COPD - Clinical Features and Pathophysiology Flashcards
What is COPD?
A common, preventable and treatable disease that is characterised by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles of gases
What % of smokers develop COPD?
15%
What are the most common respiratory symptoms of COPD?
Dyspnoea, cough and/or sputum production
What are causes of COPD?
1) Tobacco smoking (active and passive) → even if it was a long time ago, appears later bc it needs time for normal decline of respiratory system to develop the symptoms
2) Biomass fuel exposure → poorly ventilated dwellings
3) Occupational exposures → organic and inorganic dusts, chemical agents, fumes
What is the pathogenesis of COPD?
Cigarette smoke and environmental particles (trigger) and host factor amplifying mechanisms → lung inflammation and antioxidants/antiproteases not working → oxidative stress and impaired repair mechanisms → pathological changes of COPD
What are inhibitory factors to oxidative stress?
Antioxidants and antiproteases
What happens in inflammation in COPD?
Increased neutrophils, macrophages and T cells (CD8 > CD4) in the lungs
What is the extent of the inflammation related to?
The degree of airflow obstruction
Why is the inflammatory pattern of COPD markedly different from asthma?
Asthma involves eosinophilic inflammation
What are the inflammatory mediators in COPD?
1) Leukotriene B4 → neutrophil and T cell chemoattractant
2) Chemotactic factors e.g. IL-8 and growth related oncogene alpha → amplify pro-inflammatory responses
3) Pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6
4) Growth factors e.g. TGF- beta → cause fibrosis in the airways
What is the inflammatory mechanism in COPD?
1) Cigarette smoke and other environmental noxious agents activate macrophages and epithelial factors to release chemotactic factors that recruit neutrophils and CD8 cells from the circulation
2) This leads to alveolar wall destruction and mucous hypersecretion
3) Fibroblasts are also activated, leading to abnormal tissue repair
What are sources of oxidants leading to oxidative stress in COPD?
- Cigarette smoke
- Reactive oxygen and nitrogen species from inflammatory cells
What happens to markers of oxidative stress in stable and exacerbated COPD?
They increase (even more in exacerbations)
What are the actions of oxidative stress?
1) Inactivates antiproteases
2) Stimulates mucus production
3) Amplifies inflammation by enhancing transcription factor activation (e.g. NF kappaB) and gene expression of pro-inflammatory mediators
What happens to the airways in COPD (pathophysiology)?
1) Hypertrophy and hyperplasia of bronchial submucosal glands and increased number of goblet cells → mucus hypersecretion
2) Destruction of cilia → difficulty coughing (expectorating)
3) Narrowing of airways due to remodelling
4) Increased airways resistance
Where does the narrowing process of airways start and why?
In smaller airways (<2mm) bc small particles from tobacco smoke can go down these
What happens to the lung parenchyma in COPD (pathophysiology)?
1) Proteolytic enzymes destroy alveolar tissue (air spaces)
2) Elastin and collagen are destroyed → reduced elasticity and structural integrity of the lungs
3) This leads to loss of elastic recoil (increased compliance) → worse chest expansion
What are the main clinical features of COPD?
- Dyspnoea (normally main problem)
- Exercise limitation
- Wheeze
- Sputum
What are other clinical features of COPD?
- Increased RR
- Accessory muscle use
- Wheeze
- Reduced chest expansion
- Barrel chest (lung hyperinflation from gas trapping) → reaches equilibrium at more positive pressures
- Reduced breath sounds
- Asterixis
- Cyanosis
- Cor pulmonale
Why are there reduced breath sounds in COPD?
Bc there is air space between where the sound is happening and the stehoscope
What are the 4 main pathological features of COPD?
1) Airflow obstruction
2) Loss of lung elasticity
3) Loss of alveoli
4) Airway inflammation
What are the 5 main features of COPD?
