Chapter 15: Lung: Obstructive versus Restrictive Pulmonary Diseases Flashcards
Based on pulmonary function tests, chronic noninfectious diffuse pulmonary diseases can be
classified in one of two categories:
- (1) obstructive diseases (or airway diseases)
- (2) restrictive diseases,
What are is an obstructive disease ( airway dse)?
(1) obstructive diseases (or airway diseases), characterized
by an increase in resistance to airflow due to partial or complete obstruction at any level, from
the trachea and larger bronchi to the terminal and respiratory bronchioles
What is restrictive dse?
(2) restrictive
diseases, characterized by reduced expansion of lung parenchyma and decreased total lung
capacity.
In individuals with diffuse obstructive disorders, pulmonary function tests show
decreased maximal airflow ratesduringforced expiration, usually measured by___________
forced expiratory
volume at 1 second.
Expiratory airflow obstruction may be caused by a variety of conditions listed in Table 15-3 .
They are distinguished by _________ and hence different mechanisms for airflow obstruction.
As discussed below, such neat distinctions are not always
possible.
distinct anatomic lesions
In contrast, restrictive diseases are identified by a reduced total lung capacity, and an
expiratory flow rate that is normal or reduced proportionately.
Restrictive defects occur in two
general conditions:
(1) chest wall disorders (e.g., neuromuscular diseases such as poliomyelitis, severe obesity, pleural diseases, and kyphoscoliosis) and
(2) chronic interstitial and infiltrative diseases, such as pneumoconioses and interstitial fibrosis of unknown etiology.
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Clinical Term :Anatomic Site
- Chronic bronchitis : Bronchus
- Bronchiectasis :Bronchus
- Asthma : Bronchus
- Emphysema: Acinus
- Small-airway disease, bronchiolitis :Bronchiole
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Chronic
bronchitis
- Anatomic Site: Bronchus
- Major Pathologic Changes: Mucous gland hyperplasia, hypersecretion
- Etiology: Tobacco smoke, air
pollutants - S/Sx: Cough, sputum production
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Bronchiectasis
Anatomic Site: Bronchus
Major Pathologic Changes: Airway dilation and
scarring
Etiology: Persistent or severe
infections
S/Sx: Cough, sputum production
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Asthma
Anatomic Site: Bronchus
Major Pathologic Changes: Smooth muscle
hyperplasia, excess
mucus, inflammation
Etiology:Immunological or
undefined causes
S/Sx: Cough, sputum production
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Emphysema
Anatomic Site: Acinus
Major Pathologic Changes: Airspace enlargement; wall
destruction
Etiology:Tobacco smoke
S/Sx: Dyspnea
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Small-airway
disease,
bronchiolitis
Anatomic Site: Bronchiole
Major Pathologic Changes: Inflammatory
scarring/obliteration
Etiology:Tobacco smoke, air pollutants, miscellaneous
S/Sx:Cough, dyspnea
What is COPD?
Emphysema and chronic bronchitis are often clinically grouped together and referred to as
chronic obstructive pulmonary disease (COPD), since many patients have overlapping features
of damage at both the acinar level (emphysema) and bronchial level (bronchitis), almost
certainly because one extrinsic trigger—cigarette smoking—is common to both
In addition,
small-airway disease, a variant of chronic bronchiolitis, is now known to contribute to obstruction both in emphysema and chronic bronchitis.
[11] While asthma is distinguished from chronic
bronchitis and emphysema by thepresence of reversible bronchospasm,some patients with
otherwise typical asthma also develop an irreversible component (
FIGURE 15-5 Schematic representation of overlap between chronic obstructive lung
diseases.
Conversely,
some patients with otherwise typical COPD have a reversible component. It is clinically common
to label such patients as having COPD/asthma. In a recent study the overlap between these
three disorders was found to be substantial
In most patients, COPD is the result of long-term ____________
heavy cigarette smoking; about 10% of
patients are nonsmokers.
However, only a minority of smokers develop COPD, the
reason for which is still unknown
What is emphysema?
EMPHYSEMA
Emphysema is a condition of the lung characterized by irreversible enlargement of the
airspaces distal to the terminal bronchiole, accompanied by destruction of their walls without
obvious fibrosis
Incidence.
There is a clear-cut association between heavy cigarette
smoking and emphysema, and women and African Americans are more susceptible than other
groups.
How is emphysema classified?
