Session 6 (COPD AND TB) Flashcards
Describe the main causes of Chronic Obstructive Pulmonary Disease
[*] ~1 million people suffer with COPD in the UK, most presenting between the ages of 50 and 60 in the world.
- COPD is the leading cause of respiratory disability in the UK among older people
- The prevalence of COPD is increasing in the developing world in line with increases in tobacco consumption
- 30,00 deaths per year in the UK as a result of COPD
- 1 million hospital inpatient days/year
- COPD is common and a leading cause of morbidity and mortality
[*] COPD is a chronic disease state characterised by airflow obstruction. The airflow obstruction is usually progressive, not fully reversible and does not change markedly over several months. [NIC]
[*] Tobacco smoking is responsible for 90% of COPD cases.
- ~15% of smokers will develop COPD
- Why not all? Probably determined by genetic factors
[*] Air pollution and occupational exposure e.g. coal dust are other causes
[*] Alpha-1 antitrypsin deficiency (inherited) is less common (~1%)
- Alpha-1 antitrypsin is an antiproteinase; the imbalance in proteinases and antiproteinase leads to destruction of alveolar walls and to emphysema that usually presents at an early age
COPD is an umbrella term encompassing both emphysema and chronic bronchitis. What is emphysema?
In emphysema, the final outcome is elastin breakdown and subsequent loss of alveolar integrity leading to permanent destructive enlargement of the airspaces distal to the terminal bronchioles. Destruction of the terminal bronchioles and distal airspaces leads to loss of the alveolar surface area and therefore the impairment of gas exchange.
- The process often progresses to the development of larger redundant airspaces within the lung called bullae.
- Emphysema causes destruction of the supporting tissue surrounding the small airways, which therefore tend to close during expiration when the pressure outside the airways rises. This results in airflow obstruction particularly affecting the small airways.
- In addition, the loss of elastic tissue in the lung (loss of elastic recoil) causes the lungs to hyperinflate (fill up the thoracic cavity) because the lungs are unable to resist the natural tendency of the rib cage to expand outwards.
What is chronic bronchitis? Can it occur in COPD at the same time as emphysema?
In chronic bronchitis, another phenotype of COPD, the final outcome is excessive mucus secretion and impaired removal of the secretions (due to ciliary dysfunction). (frequently occurs in smokers)
- Mucus hypersecretion is caused by inflammation in the large airways leading to proliferation of mucus producing cells in the respiratory epithelium
- The result is a chronic productive cough and frequent respiratory infections. In COPD, this frequently persists even after smoking has stopped
- Chronic bronchitis is part of an inflammatory process usually triggered by smoking that results in airflow obstruction due to remodelling and narrowing of the airways (vicious cycle)
- Usually both emphysema and chronic bronchitis co-exist in patients with COPD. In both conditions, changes are progressive and usually not reversible. Patients may have features of either or both
The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases
How is airflow limitation brought on by the chronic inflammatory response?
[*] The host response to inhaled cigarette smoke and other noxious substances causes a chronic inflammatory process and oxidative injury, which affects central and peripheral airways, lung parenchyma, alveoli and pulmonary vasculature. The pathological changes in the lung include
- Enlargement of mucus-secreting glands of the central airways
- Increased number of goblet cells (which replace ciliated respiratory epithelium)
- Ciliary dysfunction
- Breakdown of elastin leading to destruction of alveolar walls and structure, and loss of elastic recoil (lungs more likely to remain hyper-expanded)
- Formation of larger air spaces with reduction in total surface area available for gas exchange
- Vascular bed changes leading to pulmonary hypertension
How does emphysema and chronic bronchitis lead to airway resistance? And what could persistent hypoxia eventually lead to?
[*] Emphysema and chronic bronchitis lead to increased airway resistance due to
- Luminal obstruction of airways by secretions
- Narrowing of small bronchioles which are usually kept open by the outward pull (radial traction) exerted on their walls by elastin in the surrounding alveoli.
- Decreased elastic recoil leads to reduced expiratory force, hence air trapping. Expiratory flow limitation promotes hyperinflation.
[*] Airway narrowing and destruction of lung parenchyma, predisposes COPD patients to hypoxia, particularly during activity.
