Diffuse pulmonary disease
classification
• Obstructive disease(airway disease)-characterised
by limitation of airflow usually resulting from an
increased resistance caused by partial or complete
obstruction at any level.
• Restrictive lung disease characterised by reduced
expansion of lung parenchyma accompanied by
decreased total lung capacity
•
1.
2.
3.
4.
Major diffuse obstructive disorders are:
Emphysema
Chronic bronchitis
Bronchiectasis
Asthma
•
Restrictive defects occur in 2 general
conditions:1. Chest wall disorders in the presence of normal
lungs eg. Severe obesity,disease of
pleura,neuromuscular disorders like GuillanBarre syndrome that affects respiratory muscles
2. Acute or chronic interstitial lung disease eg.
Pneumoconiosis, ARDS,etc.
Obstuctive pulmonary disease
• Chronic bronchitis and emphysema
• Usually both co-exist,have a common
etiological factor i.e. chronic smoking.
• Both together are grouped under “COPD”
• Irreversible airflow obstruction unlike
asthma where it is usually reversible
•
Emphysema
• Definition: Emphysema is characterised by
abnormal permanent enlargement distal to
the terminal bronchioles accompanied by
destruction of their wall without obvious
fibrosis.
• Overinflation—no destruction of wall eg.
Compensatory overinflation of opposite
lung after unilateral pneumonectomy
Types of emphysema
•
1.
2.
3.
4.
Classified according to its anatomic
distribution within the lobule(lobule –
acinus-distal to terminal bronchioles and a
cluster of 3-5 acini forms a lobule)
Centri-acinar-most common
Panacinar –next common
Distal acinar
Irregular
Centriacinar emphysema
• Respiratory bronchiole affected;distal alveoli
spared
• Therefore ,in the same lobule, normal and
emphysematous change is seen
• Common in upper lobes,esp. apical segment
• In severe cases distal part of acinus also
involved;hence difficult to differentiate from
panacinar
• Commonest cause:smoking
Panacinar emphysema
• Uniform enlargement from respiratory
bronchiole to terminal alveoli
• Common in lower lung zones
• Associated with alpha-1-anti-trypsin
deficiency
Distal acinar(paraseptal)
emphysema
•
•
•
•
•
Distal part of acinus involved
More common adjacent to pleura
Adjacent to areas of fibrosis/scarring or atelectasis
More severe in upper half of lung
Multiple contiguous enlarged airspaces,that range
in diameter from 0.5mm->2.0cms.,sometimes
forming cyst-like structures(bullae)
•
Irregular emphysema
• Irregular involvement of acinus
• Usually associated with scarring eg. Healed
inflammatory lesion
• Asymptomatic(commonest)
Pathogenesis
• Emphysema results as an imbalance of:
1. Protease-antiprotease
2. Oxidant-antioxidant
Protease-antiprotease imbalance
hypothesis
• Patients with a genetic deficiency of
antiprotease,alpha1-antitrypsin deficiency
have a markedly enhanced tendency to
develop emphysema which is compounded
with smoking
• Incidence of alpha-1-antitrypsin deficiency
– 1% of all patients with emphysema
• The following sequence is postulated:1. Neutrophils ,the principle source of cellular
proteases, are normally sequestered in peripheral
capillaries and in lungs and a few gain access to
the alveolar spaces
2. 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
• 3) With low levels of serum alpha-1antitrypsin ,elastic tissue destruction is
unchecked and emphysema results
• In people with normal amounts of alpha-1antitrypsin deficiency:• In smokers,neutrophils and macrophages
accumulate in alveoli due to
chemoattractant effect of nicotine and effect
of reactive O2 species contained in smoke
• These activate the transcription factors which
switches on genes thatencode TNF & chemokines
including IL-8. These in turn attract and activate
neutrophils
• 2.Accumulated neutrophils are activated and
release their granules,rich in a variety of cellular
proteases(neutrophil elastase,proteinase3 and
cathepsin G) resulting in tissue damage
• 3. Smoking also enhances elastase activity
in macrophages; macrophage elastase is not
inhibited by alpha-1-antitrypsin and can
digest this anti-protease(i.e.alpha-1antitrypsin)
• Also matrix metalloproteinases derived
from macrophage and neutrophils have a
role in tissue destruction
• Smoking also has a role in perpetuating the
oxidant-antioxidant imbalancein the
pathogenesis of emphysema
• Normally the lung contains a healthy
complement of antioxidants(superoxide
dismutase,glutathione) that keeps oxidative
damage to a minimum
• Tobacco smoke contains abundant reactive O2
species(free radicals) which deplete this
antioxidant mechanism thereby inciting tissue
damage.