Emphysema is classified according to its anatomic distribution within the lobule
Types of Emphysema.
Recall that the
lobule is a cluster of acini, the terminal respiratory units.
Although the term emphysema is
sometimes loosely applied to diverse conditions, there are four major types:
- (1) centriacinar ,
- (2) panacinar ,
- (3) paraseptal, and
- (4) irregular .
Of these, only the first two cause clinically significant airflow obstruction ( Fig. 15-6 ).
Among the types of emphysema, which among the four causes clinically
significant airflow obstruction
(1) centriacinar ,
(2) panacinar
Centriacinar emphysema is far more common than
the panacinar form, constituting more than 95% of cases.
FIGURE 15-6 Major patterns of emphysema.
A, Normal structure within the acinus.
B, Centriacinar emphysema with dilation that initially affects the respiratory bronchioles.
C, Panacinar emphysema with initial distention of the alveolus and alveolar duct.
What is Centriacinar (Centrilobular) Emphysema?
In this type of emphysema the central or proximal parts of the acini , formed by respiratory
bronchioles, are affected, whereas distal alveoli are spared.
Thus,
both emphysematous and normal airspaces exist within the same acinus and lobule.
The lesions are more common and usually more severe in the upper lobes, particularly in the apical
segments.
The walls of the emphysematous spaces often contain large amounts of black pigment.
Inflammation around bronchi and bronchioles is common.
In severe centriacinar
emphysema, the distal acinus may also be involved, and differentiation from panacinar
emphysema becomes difficult.
Centriacinar emphysema occurs predominantly in heavy smokers, often in association with chronic bronchitis.
What is the more common and more severe area affected in centriacinar emphysema?
The lesions are more common and usually more severe in the upper lobes, particularly in the apical
segments.
In severe centriacinar
emphysema, the distal acinus may also be involved, and differentiation from panacinar
emphysema becomes difficult.
T or F
True
What is Panacinar (Panlobular) Emphysema?
In this type, the acini are uniformly enlarged from the level of the respiratory bronchiole to the
terminal blind alveoli ( Figs. 15-6C and 15-7B ).
The prefix “pan” refers to the entire acinus but
not to the entire lung.
. This type of emphysemais associated with α1-antitrypsin ( α1-
AT) deficiency
What is the difference of centriacinar and panlobular?
In contrast to centriacinar emphysema, panacinar emphysema tends to
- *occur more commonly in the lower zones** and in the anterior margins of the lung, and it is
- *usually most severe at the bases**
What type of emphysema is associated with heavy smoking?
Centriacinar
What type of emphysema is associated with a 1 antitrypsin deficiency?
panlobular
FIGURE 15-7
A, Centriacinar emphysema. Central areas show marked emphysematous
damage (E), surrounded by relatively spared alveolar spaces.
B, Panacinar emphysema
involving the entire pulmonary lobule.
Where does Panacinar (Panlobular) Emphysema commonly occurs?
panacinar emphysema tends to
occur more commonly in the lower zones and in the anterior margins of the lung, and it is
usually most severe at the bases
cenTrilobular= Top ( most common)
Top Gun heavy smoking
panLobular= Low ( most common)
What is Distal Acinar (Paraseptal) Emphysema?
In this type, the proximal portion of the acinus is normal , and the distal part is predominantly
involved.
The emphysema is more striking adjacent to the pleura, along the lobular connective
tissue septa, and at the margins of the lobules.
It occurs adjacent to areas of fibrosis, scarring,
or atelectasisand isusually more severe in the upper half of the lungs.
What is the characteristic finding of Distal Acinar (Paraseptal) Emphysema?
The characteristic
findings are of multiple, continuous, enlarged airspaces from less than 0.5 cm to more than 2.0
cm in diameter, sometimesforming cystlike structures.
This type of emphysema probably
underlies many of the cases of spontaneous pneumothorax in young adults.
Where is the most common affected area of Distal Acinar (Paraseptal) Emphysema?
It occurs adjacent to areas of fibrosis, scarring,
or atelectasis and is usually more severe in the upper half of the lungs
What is Airspace Enlargement with Fibrosis (Irregular Emphysema).?
Irregular emphysema, so named because the acinus is irregularly involved , is almost invariably
associated with scarring.
Thus, it may be the most common form of emphysema, because
careful search of most lungs at autopsy shows one or more scars from a healed inflammatory
process.
