B4.058 Acute Lung Injury and Respiratory Distress Syndromes

Question 1

neonatal respiratory distress syndrome

Answer 1

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

Question 2

what cells produce surfactant

Answer 2

type 2 pneumocytes

Question 3

what is surfactant

Answer 3

lecithin, phosphatidyl glycerol, and hydrophobic glycoproteins
reduce surface tension and make it so there is less pressure required to keep alveoli patent and aerated

Question 4

what happens in lung parenchyma as gestation proceeeds

Answer 4

cuboidal epithelium surrounding alveoli is replaced for thinner type 1 pneumocytes
results in wider air spaces
capillaries migrate closer to air spaces

Question 5

epidemiology of NRDS

Answer 5

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

Question 6

role of surfactant in initial respiration

Answer 6

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

Question 7

what happens in initial respiration when there is a deficiency in surfactant

Answer 7

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

Question 8

what is the result of the atelectasis caused by lack of surfactant?

Answer 8

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

Question 9

factors that lead to increased surfactant production

Answer 9

intrauterine stress
fetal growth retardation
glucocorticoids
labor

Question 10

factors that lead to decreased surfactant production

Answer 10

infants of diabetic mothers
insulin
congenital deficiency

Question 11

gross appearance of NRDS

Answer 11

congested, atelectatic lung

usually sink in water

Question 12

what reparative changes occur after 48 hours of NRDS

Answer 12

alveolar epithelium grows under the hyaline membrane
may detach into the airspace
partial digestion or phagocytosis by macrophages

Question 13

management of NRDS

Answer 13

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

Question 14

potential complications of NRDS

Answer 14

air leaks due to rupture of distended air spaces
complications of oxygen therapy
complications of prematurity

Question 15

complications of oxygen therapy

Answer 15

retrolental fibroplasia (retionopathy of prematurity)
bronchopulmonary dysplasia

Question 16

pathogenesis of retinopathy of prematurity

Answer 16

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

Question 17

what is bronchopulmonary dysplasia

Answer 17

potentially reversible abnormality in alveolar septation > fewer, larger alveoli > reduction in surface area available for gas exchange
dysregulation of pulm vasculature development

Question 18

cause and outcome of bronchopulmonary dysplasia

Answer 18

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

Question 19

what is transient tachypnea of the newborn

Answer 19

pulm edema resulting from delayed resorption and clearance of fetal alveolar fluid
shortly after delivery in full or late preterm babies

Question 20

increased risk of transient tachypnea of the newborn

Answer 20

C-section

infants of diabetic mothers

Question 21

persistent fetal circulation

Answer 21

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

Question 22

causes of pulmonary hypoplasia

Answer 22

diaphragmatic hernia

renal abnormalities

Question 23

what is pulmonary edema

Answer 23

increase in interstitial fluid which then accumulated within alveolar spaces

Question 24

causes of pulmonary edema

Answer 24

1. hemodynamic disturbances (cardiogenic)
2. microvascular injury leading to direct increases in cap permeability
3. undetermined origin (head injury, high altitude)

Question 25

hydrostatic pressure

Answer 25

pushes blood out of caps

Question 26

osmotic pressure

Answer 26

protein content that pulls plasma into caps

Question 27

3 causes for hemodynamic pulmonary edema

Answer 27

1. increased hydrostatic pressure- increased pulm venous pressure (L sided heart failure, volume overload, pulm vein obstruction) 2. decreased oncotic pressure (low protein states) 3. lymphatic obstruction

Question 28

pathogenesis of cardiogenic edema

Answer 28

perivascular and interstitial fluid accumulation, particularly in the interlobular septa progressive edematous widening of alveolar septa accumulation of edema fluid in the alveolar spaces

Question 29

imaging findings in pulm edema

Answer 29

wet, heavy lungs with frothy blood tinged fluid microhemorrhages (hemosiderin containing macrophages in the alveoli) brown induration congestion of capillaries

Question 30

pathogenesis of pulm edema from microvascular injury

Answer 30

alveolar septa affected damage to vascular endothelium damage to alveolar epithelium with secondary vascular injury inflammatory exudate > interstitial space > alveoli

Question 31

causes of pulm edema from microvascular injury

Answer 31

``` infections inhaled gases liquid aspiration drugs and chemicals shock, trauma radiation transfusion ```

Question 32

what happens with pulm edema from microvascular injury becomes widespread

Answer 32

significant contributors to ARDS

Question 33

what is acute lung injury

Answer 33

noncardiogenic pulmonary edema abrupt onset of significant hypoxemia and diffuse pulmonary infiltrates in the absence of cardiac failure severe ALI = ARDS

Question 34

what leads to ALI?

Answer 34

inflammation associated increase in pulm vascular permeability epithelial and endothelial cell death

Question 35

histo manifestation of ALI

Answer 35

diffuse alveolar damage (DAD)

Question 36

what is ARDS

Answer 36

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

Question 37

4 primary causes of ARDS

Answer 37

``` diffuse pulm infections gastric aspiration sepsis trauma account for >50% of cases ```

Question 38

pathogenesis of ARDS

Answer 38

endothelial activation adhesion and migration of neutrophils intraalveolar fluid and hyaline membranes loss of diffusion capacity

Question 39

discuss the process of endothelial activation in ARDS

Answer 39

pneumocyte injury > sensed by resident alveolar macrophages > secrete mediators > circulating mediators activate pulmonary endothelium endothelial cells express increased adhesion molecules, procoag proteins, and chemokines

Question 40

discuss the process of adhesion and migration of neutrophils in ARDS

Answer 40

neutrophils degranulate and release inflamm mediators including proteases, ROS, and cytokines macrophage migratory inhibition factor (MIF) helps sustain proinflamm response > increased recruitment of leukocytes

Question 41

discuss the intraalveolar fluid and hyaline membrane formation in ARDS

Answer 41

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

Question 42

resolution of ARDS/DAD

Answer 42

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

Question 43

management of ARDS/DAD

Answer 43

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

Question 44

potential complications of ALI in adults

Answer 44

``` air leaks unresolved fibrosis (V/Q mismatch) superinfections can be fatal minority have chronic pulm disease with interstitial fibrosis ```

Question 45

pathophysiology of DAD

Answer 45

reduction in lung compliance and functional residual capacity ventilation perfusion mismatch impaired gas exchange

Question 46

what is acute interstitial pneumonia

Answer 46

ALI/DAD of unknown etiology rare acute resp failure follows an upper rest tract infection like illness radiographically and pathologically identical to organizing ALI

Question 47

acute interstitial pneumonia mortality

Answer 47

33-75% most deaths within 1 to 2 months recurrences and chronic disease may develop