# Nanotechnology and Early Human Development
## 4 Respiratory System  
The development of the respiratory system during fetal life and early childhood includes dramatic changes. Lung development can be divided into five stages--embryonic, pseudoglandular, canalicular, saccular, and alveolar--that start in fetal life (the first four stages) and take several years to complete (the alveolar phase), as shown in Figure 3.  
The phases are characterized by morphogenesis of the conducting airways, formation of alveoli (the terminal regions of the lungs where gas exchange occurs), differentiation of cells with region-specific functions of the lung (such as protection from foreign substances), efficient movement of air into and out of the lung, and efficient gas exchange at the alveolar-capillary interface. These processes are finely regulated by a complex network of cell signals, cell-derived molecules, hormones, and genetic expression. One of the key components of the respiratory system is pulmonary surfactant. Pulmonary surfactant covers and stabilizes the alveoli and has peculiar biophysical properties, including the reduction of alveolar superficial tension and defense against microorganisms and toxic substances. Surface tension is the force that develops at the interface between two or more fluids or between fluids and a solid wall. The forces of cohesion that act between the molecules of a fluid mean that those on the outer surface are subjected to a resulting force directed inwards; there is therefore a tendency of molecular stray from the limit surface of the liquid, which tends to contract and assume the minimum possible extent. In the lungs, there is an interface between the liquid that covers the alveolar walls and the gas at their internal. Again, the surface liquid layer tends to contract and expel the air outwards, resulting in  
Figure 3: Lung development. Source: Anatomy and Physiology by Rice University, licensed under a Creative Commons Attribution 4.0 International License. the collapse of the alveoli. The pressure generated within the alveoli due to surface tension is called collapse pressure and, according to Laplace's law, is directly proportional to twice the surface tension and inversely proportional to the radius of the alveoli. Thus, the increase in surface tension determines an increment in the collapse pressure of the alveoli. In the physiological lung, surface tension is greatly reduced by the presence of surfactant, a mixture of different phospholipids, proteins, and ions produced by type II alveolar epithelial cells that cover about 10% of the area of the alveolar walls. Surfactant production begins at around the 20 th week of gestation and reaches significant amounts in the amniotic fluid only after the 28 th week [12]. The main components of surfactant are phospholipid dipalmitoylphosphatidylcholine, apoproteins, and calcium ions (see below). The tensioactive capacity lies in the amphibious dipalmitoylphosphatidylcholine at the liquid-gas interface. The absence of surfactant can lead to atelectasis (collapse of the alveoli) and respiratory insufficiency. Quantitatively, the surface tension of normal liquids covering the alveoli without surfactants is 50 dine/cm; this decreases to 5-30 dine/cm with surfactant. Consequently, the collapse pressure for medium-sized alveoli (r = 100 \(\upmu\)m) falls from about 18 to 4 cm H\({}_{2}\)O. To summarize, lung surfactant has important functions:  
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2. increases lung compliance and therefore reduces the work required to expand the lung;
3. contributes to the stability of the alveoli by preventing their collapse;
4. limits the risk of pulmonary edema by decreasing the recall force of fluids inside the alveoli;
5. allows the expansion of the lung at birth during the first respiratory efforts. Moreover, surfactant can be used as a shuttle for the delivery of drugs and nanocarriers. Pulmonary surfactant is composed of approximately 90% lipids and 10% proteins. Four surfactant proteins (SP)--SP-A,-B,-C, and -D--are important for surfactant functions.