1) Expiratory flow limitation
2) Decreased elastic recoil of lungs
3) Gas exchange
4) Hyperinflation
5) Sputum production
What are some extra-pulmonary features of COPD?
- Weight loss
- Muscle wasting
- Cardiovascular co-morbidities
- Depression
- Osteoporosis
How do you diagnose COPD?
Symptoms + spirometry (to diagnose obstruction) → v important not to misdiagnose COPD
What happens to FEV1 and therefore FEV/FVC ratio in COPD?
Both decrease (FVC is the same)
What will be the post-bronchodilator FEV1/FVC in all levels of COPD?
<0.7
What are the 4 stages of COPD?
1) Mild
2) Moderate
3) Severe
4) Very severe
What is %FEV1 predicted in mild COPD?
≥ 80%
What is %FEV1 predicted in moderate COPD?
50-79%
What is %FEV1 predicted in severe COPD?
30-49%
What is %FEV1 predicted in very severe COPD?
< 30%
Why are patients with COPD breathless on exertion?
Bc the flow volume envelope is limited (look at diagram) → COPD affects normal breathing
What are the physiological features of COPD?
1) Static hyperinflation (affected by compliance)
2) Gas trapping and the equal pressure point (EPP)
3) Dynamic hyperinflation
What compliance do stiff lungs have e.g. fibrosis
Low (high elastic resistance)
What compliance in lungs with emphysema?
High (tissue destruction, floppy)
What is the effect of asthma on compliance?
Asthma does not usually affect compliance
What does the stiffness (compliance?) of lungs affect?
1) The ease with which the lungs can be inflated
2) FRC (the volume in the lungs when the muscles are relaxed → bc FRC occurs when inward recoil of lungs exactly balances outward recoil of the chest wall
What happens to FRC in a stiff lung (fibrosis)?
Increasing lug recoil → reduced FRC
What happens to FRC in floppy lungs (emphysema)
Reduced recoil → increased FRC (barrel chest)
What happens to FRC in respiratory muscle weakness?
FRC is normal bc the two recoils are normal
What happens in static hyperinflation in COPD?
1) At rest, the lungs of a patient with COPD are likely to be hyperinflated
2) FRC and RV are increased
3) Furthermore, gas trapping occurs in expiration
What happens normally to pressure during expiration?
1) Ppl +30
2) Alveolar pressure > Ppl due to elastic recoil
3) Hence, trans airway pressure is positive and the airways stay open until EPP during forced expiration → at EPP, small airways close, preventing alveoli from closing
When do small airways collapse?
No cartilage so whether they are open depends on pressure → so when pressure on outside > inside, airway will collapse
What happens to airways in disease (COPD)?
1) More airways close at EPP and this can happen in tidal breathing
2) This leads to gas trapping in airways
3) Also, due to reduced elasticity, the pressure inside the airways is lower, so you reach EPP sooner
What does dynamic hyperinflation occur (in alveoli?) in COPD?
- Reduced recoil (alveoli is stretched)
- Reduced tethering
- Increased airways resistance
- Small airways closes sooner due to airway narrowing, so ventilation decreases
What is the pressure pulling inwards on the alveoli?
Transpulmonary pressure (PL)
What happens to Vmax of flow (max capacity) in COPD and what does this mean?
Vmax decreases, meaning in COPD the flow volume loop has no ‘space’ to go into exercise breathing
When does expiratory flow limitation (EFL) occur?
When flow ceases to increase with increasing expiratory effort bc small airways close
When can EFL occur in COPD and what is the effect of this?
In tidal breathing → since max expiratory flow is reached during tidal breathing, the minimum time of lung emptying is fixed i.e. can’t empty lungs faster by pushing harder in expiration
What is the effect of EFL in tidal breathing on IC and IRV?
EFL in tidal breathing → increased RR during exercise → increased EELV despite expiratory muscle activity → decreased inspiratory capacity (IC) and inspiratory reserve volume (IRV)
What happens to the ‘shape’ of tidal breathing in COPD?
