B4.058 Acute Lung Injury and Respiratory Distress Syndromes Flashcards
neonatal respiratory distress syndrome
most common cause of respiratory distress in premature infants
due to lack of surfactant
characterized histologically by the presence of hyaline membranes in peripheral airspaces
what cells produce surfactant
type 2 pneumocytes
what is surfactant
lecithin, phosphatidyl glycerol, and hydrophobic glycoproteins
reduce surface tension and make it so there is less pressure required to keep alveoli patent and aerated
what happens in lung parenchyma as gestation proceeeds
cuboidal epithelium surrounding alveoli is replaced for thinner type 1 pneumocytes
results in wider air spaces
capillaries migrate closer to air spaces
epidemiology of NRDS
neonates = 0-4 weeks observed in premature infants 60% infants born at < 28 weeks 30% born between 28-34 weeks <5% 34 weeks or older
role of surfactant in initial respiration
first breath of life is high pressure to expand lungs
lungs retain up to 40% of the residual air volume after the first breath
subsequent breaths require much less pressure because surfactant reduce surface tension
what happens in initial respiration when there is a deficiency in surfactant
lungs collapse with each breath
successive breaths take as much effort as the first
stiff atelectatic lungs are further impeded by the soft thoracic wall that is pulled in as the diaphragm descends
what is the result of the atelectasis caused by lack of surfactant?
uneven perfusion and hypoventilation hypoxemia and CO2 retention acidosis pulm vasoconstriction pulm hypoperfusion endothelial/epithelial damage plasma leak into alveoli fibrin and necrotic cells produce hyaline membrane
factors that lead to increased surfactant production
intrauterine stress
fetal growth retardation
glucocorticoids
labor
factors that lead to decreased surfactant production
infants of diabetic mothers
insulin
congenital deficiency
gross appearance of NRDS
congested, atelectatic lung
usually sink in water
what reparative changes occur after 48 hours of NRDS
alveolar epithelium grows under the hyaline membrane
may detach into the airspace
partial digestion or phagocytosis by macrophages
management of NRDS
assess lung maturity using amniotic fluid phospholipids
delay labor
induce lung maturity with steroids
surfactant replacement therapy
oxygenation/ventilation
survival for 3-4 days indicates an excellent chance of recovery
potential complications of NRDS
air leaks due to rupture of distended air spaces
complications of oxygen therapy
complications of prematurity
complications of oxygen therapy
retrolental fibroplasia (retionopathy of prematurity) bronchopulmonary dysplasia
pathogenesis of retinopathy of prematurity
phase I: hyperoxic phase of therapy -reduction in proangionic VEGF -endothelial cell apoptosis phase II: comparatively hypoxic room air -VEGF levels recover -retinal vessel proliferation and neovascularization
what is bronchopulmonary dysplasia
potentially reversible abnormality in alveolar septation > fewer, larger alveoli > reduction in surface area available for gas exchange
dysregulation of pulm vasculature development
cause and outcome of bronchopulmonary dysplasia
superimposed effects of hyperoxemia, hyperventilation, prematurity, inflammatory mediators and vascular maldevelopment play a role
most infants gradually improve in 2-4 months
severe disease required prolonged mechanical ventilation and may develop pulmonary hypertension and cor pulmonale
what is transient tachypnea of the newborn
pulm edema resulting from delayed resorption and clearance of fetal alveolar fluid
shortly after delivery in full or late preterm babies
increased risk of transient tachypnea of the newborn
C-section
infants of diabetic mothers
persistent fetal circulation
pulmonary vascular resistance fails to decrease after birth
pulm vascular resistance remains equal to or greater than systemic vascular resistance
blood continues to flow through the foramen ovale and ductus arteriosus
causes of pulmonary hypoplasia
diaphragmatic hernia
renal abnormalities
what is pulmonary edema
increase in interstitial fluid which then accumulated within alveolar spaces
causes of pulmonary edema
- hemodynamic disturbances (cardiogenic)
- microvascular injury leading to direct increases in cap permeability
