Lung Development part 4

There are a number of physical influences on lung growth. Proper development of the lung is dependent of the presence of both lung liquid and amniotic fluid. The lung liquid is secreted by pulmonary epithelium. The volume of lung fluid  is maintained by the activity of the upper airway which acts as a gatekeeper by controlling the resistance to efflux of fluid out of the lung and trachea during non-breathing periods, and by diaphragmatic movement associated with fetal breathing movements. The larinx is the major site of regulation of efflux and therefore of lung liquid volume. During fetal breathing movements, when the upper airway resistance is decreased, diaphargmatic movements help to maintain lung liquid volume. The experimental drainage of lung liquid leads pulmonary hypoplasia.

Amniotic fluid is also required for normal lung development. Amniotic fluid originates in the lung and fetal kidney. Oligohydramnions is associated with lung hypoplasia (Potter syndrome-renal agenesis, lack of fetal urine). The mechanism of lung hypoplasia in this syndrome is uncertain but perhaps it is due to increased efflux of lung liquid into the amniotic space.

Lung hypoplasia may caused by a number of other factors that restrict or better, compress the fetal lung. Condition or lesions known to cause lung hypoplasia are:

• Congenital diaphragmatic hernia, in which usually the left hemithorax is occupied by intestinal contents
• Musculosceletal abnormalities of the thorax which do not allow full expansion of the thoracic cage
• Space occupying lesions of thorax, such as fetal pleural effussions
• Changes in geometry due to oligohydramnions associated with renal or urinary tract abnormalities

Biochemical maturation, that is, production of surfactant, appears to be independent of lung growth. What is surfactant and why is it so important? Surfactant is a mixture of phospholipids nad hydrophobic proteins, produced by type II cells, and secreted into the alveolar space.  The principle lipids are phosphatidylcholine (lecithin) and phosphatidyl glycerol, and   the principle proteins are surfactan proteins B and C.

Surfactant decreases surface tension within alveoli and prevents collapse of alveoli during exhalation. In the absence of surfactant, the alveolus would be unstable and collapse at the end of each breath. Tremendous work would be required to open up the alveolus with each breath. In fact,  a mutation in the gene coding for surfaactant protein B leading to an absence of this crucial protein is an extremely rare cause of respiratory failure in terms newborns.

Type II cells and their associated surfactant can develop in the presence of pulmonary hypoplasia. Gas exchange is possibly by 26-27 weeks, though not necessarily sustainable. Surfactant production gradually increases with advancing gestational age. The surfactant system matures by 36  weeks in most fetuses.. Production of surfactant by type II cells is hormonally influenced. Corticotrophin stimulates lung maturation via cortisol. Cortisol induces fetal lung fibroblasts to produce fibroblast pneumocyte factor which stimulates surfactant production in type II cells. Thyroid hormones are also required for development of the surfactant system. At the time of birth, epinephrine and arginin vasopressin suppress fetal lung liquid formation, and play a role in its rearbsobtion. These two hormones are in turn dependent on increasing concentrations of glucocorticoids that occur at term.
The development of the surfactant system, to the point that spontaneous respiratory function can occur, usually trakes place by 36 weeks of gestation. Birth before 36 weeks may  be associated with respiratory compromise and failure. The incidence and severity of the lung disease is greater to the degree of prematurity. A number of strategies have been developed to try to deal with this problem, including the use of antenatal steroids to promote lung maturity, the use of various forms of positive pressure to maintain the lungs in the open state, and the administration of exogenous surfactant.