Pathophysiology of COPD Flashcards
General context of COPD
COPD = the 4th leading cause of death worldwide
35,000 deaths/year in UK (3 million worldwide)
380 million people estimated to have COPD worldwide
Significant economic burden (working days lost, expense of treatments/care)
What is COPD
COPD = term used for a mixture of chronic bronchitis, irreversible airway obstruction, and emphysema, and encompasses a long-term, progressive, and accelerated decline in respiratory function.
> 95% of COPD associated with long-term tobacco smoke exposure
≈20% of long term smokers develop COPD
Other factors = genetic (e.g. Alpha-1 antitrypsin deficiency) and environmental hazards (e.g. pollution)
How does smoking reduce respiratory function and lead to COPD?
Inhalation of noxious chemicals and ROS causes direct tissue damage, which in the long term can cause tissue remodelling, reducing respiratory function
these chemicals can also inactivate antiproteases, increasing protease effects, causing more tissue damage and remodelling
Tissue damage can also
1) reduce mucociliary clearance which increases respiratory infections. This triggers the immune inflammatory response
2) This activates IlL 8 and TNF alpha, activating macrophages and neutrophils
3) These release trypsin, elastase, MMPs, increasing protease activation, further leading to tissue damage and remodelling
How is COPD severity characterised?
COPD severity is defined and quantified by airway obstruction (FEV1)
Mild FEV1 50-80% predicted
Moderate FEV1 30-50% predicted
Severe FEV1 <30% predicted
Why do you think FEV1 (vs. predicted) is used in COPD rather than FEV1/FVC?
Describe signs, symptoms and diagnosis of chronic bronchitis
Symptoms: Chronic productive cough Consistent sputum production Dyspnoea (especially on exertion) Signs: Airflow obstruction (↓FEV1 & wheeze) mostly affecting large/proximal airways Diagnostic criteria: “A sputum-producing cough on most days for a 3 months period, for 2 consecutive years”
chronic bronchitis: sputum produicng cough for over 2 years
due to to mucus hypersecretion due to irritation from sensory neruones/ or due to immune response
eplithelial cells damaged,- sticky and thick, hard to clear due to cilia damage
b2 antagonists don’t act that strongly- shows that hyper-proliferation smooth muscle not that big deal
What are the pathological features of large airways in COPD
Damage to cilia
Mucus hypersecretion (Goblet cell hypertrophy/hyperplasia, mucus gland hypertrophy)
Inflamed, swollen airway tissue
Hyper-proliferated smooth muscle
Impaired mucociliary clearance = increased risk of infection = recurrent infection
Irritation of sensory neurons = cough
Decreased luminal area = increased airway resistance and airway obstruction
Emphysema
Symptoms: Progressive dyspnoea with minimal cough/sputum Hyperinflation of lungs Signs: Hypoxemia Increased lung compliance Diagnostic criteria: “Abnormal permanent enlargement of distal airspaces accompanied by destruction of their walls without obvious fibrosis” enlarged alveoli
Decreased surface area + perfusion = ↓ gas exchange
Loss of elastin fibres = ↑compliance, ↓recoil
How to measure the extent of emphysema
CT scanning
Pulmonary function testing
Increased residual volume
Reduced gas transfer
(TLCO/KCO)
how effective is the person’s lungs in carrying out gas transfer
use small amount of carbon monoxide
look to see how much of what the person breathes in gets into their blood
shows how effective the same thing would be with oxygen
Small airway disease
Feature of COPD district from chronic bronchitis (large airways) and emphysema (alveoli/acini)
Constitutes from pathology within “small” airways, i.e. airways <2mm diameter, between 4th and 13th generation of airway branching (1st generation = trachea, 23rd = alveoli)
Further reduces airflow, increases gas trapping, and reduces ventilatory capacity of respiratory system
Pathological features of small airway disease
Thickening of airway wall (smooth muscle hyperplasia, fibrosis)
Mucus hypersecretion (↑ goblet cells +↑ mucus gland activation
Inflammation, immune cell infiltration
Loss of attachment providing radial traction
Impaired mucociliary clearance = increased risk of infection = recurrent infection
Decreased luminal area = increased airway resistance and airway obstruction
in small airways that’s different to large airways in chronic bronchitis is that you lose the attachment between the outside of the airway to the parenchyma
elastin fibres provide radial traction for the airway- stops it from collapsing when under pressure
however these are lost in damage to lung tissue due to proteases
Barrel chests, pursed lips and wheezing in COPD?
