Week 102 COPD Flashcards
What is the composition of air?
N2- 78%
O2- 21%
Ar- 1%
CO2- 0.04%
What’s the equation for diffusion?
Time (t) taken for a molecule to diffuse a specified distance (x) in one direction (from “start” to “end”
x^2 alpha t
What is in-between the parietal and visceral pleura of the thorax?
Interpleural space containing fluid with a negative pressure
Give 3 facts of parietal and visceral pleura of the thorax
• Superior and anterior borders of lungs and
pleura → identical
• Cupula of pleura – 1-2 cm above the clavicle; 2-3 cm above the 1st rib ́s border
• Sup. interpleural space at the level of the 2nd
rib ́s cartilage (thymus, Hassal’s corpuscles, connective and fatty tissue)
Name pleural recesses of the thorax
Right costodiaphragmatic recess of pleural cavity
Left costodiaphragmatic recess of pleural cavity
• Superior and anterior borders of lungs and
pleura → identical
• Cupula of pleura – 1-2 cm above the clavicle; 2-3 cm above the 1st rib ́s border
• Sup. interpleural space at the level of the 2nd
rib ́s cartilage (thymus, Hassal’s corpuscles, connective and fatty tissue)
Why is the right main bronchus more vulnerable to inhalation injury?
Shorter
Straighter
Wider
More vertical
What plain film projection is best for an accurate heart size?
PA projection (AP projection is not reliable)
Name pathological changes that occur in COPD:
Chronic bronchitis
Emphysema
Small airways disease
What are the clinical implications for the patient dependent on?
- History
- Physical signs on examination
- Radiology
- Lung function tests
What 2 disease in COPD go together?
Chronic bronchitis
Emphysema
Describe the anatomy of the normal human airway
- Cartilage is present to level of proximal bronchioles
- Gas exchange occurs beyond terminal bronchiole
- Distal airspaces kept open by elastic tension in alveolar walls
Name the cells found in the normal bronchial epithelium
- Ciliated columnar cells
- Goblet cells
- Bronchial gland
- Basement membrane
Describe a major indicative symptom of chronic bronchitis, but what must you beware of?
Symptom: cough productive of purulent sputum for at least 3 months of the year for at least 2 successive years
Beware: other chronic conditions with wheeze may fit this definition e.g. asthma, bronchiectasis
What is the WHO definition of chronic bronchitis?
Chronic bronchitis refers to an inflammatory
process in the wall of the bronchioles with
excessive production of mucus and sputum
from hypertrophic glands. The small airways
are narrow, and there is morning cough more
than 3 months per year
What can contribute to the pathology of chronic bronchitis?
-Cigarette smoke and other irritants
Describe the pathophysiology of chronic bronchitis
Irritated epithelial cells increase numbers of goblet cells, mucous glands and mucous in the airway lumen.
Increased CD8 +ve lymphocytes and neutrophils occur- inflammatory cell infiltration.
Increased inflammatory cells in submucosa.
Excess abnormal mucous “glues” and flattens cilia.
Bacterial adherence to bronchial secretions.
What do the submucosal macrophages release in chronic bronchitis?
Proteases
Name other pathological changes in bronchial epithelium
- Loss of ciliated cells
- Squamous metaplasia
How are distal airspaces of the airways kept open?
By elastic tension in alveolar walls
What is emphysema?
Destruction of lung tissue distal to the terminal bronchioles. There is degenerative loss of radial traction of the bronchial walls
What is the protease/anti-protease theory of emphysema?
Observation
Patients with alpha-1-antitrypsin deficiency (an anti-protease) develop
emphysema
Theory
Smoke causes inflammatory cell infiltration
Cells release proteases (elastase, matrix metalloproteases)
These overwhelm body’s natural anti-proteases (like α-1AT )
Causing destruction of structural proteins in alveolar walls
Describe connective tissue in the normal alveolar wall
Elastin - E • 30% lung extracellular matrix • Hydrophobic, highly X-linked complex, 3D molecule • Elastic properties • Sheets surround alveoli • Stretch & elastic recoil
Collagen - C • 60% lung extracellular matrix • Triple helical structure • Molecules overlap + X-link to form fibrils of high tensile strength • Meshwork for lung structure
Name structural abnormalities in emphysema
Loss of elastin/connective tissue in alveolar walls
Dilated airspaces
Loss of elastic tissue to support small airways
Causes floppy airways which narrow or collapse on expiration (higher intrathoracic pressure)
Describe small airway disease in COPD
Increasingly appreciated Small airway thickening & fibrosis (unlike emphysema) Progression of COPD correlates with:
- Wall volume
- Inflammatory cells
- Mucous in lumen
What are pointers towards asthma?
