Twenty Five Flashcards
What are ALI and ARDS? How are they characterized? Whom do they affect? What are the etiologies? Pathophysiologies? What treatment improves survival? What else can be done and when should it be done? What is the mortality rate? Prognosis of survivors?
Acute lung injury (ALI) and the acute respiratory distress
syndrome (ARDS) represent a spectrum of respiratory
failure of rapid onset characterized by diffuse, bilateral lung
injury and severe hypoxemia that are caused by noncardiogenic
pulmonary edema. ALI/ARDS can affect patients of
any age or preexisting condition, although both predispose
to worse outcomes. Respiratory failure may be initiated by
pulmonary or extrapulmonary insults that increase alveolar
epithelial and endothelial permeability, fl ood alveoli,
and reduce lung compliance in a pattern refl ecting an acute
restrictive lung disease. Despite numerous prospective, double-
blind clinical trials in patients with ALI/ARDS, the only
treatment that improves survival is mechanical ventilation
using a lung protective strategy in which tidal volume VT
is carefully titrated to ~6 mL/kg of predicted body weight.
Positive end-expiratory pressure (PEEP) ventilation is
useful for alveolar recruitment in lungs that will be prone
to atelectasis. Clinical vigilance must be comprehensive and
anticipatory to guard against development of ventilator-associated
pneumonia or worsened ALI. Although mortality can
exceed 50%, survivors have a good prognosis for recovery
of lung function.
What are the symptoms/clinical findings of ARDS/ALl? What kind of inflammation is exhibited? What is the pathophys?
ALI and ARDS affect over 190,000 patients annually in the
United States and cause 75,000 deaths. They occur rapidly and
show diffuse, bilateral lung injury readily evident by x-ray or CT.
Patients exhibit severe hypoxemia despite use of supplemental O2, and are considered emblematic of a noncardiogenic pulmonary
edema with low alveolar ventilation/perfusion ratios (˙VA/ Q˙ )
and abnormal physiological shunting of O2. Such acute respiratory
failure usually occurs with neutrophil (PMN)-mediated
lung infl ammation. Pathological increases in the permeability
of alveolar epithelial and endothelial cells lead to dyspnea,
tachypnea, and arterial hypoxemia. These permeability defects
increase effl ux of proteins and fl uids from blood into the
alveolar interstitium and airspaces, while alveolar liquid clearance
mechanisms are impaired that normally would resolve
the edema. Consequently, alveolar O2 exchange deteriorates.
What are some pulmonary specific initiating factors for ALI/ARDS? What are some systemic ones? How do they cause problems in lungs?
ARDS can be caused by pulmonary-specifi c mechanisms,
notably severe pneumonia, aspiration of gastric contents, embolism
of fat, air, or amniotic fl uid, chest trauma, near-drowning,
and inhalation of noxious gases. ALI/ARDS can also occur due
to systemic conditions, notably bacteremic sepsis, peritonitis,
pancreatitis, hemorrhagic shock, burns, massive transfusions,
and drug overdoses. Such indirect factors refl ect pulmonary
manifestations of acute systemic infl ammation and generalized
endothelial injury that may involve many organ systems.
What causes death in ALI/ARDS?
Approximately 15% of deaths from ALI/ARDS are due to
progressive respiratory failure with intractable hypoxemia,
increased dead space ventilation, and hypercarbia. The main
cause underlying death in ALI/ARDS (∼75% patients) is the
multiple organ dysfunction syndrome (MODS) involving the
heart, kidneys, coagulation system, and liver as well as lung.
What are the clinical criteria for ALI?
- Acute lung injury. A syndrome of acute and persistent
lung infl ammation with increased vascular permeability
characterized by:
a. acute onset (within days of exposure to predisposing
direct or indirect causes);
b. diffuse bilateral infi ltrates on x-ray consistent with
noncardiogenic edema;
c. Pao2 / FIo2 ≤300 mm Hg, regardless of the level of PEEP
during mechanical ventilation. The ratio Pao2 / FIo2 estimates
lung oxygenation effi ciency across the range of
supplemental O2 provided to patients. Pao2 is measured in
mm Hg and FIo2 is a decimal between 0.00 and 1.00. For
example, in a subject with Pao2 = 100 mm Hg on room air
(FIo2 = 0.21), the Pao2/FIo2 = 100/0.21 = 476 mm Hg;
d. no clinical evidence of left-sided heart failure or elevated
left atrial pressure, that is, an elevated PPW if a
pulmonary artery catheter (PAC) had been placed, as
in congestive heart failure (Fig. 28.1). A relatively normal
heart size by x-ray supports the clinical absence of
left ventricular failure as the explanation for pulmonary
edema. If a PAC is in use, the wedge pressure is ≤18 mm
Hg. Clinical evidence of left heart failure includes systolic
left ventricular (LV) dysfunction, plus appropriate physical
fi ndings, such as LV S3 gallop and peripheral edema,
especially when supported by LV dilation or reduced
ejection fraction by echocardiography or catheterization,
or enlarged cardiac silhouette plus pleural effusions.
