Lecture 6: The pathology of COPD Flashcards
What is Chronic Obstructive Pulmonary Disease (COPD)?
A chronic slowly progressive disorder characterized by airflow obstruction
How is COPD diagnosed?
Reduced FEV1 and FEV1/VC ratio
What is the pathophysiology of COPD?
Implicates varying degrees of airway remodelling, inflammation, and tissue destruction.
How does COPD affect large airways (trachea, bronchi) ?
Glandular hypertrophy, reduced number of cilia so increased cough with or without sputum.
How does COPD affect small airways (bronchioles)?
Goblet cell metaplasia; smooth muscle hypertrophy; fibrosis and scar tissue this increases mucus production, increased expiratory flow resistance.
How does COPD affect alveoli?
Loss of alveolar fine structure - Loss of lung recoil – this is important to push air out of the lungs, reduced gas exchange because of reduced surface area
What are the structural changes of COPD?
- Remodelling of the upper airways
- Dysanapsis: disproportionate scaling of airway dimensions to lung volume or a mismatch of airway tree caliber to lung size.
- Inflammation and mucus hypersecretion
- Ventilation heterogeneity
- Loss of alveolar attatchment
- Alveoli with emphysema
What are the clinical symptoms of COPD?
- Symptoms include cough, sputum, dyspnea (shortness of breath), and wheeze.
- Patients who have chronic cough and sputum production with a history of exposure to risk factors should be tested for airflow limitation, even if they do not have dyspnea.
What are the diagnostic features of COPD?
- History of heavy smoking for many years.
- Cough and sputum production for many years.
- Cough often present only on waking at first; later cough occurs throughout the day.
- Sputum usually mucoid – becomes purulent with exacerbation of disease, but not excessive.
- Cough and sputum often worse in winter due to infection.
- Insidious onset of breathlessness on exertion with wheezing or tightness of chest
What are the diagnostic features of COPD?
- History of heavy smoking for many years.
- Cough and sputum production for many years.
- Cough often present only on waking at first; later cough occurs throughout the day.
- Sputum usually mucoid – becomes purulent with exacerbation of disease, but not excessive.
- Cough and sputum often worse in winter due to infection.
- Insidious onset of breathlessness on exertion with wheezing or tightness of chest
What are the two clinical phenotypes of COPD?
- Emphysema
- Chronic bronchitis
What is the clinical diagnosis of chronic bronchitis?
Daily productive cough for three months or more, in at least two consecutive years
What are the signs of chronic bronchitis?
- overweight and cyanotic
- Elevated hemoglobin
- Peripheral edema
- Rhonchi and wheezing
What is the pathologic diagnosis of emphysema?
Permanent enlargement and destruction of airspaces distal to the terminal bronchiole
What are the sings of emphysema?
- Older and thin
- severe dyspnea
- Quiet chest
- Xray, hyperinflation with flattened diaphragsm
What are the three types of chronic bronchitis?
- Simple mucoid bronchitis
- Mucopurulent (pus) bronchitis
- Chronic obstructive bronchitis
What are the clinical manifestations of chronic bronchitis?
- Excessive mucus production
- Leading to Bronchospasm, dyspnea and wheezing
- Hypoxia and hypercapnia (Blue in color)-elevated CO2
- Productive cough
- Increase body weight
What are the complications of chronic bronchitis?
Cor-pulmonale
What is cor-pulmonale
Also known as right sided heart failure, is an enlargement of the right ventricle due to high blood pressure in the lungs usually caused by chronic lung disease
What is the clinical definition of chronic bronchitis?
Clinically defined as persistent productive cough for at least three consecutive months in at least two consecutive years.
What is emphysema?
An abnormal permanent enlargement of air spaces distal to the terminal bronchioles, accompanied by destruction of their walls.
What does emphysema cause?
- loss of intricate alveolar architecture
- progressive simplification of small and highly effective gas-exchanging units into large, inefficient cyst-like spaces.
- loss of alveolar gas-exchanging units and the capillary bed so blood oxygen levels eventually fall and pressures within the pulmonary circulation rise
What is the effect of emphysema?
- Alveolar enlargement leads to progressively larger lungs that are fixed within an anatomically constrained chest cavity, limiting ventilation.
- Severe difficulty breathing
- Chronic respiratory failure, evidenced by low blood oxygen levels (hypoxemia), elevated levels of carbon dioxide (hypercapnia, hypercarbia, chronic respiratory acidosis)
- Eventually death
Describe the airways of obstructive chronic bronchitis
- Thick, sticky mucous blocks up the airways rather than clears
- Inflammation and swelling further narrows airways
What are the effects of emphysema?
- Dyspnea
- Increased CO2 retention
- Pink complexion (hyperventilation)
- Minima cyanosis
- Pursed lips breathing
- Barrel chest
- Thin (due to loss of appetite, muscle wasting)
What are the effects of chronic bronchitis?
- Recurrent productive cough
- Hypoxic/hypercapnia
- Cyanotic (blue!)
- Increased respiratory rate
- Ronchi (rattling) and wheezing
- Cardiac enlargement
How is COPD diagnosed?
Spirometry
What is the expiratory airflow limitation?
Defined by a ratio of the forced expiratory volume in 1 s (FEV1) to the forced vital capacity (FVC) of less than 0.7
What is gold 1?
- Mild COPD
- FEV1 >80%
What is gold 2?
- Moderate CODP
- 50< FEV1
What is gold 3?
- Severe COPD
- 30%< FEV1
What is gold 4?
- Very severe COPD
- FEV1 <30%
What is BODE index?
Multidimensional index of disease severity in COPD that incorporates four independent predictors: BMI, degree of airflow obstrcution, dyspnea scale, exercise capacity assessed by the 6-min walking distance (6MWD) test.
How is the degree of airflow obstruction assessed?
Assessed by the Forced Expiratory Volume in one second (FEV1),
Why is COPD diagnosed at a stage when pathological changes are irreverible?
- lack of predictive biomarkers,
- under-recognised clinical symptoms,
- long latency period with no or minimal symptoms
- reliance on spirometry, an insensitive diagnostic tool.
Why is COPD diagnosed at a stage when pathological changes are irreverible?
- lack of predictive biomarkers,
- under-recognised clinical symptoms,
- long latency period with no or minimal symptoms
- reliance on spirometry, an insensitive diagnostic tool.
What are the risk factors for COPD?
- Genetics (alpha 1 atiitrypsin deficiency)
- Occupational dust and chemicals
- Indoor smoke from wood, coal, cow dungs, crop residues used for cooking
- Frequent lung infections as a child
- Smoking, passive smoking and smoke from crckers
What would greatly reduce the burden of COPD?
- prohibiting all kinds of smoking
- eliminating exposure to any form of air pollution
Describe COPD histopathology
- Cellular bronchiolitis - a narrowed and contracted airway is infiltrated by numerous inflammatory cells without a specific patterm
- Loss of alveolar structure
- Subepithelial fibrosis causes the airway lumen to narrow
- Excessive mucus plug - the airway lumen is obstructed by mucus exudates
What is Alpha-1 anti-trypsin (α1-AT) ?
A protease inhibitor
What does Alpha-1 anti-trypsin (α1-AT) do?
Balances the activity of Elastin and other destructive enzyme proteases produced during an infection/immune challenge
What is crucial to alveolar homeostasis?
Protease:antiprotease balance
What does pathogenic mutation cause?
Cause α1-AT to self-associate into polymer chains
What abolishes antiprotease activity?
Polymerisation of α1-AT
What gives higher possibility of emphysema?
Deletion
What is alveolar and interstitial tissue destruction is driven by?
Excessive proteolysis.