Never-smokers Nasal symptoms Diurnal variation Family history Exacerbating factors Childhood atopy
What are pointers towards chronic bronchitis?
Smoking history
Purulent sputum > 3 months for > 2years
What are pointers towards emphysema?
Smoking history, weight loss
What are physiological consequences of emphysema?
- Airflow obstruction
- Gas trapping (can’t get air out)
- Hyperinflation of the chest
Name physical signs of COPD:
Pursed lip breathing Hyperexpanded chest ↑ accessory muscles 1 ↓ cricoid /sternal notch 2 ↓ chest expansion Intercostal recession 3 Paradoxical costal margin ↓ hepatic /cardiac dullness to percussion
What is audible with a stethoscope in COPD?
- Heart sounds in epigastrium
- ↓ breath sounds
- Polyphonic wheezes
- Scanty insp. Crackles
Name physiological consequences of emphysema
Loss of capillary bed • Reduced blood flow through the lungs • Hypoxia & hypercarbia • Pulmonary hypertension / cor pulmonale
Name physical signs of COPD
Bounding pulse (CO2 retention) • Flapping tremor (CO2 retention) • Cyanosis (from hypoxia) • ↑ JVP • Ankle swelling • Tricuspid regurgitation • Large (pulsatile) liver
What receptor controls broncodilation?
Beta 2
What receptor controls
bronchoconstriction?
M
What type of drugs can facilitate bronchodilatation?
B2 receptor agonists
Explain the physiology when an agonist binds to a B2 receptor in the airwyas
- binds to 7 TMD
- Activates coupled Gs protein (alpha subunits detethers from beta/gamma and = conformational change)
- GDP–> GTP
- ATP–> cAMP by adenylate cyclase
= GI/vascular/bronchial/ciliary/smooth muscle relaxation
Name short acting B2 agonists (SABAs)
Salbutamol
Terbutaline
Name long acting beta2 agonists (LABAs)
Salmeterol
Formoterol
Indacaterol
Vilanterol
How can beta 2 agonists be administered?
By inhalation
How long do SABAs work for?
Acts within minutes and lasts for 4-6 hours
How long do LABAs work for?
12-24 hours after acting in minutes
What are side effects of B2 agonists?
Tremor
Hypokalaemia
Tachycardia
What type of antagonist can be used to ease airways?
Muscarinic anatagonists because they antagonise Ach to reduce bronchoconstriction
Block M1 and M3 –> bronchodilation
What pathway do M1/M3 receptors work by?
PLC–> IP3/DAG –> Ca+
Name short acting muscarinic antagnoists (SAMAs)
Ipratrpoium
Name long acting muscarinic antagonists (LAMA)
Tiotropium
Umeclidinium
Aclidinium
Glycopyrronium
How are muscarinic antagonists administered?
Inhalation
How long does ipratropium last for?
Can be used as and when required
Lasts 4-6 hours
How long do LAMAs last for?
Should be used regularly\
12-24 hr duration of action
What are side effects of LAMAs?
Dry mouth
Blurred vision
GI disturbances
Can ppt glaucoma in susceptible individuals
What typed of administrations of bronchodilators exist?
Inhaler: aerosol, dry powder
Nebuliser
Describe the step by step treatment algorithm for COPD
Step 1: SABA
Step 2: SABA LAMA
Step 3: SABA LAMA LABA
Step 4: SABA LAMA LABA ICS
At each stage give smoking cessation advice
What is most important in advising patients at all stages of COPD?
SMOKING CESSATION
• Cannot replace lost lung function but reduces rate of decline • Active programmes + nicotine replacement chance of quitting
What vaccinations can you give to help manage COPD?
Influenza (annual)
Pneumococcus (every 10 years)
How can you manage COPD pharmacologically?
