C h a p t e r 2 3
Disorders of Ventilation and Gas Exchange
593
As the disease progresses, the work of breathing becomes
greatly increased as the lung stiffens and becomes more
difficult to inflate. There is increased intrapulmonary
shunting of blood, impaired gas exchange, and hypox-
emia despite high supplemental oxygen therapy. Gas
exchange is further compromised by alveolar collapse
resulting from abnormalities in surfactant production.
When injury to the alveolar epithelium is severe, disorga-
nized epithelial repair may lead to fibrosis.
The pathogenesis of ALI/ARDS is unclear, although
both local and systemic inflammatory responses occur. It
is thought that dysregulated inflammation, accumulation
of neutrophils, uncontrolled activation of coagulation
pathways, and altered permeability of the endothelial
and epithelial barriers all play a role.
67
Initially, a direct
or indirect pulmonary insult is believed to promote the
accumulation of neutrophils in the microcirculation.
These neutrophils activate and migrate in large numbers
across the alveolar epithelial surfaces, releasing prote-
ases, cytokines, and reactive oxygen species that lead
to increased permeability in the alveolar epithelial cells
and damage to type I and type II alveolar cells. This in
turn leads to pulmonary edema, hyaline membrane for-
mation, and loss of surfactant that decrease pulmonary
compliance and make air exchange difficult.
Clinical Features
Clinically, ALI/ARDS is marked by a rapid onset, usually
within 12 to 18 hours of the initiating event, of respira-
tory distress, an increase in respiratory rate, and signs
of respiratory failure. Chest radiography shows dif-
fuse bilateral infiltrates of the lung tissue in the absence
of cardiac dysfunction (non-cardiogenic pulmonary
edema). Marked hypoxemia occurs that is refractory to
treatment with supplemental oxygen therapy. Many per-
sons with ARDS have a systemic response that results in
multiple organ failure, particularly of the renal, gastro-
intestinal, cardiovascular, and central nervous systems.
The treatment goals in ARDS are to supply oxy-
gen to vital organs and provide supportive care until
the condition causing the pathologic process has been
reversed and the lungs have had a chance to heal.
Assisted ventilation using high concentrations of oxy-
gen may be required to correct the hypoxemia. Positive
end-expiratory pressure breathing, which increases the
CHART 23-2
  Conditions inWhich ARDS Can
Develop*
Aspiration
Near-drowning
Aspiration of gastric contents
Drugs, Toxins, Therapeutic Agents
Free-base cocaine smoking
Heroin
Inhaled gases (e.g., smoke, ammonia)
Breathing high concentrations of oxygen
Radiation
Infections
Septicemia
Trauma and Shock
Burns
Fat embolism
Chest trauma
Disseminated Intravascular Coagulation
Multiple BloodTransfusions
*This list is not intended to be inclusive.
Platelets
Cellular debris
Hyaline membrane
Injured
endothelial cells
Neutrophil
Plasma proteins
Capillary
Red blood cells
Edematous interstitium
Alveolar macrophage
Type II alveolar cell
Sloughing type I alveolar cells
Protein-rich
edematous fluid
Inactivated surfactant
Fibrin
Leukotrienes
Oxidants
PAF
Proteases
Alveolus
FIGURE 23-15.
Mechanism of
lung changes in acute respiratory
distress syndrome. Injury and
increased permeability of the
alveolar capillary membrane allow
fluid, protein, cellular debris,
platelets, and blood cells to move
out of the vascular compartment
and enter the interstitium and
alveoli. Activated neutrophils
release a variety of products that
damage the alveolar cells and lead
to edema, surfactant inactivation,
and formation of a hyaline
membrane. PAF, platelet activating
factor.
