COPD Flashcards
What is COPD?
Disease of adults usually 45+ with airflow obstruction that is not fully reversible
How is COPD caused?
Long term exposure to toxic particles and gases (usually long term smoking)
Occupational coal miners (cadmium)
Air pollution
Cannabis
Intrinsic risk factors
Anti proteinase (a1-anti trypsin) deficiency
Airway hyperreactivity (easily triggered bronchospasm)
Symptoms of COPD
Productive cough
White/clear sputum
Wheeze
Breathlessness
Diagnosis of COPD
Evidence of airflow limitation
FEV1 less than 80%
FEV1:FVC ratio less than 70%
PEFR is low
a1 antitrypsin levels
Blood gases COPD
Hyoxaemia and hypercapnia
Rust coloured sputum indicates
Pneumococcal bacteria (pneumonia)
Smoking cessation
Only intervention proven to decelerate decline in FEV1
Bronchodilator treatment COPD
mild COPD: B adrenergic agonists (salbutamol)
severe COPD: long term B adrenergic agonists (salmeterol)
Antimuscarinic drugs (ipratropium) more prolonged and greater bronchodilation achieved
Theophyllines
Antimuscarinic drugs
Stops acetylcholine binding, calcium, stops lung contracting
Theophyllines
Prevents and treats wheezing, shortness of breath and chest tightness
Corticosteroids and COPD
Airway function may improve considerably
Combination of inhaled corticosteroids with long acting B2 agonists produces further improved eg in breathlessness, reduces frequency and severity of exacerbations
Antibiotics and COPD
Shortens exacerbations, should always be given in acute episodes, may prevent hospital admission and further lung damage
When sputum turns yellow/green
Oxygen therapy COPD
Improves survival, prevent progression of pulmonary hypertension, decrease incidence of secondary polycythameia
Polycythaemia
Higher amount of RBC, makes blood thicker, harder to flow through blood vessels
Why is 100% oxygen not given to patient?
In COPD, less new oxygen going in and less old CO2 coming out, therefore a higher C02 conc in alveoli, patient sensitised to this hypercapnia, relies on hypoxaemia to drive ventilation. Administering oxygen reduces hypoxaemia, reducing respiratory drive whilst CO2 remains high. Patient hypoventilates instead of hyperventilating, respiratory drive reduced = fatal
Aim of oxygen therapy
Increase Pa02 to at least 60mmHg
What % oxygen administered to COPD?
24-28%, increased to 40%
Prognosis COPD
Poor prognosis predictor: increasing age, worsening airflow limitation (fall in FEV1), Weight loss, pulmonary hypertension
Emphysema
Abnormal permanent enlargement of air spaces distal to terminal bronchiole, destruction of their walls without obvious fibrosis
Centriacinar (centrilobular) emphysema
Central or proximal parts of acini, formed by respiratory bronchioles are affected, distal alveoli spared, therefore emphysematous and normal airspace’s exist within the same acinus and lobule
Legions more common in upper lobe, particularly apical segments
Walls of emyphysematous spaces contain black pigment
Most common form
Panacinar (panlobular) emphysema
Less common
Distension and destruction involves the whole of the acinus, from respiratory bronchiole to terminal blind alveoli
Severe airflow limitation and V/Q mismatch occurs
Occurs in a1 antitrypsin deficiency
Occurs in lower lobes of lung
Distal acinar (paraseptal) emphysema
Proximal portion of acinus normal, distal part involved
Emphysema adjacent to pleura, along lobular connective tissue septa and margins of lobules
Multiple enlarged airspace’s forming cyst like structures with progressive enlargement (bullae)
Underlies many cases of spontaneous pneumothorax in young adults
Irregular emphysema (airspace enlargement with fibrosis)
Acinus irregularly involved, associated with scarring, eg resulting from healed inflammatory disease
Clinically asymptomatic
Pathogenesis of emphysema
COPD characterised by mild chronic inflammation throughout airways, parenchyma, pulmonary vasculature
Macrophages, CD8+ and CD4+ T lymphocytes, neutrophils increased in the lung
Activated inflammatory cells release mediators capable of damaging lung structures/ sustaining neutrophilic inflammation
Protease-antiprotease imbalance hypothesis
Genetic deficiency of antiprotease a1 antitrypsin, enhanced tendency to develop pulmonary emphysema
Neutrophils normally isolated in peripheral capillaries, few gain access to alveolar spaces
Any stimulus that increases number of leukocytes (neutrophils and macrophages) in the lung or the release of protease containing granules increases Proteolytic activity
Low levels of serum a1 antitrypsin, elastic tissue destruction unchecked, emphysema results
