Case 3 Flashcards
what are intrinsic risk factors for COPD?
- anti-proteinase (alpha1-antitrypsin) deficiency
- airway hyper-reactivity - easily triggered bronchospasm
what are symptoms of COPD?
- productive cough
- white or clear sputum
- wheeze
- breathlessness
what investigations can be done for diagnosis of COPD?
Lung function tests: - Evidence of airflow limitation. - FEV1 less than 80%. - FEV1:FVC ratio is less than 70%. - PEFR is low.
Blood gases:
- In advanced cases: hypoxaemia and hypercapnia.
Sputum examination:
- Useful in patients with purulent coughs.
- Sputum colour can help identify infection.
- E.g. rust-coloured sputum = pneumococcal bacteria (pneumonia).
- α1-Antitrypsin levels and genotype.
Blood count:
- Useful to exclude anaemia or document polycythaemia.
what’s treatment for COPD?
Smoking cessation remains the only intervention proven to decelerate the decline in FEV1.
Bronchodilators:
- Mild COPD: β-Adrenergic agonists (salbutamol)
- In severe COPD: long-term β-Adrenergic agonists (salmeterol)
- Antimuscarinic drugs (ipratropium):
- more prolonged and greater bronchodilation is achieved.
- Theophyllines
Corticosteroids:
- In some patients, there has been a reversible element to their disease and airway function may improve considerably.
- The combination of inhaled corticosteroids with long-acting β2-agonists produces further improvement in breathlessness and reduces the frequency and severity of exacerbations.
Antibiotics:
- Prompt antibiotic treatment shortens exacerbations and should always be given in acute episodes as it may prevent hospital admission and further lung damage.
- Patients can be given a supply of antibiotics to keep at home to start as soon as their sputum turns yellow or green.
Oxygen Therapy:
Long-term domiciliary oxygen therapy has been shown to:
o Improve survival
o Prevent progression of pulmonary hypertension
o Decrease the incidence of secondary polycythaemia
o Improve neuropsychological health
- The aim of therapy is to increase the PaO2 to at least 8 kPa (60 mmHg).
- 100% oxygen isn’t given to a COPD patient. In a COPD patient, there is less new oxygen going in and less old carbon dioxide coming out. Therefore, there is a higher carbon dioxide concentration in the alveoli. Over time the patient becomes sensitised to this hypercapnia and so relies on hypoxaemia to drive their ventilation. Administering oxygen will reduce the hypoxaemia, thus reducing the respiratory drive whilst the levels of CO2 remain high. The patient hypoventilates instead of hyperventilating, thus their respiratory drive ids reduced which is fatal (look at clinical features notes on the next page).
- Usually 24-28% oxygen is administered.
- If the respiratory rate increases above 30, then around 40% oxygen is administered.
what are the clinical features of COPD?
- oxygen and carbon dioxide
- V/Q
Va/Q mismatch occurs partly because of damage and mucus plugging of smaller airways from chronic inflammation, and partly because of the rapid expiratory closure of the smaller airways owing to loss of elastic recoil from emphysema.
- This leads to a fall in PaO2 and an increase in the work of respiration.
CO2 excretion is not impaired to the same extent.
- Many patients will show low normal PaCO2 values due to increasing their ventilation (hyperventilation) in an attempt to maintain normal blood gases by increasing their respiratory effort.
- Other patients fail to maintain their respiratory effort and as a consequence their CO2 levels increase.
- In the short term, this rise in CO2 leads to stimulation of respiration but in the long term, these patients often become insensitive to CO2 and come to depend on hypoxaemia to drive their ventilation.
o These patients appear less breathless and because of their reduced O2 saturation, they start to retain fluid and stimulate erythrocyte production (leading to polycythaemia).
o In consequence they become cyanosed.
o Attempts to abolish hypoxaemia by administering oxygen can make the situation much worse by decreasing respiratory drive in these patients who depend on hypoxia to drive their ventilation.
what are the three mechanisms for the limitation of airflow in the small airways?
- loss of elasticity and alveolar attachments of airways due to emphysema - this reduces the elastic recoil and the airways collapse during expiration
- inflammation and scarring cause the small airways to narrow
- mucus secretion which blocks the airways
each mechanism narrows the small airways and causes air trapping, what does this lead to?
hyperinflation of the lungs and breathlessness
what diseases is COPD composed of?
- emphysema
- chronic bronchitis
what is emphysema?
abnormal, permanent enlargement of the air spaces distal to the terminal bronchiole, accompanied by destruction of their walls and without obvious fibrosis
how is emphysema classified? and what are the different types of emphysema?
according to its autonomic distribution within the lobule
- centriacinar (centrilobular) emphysema
- panacinar (panlobular) emphysema
- distal acinar (paraseptal) emphysema
- irregular emphysema (airspace enlargement with fibrosis)
what is centriacinar emphysema? and when does it occur?
