22 Pathophysiology of the Obstructive Lung Diseases Flashcards Preview

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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