Emphysema results from destructive effect of high protease activity in subjects with low antiprotease activity
a1-antitrypsin
Found in serum, tissue fluids, macrophages
A proteinase inhibitor produced in liver, secreted into blood, diffuses into the lung
Inhibits Proteolytic enzymes (proteinases) eg neutrophil elastase (capable of destroying alveolar wall connective tissue)
Protease-antiprotease imbalance hypothesis and cigarette smoking
Centriacinar form
In smokers, neutrophils and macrophages accumulate in alveoli, activate transcription of factor NF-kB switching on genes that encode TNF and chemokines, attract and activate neutrophils
Accumulated neutrophils activated and release their granules rich in cellular proteases resulting in tissue damage
Smoking enhances elastase activity in macrophages, macrophage elastase can Proteolytically digest antiprotease a1 antitrypsin
Oxidant-antioxidant imbalance (smoking)
Normally the lung contains antioxidants (inhibit oxidation) preventing oxidative damage
Tobacco smoke contains reactive oxygen species (free radicals), deplete antioxidant mechanisms, inciting tissue damage
What increases amount of reactive free radicals in alveoli
Activated neutrophils
Secondary consequence of oxidative injury
Inactivation of native proteases, resulting in functional a1 antitrypsin deficiency
Elastic tissue in alveolar walls contribute to
Elastic recoil of lung parenchyma
Loss of elastic tissue
Causes respiratory bronchioles to collapse in expiration, functional airflow obstruction
Inflammation of small airways
Goblet cell Metaplasia with mucus plugging of lumen
Inflammatory infiltration of walls with neutrophils, macrophages, B cells , CD4 and CD8 T cells
Thickening of bronchioles wall, due to smooth muscle hypertrophy and peribronchial fibrosis
These changes narrow bronchioles lumen, airway obstruction
Morphology of emphysema
Advanced emphysema produces voluminous lungs
Large apical blebs/bullae characteristic of irregular emphysema secondary to scarring/distal acinar emphysema
Bullous emphysema
Large subpleural blebs/bullae (spaces more than 1cm diameter in distended state) occur
Represent localised accentuations of emphysema and occur near apex
Rupture of bullae may give rise to pneumothorax
Clinical course emphysema
Clinical symptoms Do not appear until at least 1/3 of functioning pulmonary parenchyma damaged
Dyspnoea (first symptom, progressive), cough and wheezing, reduced FEV1, normal FVC (FEV1:FVC ratio reduced), weight loss
Barrel chested, dyspneic, prolonged expiration, sits forward hunched over, breathes through pursed lips
Dyspnoea (dyspneic)
Shortness of breath
Death in emphysema due to
Respiratory acidosis, right sided heart failure, massive collapse in lungs secondary to pneumothorax
What is pneumonia?
Infection of lung interstitium, alveoli and airways, resulting in inflammation of the lungs, usually caused by bacteria
Pneumonia symptoms
Cough, purulent sputum (rust coloured: streptococcus pneumonia), breathlessness, fever, pleuritic chest pain, consolidation (filling with fluid - proteinaceous fluid/ inflammatory cells cogent airspaces, chest x ray changes
Classification of pneumonia
By site/localisation:
bronchopneumonia - more patchy alveolar consolidation associated with bronchial and bronchiole inflammation affecting both lower lobes
Lobar pneumonia - homogenous consolidation of one or more lung lobes, associated with pleural inflammation
By mechanism/pathogen:
Bacterial pneumonia, viral pneumonia, aspiration pneumonia (contents of stomach travel up oesophagus and down trachea causing infection in alveoli, making conditions acidic)
By locality:
CAP (community acquired pneumonia)
HAP (hospital acquired pneumonia)
VAP (ventilator acquired pneumonia)
Defence mechanisms (pneumonia)
Nose (filters, warms, humidifies)
Larynx (coughing)
Lungs and tract (mucociliary clearance)
Cellular/humoral immunity
Risk factors for pneumonia
Age, impaired cough (larynx problem), impaired mucociliary clearance (smoking/congenital), immunosupression
Clinical examination of pneumonia
Tachypnea, tachycardia, fever, hypotension (due to fluid loss in inflammation)
Tachypnea
Fast breathing
Pneumonia treatment
Antibiotics -must cover streptococcus pneumonia, cephalosporin (cefuroxime), macrolide (clarithromycin), oral glucocorticoids, oxygen, IV fluids, nutrition
Community Acquired Pneumonia (CAP)
Bacterial/viral
Bacterial infection follows an upper respiratory tract viral infection
