Biomedical Engineering Reference
In-Depth Information
In COPD, major structural alternations occur in the small bronchi and membra-
nous bronchiole (airway diameter
<
2 mm). Changes occur around the supporting
cartilage and bronchial glands in the peripheral airways (
2 mm diameter). Here,
the thickening occurs mainly in the inner wall area of the large airways [
9
,
82
,
86
].
The most important changes in asthma are located in the conducting airways,
which can thicken up to 300 %. Asthma patients have thickened segmental and
subsegmental bronchial walls over their entire size rage. This thickening is depen-
dent on the degree of the disease, more severe and older patients will depict these
characteristics more than young patients [
9
,
85
]. In asthma, the inflammatory re-
actions takes place in the higher part of the airways than in COPD. Unfortunately
for COPD patients, the airway obstruction that accompanies these changes is resis-
tant to medication which makes the changes persistent. By contrast, in asthma the
inflammatory processes can be controlled by the use of corticosteroids. There are
also important differences in the remodeling of the extracellular matrix and the role
of proteolytic enzymes and growth factors which lead to specific airway remod-
eling results by disease. More clinical information about inflammation mechanics
in airway remodeling can be found in [
13
]. For remodeling effects in asthma, an
important role is played by the degree to which the smooth muscle surrounds the
airway lumen. These muscles are located within the posterior membranous sheath
in the trachea and main-stem bronchi, whereas they surround the entire lumen of the
airway in the bronchioles [
53
]. Consequently, the same degree of muscle shorten-
ing in asthma patients has a smaller effect on the central airways than on the lower
situated bronchioles [
53
].
In COPD, hyperplasia and mucous metaplasia are observed in central and periph-
eral airways which ends in a more even distribution of secretary cells. This leads to
a state where the smaller airways (diameter
<
400 µm), which are normally popu-
lated with very little goblet cells, become large contributors to the excess of mucous
which characterizes COPD [
64
]. Mucous, produced in both asthma as COPD, is
quantitatively and qualitatively abnormal with alternations in its molecular and cel-
lular composition. The elevated ratio of mucous/serous acini provides a secretion
of a thicker, gel-like mucus in COPD. Partial or complete occlusion of the small
airways occurs.
The lungs consist of large surface areas with small diffusion distances to guaran-
tee proper gas exchange. The 3D structure of the alveoli can be compared to a hon-
eycomb structure of thin-walled septa which form a fractal network [
64
,
71
]. This
structure is unstable at low inflating pressures and would collapse if there would
not be a mechanical stress at the end of expiration. This 'pre-stress' is generated by
the pleural pressure around the lung. Changes in mechanical properties of the lung
tissue by pathology will influence the response on this pre-stress. Once an alveo-
lar wall starts to rupture, the stress the original wall carried is redistributed to the
neighboring walls. These areas will experience a increased pre-stress which will re-
sult in a relentless increase of the unbinding and cleavage rate and the unfolding of
new binding sites. A single rupture will induce a cascade of ruptures and serves as
a positive feedback for further breakdown. It is obvious that there must be a kind
of 'tipping point' beyond which the structure-function relationship cannot return to
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