Flashcards in 22 Pathophysiology of the Obstructive Lung Diseases Deck (19)
1
Major obstructive lung diseases
- Most common
- Less common
- Unifying physiologic feature of all forms of obstructive lung disease
- Depending on the underlying disease, this increase in resistance may be due to one or more of the following processes
- Whatever the mechanism(s), increased airway resistance leads to...
- These changes, in turn, lead to...
- Most common
- Asthma
- Chronic obstructive pulmonary disease (COPD)
- Less common
- Bronchiectasis
- Bronchiolitis
- Unifying physiologic feature of all forms of obstructive lung disease
- Increased resistance to expiratory airflow
- Depending on the underlying disease, this increase in resistance may be due to one or more of the following processes
- Obstruction within the airway lumen
- Thickening of the airway wall
- Contraction of bronchial smooth muscle
- Loss of the normal parenchymal support surrounding the small, non-cartilagenous airways
- Whatever the mechanism(s), increased airway resistance leads to...
- A drop in expiratory flow
- Alterations in gas exchange and respiratory muscle function
- These changes, in turn, lead to...
- Clinical symptoms and signs
- Characteristic changes in pulmonary function tests
- Asthma
- Chronic obstructive pulmonary disease (COPD)
- Bronchiectasis
- Bronchiolitis
- Increased resistance to expiratory airflow
- Obstruction within the airway lumen
- Thickening of the airway wall
- Contraction of bronchial smooth muscle
- Loss of the normal parenchymal support surrounding the small, non-cartilagenous airways
- A drop in expiratory flow
- Alterations in gas exchange and respiratory muscle function
- Clinical symptoms and signs
- Characteristic changes in pulmonary function tests
2
Clinical and histological features
- Chronic obstructive pulmonary disease consists of two distinct entities
- In the majority of patients, these two diseases...
- Chronic obstructive pulmonary disease consists of two distinct entities
- Chronic bronchitis
- Emphysema
- In the majority of patients, these two diseases...
- Coexist, but it is common for one to predominate
- Chronic bronchitis
- Emphysema
- Coexist, but it is common for one to predominate
3
Clinical and histological features
- Chronic bronchitis
- Diagnosed clinically by...
- Histologically, there is...
- Emphysema
- Primarily affects...
- Defined histologically by...
- There is also accompanying...
- Chronic bronchitis
- Diagnosed clinically by the presence of a productive cough for at least 3 months in each of two successive years
- Histologically, there is airway inflammation and edema, mucous gland hypertrophy, and excessive bronchial secretions
- Emphysema
- Primarily affects the pulmonary parenchyma
- Defined histologically by the destruction of alveolar walls leading to permanent airspace enlargement
- There is also accompanying destruction of the pulmonary capillary bed
- Diagnosed clinically by the presence of a productive cough for at least 3 months in each of two successive years
- Histologically, there is airway inflammation and edema, mucous gland hypertrophy, and excessive bronchial secretions
- Primarily affects the pulmonary parenchyma
- Defined histologically by the destruction of alveolar walls leading to permanent airspace enlargement
- There is also accompanying destruction of the pulmonary capillary bed
4
Clinical and histological features
- Asthma
- Characterized by...
- Histologic examination of the airways may reveal...
- Characterized clinically by...
- Bronchiectasis
- Bronchi become...
- Leads to...
- Caused by...
- Asthma
- Characterized by bronchial smooth muscle contraction
- Histologic examination of the airways may reveal inflammation, edema, and smooth muscle hypertrophy
- Characterized clinically by airflow obstruction that can be either significantly improved, or often completely eliminated with bronchodilator therapy
- Bronchiectasis
- Bronchi become dilated and fail to effectively clear secretions
- Leads to chronic airway infection, excessive bronchial secretions, and a chronic, productive cough
- Caused by inflammation and stenosis of the bronchioles, which leads to diffuse small airways obstruction
- Characterized by bronchial smooth muscle contraction
- Histologic examination of the airways may reveal inflammation, edema, and smooth muscle hypertrophy
- Characterized clinically by airflow obstruction that can be either significantly improved, or often completely eliminated with bronchodilator therapy
- Bronchi become dilated and fail to effectively clear secretions
- Leads to chronic airway infection, excessive bronchial secretions, and a chronic, productive cough
- Caused by inflammation and stenosis of the bronchioles, which leads to diffuse small airways obstruction
5
Alterations in respiratory mechanics:
Increased airway resistance
- In emphysema, airflow obstruction results from...
- These airways...
- Any effort to actively exhale...
- Patients with advanced emphysema may have...
- In emphysema, airflow obstruction results from...
