The fundamental defect in RDS is the inability of the immature lung to synthesize sufficient surfactant. Surfactant is a complex of surface-active phospholipids, principally dipalmitoylphosphatidylcholine (lecithin) and at least two groups of surfactant-associated proteins. The importance of surfactant-associated proteins in normal lung function can be gauged by the occurrence of severe respiratory failure in neonates with congenital deficiency of surfactant caused by mutations in the corresponding genes. Surfactant is synthesized by type II pneumocytes and, with the healthy newborn’s first breath, rapidly coats the surface of alveoli, reducing surface tension and thus decreasing the pressure required to keep the alveoli open. In a lung deficient in surfactant, alveoli tend to collapse, and a relatively greater inspiratory effort is required with each breath to open the alveoli. The infant rapidly tires from breathing and generalized atelectasis sets in. The resulting hypoxia sets into motion a sequence of events that leads to epithelial and endothelial damage and eventually to the formation of hyaline membranes (
Fig. 7.24 ). As discussed later, this classical picture of surfactant deficiency is greatly modified by surfactant treatment.
Hormones regulate surfactant synthesis. Corticosteroids stimulate the formation of surfactant lipids and associated proteins. Therefore, conditions associated with intrauterine stress and fetal growth restriction, which increase corticosteroid release, lower the risk of developing RDS. Conversely, the compensatory high blood levels of insulin in infants of diabetic mothers can suppress surfactant synthesis, counteracting the effects of steroids. This may explain, in part, why infants of diabetic mothers are at higher risk for developing RDS. Labor is known to increase surfactant synthesis; accordingly, cesarean section performed before the onset of labor also may be associated with increased risk for RDS.
MORPHOLOGYThelungsininfantswithRDSareofnormalsizebutareheavyandrelativelyairless.Theyhaveamottledpurplecolor,andonmicroscopicexaminationthetissueappearssolid,withpoorlydeveloped,generallycollapsed(atelectatic)alveoli.Iftheinfantdieswithinthefirstseveralhoursoflife,onlynecroticcellulardebriswillbepresentintheterminalbronchiolesandalveolarducts.Laterinthecourse,characteristiceosinophilic hyaline membranes linetherespiratorybronchioles,alveolarducts,andrandomalveoli(
Fig.7.25 ).These“membranes”containnecroticepithelialcellsadmixedwithextravasatedplasmaproteins.Thereisaremarkablepaucityofneutrophilicinflammatoryreactionassociatedwiththesemembranes.Thelesionsofhyalinemembranediseaseareneverseeninstillborninfantsorinlive-borninfantswhodiewithinafewhoursofbirth.IftheinfantwithRDSdiesafterseveraldays,evidenceofreparativechanges,includingproliferationoftypeIIpneumocytesandinterstitialfibrosis,isseen.
The classic clinical presentation before the era of treatment with exogenous surfactant was described earlier. Currently, the actual clinical course and prognosis for neonatal RDS vary, depending on the maturity and birth weight of the infant and the promptness of therapy. The control of RDS focuses on prevention, either by delaying labor until the fetal lung reaches maturity or by inducing maturation of the lung in the at-risk fetus. Critical to these objectives is the ability to assess fetal lung maturity accurately. Because pulmonary secretions are discharged into the amniotic fluid, analysis of amniotic fluid phospholipids http://ebooksmedicine.net
Reduced surfactant synthesis, storage, and release
Fig. 7.24 Pathophysiologyofrespiratorydistresssyndrome(seetext).