Barrel chests:
Small airways disease + emphysema = lungs with reduced recoil and airways that collapse during expiration.
This causes “air-trapping”, a greater volume of air than normal is left in the lungs at the end of expiration (increased residual volume).
Tidal volume then has to occur ‘on top of’ the increased residual volume.
reduced recoil, increased compliance, airways collapse suring expiration
greater volume of air than normal left after expiration
increased residual volume
tidal volume is on top of residual volume making chest larger
if you think about lungs pulling in one direction and chest in another in chest cavity,
lungs have weaker recoil so chest pulls everything in other direction giving barrel shape
Pursed lips:
Pursed lips generate increased resistance to the outflow of air
↓
This helps to prevent airway collapse by increasing airway pressure
↓
An increased volume and rate of air can be expired
↓
Patient able to breathe more normally
in small airway disease of copd, due to the loss of radial traction (weakening of wall), airways more likely to collapse during expiration
if you purse your lips, slows down how quickly air flows out of your mouth
increases resistance during expiration
increases pressure in airway, preventing collapse
this is because collapse happens due to relative pressure between the inside and outside of the structure
by increasing air pressure within, reduces pressure difference and allows for increased volume to be expired
wheezing:
when there is airway obstruction, air changes from laminar flow to turbulent flow (multi directional), causing vibration of air and generating sound- the wheezing
How does hypercapnia occur in COPD patients?
Hypercapnia always results from insufficient ventilation to cope with metabolic demands of the body
(I.e. the level of breathing is insufficient to remove the CO2 produced by the body = the definition of hypoventilation)
Chronic hypercapnia in COPD due to:
Airway obstruction
Changes to central control of breathing (tolerance to ↑PaCO2)
Central respiratory chemo-receptors play a dominant role in determining the rate of ventilation.
They are activated by increased [H+] within the CSF.
If [H+] remains high for an extended time, secondary changes occur that lead to tolerance (e.g. neutralisation of CSF acidity)
in a healthy person, when you increase co2 in blood, diffuses to CSF, react with water to make carbonic acid, dissociate into H+- detected by central chemoreceptors which increase ventilation, removing more co2 and more negative feedback
eventually systems that detect co2 become tolerant,pH changes in CSF
causes increase of bicarbonate ions
same amount of co2 that previously generated acid
and for more ventilation we need more co2, causing less removal of co2 and chronic hypocapnia
How does COPD generate airway obstruction
Airway narrowing generates ↑ resistance to airflow
Generated by a combination of:
Large airway disease
Mucosal inflammation → bronchoconstriction
Intra-luminal mucus
Smooth muscle hypertrophy
Small airway disease
As above, plus…
Loss of patency due to degradation of elastin/alveoli and reduced outward traction
in healthy lungs:
During inspiration, expansive forces act on airways & alveoli
During (forced) expiration, compressive forces act on airways & alveoli
Elastin fibres connecting airways to surrounding tissue produces radial traction → airways resists collapse
In COPD:
Degradation of structural fibres (e.g. elastin) due to chronic inflammation
With less elastin fibres & radial traction,
airways collapse under compressive force, resulting in obstruction
Hypoxaemia in COPD
Air-space enlargement reduces surface area for gas exchange.
Damage to vascular bed reduces perfusion/innervation of alveoli, further reducing capacity for O2 exchange.
Pulmonary (hypoxic) vasoconstriction Pulmonary hypertension Right heart failure Increased erythropoietin production Increased red cells (polycythaemia) Increased haematocrit and viscosity Increased risk of stroke, etc.
hypoxia in alveoli, generates pulmonary hypoxia, vasoconstriction, increasing pulmonary hypertension, increased strain on right side of heart
eventually right heart can’t function to maintain this- right heart failure
kidneys would try to compensate not being able to get oxygen into body from lungs due to poor gas exchange, increasing production of erythropoietin- increasing rbc too much increases haematocrit viscosity, increasing risk of stroke
COPD summary
COPD is a complex condition that reflects the harmful impact of long-term exposure of multiple respiratory tissues to (usually) tobacco smoke and the resulting destructive inflammation.
The symptoms of COPD reflect a simultaneous reduction in the function of large airways (productive cough), small airways (hypercapnia), and alveoli (hypoxaemia).