- Loss of the normal “tethering” effect of the pulmonary parenchyma on the small, non-cartilaginous airways
- These airways...
- Have little structural rigidity
- Depend on the elastic recoil of the surrounding pulmonary parenchyma to maintain their patency during expiration
- Any effort to actively exhale...
- Makes this problem worse, since pleural pressure (which is also the pressure outside the airways) becomes more positive and causes the airways to collapse
- Patients with advanced emphysema may have...
- Positive pleural pressure and small airways closure even during passive exhalation
- Loss of the normal “tethering” effect of the pulmonary parenchyma on the small, non-cartilaginous airways
- Have little structural rigidity
- Depend on the elastic recoil of the surrounding pulmonary parenchyma to maintain their patency during expiration
- Makes this problem worse, since pleural pressure (which is also the pressure outside the airways) becomes more positive and causes the airways to collapse
- Positive pleural pressure and small airways closure even during passive exhalation
6
Alterations in respiratory mechanics:
Increased airway resistance
- Airflow obstruction in chronic bronchitis and bronchiectasis results from...
- Both processes lead to...
- Similar processes occur in...
- Airflow obstruction in bronchiolitis is due to...
- Airflow obstruction in chronic bronchitis and bronchiectasis results from...
- Inflammation and edema of the airway wall and from excessive airway secretions
- Both processes lead to...
- Narrowing of the airway lumen, thereby increasing airway resistance
- Similar processes occur in...
- Asthma, although contraction of bronchial smooth muscle is an additional cause of airway narrowing
- Airflow obstruction in bronchiolitis is due to...
- Inflammation and edema of the airway wall and/or the deposition of connective tissue in the airway wall or lumen
- Inflammation and edema of the airway wall and from excessive airway secretions
- Narrowing of the airway lumen, thereby increasing airway resistance
- Asthma, although contraction of bronchial smooth muscle is an additional cause of airway narrowing
- Inflammation and edema of the airway wall and/or the deposition of connective tissue in the airway wall or lumen
7
Alterations in respiratory mechanics:
Decreased elastic recoil
- In most of the obstructive lung diseases, decreased expiratory flow is due simply to...
- In emphysema, however, there is another important factor
- This is what happens in emphysema
- In most of the obstructive lung diseases, decreased expiratory flow is due simply to...
- Increased airway resistance
- In emphysema, however, there is another important factor
- A major determinant of expiratory flow is the elastic recoil of the lungs
- A large amount of elastic recoil causes air to be forced rapidly from the lungs, but a decrease in elastic recoil causes a drop in the pressure driving expiratory flow
- This is what happens in emphysema
- Destruction of collagen and elastin fibers in the lung parenchyma causes elastic recoil to decrease, thereby decreasing the expiratory flow rate
- Increased airway resistance
- A major determinant of expiratory flow is the elastic recoil of the lungs
- A large amount of elastic recoil causes air to be forced rapidly from the lungs, but a decrease in elastic recoil causes a drop in the pressure driving expiratory flow
- Destruction of collagen and elastin fibers in the lung parenchyma causes elastic recoil to decrease, thereby decreasing the expiratory flow rate
8
Alterations in lung volumes
- Several of the commonly measured lung volumes are influenced by...
- Functional residual capacity (FRC) represents...
- Not surprisingly, loss of lung elastic recoil often causes...
- Total lung capacity (TLC) is...
- A decrease in lung elastic recoil may, therefore,...
- Several of the commonly measured lung volumes are influenced by...
- Lung elastic recoil, and therefore are frequently altered in patients with emphysema
- Functional residual capacity (FRC) represents...
- The equilibrium position of the respiratory system
- The point at which the inward elastic recoil of the lungs is exactly balanced by the outward recoil of the chest wall
- Not surprisingly, loss of lung elastic recoil often causes...
- FRC to increase
- Total lung capacity (TLC) is...
- The volume at which the combined inward elastic recoil of the lungs and chest wall is exactly balanced by maximal inspiratory effort
- A decrease in lung elastic recoil may, therefore,...
