Lung B37 Diffuse alveolar damage, pneumoconioses Flashcards
What is diffuse alveolar damage?
DAD, The pathological changes of tissue that are associated with the clinical syndrome ARDS.
How does diffuse alveolar damage produce its clinical symptoms?
Any source of injury to the pulmonary capillary endothelium or alveolar epithelium
- Excessive inflammatory signalling, for example in sepsis, anaphylaxis, DIC. Proteolytic damage of the capillary endothelium, and excessive pulmonary capillary permiability –> fibrin exudate, hyaline membrane formation and ARDS.
- Alveolar type 2 pneumocyte damage. Decreased production and loss of surfactant, alveolar collapse, ARDS.
What is the morphology of diffuse alveolar damage-
on gross specimen? histology?
Acute stage:
- Lungs are very large, heavy, and firm, due to edema and hyaline membranes
- Dark red (not blue) and airless
- Edema and intra-alveolar _hyal_ine membranes
Organizing stage, chronic stage. (doesn’t occur often, as mortality is near 100% in acute stage)
- Diffuse interstitial fibrosis, heavy lungs
- Thickened, collagenous, fibrotic intralveolar septa and proliferation of Type 2 pneumocytes.
What things can cause diffuse alveolar damage?
- Sepsis, usually from gram negative bacteria
- Septic shock,
- Anaphylactic shock,
- neurogenic shock,
- severe pulmonary infection,
- DIC,
Contrast the general changes of obstructive disorders vs. restrictive disorders
Obstructive diseases: emphysema, chronic bronchitis, bronchiectasis, athsma
- Increased resistance of airflow
- FVC is normal or slightly decreased, but FEV1 is strongly decreased.
- FEV1/FVC is strongly decreased
- In some of the the RV and FRC is increased
Restrictive diseases: pneumoconiosis, idiopathic pulmonary fibrosis, sarcoidoses, pleuritis, pleural effusion, Guillian-Barre syndrome, ARDS
- Reduced compliance of lung tissue
- FVC is decreased, FEV1 is decreased,
- FEC1/FVC is normal.
Define pneumoncoiosis
A diffuse interstitial lung disease, fibrosing, restrictive.
A term used to describe the non-neoplastic reaction of the lung to inhaled dusts, particles, or in some cases chemical fumes and vapors.
What are the inhaled substances that cause the 3 major types of pneumoconiosis?
Coal: Coal miners pneumoconiosis
Silica: Silicosis
Asbestos: Asbestosis
How does the size of the inhaled particles affect the severity of pneumoconiosis?
1-5uM sized particles are the most dangerous. Get loged at bifurcations of the small airways.
Bigger particles do not reach the distal airways.
Smaller particles move to the alveoli but can be readily absorbed/removed by the macrophages/blood without much deposition.
Describe the general pathogenesis of pneumoconiosis
Inhaled particles accumulate in the lung. Alveolar macrophages phagocytose them, the macrophages are damaged or have the inflammasome activated and release IL-1.
IL1 triggers inflammatory mediators, tissue damage, fibrosblast proliferation, collagen deposition, and fibrosis
Smoking synergistically worsens the effects of all inhaled mineral dusts.
Describe Coal Worker’s Pneumoconiosis
From inhaled coal, which is composed of mostly carbon and varying degrees of silica. Silica and Iron content increasesseverity. Silica forms SiOH, which is kills macrophages that engluf it without being cleared, and continues to chronically stimulate fibrosis.
3 forms:
- Anthracosis is the mildest form of the disease.
- Simple CWP, Nodes of dense, black anthrocotic pigment deposition surrounded by lots of collagenous fibrosis.
- Progressive Massive Fibrosis or Complicated CWP, Black lung. Extensive anthracosis and fibrosis throughout the whole lung, compromised lung function.
- It begins in the Upper parts of the lung first.
It does not increase the risk for lung cancer.
Describe Silicosis
The most common chronic occupational health disease in the world.
Silica causes the SiOH molecules which are toxic to macrophages without being cleared, causing a more rapid progression to Progressive Massive Fibrosis (end stage honeycomb lung) than coal.
TNF and IL-1 release by macrophages drive inflammatory damage and progressive fibrosis.
Generates nodules of concentric, hyalinized, eosinophillic collagen fibers (hyalinized here means the glasslike appearance). Whorled collagen depositions with birefringent silca particles in the center.
Describe Asbestosis.
What disorders can asbestos exposure cause?
Asbestos: Crystalline hydrated silicate molecules
Asbestos exposure can cause:
- Parenchymal interstitial fibrosis (asbestosis)
- Localized fibrosis or diffuse pleural fibrosis.
- Lung carcinomas
- Mesotheliomas
- Laryngeal Carcinomas
Asbestosis:
- Diffuse pulmonary interstitial fibrosis, that looks identical to usual interstitial pneumonia, seen in idiopathic pulmonary fibrosis
- With the addition of asbestos bodies.
- Look like brown beads or beaded rods, are the asbestos fibers that become coated with iron-containing proteins inside of macrophages.
- Asbestosis begins in the lower lobes and progresses upwards.
- Pleural plaques are the hallmark feature of asbestos exposure. Well circumscribed plaques of calcified collagen deposition on the parietal pleura, usually over the domes of the diaphragm (again at the bottom) they do not contain asbestos bodies.
What is honeycomb lung and what causes it?
It is the generic term for the end stage of chronic interstitial lung disease.
With thickened fibrotic regions and many wide cystic spaces.
Causes:
Fibrosing
Idiopathic pulmonary fibrosis - usual interstitial pneumonia
Nonspecific interstitial pneumonia
Cryptogenic organizing pneumonia
Associated with collagen vascular disease
Pneumoconiosis
Associated with therapies (drugs, radiation)
Diffuse scleroderma
Granulomatous
Sarcoidosis
Hypersensitivity pneumonia
Eosinophilic
Loeffler syndrome
Drug allergy–related
Idiopathic chronic eosinophilic pneumonia
Smoking-Related
Desquamative interstitial pneumonia
Respiratory bronchiolitis