Usually caused as a result of infection by streptococcus pneumonia
Pathogenesis of CAP
1.Attachment of bacteria to upper respiratory tract epithelium
2. Necrosis of cells
3.inflammatory response
4. This extends to alveoli (interstitial inflammation, inhibition of mucociliary clearance)
Streptococcus pneumonia
Gram positive bacteria
False positives may be obtained (S. pneumoniae 20% of flora in adults)
Presence of numerous neutrophils containing gram positive, lancet shaped diplococci supports diagnosis of pneumococcal pneumonia
Streptococcus pneumonia effects
Rapidly ill with high temp (up to 39.5)
Pleuritic pain
Dry cough
Hyperventilation and shallow breathing (affected side of chest moves less, signs of consolidation together with a pleural rub - where inflamed visceral pleura rubs against non inflamed parietal pleura)
Hospital acquired pneumonia (HAP)
Result of infection by staphylococcus aureus/ gram negative rods (enterobacterium)
New episode of pneumonia at least 2 days after admission to hospital
Common in patients with severe underlying disease and immunosuppressive
Elderly/mechanical ventilation at risk
Aspiration pneumonia
Occurs mainly in debilitated patients, patients that aspirate gastric contents (gag and swallowing reflexes that facilitate aspiration)
Resultant pneumonia partly chemical, resulting from irritating effects of gastric acid, partly bacterial
Anaerobic bacteria predominate
Necrotising, severe and sudden onset, frequent cause of death
Fulminant
Severe and sudden
Lung abscess (pneumonia)
Swollen and containing pus caused by tissue destruction and necrosis
Cavity formation on chest x ray, presence of a fluid level
Common cause is aspiration
Suppuration
Formation of disease causing matter and discharge of pus
Clinical features of lung abscess
Persisting and worsening pneumonia, large quantities of sputum (foul smelling due to growth of anaerobic organisms)
Swinging fever, malaise and weight loss
Malaise
Discomfort
Empyema (pneumonia)
Spread of infection to pleural cavity
Presence of pus in pleural cavity
Arises from bacterial spread from pneumonia, after a rupture of lung abscess in pleural space
Empyema cavity becomes infected with anaerobic organisms, patient severely ill with high fever and neutrophil granulocytosis
Yellow/green sputum
Sputum neutrophils, bacterial colonisation/infection. Antibiotics will be effective
Blood in sputum
Neoplasm/pulmonary infarct
Serous/frothy/pink sputum
Blood present
Foamy white sputum
Obstruction
Odema
Ineffective against antibiotics, may be viral
Rusty coloured sputum
Pneumococcal bacteria
Erythromycin (macrolides)
Macrolides inhibit bacterial protein synthesis by inhibitory effect on translocation (tRNA shifting from A to P site)
A remains occupied, therefore addition of incoming tRNA and its attached amino acid to the polypeptide chain is inhibited, interfering with production of functional proteins
Macrolide antibiotics bind reversibly to P site on subunit 50S of bacterial ribosome (bacteriostatic, may be bactericidal at high conc.)
Antimicrobial spectrum of erythromycin
Similar to penicillin, safe and effective alternative for penicillin sensitive patients
Erythromycin effective against
Gram positive bacteria and spirochaetes, not against gram negative organisms
Can resistance against erythromycin occur
Yes
Side effects of erythromycin
Gastrointestinal disturbances
Hypersensitivity reactions (skin rashes and fever)
Cefuroxime (cephalosporin)
Treats pneumonia
All B lactam antibiotiss interfere with synthesis of bacterial cell wall peptidoglycan
Action of Cefuroxime (cephalosporin)
- Attacks cell wall
- Attaches via B lactam ring to the target cell wall (Penicillin binding protein PBP)
- Changes functional group of protein on cell wall, causes inhibition of transpeptidition enzyme that cross links the peptide chains attached to backbone of peptidoglycan
- Cell wall weakened and crumbles. Extracellular fluid enters bacteria, leading to death of bacteria
- Bacteria can respond by producing B lactamase, however cefuroxime is B lactamase resistant
Side effects of cefuroxime (cephalosporin)
Hypersensitivity reactions
What is Lung fibrosis?
Excessive deposition of collagen and other Extracellular matrix components in lungs
“Scarring of the lung”
Lung fibrosis symptom
Shortness of breath
Pathogenesis of lung fibrosis
Result of chronic injury leading to chronic inflammation associated with: proliferation and activation of macrophages and lymphocytes, production of inflammatory and fibrogenetic growth factors, production of cytokines
