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Development of the Respiratory System and Birth


Development of the Respiratory System and Birth
The embryological origins of the lung are primitive endoderm of the foregut, which eventually forms the epithelium and glands of the larynx, trachea and lungs, and splanchnic mesoderm, which forms cartilage, smooth muscle, lung parenchyma and connective tissue. In common with many glandular organs, the lung develops by branching morphogenesis (Fig. 16a), with budding and branching of the endoderm/epithelium into mesoderm. The process requires reciprocal signalling between epithelium and mesoderm, with the mesoderm being primarily responsible for programming development of adjacent epithelium into the relevant structures. Many signalling molecules are vital for the orchestration of branching morphogenesis during lung development, including growth factors such as fibroblast growth factor (FGF), epidermal growth factor (EGF) and platelet-derived growth factor (PDGF); vascular endothelial growth factor (VEGF) is critical for pulmonary vascular development. Development of the respiratory system is generally divided into five stages or periods.

Fetal circulation and birth

1.   Embryonic period: The tracheobronchial tree originates from the laryngotracheal tube, below the fourth pharyngeal pouch at the caudal (tail) end of the primordial pharynx. The laryngotracheal tube starts to appear just prior to the fourth week of development, after the heart begins to beat. By the end of the fourth week, its end has bifurcated into two bronchial buds, progenitors of the two main bronchi and bronchial tree (Fig. 16b).
2.      Pseudoglandular period (5-17th weeks): The bronchial buds have now developed into the primordial left and (slightly larger) right primary bronchi, which subsequently divide by branching morphogenesis into five secondary bronchi (three right, two left). At the seventh week, these have started to branch progressively into ten (right) or eight to nine (left) segmental (tertiary) bronchi, each of which eventually forms a bronchopulmonary segment. By the 17th week, most major structures of the lung have formed and are lined with columnar epithelial cells. Conducting blood vessels are present, but the gas exchange surfaces have not yet developed and fetuses delivered during this period are therefore not viable.
3.    Canalicular period (16-25th weeks): Bronchial cartilage, smooth muscle, pulmonary capillaries and connective tissue develop from the mesoderm. There is progressive differentiation and thinning of epithelial cells. The bronchi will have subdivided approximately 17 times after 24 weeks, finall forming the respiratory bronchioles which themselves divide into three to six alveolar ducts and some thin-walled terminal sacs. These are lined by very thin type I alveolar pneumocytes (squamous epithelium), which together with endothelial cells from capillaries form the future alveolocapillary membrane (gas exchange surface). There are a few type II alveolar pneumocytes, secretory epithelial cells that produce surfactant. This reduces surface tension and allows expansion of the terminal sacs/alveoli (Chapter 6), but although it is present in small amounts from about the 20th week, there is insuf- ficien to support unaided breathing until after 26 weeks (see neonatal respiratory distress syndrome, Chapter 17). Some gas exchange can occur at the end of this period, as there are both thin-walled terminal sacs and good vascularization, but the general level of immaturity means that fetuses born before the end of the 24th week normally die despite intensive care.
4.  Saccular (terminal sac) period (24th week to parturition): Associated with rapid development in the number of terminal sacs and the pulmonary and lymphatic capillary networks. Budding from terminal sacs and walls of terminal bronchioles and thinning of type I pneumocytes lead to formation of immature alveoli from around week 32. Suff cient surfactant and vascularization are normally present between the 24 and 26th week to allow survival of some premature fetuses, although this is very variable (Chapter 17). Surfactant increases significantly in the 2 weeks before birth.
5.     Alveolar period (late fetal to childhood): Clusters of immature alveoli form during the early part of this period; mature-type alveoli with thin interalveolar septa and gas exchange surfaces do not appear until after birth. Fetal breathing movements are present before birth, with aspiration of amniotic fluid and these stimulate lung growth and respiratory muscle conditioning. Lung development is impaired in the absence of fetal breathing, inadequate amniotic flui (oligohydramnios) or space for lung growth (Chapter 17). The increase in lung size over the firs 3 years is due primarily to an increase in number of alveoli and respiratory bronchioles; thereafter, both the number and size of alveoli increase. More than 90% of alveoli are formed after birth, reaching a maximum after 7-8 years. At the end of lung development, there are approximately 23 generations of airways, with approximately 17 million branches.

Fetal circulation and birth
Gas exchange in the fetus occurs in the placenta. Oxygen-rich blood from the umbilical vein fl ws into the liver and ductus venosus, and thus into the vena cava. Most blood entering the right atrium is diverted into the left atrium via the foramen ovale; the remainder enters the right ventricle and is pumped into the pulmonary artery as in the adult (Fig. 16c). However, the vascular resistance of the pulmonary circulation is high due to the collapsed state of the lungs and vasoconstriction, and 90% of the blood is therefore shunted via the ductus arteriosus into the aorta (Fig. 16c). Note that the Pao2 in the fetus is much lower ( 4 kPa, 30 mmHg) than in the adult; oxygen transport is sustained by high-affinit fetal haemoglobin (Chapter 8).
At birth, the lungs are initially 50% full of flui which is replaced by air. During and immediately following birth, flui is removed via the pulmonary and lymphatic circulations, and through the mouth as a result of squeezing during delivery. Expansion and fillin of the alveoli with air is critically dependent on the presence of surfactant to lower surface tension. The initiation of gas exchange in the lungs and consequent rise in blood Po2 cause vasodilatation of the pulmonary circulation and constriction of the ductus arteriosus, so that blood from the right side of the heart now follows its adult course via the lungs. The consequent fall in right atrial pressure causes the pressure gradient across the foramen ovale to reverse, causing functional closure within hours. The removal of venous return from the placenta also causes closure of the ductus venosus. Initially, pressure gradients keep the three fetal shunts closed, but after several months structural changes cause permanent closure. In 20% of adults this may remain incomplete for the foramen ovale, but is generally of no consequence.