- Increase TLC, assuming that inspiratory muscle strength is maintained
- Lung elastic recoil, and therefore are frequently altered in patients with emphysema
- The equilibrium position of the respiratory system
- The point at which the inward elastic recoil of the lungs is exactly balanced by the outward recoil of the chest wall
- FRC to increase
- The volume at which the combined inward elastic recoil of the lungs and chest wall is exactly balanced by maximal inspiratory effort
- Increase TLC, assuming that inspiratory muscle strength is maintained
9
Alterations in lung volumes:
Several other factors may alter lung volumes in patients with any of the obstructive lung diseases
- Air trapping
- Dynamic hyperinflation
- Intrinsic or auto- positive end-expiratory pressure (PEEP)
- Air trapping
- In the presence of high airway resistance, forced expiration may be accompanied by collapse of the small airways
- This process prevents further exhalation and leads to elevation of RV (and to a decrease in VC)
- May be so severe that it limits the volume that can be exhaled even during tidal breathing
- Dynamic hyperinflation
- End-expiratory volume may also increase simply because the time available for expiration is insufficient to allow the respiratory system to return to its equilibrium volume
- May also lead to worsening airflow obstruction
- Intrinsic or auto- positive end-expiratory pressure (PEEP)
- Distinguished from “extrinsic” PEEP that is intentionally applied during mechanical ventilation
- Because its equilibrium volume has not been reached, the elastic recoil pressure of the respiratory system remains positive
- Since end-expiratory volume is above the equilibrium volume of the respiratory system, pleural pressure will be less negative and is, in fact, often positive at the end of expiration
- This leads to further airway compression and collapse
- In the presence of high airway resistance, forced expiration may be accompanied by collapse of the small airways
- This process prevents further exhalation and leads to elevation of RV (and to a decrease in VC)
- May be so severe that it limits the volume that can be exhaled even during tidal breathing
- End-expiratory volume may also increase simply because the time available for expiration is insufficient to allow the respiratory system to return to its equilibrium volume
- May also lead to worsening airflow obstruction
- Distinguished from “extrinsic” PEEP that is intentionally applied during mechanical ventilation
- Because its equilibrium volume has not been reached, the elastic recoil pressure of the respiratory system remains positive
- Since end-expiratory volume is above the equilibrium volume of the respiratory system, pleural pressure will be less negative and is, in fact, often positive at the end of expiration
- This leads to further airway compression and collapse
10
Alterations in gas exchange
- Airway narrowing in all forms of obstructive lung disease leads to...
- In emphysema, alveolar and capillary destruction leads to...
- Obstructive lung diseases, therefore, cause...
- Increased numbers of low V/Q lung units cause...
- High V/Q units lead to...
- Airway narrowing in all forms of obstructive lung disease leads to...
- Abnormal distribution of ventilation throughout the lungs
- In emphysema, alveolar and capillary destruction leads to...
- Both abnormal ventilation and perfusion
- Obstructive lung diseases, therefore, cause...
- Significant mismatching of ventilation and perfusion
- Increased numbers of low V/Q lung units cause...
- A decrease in PaO2 and an increase in the PA-aO2
- High V/Q units lead to...
- An increase in alveolar and physiologic dead space
- Abnormal distribution of ventilation throughout the lungs
- Both abnormal ventilation and perfusion
- Significant mismatching of ventilation and perfusion
- A decrease in PaO2 and an increase in the PA-aO2
- An increase in alveolar and physiologic dead space
11
Alterations in gas exchange
- Exercise-induced hypoxemia is common in patients with...
- In the normal lung, equilibration between...
- In emphysema, capillary destruction leads to...
- Exercise-induced hypoxemia is common in patients with...
- Moderate to severe emphysema but is not seen in other forms of obstructive lung disease
- This is because only emphysema causes destruction of the pulmonary capillaries
- In the normal lung, equilibration between...
- The PO2 of alveolar gas and pulmonary capillary blood occurs even during peak exertion
- In emphysema, capillary destruction leads to...
- Increased blood velocity even at rest, since the same cardiac output must go through many fewer capillaries
- With exertion and the consequent increase in cardiac output, blood transit time may be insufficient for equilibration to occur, and PaO2 falls
- Moderate to severe emphysema but is not seen in other forms of obstructive lung disease
- This is because only emphysema causes destruction of the pulmonary capillaries
- The PO2 of alveolar gas and pulmonary capillary blood occurs even during peak exertion
- Increased blood velocity even at rest, since the same cardiac output must go through many fewer capillaries
- With exertion and the consequent increase in cardiac output, blood transit time may be insufficient for equilibration to occur, and PaO2 falls
12
Alterations in gas exchange
- Patients with severe obstructive lung disease may develop...due to...
- In patients with chronic hypercapnia, administration of oxygen may lead to...
- Patients with severe obstructive lung disease may develop...
- Acute or chronic hypercapnia due to...
- Abnormal mechanics (i.e. high airways resistance)
- Increased dead space ventilation
- Impaired respiratory muscle function
- In patients with chronic hypercapnia, administration of oxygen may lead to...