[*] Progressive hypoxia causes pulmonary vasoconstriction and vascular smooth muscle thickening with subsequent pulmonary hypertension and right heart failure (Cor pulmonale)
Describe the symptoms and signs of COPD
COPD has a gradual onset and usually presents in older people with a long history of smoking. Cough and sputum production are frequently the first symptoms of COPD but many patients do not present until they are breathless
Describe the cough in COPD
- Usually the initial symptom of COPD
- Frequently a morning cough, but becomes constant as disease progresses
- Usually productive and sputum quality may change with exacerbations or superimposed infection
- Sputum may be white or clear but give antibiotics as soon as sputum turns yellow or green
Describe SOB in COPD
[*] Shortness of breath occurs initially on exertion but may progress to shortness of breath even at rest. The MRC Dyspnoea Score grades breathlessness related to activities. It is a useful for measuring progress and the baseline for when looking at exacerbations.
- Not troubled by breathlessness except on strenuous exercise
- Short of breath when hurrying or walking up a slight hill
- Walks slower than contemporaries on level ground because of breathlessness or has to stop for breath when walking at own pace
- Stops for breath after walking about 100m or after a few minutes on level ground
- Too breathless to leave the house, or breathless when dressing or undressing
What are exacerbations?
[*] Exacerbations (acute flare-ups) are associated with increases in breathlessness (compared to baseline) and increased cough and sputum production. Patient may be infective or non-infective
Why do you get the pursed lip sign in COPD?
The “purse lip” breathing often seen in patients with COPD is a protective manoeuvre that increases the pressure within the airways. This causes a reduction or a delay in the closure of these airways
Describe the signs in physical examinations indicative of COPD
[*] Physical examination (more Signs)
- Tachypnoea: increased respiratory rate to compensate for hypoxia and hypoventilation
- Use of accessory muscles of respiration due to difficulty in moving air in and out lungs
- Barrel chest (increased antero-posterior diameter of the chest) is due to hyperinflation and air trapping secondary to incomplete expiration – diaphragm and other respiratory muscles have to work much harder to ventilate the lungs
- Hyper-responance on percussion due to hyperinflation and air trapping
- Patients may have wheeze or quite breath sounds on auscultation
- Reduced intensity (distant) breath sounds caused by barrel chest, hyperinflation and air trapping.
- Reduced air entry (poor air movement) secondary to loss of lung elasticity and lung tissue breakdown.
- Wheezing may be present.
Late features include
- Central cyanosis – hypoxia due to respiratory failure
- Flapping tremors due to CO2 retention (hypercapnia)
- Signs of right-sided heart failure (distended neck veins, hepatomegaly and ankle oedema) secondary to pulmonary hypertension
Explain about Lung Function Tests used in diagnosis of COPD
- The measurement of airflow obstruction is necessary for the diagnosis of COPD – achieved with spirometry, a non-invasive and reproducible technique.
- Spirometry shows an obstructive pattern with FEV1/FVC ratio (<70%) and FEV1 <80% predicted and limited reversibility following treatment with bronchodilators. Time volume plots (vitalograph) and flow volume loops) show the typical obstructive pattern
- In COPD there is limitation to the flow of air during expiration and therefore the volume of air expired in the first second (the FEV1 is reduced). This is further compounded by airways collapse on expiration.
- As well as confirming the diagnosis of COPD, spirometry gives a measure of the severity of airflow obstruction. The NICE guidelines suggest the following:
Mild airflow obstruction: FEV1 (50-80%) predicted
Moderate airflow obstruction FEV1 (30-49%) predicted
Severe airflow obstruction (FEV1 <30%) predicted
- Decreased diffusing capacity of the lung for carbon monoxide (DLCO – Transfer factor) is a feature of emphysema
Why are Chest X-rays performed when considering COPD?
[*] Chest X Ray (not diagnostic but is mandatory to exclude other diagnoses): hyper-inflated lungs may result in
- A flattened diaphragm
- Hyperlucent lungs
- An increased antero-posterior diameter of the chest
May also show complications of COPD such as pneumonia and pneumothorax and is also useful to rule out other pathologies (e.g. lung CA in a patient presenting with chronic cough)
Explain about HRCT, pulse oximetry and Alpha1-antitrypsin level testing
[*] High-resolution computed tomography (HRCT) scanning provides a detailed assessment of the degree of macroscopic alveolar destruction in emphysema. This may be helpful if surgical intervention is contemplated or if the diagnosis is in doubt, but is not required for routine assessment of COPD.
[*] Pulse oximetry and/or ABG analysis: is carried out in acutely unwell patients to assess for hypoxia and hypercapnia (respiratory failure). ABG is also done to screen for those requiring treatment with home oxygen therapy.
[*] Alpha-1 antitrypsin level: checked if there is high suspicion such as a positive family history and atypical COPD (young patients and non-smokers). The levels are low in patients with alpha-1 antitrypsin deficiency
How would you differentiate between asthma and COPD clinically?
