Pathophysiology of chronic airflow limitation Flashcards
Types of chronic obstructive airway diseases (4)
1) Asthma
2) COPD
3) Bronchiectasis
4) Bronchiolitis
What is difference between bronchus and bronchiole
Presence of cartilage
Symptoms of chronic obstructive airway diseases
- cough
- sputum
- dyspnea
- wheeze
Cough reflex - what does it involve in the nervous system
1) Afferent stimulation of irritant receptors in the airway - vagus nerve
2) Efferent activation of inspiration muscles including the diaphragm- phrenic nerve
3) Activation of expiatory muscles and the larynx - vagus
Cough reflex
1) mechanical/chemical stimulation of the irritant receptors within airway
2) Info goes to the brain -integration
3) Stimulation to the inspiratory muscles to take a deep breath in at the same time signal to larynx to close glottis
4) Expire against a closed glottis causing the cough reflex to occur and expel whatever was in the airway
Sputum -definition
A mixture of saliva, airway lining liquid, mucus and pus that is expelled (expectorated) from the respiratory tract during coughing
Phlegm
Airway mucus
Varieties of sputum
1) White or grey (mucoid)
2) Bloody /blood streaked (hemoptysis)
3) Rusty colored - old blood, fungal infections (aspergillus) -brown
4) purulent - containing pus - yellow-yellower-green-greener – indicated right blood cells
5) Muco-purulent
6) Foamy (pulmonary edema)
Sources of sputum in the airway
1) Bronchial mucus gland (main source)
2) Goblet cells (in the respiratory epithelium)
Mucus production during obstructive lung disease - sources
Both the bronchial mucus gland and goblet cells increase their production during obstructive lung disease
i.e in asthma get proliferation and increase in size of goblet cells
Dyspnea- causes
Increased work of breathing due to:
a) increased airway resistance
b) hypoxemia
c) hyperinflation
Cause of airway resistance
- flow of gas goes from area of high pressure to low pressure
- pressure gradient needs to be positive (P1-P2)
- resistance proportional to pressure difference and inversely proportional to the flow
Airway resistance in obstruction/narrowing of vessels
If get an obstruction/narrowing of the tube
- increase pressure
- decrease flow
- so overall increased resistance
Mechanisms of airway resistance in the lungs
1) Smooth muscle contraction
2) Wall thickening
3) Lumenal occlusion
4) Decreased lung elasticity
5) Obliteration
Smooth muscle contraction
1) Cause of constriction - nervous stimulation, inflammation (acetylcholine, histamine, leukotrienes, prostaglandins…)
2) Smooth muscle contraction causes reduction in radius of lumen
3) resistance proportional to 1/r^4
Wall thickening -how causes increased resistance
1) Chronic inflammation leads to remodelling wall of lumen hypertrophy and hyperplasia of the epithelium, inflammatory cell infiltration and connective tissue deposition
2) Overall thickening wall and consequently reduction of luminal radius
Occlusion -how causes increased resistance
Can’t clear mucous –> air way occluded = increased airway resistance
Lung elasticity- how causes increased resistance
1) inflammation induced proteolytic damage of the connective tissue framework of the lung and death of alveolar epithelial cells
2) loss of framework around lumen -airway collapses in on itself
3) increased resistance
ex: emphysema
Obliteration - how causes increased resistance
Significant insult to airway
Lung tries to heal
Becomes fibrosed and radius decreases over time
Site of inflammation in COPD (4)
- central airway
- peripheral airway
- lung parenchyma
- pulmonary vasculature
Sites of inflammation in asthma (2)
- central airway
- peripheral airway
Sites of inflammation in bronchiectasis (2)
- major bronchi
- bronchioles
Sites of inflammation in bronchiolities (2)
- membranous and respiratory bronchioles
- immediately adjacent aveoli
Inflammatory cells COPD (4)
- neutrophils
- macrophages
- CD8, CD4, lymphocytes
- B lymphocytes
Inflammatory cells in asthma (5)
- eosinophils
- CD4 Th2 lymphocytes
- mast cells
- neutrophils
- epithelial cells
Inflammatory cells in bronchiectasis (1)
-neutrophils
Inflammatory cells in bronchiolitis (5)
- neutrophils
- eosinophils
- macrophages
- lymphocytes
- mast cells
Mechanisms of increased reistance: asthma
1) Mainly due to smooth muscle contraction (+++)
2) Also due to wall thickening (+ to +++)
3) Lumenal occlusion (++)
Not due to
a) increased lung elasticity
b) obliteration
Mechanisms of increased reistance: COPD
1) Mainly due to decreased lung elasticity and obliteration (+++)
2) Slightly due to smooth muscle contraction, wall thickening and lumenal occlusion (+)
Mechanisms of increased reistance: Bronchiectasis
1) Combo of wall thickening, lumenal occlusion, obliteration (++)
2) Somewhat due to smooth muscle contraction (+)
Not due to decreased lung elasticity
Mechanisms of increased reistance: Bronchiolitis
1) Mainly due to obliteration (+++)
2) Wall thickening (++)
3) Smooth muscle contraction and lumenal occlusion (+)
Not due to decreased lung elasticity
Where does increased resistance occur + repercussions
- resistance naturally decreases as one goes from central to peripheral pathway (large increase in surface area)
- but alot of resistance changes occur in smaller airways (where damage is) - so considerable changes can occur before symptoms develop (as naturally lower resistance than larger conducting airways)
