COPD/Asthma/ILD (8/27-9/4) Flashcards
What part of the airway is the most susceptible to significant airflow obstruction?
Bronchioles - not supported by cartilage - lack submucosal glands - contain circumferential smooth muscles
What type of lung defect is COPD?
obstructive (air intake is limited)
What two diseases fall under COPD?
chronic bronchitis emphysema
What is the main symptoms of COPD?
dyspnea
Bronchitis has what type of lung defect?
obstructive (air intake is limited)
What is the pathogenesis of/causes bronchitis?
1) hypertrophy of the mucus-secreting glands in the bronchi leads to:
a) hypersecretion -> mucus plugging
b) thickening of the bronchial wall
2) (recurrent) infections due to altered epithelium, cilia, and mucus production (inadequate clearance) -> inflammation/formation of lymphoid follicles
3) intermittent bronchospasms of smooth muscle surrounding airways
all impedes air flow
What are pathological findings of bronchitis? (4)
1) inflammatory cells (macrophage, neutrophils) and lymphoid follicles
2) thickening of bronchiole wall due to hypertrophy of mucus glands (reid index >50%)
3) luminal mucus plugging
How is chronic bronchitis diagnosed?
productive cough >3 months for 2 consecutive years
What are some general characteristics of emphysema in terms of: type of defect? histological finding? elastic recoil? compliance? fibrosis?
- obstructive lung defect
- permanent enlargement of airspaces distal to the terminal bronchioles + destruction of alveolar walls/decrease in airway tethering
- loss of elastic recoil
- increased compliance
- NO FIBROSIS
What are the 2 main patterns of emphysema? Where are they located? What are they caused by?
1) centriacinar - focal destruction of respiratory bronchioles due to cigarette smoking 2) panacinar - destruction of alveoli distal to the terminal bronchioles due to A1AT deficiency
What is the role of A1AT? How does it protect against smoke?
Alpha-1-antitrypsin - blocks elastase Smoke recruits inflammatory cells, which increase elastase production to destroy lung parenchyma, thus reducing elastic recoil
How does smoking cause emphysema?
Smoke does 2 things: 1) it recruits inflammatory cells, which increase elastase production to destroy lung parenchyma, thus reducing elastic recoil. 2) it inactivates A1AT, which causes results in increased elastase activity, thus resulting in an increased lung parenchyma destruction and ultimately reduction of elastic recoil.
What type of lung defect is asthma?
obstructive defect (air can’t get in)
What is asthma?
hyper-responsiveness of the tracheobronchial tree to stimuli, which leads to repeated episodes of reversible bronchoconstriction
What are the two main types of Asthma?
EXtrinsic
- allergic/Type I hypersensitivity
- atopy/genetic predisposition to producing IgE to allergens
- may be due to increased Th2 production, which secrete IL’s to stimulate B cells to produce IgE and activate eosinophils to produce major basic protein.
INtrinsic
- non-allergic - non-hereditary
Which T cell is a key player in the extrinsic pathway of asthma?
Th2 - secrete IL’s to stimulate B cells to produce IgE, which stimulates mast cells - activate eosinophils to produce major basic protein both result in damage to the epithelium and airway constriction
What are the pathological findings of asthma? 93)
1) thick mucus plugs
2) thickened epithelial basement membranes
3) eosinophils
4) inflammation
5) edema
6) hypertrophied smooth muscle + submucosal gland proliferation
What is bronchiectasis?
permanent airway DILATION due to the sequelae of continued airway damage (repeat infections, aspirations of drugs and chemicals, obstruction)
What is the pathology of bronchiectasis?
loss of cilia increased mucus destruction of alveolar wall due to inflammation w. or w.o microabscesses, squamous metaplasia, peribronchial fibrosis
What inflammatory cells predominate in COPD lungs?
macrophages, CD8, and neutrophils, which promote inflammation that ultimately lead to small airway narrowing and alveolar destruction.
What is the difference betwen reversible and irreversible airflow limitation in COPD lungs?
Reversible: airway inflammation + airway remodeling
Irreversible: parenchymal destruction, loss of elastic recoil
What are 5 mechanisms of airflow obstruction?
- mucus hypersecretion -> luminal obstruction
- disruputed alveolar attachments -> easier for airway to collapse (ie emphysema)
- mucosal inflammation/fibrosis -> thickened alveolar walls (ie bronchitis)
- reduced elastic recoil -> reduced airflow (emphysema)
- smooth muscle contraction -> narrowing of the airways (ie bronchitis)
How are the symptoms of chronic bronchitis different than that of emphysema, even though they both fall under the umbrella term of COPD?
