Week 5 - RESP Flashcards
Asthma, Pneumoconioses, Acute Lung Injury
What is the pathogenesis of acute lung injury?
- noxious/irritant stimulus
- necrosis of type I pneumocytes
- epithelial/endothelial injury and inflammation
- neutrophils –> inflamm. mediators and proteases
- breakdown of tissue, vasodilation and plasma protein leakage (EXUDATION)
- leaked plasma proteins deposited as protein layers which line alveolus and inhibit oxygenation (HYALINE MEMBRANE) –> diffuse alveolar damage (DAD)
- severe hypoxia, atelectasis, wet heavy lungs filled with exudate
- healing –> type II pneumocyte proliferation
What is goodpasture syndrome?
- autoimmune disorder of both kidneys and lungs –> anticollagen Ab!
- diffuse alveolar hemorrhage + rapidly progressive glomerulonephritis
- rapidly progressive pulmonary and renal failure
What are 2 important complications in newborns with respiratory distress syndrome?
- Retrolental Fibroplasia
2. Bronchopulmonary Dysplasia
What is the definition of acute lung injury?
- rapid onset hypoxemia and alveolar damage in the absence of heart failure
- non-cardiogenic pulmonary oedema
- more severe form = Adult Respiratory Distress Syndrome (ARDS)
What are to common etiologies of acute lung injury?
- pneumonia/sepsis
- shock
- gastric aspiration
True or False?
There is clubbing in asbestosis
True
-there is clubbing in 50% of patients
What do asbestos bodies cause?
- very severe extensive fibrosis
- they are very small fibres which are carried to the lung periphery to small bronchioles –> pleural surface –> form PLEURAL PLAQUES
- Asbestosis
- diffuse fibrosis, honeycombing, pleural thickening, pleural effusions, dyspnoea, cough
What is sarcoidosis?
- granulomatous multisystem inflammation in response to an UNKNOWN antigen
- 90% pts show lung involvement (diffuse interstitial fibrosis)
What are the clinical features of sarcoidosis?
- fever
- fatigue
- weight loss
- anorexia
- night sweats
- lymphadenopathy
- SOB from diffuse interstitial fibrosis
- erythema nodosum
- hypercalcemia
- nephrocalcinosis
What is the most characteristic finding in sarcoidosis?
Granuloma formation
- non-caseating
- contain ASTEROID bodies in giant cells!
*asteroid bodies = star-like shaped inclusions within the giant cells of the non-caseating granulomas
What are the 2 types of asbestos bodies?
- Flexible serpentine
- Stiff straight amphibole
*both cause severe damage and fibrosis
What is the commonest type of pneumoconioses?
silicosis
What are the morphologic types of pneumoconioses?
Inert - coal workers pneumonia
Fibrous - asbestosis, silicosis
Allergic - bird watchers lung
Neoplastic - mesothelioma -> cancer of pleural laye - common in asbestosis
What are the 5 various grades of coal miners lung?
- Asymptomatic anthracosis (carbon only)
- Simple coal workers pneumonia
- Complicated coal workers pneumonia (fibrosis)
- Progressive massive fibrosis (PMF) - severely decreased pulmonary function
- Honeycomb lung –> end-stage lung (total destruction)
What is the etiology of silicosis?
- inorganic sand & stone dust
- lung injury
- activated lymphocytes/macrophages
- proteases/oxidants also from neutrophils
- destruction of type I pneumocytes
- increased type II pneumocytes
- increased FGFs/fibroblasts –> FIBROSIS!
What is the morphology of silicosis?
- multiple focal fibrotic nodules (with silica particles in the centre of nodules)
- carbon pigment
- surrounding irregular emphysema
- diffuse fibrosis –> honeycomb
What are the microscopic features of idiopathic pulmonary fibrosis?
- irregularly thickened alveolar septum with marked fibrosis and lymphocytes/macrophages within
- marked hypertrophy of type II pneumocytes (forming clusters)
What is heard on auscultation of idiopathic pulmonary fibrosis?
dry “velcro-like” inspiratory crackles
What is the pathogenesis of restrictive lung diseases?
- Lung injury (inhaled agents, dusts, toxins)
- Activated lymphocytes + macrophages/neutrophils –> oxidants/proteases damage type I pneumocytes –> increased replication of type II pneumocytes
- Interstitial inflammation and fibrosis –> type II pneumocytes secrete FGFs –> fibroblasts –> FIBROSIS
- Stiff Lung!
What are the 2 key features in sputum microscopy of asthma?
- Charcot-Leyden Crystals
- eosinophil basic protein
- part of eosinophil granules –> form big crystals in sputum - Curschmann Spirals
- long mucous threads with eosinophils inside
What are the microscopic features of asbestosis?
- pulmonary oedema
- emphysema with asbestos bodies
True or False?
Asbestosis typically causes pulmonary oedema
True
Progressive Massive Fibrosis (PMF) is typically seen in?
Coal Miner’s Lung
Fibrotic nodules on microscopy are typically seen in?
Silicosis
What are gross and microscopic features of respiratory distress syndrome? (infants)
Gross:
-purple, congested, wet, heavy, airless lungs (airless due to lack of surfactant)
Micro:
- collapsed, inflamed alveoli
- hyaline membrane of plasma proteins lining alveoli with necrotic cells
*total dysfunction –> severe hypoxemia
What is the etiology of respiratory distress syndrome?