- A further, acute increase in PaCO2
- For many years, this was thought to be due to loss of “hypoxic drive”
- Several studies have confirmed, however, that acute CO2 retention accompanying oxygen administration is not caused by a decrease in minute ventilation
- Instead, it appears to be due to worsening V/Q imbalance
- Acute or chronic hypercapnia due to...
- Abnormal mechanics (i.e. high airways resistance)
- Increased dead space ventilation
- Impaired respiratory muscle function
- A further, acute increase in PaCO2
- For many years, this was thought to be due to loss of “hypoxic drive”
- Several studies have confirmed, however, that acute CO2 retention accompanying oxygen administration is not caused by a decrease in minute ventilation
- Instead, it appears to be due to worsening V/Q imbalance
13
Alterations in respiratory muscle function:
The abnormal respiratory mechanics adversely affect the function of the respiratory muscles
- Increased pressure must be generated to overcome...
- In addition, the ability of the diaphragm to expand the lungs and chest wall progressively falls as...
- Intrinsic PEEP acts as...
- Since inspiration can begin only after...
- ...the inspiratory muscles...
- Increased pressure must be generated to overcome...
- Viscous forces, and this leads to high levels of respiratory muscle work and energy consumption
- In addition, the ability of the diaphragm to expand the lungs and chest wall progressively falls as...
- Air trapping and hyperinflation cause it to lose its normal dome-shaped configuration
- This reduces its efficiency, since an increasing amount of energy must be expended to perform the same amount of work
- Intrinsic PEEP acts as...
- A threshold load on the respiratory muscles and further increases energy expenditure
- Since inspiration can begin only after...
- Sufficient pressure has been generated to stop expiratory flow and balance the elastic recoil of the respiratory system
- ...the inspiratory muscles...
- Contract but do not generate airflow until this critical pressure has been reached
- Viscous forces, and this leads to high levels of respiratory muscle work and energy consumption
- Air trapping and hyperinflation cause it to lose its normal dome-shaped configuration
- This reduces its efficiency, since an increasing amount of energy must be expended to perform the same amount of work
- A threshold load on the respiratory muscles and further increases energy expenditure
- Sufficient pressure has been generated to stop expiratory flow and balance the elastic recoil of the respiratory system
- Contract but do not generate airflow until this critical pressure has been reached
14
Pulmonary function tests and arterial blood gases:
Alterations in the mechanics of the respiratory system account for the characteristic findings demonstrated by pulmonary function testing
- Increased airway resistance leads to...
- FVC and FEV1
- RV and FRC
- TLC
- Diffusing capacity
- Increased airway resistance leads to...
- A decrease in all measured expiratory flow rates, including PEFR and FEF25-75 and to a prolonged expiratory time. Because flow is reduced, the FEV1 is also abnormally low
- FVC and FEV1
- The FVC is often normal, but will be decreased in the presence of significant air trapping
- Even when the FVC is reduced, the FEV1 is always reduced more
- This means that the FEV1/FVC will always be abnormally low in patients with obstructive lung disease. This is the spirometric hallmark of airflow obstruction
- RV and FRC
- May be normal or elevated
- TLC
- May be increased in emphysema
- Will be normal in other obstructive diseases
- Diffusing capacity
- Abnormal only in emphysema, since this is the only obstructive disease that reduces the surface area of the pulmonary-capillary interface
- A decrease in all measured expiratory flow rates, including PEFR and FEF25-75 and to a prolonged expiratory time. Because flow is reduced, the FEV1 is also abnormally low
- The FVC is often normal, but will be decreased in the presence of significant air trapping
- Even when the FVC is reduced, the FEV1 is always reduced more
- This means that the FEV1/FVC will always be abnormally low in patients with obstructive lung disease. This is the spirometric hallmark of airflow obstruction
- May be normal or elevated
- May be increased in emphysema
- Will be normal in other obstructive diseases
- Abnormal only in emphysema, since this is the only obstructive disease that reduces the surface area of the pulmonary-capillary interface
15
Pulmonary function tests and arterial blood gases:
Summary
- FVC
- FEV1
- FEV1/FVC
- PEFR
- FEF25-75
- FRC
- RV
- TLC
- DLCO
-
FVC N - ↓
-
FEV1 ↓
-
FEV1/FVC ↓
-
PEFR ↓
-
FEF25-75 ↓
-
FRC N - ↑
-
RV N - ↑
-
TLC N - ↑
-
DLCO N - ↓
16
Pulmonary function tests and arterial blood gases:
The flow-volume and volume-time curves have a characteristic appearance in patients with obstructive lung disease
- Expiratory resistance
- Expiratory time
- Volume-time curve demonstrates...
- As disease severity increases, expiratory flow...