What are the clinical criteria for ARDS?
- Acute respiratory distress syndrome. A more severe
physiological expression of ALI, at the further end of a
spectrum of evolving lung injury characterized by:
a. acute onset;
b. diffuse bilateral infi ltrates on x-ray consistent with pulmonary
edema;
c. Pao2/FIo2 Ä 200 mm Hg;
d. no evidence of left-sided heart failure, including normal
heart size on x-ray (Fig. 28.2). If a PAC is used, the
measured PPW is ≤18 mm Hg.
List 3 things that occur in the pathophys of ALI/ARDS.
- Increased microvascular permeability (noncardiogenic
pulmonary edema) - Alveolar instability and de-recruitment with decreased
lung compliance: pathophysiology and potential for
ventilator-associated lung injury - Dysregulated and excessive acute lung infl ammatory
responses
Describe 4 mechanisms that promote fluid retention in capillaries and prevent interstitial edema? What are 4 abnormalities that lead to interstitial/alveolar edema in ALI/ARDS? What kind of edema is caused? What are the physiological results?
At least four mechanisms promote fl uid retention in capillaries
to prevent interstitial edema and alveolar fl ooding.
First, airspace liquid is cleared by apical Na+ transporters in
alveolar epithelial cells. Second, larger plasma proteins like
albumin maintain osmotic gradients favoring water reabsorption.
Third, tight junctions between pulmonary endothelial
cells prevent leakage. Fourth, interstitial lymphatics return
alveolar fl uid to the circulation. Abnormalities in Starling’s
forces during ALI/ARDS include:
a. Decreased σ during sepsis, causing larger proteins like
albumin to enter the interstitium, so that protein-rich edema
fl oods alveoli.
b. Reduced πMV from excessive IV infusions and/or reduced
acute phase protein synthesis, favoring increased transvascular
fl uid fl ux into distal airspaces.
c. Increased PMV from IV fl uids to treat hypovolemia, or
decreased venous return due to increased intrathoracic
pressures during positive-pressure ventilation.
d. Increased πPMV from plasma proteins entering alveolar
interstitium, or from loss of alveolar epithelial Na+ transport,
both retarding alveolar liquid clearance.
These cause gravitationally dependent alveolar edema, fi rst
evident in inferior lung zones of supine patients (Fig. 28.3),
worsening ˙VA/ Q˙ mismatch and reducing Pao2.
What happens to compliance in ALI/ARDS? What does this lead to? What is this referred to as? What are four factors that cause this?
As described in Chap. 5, compliance quantifi es changes in
lung volumes (ΔV) that are caused by distending airway or
intrapleural pressures (ΔP) as occur during spontaneous respiration.
Compliance (ΔV/ΔP) is often reduced in ALI/ARDS,
leading to alveolar instability and collapse when approaching
end-expiratory pressures. This de-recruitment of formerly
functioning alveoli results from several factors:
a. Alveolar edema inactivates surfactant as plasma proteins leak into airspaces.
b. Edematous alveoli show increased surface tension, and are prone to collapse (ie, they undergo atelectasis) during end-expiratory pauses in patients with ALI/ARDS. Such distal airspaces fail to expand cyclically during inspiration due to excessively high alveolar opening pressures (see Chaps. 5 and 6).
c. Functional residual capacity (FRC) declines in ALI/
ARDS patients, who often breathe rapidly and shallowly
to maximize their ˙VE while minimizing the work of breathing that would be required to expand their noncompliant or “stiff ” lungs.
d. Superimposed mechanical ventilation-associated lung
injury (VALI) may occur, especially at VT’s exceeding
10 mL/kg of predicted body weight (PBW) that were historically used to ventilate adults with ALI/ARDS.
What is VALI? What causes it? Describe the 3 forms.
When previously normal alveoli become atelectatic due to
alveolar fl ooding and infl ammatory exudates, mechanical ventilation
of patients with high VT’s to sustain ˙VE is equivalent
to forcing each positive-pressure inspiration into infant-sized
lungs. At the same time, alveoli that are not yet edematous
receive excessive ventilation that is redirected toward the open
lung and away from atelectatic regions (Figs. 28.3 and 28.4).