- prematurity (<28wks) = MOST COMMON
- maternal diabetes, maternal sedation, trauma
What is the pathogenesis of respiratory distress syndrome?
- immature lung
- decreased surfactant (as type II pneumocytes have not fully developed)
- when child takes first breath, there is no surfactant to increase compliance/decrease surface tension –> atelectasis as alveoli cannot stay open
- inflammation results –> exudation
*similar to ARDS but this is in a newborn (HMD)
What is respiratory distress syndrome?
Hyaline Membrane Disease of new born (HMD)
What is DAD/Acute Lung injury referred to as when it is severe? and how does healing occur?
ARDS –> Adult Respiratory Distress Syndrome
*Healing by type II pneuomocyte proliferation
True or False?
normal/near normal FEV1/FVC ratio is a typical feature of obstructive pulmonary disease COPD
False
-restrictive (but decreased TLC)
True or False?
sarcoidosis is more common in smokers
False
-smoking may give protection
True or False?
Carbon alone does not cause damage in coal miner’s lung
True
- acanthrosis + silicosis = coal workers pneumonia
- associated SILICA causes fibrosis
- carbon alone causes blackening of lung tissue but is usually asymptomatic –> “asymptomatic acanthrocis”
What is the etiology of pneumoconioses?
Due to inhaled dusts -inorganic (mineral) or organic Reaction may be: -inert -fibrous -allergic -neoplastic *depending on type of dust
What is idiopathic pulmonary fibrosis also referred to as?
Usual Interstitial Pneumonia (UIP)
What size particles cause most damage to alveoli?
1-5microns
- <1 micron = easily removed
- > 5 microns = too large to reach/deposited in terminal alveoli
*carbon, SILICA, asbestos –> commonest particles
Compare type I and type II pneumocytes
Type I:
- larger, squamous cells –> make up most of alveolar wall
- involved in gas exchange
- susceptible to toxic insults and CANNOT replace itself
Type II:
- cuboidal type cells occur more diffusely
- secrete surfactant and FGFs –> fibrosis
- CAN replicate itself and will replace damaged type I pneumocytes
What is an example of an extrinsic disorder causing restrictive lung disease?
- kyphosis
- scoliosis
- gross obesity
True or False?
Expiration on a respiratory flow curve occurs over a longer duration in restrictive lung disorders
False
-restrictive lung disorders = lung cannot expand –> therefore decreased compliance –> expiration occurs over a SHORTER duration
*whereas obstructive disorders –> expiration occurs over a longer duration
What is the definition of restrictive lung disorders?
- decreased expansion of lung due to diffuse fibrosis (“stiff lung” –> decreased lung compliance)
- decreased FEV1/FVC –> therefore FEV1:FVC ratio is roughly normal (but TLC id decreased)
What is status asthmaticus?
- persisting, severe exacerbation of an asthmatic attack with NO response to therapy –> excess mucous plugging major bronchi
- severe hypoxia, hypercapnia, and acidosis –> may be FATAL
- hyperinflation of lungs –> bronchi constricted so air retained in alveoli
What is the only difference in microscopy between asthma and chronic bronchitis?
Very similar microscopy
-except, plenty of eosinophils in asthma and in chronic bronchitis = increase neutrophils
What are gross and microscopic features of asthma?
Gross:
- inflamed, thick bronchi
- mucous plugs
Micro:
- excess mucous (with eosinophils in mucous)
- goblet cell hyperplasia
- inflammation with eosinophilia
- smooth muscle cell hyperplasia
- mucous gland hyperplasia
- increased capillaries/vasodilation
What is the hygiene hypothesis?
- proposes that childhood exposure to germs and certain infections helps immune system to develop
- teaches body to differentiate harmless substances from harmful substances that trigger asthma
- exposure to certain germs ‘teaches’ immune system NOT to overreact (hypersensitivity)
What is the pathogenesis of asthma?
- Th2 lymphocyte stimulation via dendritic cell with allergen attached
- IL-4 release –> B cells for IgE secretion –> attach to mast cells
- IL-5 release recruits eosinophils which release chemical mediators and granules
- IL-13 causes mucous production
- mast cells –> histamine release, etc
- inflammation + episodic bronchospasm –> from exposure to irritants (caused by mast cell secretions)
What do allergens stimulate in acute vs. chronic allergic reactions?
Acute = Mast cells Chronic = Dendritic cells --> Th2 cells
Which inflammatory cells are predominantly present in asthma?
eosinophils
What are asthma triggers and in which types of asthma do they occur?
- infections
- smoke
- fumes
- stress
- exercise
*ALL types
What are the types of asthma?
Atopic *COMMONEST
-allergen, early age, FHx.
Non-atopic
-no allergen, adult, no FHX., usually due to reaction to pollutants/viral infection
Other
- drug-induced (aspirin)
- occupational
What is the commonest type of asthma?
Atopic
- allergen (hypersensitivity to environmental allergen)
- early age (childhood)
- FHX. (either autoimmune or hypersensitivity disorders)
What is the key difference between asthma and COPD?
COPD = permanent/irreversible due to scarring Asthma = intermittent bronchospasm + reversible (no scarring)
