PATHOLOGY and

PATHOGENESIS
Chronic Obstructive Pulmonary Disease
PATHOLOGY

Cigarette smoke exposure may

affect the large airways, small airways
( <2 mm diameter), and alveolar space
Changes in large airways cause
cough and sputum, while changes in
small airways and alveoli are
responsible for physiologic
alterations
PATHOLOGY

Emphysema and Small airway

pathology are both present in most
persons with COPD, and their
relative contributions to obstruction
vary from one person to another.
Large Airway
Cigarette smoking often results:
mucous gland enlargement
goblet cell hyperplasia
These changes are proportional to
cough and mucus production that define
chronic bronchitis, but these
abnormalities are not related to airflow
limitation
Large Airway
Bronchi also undergo
squamous metaplasia, which
not only predisposes to
carcinogenesis but also
disrupts mucociliary clearance
Large Airway
In asthma, patients may have
smooth-muscle hypertrophy

bronchial hyperactivity

= leading to airflow limitation

Large Airway
Neutrophil influx has been
associated with purulent sputum of
upper respiratory tract infections
that hamper patients with COPD.
Neutrophil Elastase is among the
most potent secretagogues
identified.
Small Airways

The major site of increased

resistance in most individuals
with COPD is in airways <2
mm diameter
Small Airways

Characteristic cellular changes

Goblet cell Metaplasia
Replacement of surfactant-secreting
Clara cells with mucus-secreting
Infiltrating mononuclear inflammatory
cells
Small Airways

Abnormalities may cause

luminal narrowing by
Excess mucus
Edema
Cellular infiltration
Small Airways

Reduced surfactant may

increase surface tension at
the air-tissue interface,
predisposing to airway
narrowing or collapse
Small Airways
Fibrosis in the wall may cause airway
narrowing directly
Respiratory bronchiolitis (with mononuclear
inflammatory cells ) may cause proteolytic
destruction of elastic fibers in the
respiratory bronchioles and alveolar
ducts where the fibers are concentrated
as rings around alveolar entrances.
Small Airways
Small airway patency is maintained by the
surrounding lung parenchyma
That provides radial traction on bronchioles
at points of attachment to alveolar septa
Loss of bronchiolar attachments as a result
of extracellular matrix destruction may
cause airway distortion and narrowing in
COPD
Lung Parenchyma

Emphysema is characterized
by destruction of gas-
exchanging airspaces
Emphysema is classified
into distinct pathologic
types;
Lung Parenchyma
Centriacinar Emphysema
The type most frequently associated with
cigarette smoking,
Characterized by enlarged airspaces found
(initially) in association with respiratory
bronchioles.
Most prominent in the upper lobes and
superior segments of lower lobes and is often
quite focal
Lung Parenchyma
Panacinar Emphysema
Refers to abnormally large airspaces
evenly distributed within and across
acinar units
Usually observed in patients with
alpha 1AT deficiency, which has a
predilection for the lower lobes
Pathogenesis of COPD

Airflow limitation, the major

physiologic change in COPD
Can result from both small
airway obstruction and
emphysema
Pathogenesis of COPD
Fibrosis surrounding the small airways
appears to be a significant contributor
Mechanisms leading to collagen
accumulation around the airways in
the face of increased collagenase
activity remain an enigma
Pathogenesis of COPD
There are several potential
mechanisms whereby a proteinase
can predispose to fibrosis, including
Proteolytic activation of transforming
growth factor (TGF- )
Insulin-like growth factor (IGF) binding
protein degradation releasing
profibrotic IGF