Biomedical Engineering Reference
In-Depth Information
mice lungs 7 and 90 days after intratracheal instillation, which was found to be higher as compared
with other NPs, such as carbon black and quartz particles. Oxidative stress is most likely the major
underlying mechanism for inflammation responses by NPs, which lead to the activation of different
transcription factors with subsequent enhanced synthesis of proinflammatory proteins [27].
CNTs and NPs are also believed to cause adverse effects through inflammation and induction
of proinflammatory molecules. However, it must be noted that some researchers have found metal
contaminants (such as iron and nickel) in the nanotube production process to be the main caus-
ative agent of oxidative stress. Pulmonary inflammation may also result in changes in membrane
permeability, which in turn can result in particle distribution extending beyond the lung and indi-
rectly affecting cardiovascular performance. Moreover, NPs have the potential to enter the brain
and blood circulation and subsequently other major organs, inciting inflammation in these places.
Inflammation arising as a result of NP exposure could lead to pulmonary diseases or exacerbation
of existing lung disorders [27].
20.13.2 l
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20.13.2.1 Pulmonary Fibrosis
Pulmonary fibrosis occurs as a result of increased tissue reactivity leading to the formation and accu-
mulation of fibrous connective tissue. Fibrosis can take many forms, varying from severe forms that
cause distortion of lung architecture, inducing bronchiectasis and chronic respiratory infection, to
milder forms, which comprise of restrictive ventilatory defects causing hypoxemia, cor pulmonale, and
pulmonary hypertension. The first step in pulmonary fibrosis is inflammatory response when immune
cells comprising macrophages and neutrophils are excessively activated. These immune cells release
toxic mediators, which result in the loss of epithelial integrity and promotion of tissue injury. When
this happens, the cell normally employs a repair mechanism wherein mesenchymal cells are activated.
These mesenchymal cells have a threefold function, which includes extracellular matrix deposition,
reepithelialization, and restoration of normal lung architecture. However, certain patients show an
abnormality in tissue remodeling and excessive matrix deposition, which leads to progressive scarring
and fibrosis. The presence of MWCNTs in the subpleural region in the lungs of mice leads to fibrosis
and scarring. This has become a matter of grave concern as nonclearance and persistence of MWCNTs
could cause inflammation in the sensitive mesothelium, leading to mesothelioma formation. Another
study also suggests that pulmonary fibrosis induced by MWCNTs may be exacerbated in people with
existing lung inflammation. The irregularity in tissue remodeling and fibrosis, with reference to particle
inhalation, may be due to an exaggerated inflammatory response that is driven by the inability to clear
toxic particles from the lungs via the usual protective mechanisms. This whole cascade may be initi-
ated by interactions of alveolar macrophages with lung epithelial cells, or even directly by interstitial
fibroblasts. The extent of fibrotic response may also determine the severity of loss of tissue function.
Generally, fibrosis occurs in the following sequence: (a) organization of the immature fibrinous tissue
with the formation of new blood vessels and increased blood supply; (b) proliferation of myofibroblasts;
(c) increased deposition of extracellular matrix; and finally (d) scar formation. Under conditions of
normal lung function, immature intralumenal collagenous tissue may be eliminated by the fibrinolytic
system with concomitant apoptosis of myofibroblasts, thus favoring reepithelialization. Depending on
the degree of injury to the alveoli, removing the continual exposure to NPs may allow reepithelializa-
tion. In chronic cases of injury, however, lung function may be lost [29].
20.13.2.2 Pneumoconiosis
Pneumoconiosis, an occupational lung disease, is clinically classified into two categories, fibrotic
and nonfibrotic. While the fibrotic process involves focal nodular or diffuse fibrosis, nonfibrotic
lesions involve particle-laden macrophages, with minimal or no fibrosis. The former comprises
silicosis, coal worker's pneumoconiosis, asbestosis, and berylliosis, which are caused by persis-
tent inhalation of silica particles, washed coal particles, asbestos fibers, and beryllium particles,