In most instances, these foci of irregular emphysema are asymptomatic and clinically
insignificant.
What is pathogenesis of the Airspace Enlargement with Fibrosis (Irregular Emphysema) ?
COPD is characterized by mild chronic inflammation throughout the airways, parenchyma, and
pulmonary vasculature.
Macrophages, CD8+ and CD4+ T lymphocytes, and neutrophils are
increased in various parts of the lung.
Activated inflammatory cells release a variety of
mediators, includingleukotriene B4, IL-8, TNF, and others, that are capable of damaging lung
structures or sustaining neutrophilic inflammation. [20]
Although details of the genesis of the two
common forms of emphysema—centriacinar and panacinar—remain unsettled, the most
plausible hypothesis to account for the destruction of alveolar walls is the proteaseantiprotease
mechanism,aided and abetted byimbalance of oxidants and antioxidants.
The protease-antiprotease imbalance hypothesis is based on the observation that patients with
a genetic deficiency of the antiprotease α1-antitrypsin have a markedly enhanced tendency to
develop pulmonary emphysema, which iscompounded by smoking ( Fig. 15-8 ).
About 1% of all
patients with emphysema have this defect. α1-antitrypsin, normally present in serum, tissue
fluids, and macrophages, is a major inhibitor of proteases (particularly elastase) secreted by
neutrophils during inflammation.
α1-antitrypsin is encoded by codominantly expressed genes on
the proteinase inhibitor (Pi) locus on chromosome 14. The Pi locus is extremely polymorphic,
with many different alleles. Most common is the normal (M) allele and the corresponding
phenotype. Approximately 0.012% of the US population is homozygous for the Z allele,
associated with markedly decreased serum levels of α1antitrypsin.
More than 80% of these
individuals develop symptomatic panacinar emphysema, which occurs at an earlier age and with
greater severity if the individual smokes.
What is α1-antitrypsin
α1-antitrypsin is encoded by codominantly expressed genes on the proteinase inhibitor (Pi) locus on chromosome 14.
The Pi locus is extremely polymorphic,
with many different alleles.
α1-antitrypsin, normally present in serum, tissue
fluids, and macrophages, is amajor inhibitor of proteases (particularly elastase) secreted by
neutrophils during inflammation
More than 80% of these
individuals develop symptomatic panacinar emphysema, which occurs at an earlier age and with
greater severity if the individual smokes. The following sequence is postulated:
- Neutrophils (the principal source of cellular proteases) are normally sequestered in
peripheral capillaries, including those in the lung, and a few gain access to the alveolar
spaces.
- Any stimulus that increases either the number of leukocytes (neutrophils and
macrophages) in the lung or the release of their protease-containing granules
increases proteolytic activity.
- With low levels of serum α1-antitrypsin, elastic tissue destruction is unchecked and
emphysema results
FIGURE 15-8 Pathogenesis of emphysema.
Excessive protease activity and reactive oxygen
species are additive in their effects and contribute to tissue damage.
α1-antitrypsin (α1-AT)
deficiency can be either congenital or “functional” as a result of oxidative inactivation
See
text for details. IL-8, interleukin 8; LTB4, leukotriene B4; TNF, tumor necrosis factor.
Thus, emphysema is seen to result from the destructive effect of high protease activity in
subjects with low antiprotease activity.
The protease-antiprotease imbalance hypothesis also
- *helps explain the effect of cigarette smoking in the development of emphysema,** particularly the
- *centriacinar** form in subjects with normal amounts of α1-antitrypsin:
- In smokers, neutrophils and macrophages accumulate in alveoli . The mechanism of inflammation is not entirely clear, but possibly involves the direct chemoattractant effects of nicotine as well as the effects of reactive oxygen species contained in smoke. These activate the transcription factor NF-κB, which switches on genes that encode TNF and chemokines, including IL-8. These, in turn, attract and activate neutrophils
- Accumulated neutrophils are activated and release their granules, rich in a variety of cellular proteases (neutrophil elastase, proteinase 3, and cathepsin G), resulting in tissue damage.
- Smoking also enhances elastase activity in macrophages; macrophage elastase is not
inhibited by α1-antitrypsin) and, indeed, can proteolytically digest this antiprotease. There is increasing evidence that in addition to elastase, matrix metalloproteinases derived from macrophages and neutrophils have a role in tissue destruction.
In addition, smoking has a seminal role in perpetuating the oxidant-antioxidant imbalance in the pathogenesis of emphysema.