Predominant triggers asthma
- primarily allergen driven Th2 response
- also episodically by viruses and pollutants
COPD triggers
-cigarette and biomass smoke exposure = oxidant damage
Bronchiectasis triggers
-bacteria
Bronchiolitis triggers
- inhaled gases and fumes
- immune rejection
- signifcant viral infections
Pathophysiology allergic asthma
1) Normally when dendritic cells present to naive T cell activate it to develop into Th1 which will secrete IFN y
2) In allergic asthma the allergen is presented to the dendritic cell which drives the naive T cell to become Th2 (people without asthma would generate mainly Th1 response to allergens)
3) Th2:
a) produces IL4, IL5, IL13
b) Leads to allergic inflammation
c) production of IgE
5) Cytokines stimulate plasma B cells
6) B cells produce further IgE, which then sensitizes the mast cells so that when the allergen represents to the mast cell activates it to release histamine and leukotrienes (degranulation)
7) leading to bronchoconstriction + inflammation = acute exacerbation of asthma
Pathophysiology COPD
-multifactorial
-predominate = smoking
Then combined with…
-also genetic susceptibility (ex alpha 1 anti trypsin deficiency), respiratory infections, occupational and environmental air pollution
Leads to either of two outcomes:
1) Parenchymal inflammation, cell death leading to tissue destruction and reduced lung recoil –» leads to emphysema
2) Airway inflammation remodelling and thickening –> leads to small airway disease (wheezing, increased airway resistnace)
End result in either=
- reduced expiratory flow
- hyperinflation
- gas exchange abnormalities
Which produces SYMPTOMS
What drives development of emphysema
- Proteolytic destruction of alveolar walls
Subtypes of emphysema
1) Centrilobular (acinar) emphysema - affects more proximal part of respiratory bronchioles
- cigarette smoking and dust inhalation
- affecting upper lobes
2) Panlobular (acinar) emphysema - affects more of distal part of respiratory bronchioles
- affecting more of lower lobes
- honeycoming of airways
- seen more in alpha-1 antitrypsin deficiency (causing bi-basal hyperinflation and lucency)
Bronchiectasis -definition
Irreversible dilation of the bronchial tree
Cause of bronchiectasis
- irreversible destruction of peripheral small airways
- due to repetitive/persistent infection of the upper or lower respiratory tract
Effect of viral infections on cilia + consequences
1) Viral infection causing
- reduction in ciliary beat frequency
- increased dyskinetic beat pattern (abnormal beating)
2) Therefore start coughing -need to rely on alternative mechanisms to get mucous out
Pathophysiology bronchiectasis
Cycle of infection and inflammation (usually due to underlying susceptibility or trigger
ex: primary ciliary dyskinesia-cilia don’t move
- mucous stuck down there which gets infected
- body tries to try and fight off infection get influx of inflammatory cells into lung which further disrupts mucocilliary clearance
- get more pooling of secretions and further infection
- eventually get lung damage (coughing??) - destruction of airway leading to collapse and dilation
Causes of bronchiectasis (underlying conditions)
1) Cystic fibrosis - most common
2) Ciliary dysfunction syndromes
- primary cilial dyskinesia syndromes
- young’s syndrome
3) Foreign bodies
- bronchial occlusion due to foreign body
- build up of secretions which gets infected
- causes localized infection and inflammation leading to lung damage
4) Tracheomalacia
5) Relapsing polychondritis
- chronic aspiration and can’t swallow
6) Inhalation of noxious fumes/gases
ex: nitrogen mustard
6) Infection
- ex: whooping cough, TB
Bronchiolitis
Home work
Hypoxemia- how causes dyspnea
1) Ventilation/perfusion mismatch
2) Reduced surface area for diffusion
Hyperinflation -how causes dyspnea
-increased lung volume shortens inspiratory muscles
Wheeze -cause
Airway narrowing especially due to bronchoconstriction
Detecting a wheeze
-detected/quantified by measuring maximal expiratory flow
Spirometry - how, what do get
- Take a maximum breath in to fill to vital capacity
- Blow out to empty
- Get FEV1 and FVC
What does FEV1 and FVC tell us
-whether airflow obstruction or restrictive lung disease
-FEV1 should be above 80% predicted
-FVC should be above 90% predicted
-ratio FEV1/FVC < 75% obstructive
>99% suggestive restrictive lung disease
Obstructive lung disease
- fall in rate of lung emptying (FEV1 decreased)
- because exhalation at this part is effort dependent - no matter how much force develop is only a certain flow rate that will come out
- eventually will empty out but usually with spirometry stop after 6s expriation so FVC is also increased
Mean expiratory flow - limits
MEF is limited - flow will increase with increasing effort up to a point
-beyond that point increasing effort and pleural pressure does not produce increased flow
Decrease in MEF-what can tell you
- is characteristic feature of obstructive airway diseases
- serves as a relatively effort-independent measure of the severity of airway obstruction
Restrictive lung diseases
- last bit of air out not dependen on effort but on elastic property of alveoli
- wont get increased FEV1 but will get increased FVC