- Patients with a significant degree of airflow obstruction typically have...
- Patients with moderate to severe emphysema experience...
- Chronic hypercapnia is common in patients with...
- Expiratory resistance
- High
- Expiratory time
- Prolonged
- Volume-time curve demonstrates...
- A progressive increase in volume throughout expiration, rather than the plateau that is quickly reached in patients without airflow obstruction
- As disease severity increases, expiratory flow...
- Progressively falls, especially in the middle and final third of expiration
- This causes the flow-volume curve to have a “scooped-out” appearance that becomes more prominent as airflow obstruction worsens
- Patients with a significant degree of airflow obstruction typically have...
- An abnormally low PaO2 and an elevated PA-aO2
- Patients with moderate to severe emphysema experience...
- A further decline in PaO2 during exercise
- Chronic hypercapnia is common in patients with...
- Severe obstructive lung disease, especially COPD
- High
- Prolonged
- A progressive increase in volume throughout expiration, rather than the plateau that is quickly reached in patients without airflow obstruction
- Progressively falls, especially in the middle and final third of expiration
- This causes the flow-volume curve to have a “scooped-out” appearance that becomes more prominent as airflow obstruction worsens
- An abnormally low PaO2 and an elevated PA-aO2
- A further decline in PaO2 during exercise
- Severe obstructive lung disease, especially COPD
17
Long-term pathophysiologic changes
- Pulmonary hypertension may occur in patients with...
- Capillary destruction and hypoxia-induced vasoconstriction lead to...
- Pulmonary hypertension is often worsened by...
- Cor pulmonale
- Pulmonary hypertension may occur in patients with...
- Severe obstructive lung disease
- Capillary destruction and hypoxia-induced vasoconstriction lead to...
- A decrease in total vascular cross-sectional area and to an increase in pulmonary vascular resistance
- With time, thickening of the intima of the pulmonary arteries produces additional irreversible increases in vascular resistance
- Pulmonary hypertension is often worsened by...
- Hypoxemia-induced erythrocythemia, which increases blood viscosity
- Cor pulmonale
- Pulmonary hypertension can, in turn, lead to pressure overload and failure of the right ventricle
- Characterized clinically by increased jugular venous pressure, hepatomegaly, and peripheral edema
- Severe obstructive lung disease
- A decrease in total vascular cross-sectional area and to an increase in pulmonary vascular resistance
- With time, thickening of the intima of the pulmonary arteries produces additional irreversible increases in vascular resistance
- Hypoxemia-induced erythrocythemia, which increases blood viscosity
- Pulmonary hypertension can, in turn, lead to pressure overload and failure of the right ventricle
- Characterized clinically by increased jugular venous pressure, hepatomegaly, and peripheral edema
18
Pathophysiology of dyspnea and exercise limitation:
The relationship between expiratory flow and lung volume during both quiet breathing and a maximal effort in a patient without lung disease and in patients with airflow obstruction of increasing severity
- Expiratory flow and tidal volume
- Maximum flows in patients with obstructive lung disease...
- This means that the time required for exhalation must...
- In addition, air trapping and dynamic hyperinflation...
- With limited respiratory rate and tidal volume, maximum minute ventilation...
- With severe disease
- Expiratory flow and tidal volume
- Can normally be markedly increased (the difference between the two curves) if needed to meet ventilatory demands (e.g. during exercise)
- Maximum flows in patients with obstructive lung disease...
- Progressively decrease with disease severity
- This means that the time required for exhalation must...
- Increase, and this limits the total respiratory rate that can be achieved
- In addition, air trapping and dynamic hyperinflation...
- Reduce the maximum tidal volume
- With limited respiratory rate and tidal volume, maximum minute ventilation...
- Must fall
- This is the main reason that increasing airflow obstruction is accompanied by a progressive fall in exercise capacity
- With severe disease
- The resting and maximal curves become superimposed
- Patients become dyspneic even at rest
- Can normally be markedly increased (the difference between the two curves) if needed to meet ventilatory demands (e.g. during exercise)
- Progressively decrease with disease severity
- Increase, and this limits the total respiratory rate that can be achieved
- Reduce the maximum tidal volume
- Must fall
- This is the main reason that increasing airflow obstruction is accompanied by a progressive fall in exercise capacity
- The resting and maximal curves become superimposed
- Patients become dyspneic even at rest
19
Pathophysiology of dyspnea and exercise limitation:
Other factors contributing to dyspnea and exercise limitation
- Arterial hypoxemia
- Excessive alveolar dead space (which increases ventilation requirements)
- Increased work and energy expenditure by the respiratory muscles