- Asthma: onset of asthma is in early life. A personal or family history of allergy, rhinitis and eczema is often present. Symptoms may be episodic with obvious triggering factors. There is daily variability in symptoms and patients have over wheezing that rapidly responds to bronchodilators.
- In asthma lung function test show reversibility with bronchodilators and no decrease in DLCO. Sputum or blood eosinophilia is suggestive of asthma.
Describe the diagnosis of COPD
The diagnosis of COPD relies on the combination of suggestive symptoms and signs together with the presence of airflow obstruction on spirometry (FEV1 <80% predicted and FEV1/FVC ratio <70%)
The following features are suggestive of COPD:
- Smoker or ex-smoker
- Older patient (>40 years old) and onset of symptoms in later life
- Chronic productive cough
- Breathlessness that is usually persistent and progressive
Describe the management of stable COPD
[*] Smoking cessation
[*] Patient education
[*] Pneumococcal vaccination is strongly recommended in COPD patients (flu vaccine, preventing other complications)
[*] Patient weight, nutrition status and physical activity should be monitored
[*] Bronchodilators
[*] Inhaled corticosteroid – steroids
[*] Mucolytics
[*] Antimuscarinics
[*] Methylxanthines
[*] Long term oxygen therapy if appropriate
[*] Lung volume reduction if appropriate (surgical procedure)
[*] Pulmonary rehabilitation
[*] Long term Oxygen Treatment: such as removal of large bullae, lung volume reduction and lung transplant are the last step in the management of COPD. They are used to improve lung dynamics, exercise adherence and a quality of life.
[*] Smoking Cessation, Long term oxygen therapy and lung volume reduction: evidence-based medicine suggests increased survival.
[*] The other approaches focus on improving quality of life. Drugs can help improve quality of life and reduce exacerbation frequency but do not provide cure or improve survival in COPD.
[*] Patient education and review regarding adherence and inhaler technique is essential.
Why is smoking cessation important in the management of COPD?
Smoking cessation is a key management step in COPD patients to prevent disease progression (and for all smokers to prevent diseases such as respiratory, cardiovascular, cancer, stroke etc)
The single most useful measure in the management of COPD is persuading the patient to stop smoking (if they do). Even in advanced disease, this may slow down the rate of deterioration
Describe the action of bronchilators and possible side effects
B2-agonist (e.g. salbutamol) mechanism of action: ligand binds to receptor activity adenyl cyclase, increasing cAMP and activating Protein Kinase (PKA), leading to phosphorylation of downstream targets (myosin light chain kinase – MLCK) leading to relaxation of smooth muscle in airway => bronchodilation
Adverse effects
- Tachycardia (atrial B2-receptors)
- Tremor (skeletal B2 receptors)
- Anxiety
- Palpitations
- Hypokalaemia (skeletal muscle uptake K+)
Describe the action of steroids and potential adverse effects
[*] Inhaled corticosteroid – steroids
- Inhibit antigen presentation, cytokine production and proliferation of lymphocytes – reduce the production of inflammatory chemicals and reduce the activity of the immune system by affecting the function of white blood cells
- Glucocorticoids bind to glucocorticoid receptors and up-regulates the expression of anti-inflammatory proteins in the nucleus and repressing the expression of proinflammatory proteins in the cytosol by preventing the translocation of other transcription factors from the cytosol into the nucleus.
- Generally, if on less than 800mcg inhaled steroid/ day, unlikely to get significant systemic effects.
- If above this dose or on oral steroids:
Thin skin
Bruising
Cataracts
Adrenal insufficiency. Patients on long-term steroids must be careful not to suddenly stop taking steroids as over time the HPA axis produces less steroids – gets used to the drugs – so patients might become unwell due to the adrenal insufficiencies if there is sudden medication cessation.
Osteoporosis
Diabetes
Increased weight (fluid retention)
Mental disturbance
Gi symptoms proximal myopathy
Describe the pathology of TB
[*] Alveolar macrophages phagocytose MTB deposited in alveoli but are unable to kill them (the cell wall lipids of MTB apparently block fusion of the phagosomes and lysosomes)
[*] These macrophages initate the development of cell-mediated immunity which eventually leads to the emergence of activated macrophages with enhanced ability to kill MTB. This takes about six weeks to develop.
[*] Ingestion of MTB by macrophages causes a granulomatous reaction. The characteristic lesion of tuberculosis is a spherical granuloma with central caseation (also known as tubercles)
[*] Microscopically a TB granuloma consists of necrotic cheese like core (caseous necrosis) surrounded by epitheloid macrophages, Langerhans giant cells and lymphocytes (REVISE MOD)
