for developing lung carcinomas
- 5x increase
Mesothelioma
- 1000x increased
note both values increase even more if you are smoking also
