When congenital diaphragmatic hernia (CDH) was first described in the early 18th century, it was considered as a result of an opening in the diaphragm that theoretically could be easily corrected after birth by removal of the herniated viscera and subsequent closure of the diaphragm. Over the past three decades, however, it has become evident that CDH is an anomaly characterized by not only a diaphragmatic defect, but also a variable amount of pulmonary hypoplasia (PH) and lung immaturity in some cases. Apart from these features, pulmonary vascular abnormalities may occur and cause persistent pulmonary hypertension of newborn (PPHN).1,2 Hypoplastic lungs are characterized by fewer airways and smaller air spaces, and thus the lower number of vascular generations and increased adventitia and medial thickness of pulmonary arterial walls give rise to pulmonary hypertension.1,2 Apart from the morphologic abnormalities in the pulmonary vasculature, an alternate expression of various cellular mediators, such as nitric oxide, endothelin, prostaglandins, catecholamines, and renin-angiotensin system, have been suggested to contribute to the pathogenesis of PPHN in CDH patients.3,4 Classically, CDH is considered as a primary defect of diaphragmatic embryogenesis resulting from failure of formation or fusion of pleuroperitoneal membranes. Consequently, the abdominal organs herniate into the ipsilateral thoracic cavity when the midgut returns to the abdominal cavity around the 10th gestational week. The timing of herniation coincides with the critical period of lung development and in utero competition for space of the developing lung and the 'abdominal viscera' leads to pulmonary hypoplasia.5 However, more recent experimental evidence suggests that lung hypoplasia may occur independently as a result of defects in signaling pathways.6 Recently the retinoid hypothesis has gained much interest – reviewed by Clugston et al.7 – and also we have gained much greater understanding of the role of specific genes in the etiology of CDH.8 Different animal models have been used to study the natural history of CDH, but current understanding of its etiology and pathophysiology remains limited.

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Tibboel, Prof. Dr. D. (promotor) Chulalongkorn University, Bangkok, Thailand.
D. Tibboel (Dick)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

Rajatapiti, P. (2007, June 20). Pulmonary Development in Congenital Diaphragmetic Hernia. Retrieved from http://hdl.handle.net/1765/10705