- the central or proximal parts of the acini, formed by respiratory bronchioles are affected, while distal alveoli are spared
- thus, both emphysematous and normal airspaces exist within the same acinus and lobule
- the lesions are more common in the upper lobes, particular in the apical segments
- the walls of the emphysematous spaces often contain large amounts of black pigment
- centriacinar emphysema occurs predominantly in heavy smokers, often in association with chronic bronchitis
what is panacinar emphysema? and when does it occur?
- this is less common
- distension and destruction appear to involve the whole of the acinus, from the level of the respiratory bronchiole to the terminal blind alveoli
- severe airflow limitation and V/Q mismatch occur
- this type of emphysema occurs in alpha1-antitrypsin deficiency
- panacinar emphysema tends to occur in the lower lobes of the lungs
what is distal acinar (paraseptal) emphyema? and when does it occur?
- the proximal portion of the acinus is normal but the distal part is primarily involved
- the emphysema is more striking adjacent to the pleura, along the lobular connective tissue septa and at the margins of the lobules
- the characteristic findings are the presence of multiple, contiguous, enlarged airspaces that form cyst like structures that with progressive enlargement are referred to as bullae
- this type of emphysema probably underlies many of the cases of spontaneous pneumothorax in young adults
what’s irregular emphysema?
- airspace enlargement with fibrosis
- the acinus is irregularly involved, is almost invariably associated with scarring, such as resulting from healed inflammatory diseases
- although clinically asymptomatic, this may be the most common form of emphysema
what is the protease-antiprotease imbalance hypothesis?
- Based on the observation that patients with a genetic deficiency of the antiprotease α1-antitrypsin have a markedly enhanced tendency to develop pulmonary emphysema, which is compounded by smoking.
- (Normally) α1-Antitrypsin:
- Found in serum, tissue fluids, and macrophages.
- Is a proteinase inhibitor which is produced in the liver, secreted into the blood and diffuses into the lung.
- Here it inhibits proteolytic enzymes (proteinases) such as neutrophil elastase, which are capable of destroying alveolar wall connective tissue.
The following sequence is postulated:
- Neutrophils (the principal source of cellular proteases) are normally sequestered (isolated) in peripheral capillaries, including those in the lung, and a few gain access to the alveolar spaces.
- Any stimulus that increases either the number of leukocytes (neutrophils and macrophages) in the lung or the release of their protease-containing granules increases proteolytic activity.
- With low levels of serum α1-antitrypsin, elastic tissue destruction is unchecked and emphysema results.
how does the protease-antiprotease hypothesis help explain the effect of cigarette smoking on the development of emphysema?
and so what is the main factor leading to emphysema in smokers?
The protease-antiprotease imbalance hypothesis also helps explain the effect of cigarette smoking in the development of emphysema, particularly the centriacinar form in subjects with normal amounts of α1-antitrypsin:
In smokers, neutrophils and macrophages accumulate in alveoli:
- The mechanism of inflammation is not entirely clear.
- These activate the transcription factor NF-κB, which switches on genes that encode TNF and chemokines.
- These, in turn, attract and activate neutrophils.
Accumulated neutrophils are activated and release their granules:
- The granules are rich in a variety of cellular proteases resulting in tissue damage.
Smoking also enhances elastase activity in macrophages:
- Macrophage elastase is not inhibited by the antiprotease α1-antitrypsin and, indeed, can proteolytically digest this antiprotease. Therefore the accumulation of macrophages is the main factor leading to emphysema in smokers.
what’s another way that smoking causes tissue damage?
Normally:
- The lung contains antioxidants (substances that inhibit oxidation).
- This prevents oxidative damage.
Tobacco smoke:
- Contains abundant reactive oxygen species (free radicals).
- These deplete the antioxidant mechanisms, thereby inciting tissue damage.
• Activated neutrophils increase the amount of reactive free radicals in the alveoli.
• A secondary consequence of oxidative injury is inactivation of native antiproteases:
- This results in “functional” α1-antitrypsin deficiency even in patients without enzyme deficiency.
what does the loss of elastic tissue lead to?
- this causes the respiratory bronchioles to collapse during expiration
- this leads to functional airflow obstruction despite the absence of mechanical obstruction
apart from loss of elastic tissue, what else leads to airway obstruction in emphysema?
- goblet cell metaplasia with mucus plugging of the lumen
- inflammatory infiltration of the walls with neutrophils, macrophages, B cells, CD4 and CD8+ T cells
- thickening of the bronchiolar wall due to smooth muscle hypertrophy and peribronchial fibrosis
what stage of emphysema are the lungs voluminous?
advanced
which type of emphysema are large apical blebs or bullae more characteristic of?
irregular emphysema secondary to scarring and of distal acinar emphysema
what is bullous emphysema?
- Large subpleural blebs or bullae (spaces more than 1 cm in diameter in the distended state) that can occur in any form of emphysema.
- They represent localized accentuations of emphysema and occur near the apex.
- On occasion, rupture of the bullae may give rise to pneumothorax.
why is the FEV1:FVC ratio reduced?
because FEV1 is reduced but FVC is normal
what is death in most patients with emphysema due to?
