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There are two major
stages – the acute phase characterized by disruption of the
alveolar-capillary interface, leakage of protein rich fluid into the
interstitium and alveolar space and extensive release of cytokines and
migration of neutrophils.
A later reparative phase
is characterized by fibroproliferation, and organization of lung tissue
If
resolution does not occur, disordered collagen deposition occurs leading
to extensive lung scarring.
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The core pathology is disruption of the capillary-endothelial interface:
this actually refers to two separate barriers – the endothelium and the
basement membrane of the alveolus. In the acute phase of ALI, there is
increased permeability of this barrier, and protein rich fluid leaks out
of the capillaries. There are two types of alveolar epithelial cells –
Type 1 pneumocytes represent 90% of the cell volume, and are easily
damaged. Type 2 pneumocytes are more resistant to damage, which is
important as these cells produce surfactant, transport ions and
proliferate and differentiate into Type 1 cells.
The damage to the
endothelium and the alveolar epithelium results in the creation of an open
interface between the lung and the blood, facilitating the spread of
micro-organisms from the lung systemically, stoking up a systemic
inflammatory response. Moreover, the injury to epithelial cells handicaps
the lung’s ability to pump fluid out of airspaces. Fluid filled airspaces,
loss of surfactant, microvascular thrombosis and disorganized repair
(which leads to fibrosis) reduces resting lung volumes (decreased
compliance), increasing ventilation-perfusion mismatch, right to left
shunt and the work of breathing. In addition, lymphatic drainage of lung
units appears to be curtailed – stunned by the acute injury: this
contributes to the build up of extravascular fluid.
Some patients rapidly
recover from acute lung injury, and have no permanent sequelae. Prolonged
inflammation and destruction of pneumocytes leads to fibroblastic
proliferation, hyaline membrane formation and lung fibrosis. This
fibrosing alveolitis may become apparent as early as five days after the
initial injury. Subsequent recovery may be characterized by reduced
physiologic reserve, and increased susceptibility to further lung
injuries. Extensive microvascular thrombosis may lead to pulmonary
hypertension, myocardial dysfunction and systemic hypotension.
Finally, it is essential
to understand that although ALI is a diffuse process, it is also a
heterogeneous process, and not all lung units are affected equally: normal
and diseased tissue may exist side-by-side.
Copyright Patrick Neligan
2001-2002 |
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