Restrictive lung diseases
cause reduced compliance of the lungs, i.e. they are difficult to expand with
The main reason for this pattern of respiratory dysfunction is
abnormality of alveolar walls that renders them rigid, usually by oedema or
Those affected complain of breathlessness (dyspnoea) as they feel the
greater effort needed to inflate the lungs.
Fibrosis and oedema of alveolar
walls causes a dffusional defect so that hypoxia develops.
Diffuse alveolar wall damage
is the main feature of restrictive lung diseases
The restrictive lung
diseases are characterized by damage to alveolar walls.
Injury to the alveolar
walls leads to three main phases of reaction in the lung:
• Haemorrhage and high
protein exudation into alveoli (causes so-called Hyaline membranes).
and inflammation of the interstitium.
• Fibrosis in the interstitium.
Two main clinical patterns
of disease are recognized, depending on which phase of diffuse alveolar damage
is most evident: acute restrictive lung disease, the main features of which are
exudation and oedema; and chronic restrictive lung disease, the main features of
which are inflammation and fibrosis.
Adult respiratory distress
syndrome (ARDS) is an acute restrictive lung disease caused by diffuse alveolar
The adult respiratory
distress syndrome is a manifestation of diffuse alveolar damage leading to
widespread systemic metabolic derangements.
Many conditions predispose to this
serious reaction in lung, most commonly systemic sepsis and severe trauma.
Systemic liberation of
chemical mediators of inflammation, particularly cytokines, is important in
progression of disease.
Pathophysiology of ARDS
The events that take place
in the lung in ARDS are termed diffuse alveolar damage (DAD) and occur in two
1. Acute exudative phase,
with destruction of alveolar lining cells.
2. Late organization phase,
with cell proliferation and fibrosis.
Following the damaging
stimulus, there is a latent period of 4-24 hours before symptoms develop.
Dyspnoea develops before changes are visible on chest radiographs.
progressively over a period of 24-48 hours.
In the acute phase, there is:
• Necrosis of alveolar
• Exudation of fibrin and
fluid into alveolar spaces forming hyaline membranes.
• Microthrombosis in
• Adherence and activation
of neutrophils, with release of neutrophil enzymes.
• Haemorrhage into alveoli.
In the organization phase
the lungs are congested and ventilation is impaired by disturbance of alveolar
walls with exudation into alveolar spaces There is re-generation of type 2
alveolar lining cells and organization of hyaline membranes with pulmonary
Organization may result in interstitial fibrosis with thickening of
alveolar walls, or may cause fibrous obliteration of alveolar spaces.
If ARDS has been caused by
septicaemia, endotoxin causes endothelial and neutrophil activation, with
activation of complement.
Treatment with high concentrations of oxygen may,
paradoxically, increase damage by generation of oxygen-derived free radicals.
ARDS is often complicated by secondary infection in the lungs.
In severe cases of ARDS from
any cause, cytokines liberated from the lung vascular bed can enter the systemic
circulation and may cause systemic endothelial activation with systemic
neutrophil activation leading to multi-organ failure (systemic inflammatory
The clinical diagnosis of
ARDS depends on:
• Presence of a condition known to precipitate ARDS.
• Refractory hypoxaemia
(PaO2 <8.0 kPa on >40% O2).
• Radiographic evidence of
evolving diffuse pulmonary shadowing.
• Clinical signs of lungs
becoming abnormally rigid with low total compliance.
Treatment of ARDS is by
continuous positive airway pressure ventilation, and intensive support of
cardiac, circulatory and renal function.
Patients with ARDS usually die from
systemic inflammatory response syndrome with multi-organ failure, mortality
being around 70% Of those who survive ARDS, 20% have some permanent lung
dysfunction due to organization of exudate and persisting restrictive defect.