• Activated neutrophils also add to the pool of
reactive O2 species in the alveoli
• A secondary consequence of oxidative injury is
inactivation of native antiproteases,resulting in
functional alpha-1- antitrypsin deficiency even in
patients without enzyme deficiency
Oxidant –antioxidant imbalance
• Smoking also has a role in perpetuatingthe
oxidant antioxidant imbalance in the
pathogenesis of emphysema
• Normally the lung contains a healthy
complement of antioxidants(superoxide
dismutase,glutathione)that keeps oxidative
damage to a minimum
• Tobacco smoke contains abundant reactive O2
species(free radicals)which deplete this
antioxidant mechanism,thereby inciting tissue
damage.
• Activated neutrophils also add to the pool of
rective O2 species in the alveoli
• A secondary consequence of oxidative injury is
inactivation of native antiproteases, resulting in
functional alpha1antitrypsin deficiency even in
patients without enzyme deficiency
Morphology
• Gross: 1)Panacinar:- pale voluminous lungs
that obscure the heart when anterior chest
wall is opened at autopsy.
• 2)Centriacinar:-less impressive;less
voluminous;upper two-third of lung affected
•
Microscopy
• Thinning and destruction of alveolar walls
• In advanced disease,adjacent alveoli
become confluent creating large air spaces
•
Clinical course
• Dyspnoea-steadily progressive
• Weight loss
• Pulmonary function tests show decreased
FEV with normal or near normal FVC
• Barrel-chest
• Pink –puffers,if associated with chronis
bronchitis—”blue-bloaters”
• In all secondary pulmonary hypertension
develops gradually because of hypoxiainduced pulmonary vascular spasm andloss
of pulmonary capillary surface from
alveolar destruction
• Death due to either pulmonary failurewith
respiratory acidosis,hypoxia and coma OR
right heart failure(cor pulmonale)
•
•
Chronic bronchitis
• Common among cigarette smokersand
urban dwellers in smog ridden cities
• Incidence:- 20-25% of individual in the age
group of 40-65 years
• Diagnosis on clinical grounds i.e person
with persistent productive coughfor at least
3 consecutive months in at least 2
consecutive years
• It occurs in several forms
1. Most patients have simple chronic
bronchitis: productive cough with mucoid
sputum; no air flow obstruction
2. Chronic asthmatic bronchitis- some
patients withchronic bronchitis will have
hyper-responsiveairwayswith intermittent
bronchospasm and wheezing
• 3)a few bronchitic patients,esp. heavy
smokers , develop chronic outflow
obstruction,usually with emphysema and
these are said to have chronic obstructive
bronchitis
Pathogenesis
• The distinctive feature of chronic bronchitis is
hypersecretion of mucus,beginning in the large
airways
• Cause :-cigarette smoking & inhalation of sulfur
dioxide and nitrogen dioxide
• These irritants cause hypertrophy of mucous
glands in the trachea and main bronchi and goblet
cell metaplasia in the surface epithelium lining
smaller bronchi and bronchioles
• Also irritants cause inflammation with infiltration
of CD8+ T-cells,macrophages and neutrophils(no
eosinophils are seen unlike as in asthma)
• The morphological basis of airflow obstruction is
more peripheral and results from:-1)so-called
“small airway disease” induced by goblet cell
metaplasia with mucus plugging of the bronchiolar
lumen,inflammation & bronchiolar wall fibrosis
and 2) co-existent emphysema
• It is postulated that many of the respiratory
effects of environmental irritants are
mediated by T-cell cytokines such as IL-3
• There has been some experiment donein
which some genetic changes has been
implicated as a result of exposure to tobacco
smoke
Morphology
• Gross:mucosal lining hyperaemic and
edematous/swollen.The mucosa is covered by
mucinous and mucopurulent secretions.
• Micro:In larger bronchi and trachea-hypertrophy
of the mucous glands.(Reid index-normally 0.4)
• Chronic inflammatory cells in the wall of the
bronchi
• Chronic bronchiolitis:goblet cell metaplasia,mucus
plugging,inflammation and peribronchiolar
fibrosis obstruction to airway.
•
•
Clinical course
• Chronic cough with expectoration
• May develop COPD – patient will then have
hypercapnia, hypoxemia and in severe cases
cyanosis(blue bloaters)
• With progressive disease –pulmonary
hypertension and cardiac failure