- undetermined origin (head injury, high altitude)
hydrostatic pressure
pushes blood out of caps
osmotic pressure
protein content that pulls plasma into caps
3 causes for hemodynamic pulmonary edema
- increased hydrostatic pressure- increased pulm venous pressure (L sided heart failure, volume overload, pulm vein obstruction)
- decreased oncotic pressure (low protein states)
- lymphatic obstruction
pathogenesis of cardiogenic edema
perivascular and interstitial fluid accumulation, particularly in the interlobular septa
progressive edematous widening of alveolar septa
accumulation of edema fluid in the alveolar spaces
imaging findings in pulm edema
wet, heavy lungs with frothy blood tinged fluid
microhemorrhages (hemosiderin containing macrophages in the alveoli)
brown induration
congestion of capillaries
pathogenesis of pulm edema from microvascular injury
alveolar septa affected
damage to vascular endothelium
damage to alveolar epithelium with secondary vascular injury
inflammatory exudate > interstitial space > alveoli
causes of pulm edema from microvascular injury
infections inhaled gases liquid aspiration drugs and chemicals shock, trauma radiation transfusion
what happens with pulm edema from microvascular injury becomes widespread
significant contributors to ARDS
what is acute lung injury
noncardiogenic pulmonary edema
abrupt onset of significant hypoxemia and diffuse pulmonary infiltrates in the absence of cardiac failure
severe ALI = ARDS
what leads to ALI?
inflammation associated increase in pulm vascular permeability
epithelial and endothelial cell death
histo manifestation of ALI
diffuse alveolar damage (DAD)
what is ARDS
clinical syndrome characterized by the rapid onset of severe, life threatening respiratory insufficiency, cyanosis, and severe arterial hypoxemia that is refractory to oxygen therapy
CXR shows diffuse infiltrates
may progress to multisystem organ failure
4 primary causes of ARDS
diffuse pulm infections gastric aspiration sepsis trauma account for >50% of cases
pathogenesis of ARDS
endothelial activation
adhesion and migration of neutrophils
intraalveolar fluid and hyaline membranes
loss of diffusion capacity
discuss the process of endothelial activation in ARDS
pneumocyte injury > sensed by resident alveolar macrophages > secrete mediators > circulating mediators activate pulmonary endothelium
endothelial cells express increased adhesion molecules, procoag proteins, and chemokines
discuss the process of adhesion and migration of neutrophils in ARDS
neutrophils degranulate and release inflamm mediators including proteases, ROS, and cytokines
macrophage migratory inhibition factor (MIF) helps sustain proinflamm response > increased recruitment of leukocytes
discuss the intraalveolar fluid and hyaline membrane formation in ARDS
endothelial damage > leaky caps > interstitial and intraalveolar edema
necrosis of type 2 pneumocytes leads to surfactant abnormalities > compromising gas exchange
protein rich fluid and debris from deal alveolar epithelial cells organize into hyaline membranes
resolution of ARDS/DAD
resolution is by resorption of the exudate and dead cell removal by macrophages
macrophages also discharge fibrogeneic cytokines > fibroblastic proliferation and collagen deposition > alveolar wall fibrosis
epithelial cell repopulation is from proliferation of bronchiolar stem cells
endothelial cell repopulation transpires by proliferation of undamaged capillaries
management of ARDS/DAD
treatment of underlying precipitating and secondary conditions (sepsis) as well as supportive care (intubation and mechanical ventilation)
avg mortality is 40% depending on cause and severity
potential complications of ALI in adults
air leaks unresolved fibrosis (V/Q mismatch) superinfections can be fatal minority have chronic pulm disease with interstitial fibrosis
pathophysiology of DAD
reduction in lung compliance and functional residual capacity
ventilation perfusion mismatch
impaired gas exchange
what is acute interstitial pneumonia
ALI/DAD of unknown etiology
rare
acute resp failure follows an upper rest tract infection like illness
radiographically and pathologically identical to organizing ALI
acute interstitial pneumonia mortality
33-75%
most deaths within 1 to 2 months
recurrences and chronic disease may develop