Chronic bronchitis:
1) productive cough
2) hypoxemia
3) pulmonary HTN
Emphysema
1) breathlessness
2) adequate oxygen saturation
3) cachexia (wasting disease - loss of weight, muscle atrophy, fatigue, weakness)
What is the elastase hypothesis?
A1AT is a major inhibitor of serine proteases in the lungs, and it antagonizes the effects of the neutrophils in the lungs.
Deficiency is caused by a recessive mutation, where the liver (site of A1AT production) does not synthesize it or release it.
Thus, a smoker with A1AT deficiency is at high risk of developing COPD at an earlier age (30-50) compared to the usual onset (50-60)
In what diseases would you see a decreased FEV1/FVC ratio? (3)
What is the name of this type of defect?
COPD
asthma
Cystic fibrosis
aka _O_BSTRUCTIVE DEFECT - can’t get air _O_ut
Predict and compare what you would see for emphysema vs chronic bronchitis in terms of:
FRC
RV
FVC
TLC
DLCO
FEV1/FVC ratio
Emphysema
FRC - increase due to elastic recoil (less inward force, more outward force of the thorax)
RV - increase due to air trapping/loss of elastic recoil
FVC - decrease due to air trapping
TLC - increase
DLCO - decrease due to neutrophil-mediated alveolar destruction
FEV1/FVC ratio - decrease, since it’s an obstructive defect
Chronic Bronchitis
FRC - normal because only the conducting zones of the airway are altered
RV - increase due to air trapping since patient is unable to exhale all of the air completely due to thickened walls and phlegm
FVC - decrease or normal due to air trapping
TLC - normal because elastic recoil is NOT affected
DLCO - normal, since the respiratory zones (site of gas exchange) is not affected
FEV1/FVC ratio - decrease, since it’s an obstructive defect
What are 3 types of bronchodilators? What is their mode of action?
1) b-agonists: albuterol, salmeterol, formoterol
2) anti-cholinergics: block muscarinic reeptors that release ACh (normally bronchoconstrictors): ipratropium and tiotropium
3) methylxanthines: phosphodiesterase inhibitor (increases cAMP bioavailability) - theophylline
All serve to increase cAMP, which causes smooth muscle relaxation
Why are glucocorticosteroids used for treatments with COPD?
anti-inflammatory
inhaled - for patients with COPD and FEV1 <50% of predicted + frequent exacerbations
oral - long-term treatment not recommended due to site effects
What is the # 1 therapy for patients with COPD/emphysema?
STOP SMOKING. shiz.
What are the 4 characteristic symptoms of asthma?
What are some of the physical findings of asthma?
Clinical symptoms:
- dyspnea
- cough
- wheeze
- chest tightness
symptoms are worse at night.
Physical findings:
- expiratory wheezes
- hyperresponsance
- diminshed breath sounds
- use of accessory muscles to breath
- CXR: hyperinflation of the lungs
NOTE: physical exam may be normal if the patient isn’t undergoing an attack
What is the most important risk factor for asthma?
atopy - a genetic predisposition to forming IgE and Th2 phenotypes
What are the 4 clinical manifestations of asthma?
- airway inflammation (narrow, reddened, edematous)
- enhanced bronchial responsiveness -> bronchoconstriction
- reversible airway obstruction
- excess mucus secretion
5.
What is the gross pathological features of asthma? microscopic features?
Gross:
- narrowed, reddened, and edematous airways
Microscopic:
- inflammation - eosinophils, Th2, mast cells
- thickened basement membrane due to collagen deposition
- decreased attachment to airway walls
- increased epithelial cells (hyperplasia) lining the lumen
- hypertrophied smooth muscle
- mucus plugging
- airway edema (exudative)
- vascular congestion
T/F Asthma pathology is observed throughout lung parenchyma
False. It is only observed in the conducting airways and does NOT extend into the lung parenchyma
Asthma is characterized by acute inflammation, chronic inflammation, and remodeling. What is the difference between these three stages?
Acute: altered airway pathophysiology - hyperresponsiveness, mucus production, and bronchoconstriction (all leads to airflow obstruction
Chronic: increased airway dsfunction due to epithelial cell damage
Remodeling: permanently injured/altered lung function due to hyperplasia
Would you expect to find exudate or transudate in asthmatic lungs?
Exudate - extravascular fluid with high protein content due to vessel obstruction during inflammation
What is the expected spirometry results of a patient with Asthma?
decreased FEV1 (due to obstructive airflow limitation)
decreased FEV1/FVC ratio
What is the pathogenesis of asthma?
allergens that trigger acute or chronic responses:
acute: mast cell and IgE mediated bronchoconstriction
chronic: eosinophil-mediated inflammation
What are some viral causes of asthma?