- respiratory acidosis
- right-sided heart failure
- massive collapse of the lungs secondary to pneumothorax
what is chronic bronchitis?
long-term inflammation of the mucous membranes of the bronchi
how is chronic bronchitis diagnosed?
by the presence of a persistent productive cough that lasts for more than three consecutive months or more per year for at least two consecutive years
when chronic bronchitis persists for years, what may it lead to?
- progress to COPD
- lead to cor pulmonale and heart failure
- cause atypical metaplasia and dysplasia of the respiratory epithelium providing a rich soil for cancerous transformation
describe the pathogenesis of chronic bronchitis
- The primary or initiating factor in the genesis of chronic bronchitis seems to be long-standing irritation by inhaled substances such as tobacco smoke, & dust from grain/cotton.
- Initially, proteases released from neutrophils stimulate mucus hypersecretion in the large airways.
- This results in hypertrophy of the submucosal glands in the trachea and bronchi.
- As chronic bronchitis persists, there is also a marked increase in goblet cells of small airways—small bronchi and bronchioles—leading to excessive mucus production that contributes to airway obstruction.
- It is thought that both the submucosal gland hypertrophy and the increase in goblet cells are protective metaplastic reactions against tobacco smoke or other pollutants.
- Although mucus hypersecretion in large airways is the cause of sputum overproduction, it is now thought that accompanying alterations in the small airways of the lung can result in physiologically important and early manifestations of chronic airway obstruction. This feature is similar to that described earlier in emphysema and seems to be a common denominator in COPD.
- The role of infection seems to be secondary. It is not responsible for the initiation of chronic bronchitis but is probably significant in maintaining it and may be critical in producing acute exacerbations.
- Cigarette smoke predisposes to infection.
what happens to the mucous membranes in chronic bronchitis?
• There is hyperemia (excess of blood in vessels), swelling, and edema of the mucous membranes, frequently accompanied by excessive mucinous or mucopurulent secretions.
• The characteristic histologic features are chronic inflammation of the airways and enlargement of the mucus-secreting glands of the trachea and bronchi.
- Although the numbers of goblet cells increase slightly, the major change is in the size of the mucous gland (hyperplasia).
what is cor pulmonale?
- Is enlargement and failure of the right ventricle of the heart as a response to increased vascular resistance or high blood pressure in the lungs (pulmonary hypertension).
- Pulmonary vascular resistance is increased because of loss of pulmonary vascular tissue and because of pulmonary vasoconstriction caused by hypoxia and acidosis.
- The increased pulmonary vascular resistance leads to pulmonary hypertension, which initially occurs only during an acute respiratory infection.
- Eventually, the pulmonary hypertension becomes persistent and progressively more severe.
- The pulmonary vascular bed is gradually obliterated by muscular hypertrophy of the arterioles and thrombus formation.
- Right ventricular function is progressively compromised because of the increased pressure load.
- Hypoxia further impairs right ventricular function and, as it develops, left ventricular function is also depressed.
what are some acute and chronic lung infections?
acute:
- mainly lower respiratory tract infections
- acute bronchitis
- pneumonia
chronic:
- bronchiectasis
what is pneumonia?
infection of the lung interstitium, alveoli and airways, resulting in inflammation of the lungs; usually caused by bacteria
what are symptoms of pneumonia?
- Cough - Sputum (purulent) - rust-coloured - Breathlessness - Fever - Pleuritic chest pain - Signs of consolidation (filling with fluid) -Proteinaceous fluid and inflammatory cells congest the airspaces. - Chest x-ray changes
why causes rust-coloured sputum?
Streptococcus pneumonia
how is pneumonia classified?
By site/localization:
- Bronchopneumonia – refers to more patchy alveolar consolidation associated with bronchial and bronchiolar inflammation often affecting both lower lobes.
- Lobar pneumonia - is a radiological and pathological term referring to homogeneous consolidation of one or more lung lobes, often with associated pleural inflammation.
By mechanism/ pathogen: - Bacterial pneumonia - Viral pneumonia - Aspiration pneumonia: - Contents of the stomach travel up the oesophagus and down the trachea, causing infection in the alveoli and making the conditions acidic.
By locality:
CAP: community acquired pneumonia
HAP: hospital acquired pneumonia
VAP: ventilator acquired pneumonia
what are our defence mechanisms?
Nose
- Filters
- Warms
- Humidifies
Larynx
- Coughing
Lungs and Tract
- Mucociliary clearance
Cellular/ humoral immunity
what are risk factors for pneumonia?
- age
- impaired cough (problem with larynx)
- impaired mucociliary clearance - smoking, congenital
- immunosuppression
community-acquired pneumonia
- pathogen
- most common cause
- pathogenesis
• Bacterial or viral.
• Bacterial infection follows an upper respiratory tract viral infection.
• Usually caused as a result of infection by Streptococcus pneumonia.
• Pathogenesis:
1. Attachment of bacteria to the upper respiratory tract epithelium.
2. Necrosis of the cells.
3. Inflammatory response.
4. This extends to the alveoli.
- Interstitial inflammation .
- Inhibition of mucociliary clearance.