Rational use of bronchodilators
Inhaled corticosteroids
Mucolytics - carbocisteine
What drugs are controversial in managing stable COPD?
Inhaled corticosteroids
There is limited evidence for the benefit of inhaled corticosteroids:
• No survival benefit independent of effects of long acting bronchodilators
• No effect in decline in FEV1
• Possible effect of reducing rate of acute exacerbations is unclear
• Substantial adverse effects notably increased risk of pneumonia
What hospital investigations take place when managing acute exacerbations of COPD?
Arterial blood gas ideally breathing air - or note inspired pO2) • CXR (?pneumonia. ? pneumothorax) • ECG • FBC & renal profile • CRP (crude measure of ‘infection’) • Theophylline blood level (if taking) • Sputum for bacteriology – but don’t wait to treat • Blood culture (if febrile)
How can acute exacerbations of COPD be managed?
- Nebulised bronchodilators
- Controlled oxygen therapy (? risk of CO2 retention)
- Antibiotics if sputum purulent
- IV fluids
- IV or oral corticosteroids
- Consider iv aminophylline (monitor blood levels beware interactions)
- Chest physiotherapy
- Consider Non-Invasive Ventilation (NIV) if CO2 rising
- Consider ITU if appropriate (? ceiling of treatment)
What are advantages of acute Non-Invasive Ventilation (NIV)
for exacerbations of COPD?
• reduces mortality, rate of intubation & LOS • more cost effective than intubation / ventilation on ITU
When do you administer long-term o2 therapy (LTOT)?
- Patients with COPD and cor pulmonale
- Arterial pO2 < 7.3 kPa – when stable
- Flow rate to bring pO2 < 10 kPa
- Without significant ↑ pCO2
Name common causes of obstructive lung diseases
Asthma
Emphysema
Chronic bronchitis
Name less common causes of obstructive lung disease
Bronchiectasis Cystic fibrosis (inherited form of bronchiectasis)
Name rare causes of obstructive lung disease
Obliterative bronchiolitis
What are common COPD symptoms
Cough
Sputum
Wheeze
Breathlessness
What does diagnosis of asthma require?
demonstration of variability or reversibility
in lung function
e.g. spirometry before and after bronchodilator
How can you identify asthma in particular from histology of the bronchial epithelium?
Eosinophil infiltration
What is stridor?
• High-pitched inspiratory wheeze
• Audible at a distance
• Caused by laryngeal oedema, vocal cord
spasm or tracheal obstruction e.g.
Describe wheeze
Continuous musical sound with a definite pitch
• Generated at site of stenosis when walls of lightly
touching bronchi are set in oscillation by jet of air
• Wheeze frequency is independent of airway size
• Varies with velocity of airflow at point of stenosis
• Most prominent in EXPIRATION
What are the types of wheeze?
Monophonic
Polyphonic
Describe polyphonic wheeze
• Common in COPD and asthma
• ‘Polyphonic’ = cluster of harmonically unrelated
sounds
• Regional variations in airway narrowing and
‘floppiness’ result in sequential, dynamic
compression
• May be absent on tidal breathing (if present =
severe disease
• Number increase with forced expiratory effort§
Describe monophonic wheeze
• Low pitched
• Occurs when bronchus narrowed by critical
stenosis or intrabronchial mass (tumour)
• Tend to be ‘focal’ or at least louder in one
lung than the other
• Relatively uncommon
• Can get transient & random monophonic
wheeze with COPD / Asthma
Name some causes of monophonic wheeze
Bronchial tumour
Inhaled foreign body e.g. peanut
Describe crackles
• Non-musical explosive sounds • Most common in inspiration • Airways that have closed during expiration ‘snap’ open on inspiration • Can be early, middle or late
What types of crackles can you get?
early
mid
late
Describe features of early inspiratory crackles
- Typical of COPD (though rarely appreciated!)
- Scanty - only present in severe disease
- Also audible at the mouth (i.e. larger airways)
Describe features of mid inspiratory crackles
- Typical of bronchiectasis
- Also audible at the mouth (i.e. larger airways)
- May also represent bubbling secretions
Describe features of late inspiratory crackles
Generated by small, sub-pleural, fibrotic airways Sound like ‘velcro’ and usually profuse Predominantly basal Not audible at the mouth