RSV - triggers a Th2 response; infections early in life have been linked to asthma development
Rhinovirus ** most common cause of acute episodes of wheezing
How does exercise trigger asthmatic attacks?
hyperventilation increases osmolality of fluid in the airway, which leads to mast cell degranulation
What are the 3 diagnostic tools used to diagnose asthma?
- spirometry
- methacholine test - delivers various concentrations to induce bronchoconstriction and measures FEV1
- exhaled NO test
Note that CXR is not a useful diagnostic tool for asthma
What is the difference between rescue therapy and controller therapy for asthma treatment? What are some examples of each?
- *rescue**: quick relief fo bronchoconstriction and associated symptoms
- b2 agonist (albuterol)
- antichoinergics (ipratropium)
- corticosteroids
- *controller therapy**: long-term management/antiinflammatory medication
- **cortiosteroids
- b-agonists
- anti-leukotrienes
- immunomodulators
- allergen immunotherapy
- mast-cell stabilizers
- theophylline**
What is ILD?
interstitial lung disease - diffuse parenchymal lung disease that is affected by interstitial inflammation and/or fibrosis
ILD is broken down into 3 major branches:
- Granulomatous
- Non-granulomatous (idiopathic)
- Known cause
What are some examples of each?
- *Granulomatous**
- Sarcoidosis
- hypersensitivity pneumonitis
- *Non-granulomatous (idiopathic)**
- Usual interstitial pneumonitis, UIP (Idiotpathic pulmonary fibrosis)
- Non-UIP
- *Known cause**
- ARDs
- Pneumoconiosis (coal miners, silicosis, asbestosis)
- Collagen dz
- SLE/RA
- Drugs
What is the biological processes that lead to iLD?
What is the INITIAL step of ILD? What is the END-STAGE step of ILD?
inhaled substance/immune host response causes INTERSTITIAL DAMAGE, which activates type II neumocytes, causes alveolar capillaries and epithelial cells, and macrophages.
- Type II pneumocytes become reactive and stick out from the interstitium
- Alveolar capillaries become leaky, which allows fibroblasts + fibrin + inflammatory cells to enter the interstitum and organize granulation tissue
- fibroblasts organizes fibrin into granulation tissue AND produce collagen, which ultimately leads to fibrosis
- macrophages recruits inflammatory cells and engulfs debris.
all of these ultimately leads to honeycomb lungs, which is the end-stage fibrosis
Initial: alveolitis
End stage: honeycomb lungs
What is granulation tissue?
healing/reparative tissue response
What is ARDs?
What causes ARDs?
What cell types are affected in ARDs? (this will also help you answer the next question)
What is the pathophysiology of ARDs?
What is the histolocal appearance of ARDs?
How does it resolve?
Acute respiratory distress
caused by acute lung injury due to:
1) trauma
2) sepsis
3) infections
4) gastric aspiration
cells affected:
1) alveolar capillary/endothelial cells → edematous fluid + inflammatory cells in interstitum
NOTE: edematous fluid mixes with cellular debris to form a hyaline membrane
2) type I pneumocytes get damaged and die → altered surfactant production
3) type II is also damaged, but the remaining cells try to repopulate the damaged alveoli.
- *Pathophysiology**: formation of the hyaline membrane results in a thickened diffusion barrier, which does two things:
1) lack of oxygen diffusion → hypoxemia and cyanosis
2) makes the surface more “sticky”, which increases the surface tension and consequently increases the
Histological appearance:
1) edema in interstitial space
2) hyaline membrane (when edematous fluid mixes with cellular debris in the alveolar septum)
- *early: typical diffuse alveolar damage (DAD)
late: organization into fibrous tissue OR complete resolution**
What is pneumoconiosis?
What are examples of pneumoconiosis?
Pneumoconiosis - ILD caused by inhalation of dust, characterized by inflammation, coughing, and fibrosis; many are related to occupational exposures
Examples:
coal minors lungs
silicosis
asbestosis
What is coal minors pneumoconiosis?
What are the 2 phases of the disease?
ILD that results in progressive fibrosis
due to coal dust +/- silica inhalation
Early phase: presence of
- anthracosis - carbon-laden macrophage
- macules - aggregates of carbon-laden macrophages
- nodules - macules + fibrosis
Complex phase: coalescence of nodules, leads to progressive massive fibrossi (mostly silica-induced)
What is silicosis pneumoconiosis?
There are two types of silica (crystalline/quartz and amorphous silica), which one is more dangerous?
What are the 2 phases of the disease?
ILD due to silica inhalation
Crystalline/quartz is most fibrogenic and is harder to get rid of; impairs macrophage form
Early: fibrotic nodules with collagen core (usually in upper lobe)
Complex: coalescence into hard scars, esp. in the lungs + lymph nodes
What is asbestosis pneumoconiosis?