This dilemma sets the stage for three forms of VALI that are
not mutually exclusive:
a. barotrauma: pressure-related lung injury
b. volutrauma: alveolar over-distention injury
c. cyclical shear stress from excessive tidal swings in alveolar diameters
What role does inflammation have in ALI/ARDS? What kind of inflammation is it? What causes it? How is the inflammation mediated? What chemokines are responsible?
ALI/ARDS refl ects excessive infl ammation in the alveolar
interstitium and airspaces (Fig. 28.5), involving massive
neutrophil infl ux due to upregulated adhesion molecules on
PMNs and vascular endothelia. The infl ammation is sustained by additional chemotactic signals and host-derived mediators.
As a result, PMNs in bronchoalveolar lavage fl uid (BALF)
may approach 50% of all cells recovered, versus ≤3% PMNs
in BALF from healthy volunteers. Major infl ammatory mediators
in this acute phase include:
a. cytokines, notably TNF-α, I L-1β, I L-6, I L-8, I L-10, G-CSF,
and GM-CSF;
b. chemokines, such as macrophage inhibitory factor and
chemoattractant protein;
c. arachidonic acid metabolites, including prostanoids and
leukotrienes;
d. oxyradicals/oxidants, including superoxide anion and peroxynitrite;
e. proteases that degrade alveolar structures and enhance
infl ammation;
f. fi brin, following activation of tissue factor and the coagulation
system.
What are the clinical findings/symptoms in ALI/ARDS?
Together, these processes cause acute lung dysfunction, tachypnea
with distress, declining Pao2 by blood gases or declining
Sao2 by pulse oximetry, and chest radiographs or CT scans
showing bilateral infi ltrates. Of note, such infi ltrates may be
asymmetric in patients with coexisting chronic obstructive
pulmonary disease. Thus progressively impaired gas exchange
occurs, with ˙VA/ Q˙ mismatch and physiological shunt causing
hypoxemia. Additionally, physiological dead space may
increase despite a constant ˙VE, retarding CO2 elimination.
Ventilator-induced rises in intrathoracic pressure also inhibit
venous return, with fewer alveoli perfused despite ongoing
ventilation. In advanced cases of ALI/ARDS, CO2 excretion
falls and Paco2 rises
Explain TRALI.
Transfusion-related acute lung injury (TRALI) is an
important form of ALI/ARDS with similar clinical features
but is temporally related to transfusion of blood products.
TRALI is the leading cause of transfusion-related death in the
United States. Patients aff ected with TRALI typically develop
fever with cough, dyspnea, and hypoxemia within 6 hours of
receiving red cells, platelets, or fresh frozen plasma.
How is the clinical course of ALI/ARDS initially? Describe the 3 phases.
Despite these diverse precipitating factors, most ALI/ARDS
patients follow similar clinical courses that are characterized
initially by severe hypoxemia requiring prolonged mechanical
ventilatory support (days to weeks). Patients generally
progress through three pathologic stages (see Chap. 26). An
initial exudative stage with diffuse alveolar damage gives
way over the fi rst week to a proliferative stage with resolving
pulmonary edema, proliferating type II cells, squamous metaplasia,
interstitial infi ltration by myofi broblasts, and deposition
of collagen. For unclear reasons, some patients progress
to a third fi brotic stage with accelerated collagen deposition obliteration of normal lung architecture, diffuse fi brosis, and
parenchymal cyst formation. This last subgroup accounts
for most patients who die “of ” ALI/ARDS with intractable
hypoxemia and increasing dead space ventilation that require
progressively higher FIo2 and the associated risk of lung O2
toxicity. Prolonged ventilation with FIo2 ≥0.60 is associated
with increased infl ammation and fi brosis.
What physical exam, lab, and radiographic findings are there in ALI/ARDS?
The bedside physical exam usually reveals tachycardia,
tachypnea, diffuse crackles over the chest, increased work of
breathing, and frequent dependence on the accessory respiratory
muscles (trapezius, scalene, sternocleidomastoid, and
pectoralis). Typical laboratory fi ndings in ALI/ARDS are nonspecifi
c and may include leukocytosis, evidence of disseminated
intravascular coagulation (DIC), and lactic acidosis. Arterial
blood gases usually show acute respiratory alkalosis, reduced
Sao2 (<90%), decreased Pao2/ FIo2 ratio, and severe hypoxemia
that collectively refl ect right-to-left shunt physio logy. Chest
radiographic fi ndings, while distinctive, are also seen in diffuse
lung hemorrhage and acute interstitial edema. Importantly,
ALI/ARDS is a clinical syndrome, not a specifi c disease. It is
always caused by underlying conditions that must be diagnosed
and treated, in addition to the respiratory failure.