Why?
Normally, the lung contains a healthy complement of antioxidants (superoxide dismutase, glutathione) that keep oxidative damage to a minimum.
Tobacco smoke
- *contains abundant reactive oxygen species** (free radicals), which deplete these antioxidant
- *mechanisms**, thereby inciting tissue damage ( Chapter 1 ).
- *Activated neutrophils also add to the**
- *pool of reactive oxygen species in the alveoli.**
A secondary consequence of oxidative injury is
- *inactivation of native antiproteases, r**esulting in “functional” α1-antitrypsin deficiency even in
- *patients without enzyme deficiency.**
How does emphysema leads to funcitonal ariflow obstruction despite absence of mechanical obstruction?
Since small airways are normally tethered by the elastic recoil of the lung parenchyma, the loss
of elastic tissuein thewalls of alveolithat surround respiratory bronchiolesreduces radial
traction and thus causes the respiratory bronchioles to collapse during expiration.
This leads to
functional airflow obstruction despite the absence of mechanical obstruction.
Until recently loss of elastic recoil was considered to be the sole mechanism of airflow
obstruction in emphysema. However, careful studies in young smokers who died in accidents
have revealed that inflammation of small airways, defined as bronchioles less than 2 mm in
diameter, occurs early in the evolution of COPD. Several changes are seen:
- goblet cell metaplasia with mucus plugging of the lumen
- inflammatory infiltration of the walls with neutrophils, macrophages, B cells (sometimes
forming follicles), CD4 and CD8+ T cells -
thickening of the bronchiolar wall due to smooth muscle hypertrophy and peribronchial
fibrosis
Together these changes narrow the bronchiolar lumen and contribute to airway
obstruction.
One of the perplexing features of COPD is that smoldering inflammation and slow progressive
destruction of the lung parenchymaoften continuefor decades after cessation of smoking. [22]
While there are no clear answers, there is emerging evidence that the initial insult in the form of
tobacco smoke, or other irritants, triggers amaladaptive, self-perpetuating immune response in
which both innate and adaptive components play a role.
Fingers are pointing to pathogenic
CD4+TH17 cells similar to those that are involved in other immunemediated inflammatory
diseases such as Crohn disease, but much remains to be known.
What is the morphology of emphysema?
Advanced emphysema produces voluminous lungs, often overlapping the
heartandhiding it when the anterior chest wall is removed.
Generally, the upper two thirds of
the lungs are more severely affected.
Large apical blebs or bullae are more characteristic of
irregular emphysema secondary to scarring and of distal acinar emphysema. Large alveoli
can easily be seen on the cut surface of formalin-inflated fixed lung
What is the more characteristic of irregular emphysema?
Large apical blebs or bullae are more characteristic of
irregular emphysema secondary to scarring and of distal acinar emphysema
What is the appearance of emphysema microscopically ?
Microscopically, there are abnormally large alveoli separated by thin septa with only focal
centriacinar fibrosis.
There is loss of attachments of the alveoli to the outer wall of small
airways.
The pores of Kohn are so large that septa appear to be floating or protrude blindly into alveolar spaces with a club-shaped end.
As alveolar walls are destroyed, there is
decrease in the capillary bed.
With advanced disease, there are even larger abnormal
airspaces and possibly blebs or bullae, which often deform and compress the respiratory
bronchioles and vasculature of the lung.
Inflammatory changes in small airways were
described earlier.
The clinical manifestations of emphysema do not appear until at least ________
one third of the
functioning pulmonary parenchyma is damaged
What is the Clinical Course of emphysema?
- Dyspnea is usually the first symptom; it begins insidiously but is steadily progressive.
- In some patients, cough or wheezing is the chief complaint, easily confused with asthma.
- Cough and expectoration are extremely variable and depend on the extent of the associated bronchitis.
- Weight loss is common and can be so severe as to suggest a hidden malignant tumor.
- Classically, the patient is barrel-chested and dyspneic, with obviously prolonged expiration, sits forward in a hunched-over position, and breathes through pursed lips.
What is the first symptom in emphysema?
Dyspnea is usually the first symptom; it begins
insidiously but is steadily progressive
In some patient what is the chief complaint of emphysema?
In some patients, cough or wheezing is the chief
complaint, easily confused with asthma.
Expiratory airflow limitation, best measured through spirometry, is the key to diagnosis.