There are two types of abestos (serpentine and amphibole), which one is more dangerous?
What is the histological features of asbestosis pneumoconiosis?
ILD due to inhalation of crystalline-hydrated silica (asbestos), causes diffuse interstitial fibrosis
amphibole is the more pathogenic form
histological feature: long asbestos fibers present as iron coated bodies within macrophages.
What is hypersensitivity Pneumonitis?
What type of hypersensitivity dominates the early stages? later stages?
What type of lung pathology would you expect to see?
ILD - granulomatous type
it is an ** immune response** to inhaled organic dust, mold, occupational antigens.
early stages: Type III - immune complex
later stages: Type IV - delayed hypersensitivity
Pathology: granulomatous inflammation, thickened interstitium, late stage fibrosis + honeycomb lungs
What is sarcoidosis?
What type of lung pathology would you expect to see?
ILD - granulomatous type
it is a T-CELL mediated immune response to inhaled an unknown antigen.
Pathology:
- *- bilateral hilar lymphadenopathy**
- *- granulomatous inflammation** that may ultimately fuse to form non-nucleated giant cells
- *- fibrosis**
Treatment:
- asymptomatic patients: no treatment
- severe symptoms: corticosteroids
What are the two major symptoms of ILD? What is the underlying causes of these two major symptoms?
What are the physical findings in a patient with ILD?
dyspnea
- decreased lung compliance (stiffer) - lungs need to generate a greater inspiratory pressure to inflate the lungs
- increased physiological dead-space - need to increase ventilation to maintain a nomral PCO2
coughing
- stimulation of vagal afferent pathways + receptors in the airways
Physical findings:
- crackles (rales)
- clubbing in distal phalynx
What is idiopathic pulmonary fibrosis?
What type of lung pathology would you expect to see?
What is unique about IPF compared to all of the other ILD’s?
IPF is an ILD of uknown etiology, but the pathology is the typical ILD pathology (interstitial thickening + honeycomb lung).
note that IPF can occur independently of inflammation, ie there is excess pro-fibrotic growth factors and cytokines that promote fibrosis, rather than inflammation (as in the case with hypersensitivity pneumonitis)
What is the expected PFT values for a patient with ILD?
TLC
FRC
RV
VC
FEV1/FVC ratio
flow rates
TLC, FRC, RV, and VC will decrease - there is LESS compliance in ILD lungs and therefore the inspiratory muscles can’t overcome the elastic recoil of the lungs and can only inflate the lung to a lower volume
FEV1/FVC ratio will INCREASE since this is a RESTRICTIVE disease
Flow rate: decreased due to decreased TLC, but since the elastic recoil is increased (as a result of decreased compliance) the flow rate wil be higher at a given lung volume in an ILD patient compared to normal.
Comment on the lung function of a patient with ILD in terms of:
compliance
diffusion
VQ mismatch
exercise
- compliance - decreased due to inflammation/collagen deposition
- diffusion - decreased due to thickened alveolar-capillary interface/loss of surface area
- VQ mismatch - increased due to less compliant areas that receive less ventilation + thickened septums increase equilibration time
- exercise - induces O2 desaturation even with mdoest activities; mostly due to VQ mismatch
What is the breathing pattern for a patient with ILD? Differentiate between when the person is asleep vs when they’re awake.
Awake: patient has rapid shallow breathing to miminize discomfort associated with dyspnea.
Asleep: no real difference in breathing pattern between normal and ILD patient since the patient is unaware of the dyspnea.
What is the prognosis for a patient with ILD?
Shit hits the fan. It’s bad. Mean survival time: 3years at the time of diagnosis.
What are some of the diseases caused by inspired substances?
- *pneumoconiosis** - chronic inhalation of inorganic dust that leads to parenchymal inflammation and fibrosis
- *asthma** - inhalation of inorganic dust exposure that causes acute symptoms
- *hypersensitivity pneumonitis** - inhalation of organic particles (ie malt worker’s lungs caused by Aspergillus fumigatus)
- *occupational asthma** - inhalation of organic particles (ie grains)
Smoking: what type of physiological responses does smoking cause?
Smoking contains nicotine, which binds to ACh receptors at autonomic ganglia, thereby
- increase HR, BP, CO
- increase catecholamine release + ACTH release from adrenal medulla
- increase relaxation at the NMJ (due to persistant activation-inactivation of the NM receptors)
- promotes mental stimulation, relaxtion, learning, memory, and attention
- promotes thrombosis, platelet aggregation, and vasospasms
What are 3 pharmacological agents used for smoking cessation?
Nicotine (patches)
bupropion (Zyban)
varenicline (chantix)