It loses its circle shape
Why can’t COPD patients increase their tidal volume by v much?
Bc they breathe much closer to TLC → IC is smaller
What happens to IRV in COPD?
It is lower
What causes exercise limitation in COPD?
1) Once IRV is within 0.5L of TLC, TV can’t increase anymore despite continued increases in contractile respiratory effort
2) This causes dyspnoea to increase to intolerable levels
3) This leads to exercise limitation
Why does it get harder to breathe when your lungs hyperinflate?
Dynamic hyperinflation forces COPD patients to breathe at higher lung volumes where…
1) Lung compliance is lower
2) Work of breathing (PxV) is higher)
3) There is limitation to tidal volume expansion
What is another consequence of dynamic hyperinflation?
Threshold load
What causes functional diaphragm weakness in COPD?
Hyperinflation
Why do patients with COPD tend to use accessory muscles?
Due to the functional diaphragm weakness, the diaphragm contracts parallel to the ground so it doesn’t increase volume (no anatomical weakness of diaphragm)
What are the increased loads on the respiratory system as a result of COPD?
- Resistive
- Dynamic hyperinflation → threshold, elastic
What leads to reduced muscle pump capacity as a result of COPD?
1) Functional weakness of the diaphragm
2) Limitation of tidal volume expansion (hyperinflation)
How does the load-capacity imbalance (high load, low capacity) in COPD manifest?
As an increase in the drive to breathe → breathlessness
Why does the load-capacity imbalance lead to breathlessness?
1) Signal from brain to breathe goes to the periphery, however bc of increased load this signal goes back to the brain
2) Bc the desired outcome wasn’t achieved, there is the sensation of breathlessness
3) Increased neural drive → increased dyspnoea
What else can develop in COPD?
Pulmonary hypertension
Why does pulmonary hypertension develop in COPD?
1) Chronic hypoxia, leading to pulmonary vasoconstriction
2) Muscularisation, intimal hyperplasia, fibrosis and obliteration
What are the effects of pulmonary hypertension?
Cor pulmonale → oedema, death
What is exercise limitation in COPD due to?
Lung mechanics and peripheral muscle performance
What is peripheral muscle fatigue in COPD?
A reversible decrease in force-generating ability of a muscle resulting from recent activity
What are causes of peripheral muscle fatigue?
1) Lower limb atrophy
2) Reduced muscle metabolism
3) Morphological muscle changes
What is the effect of lower limb atrophy?
1) Muscle weakness
2) Increased susceptibility to fatigue
3) Poor resistance to exercise
What muscle morphological changes occur in COPD?
1) Decreased type 1 fibres
2) Decreased CSA for type 1 and type 2 fibres
3) Decreased myosin heavy chain I and decreased oxidative enzyme activity (strong determinants of muscle endurance)
4) Increased anaerobic metabolism
What is evidence for significance of peripheral muscle fatigue in exercise limitation?
1) Persistent exercise limitation after full restoration of lung function after lung transplantation
2) Bronchodilators in quadriceps of pre-fatigued patients failed to improve exercise tolerance
3) Patients reporting leg fatigue as exercise-limiting symptoms less likely to improve exercise tolerance with bronchodilators
What is used as a biomarker of peripheral muscle fatigue and can predict survival in severe COPD?
Quadriceps muscle strength
What features in a patient should make you consider a diagnosis of COPD?
- Over 35
- Progressive, persistent dyspnoea, usually worse with exercise
- Chronic cough (may be intermittent and unproductive)
- Chronic sputum
- Frequent ‘winter bronchitis’
- Exposure to cigarette smoke (active or passive), occupational dusts and chemicals, smoke from home cooking/heating fuels
What test should you perform on someone to diagnose COPD?
Spirometry
What predicts levels of hospitalisation and death in COPD patients independent of disease severity/lung function?
Physical activity levels
