1. Fetal Heart and Lung Development
Christopher Casteel, RRT-ACCS, NPS, AE-C, C-NPT

2. Fetal Development / Early Stages
The fertilized egg, or zygote, implants into the uterus.
The zygote is completely dependent on the uterine lining for nourishment. Cell division begins to occur and the grouping of cells at this point is called a blastocyst.
The outer layer of the blastocyst forms the trophoblast and will eventually form the chorionic membrane.

3. Fetal Development / Early Stages
Inside the blastocyst a figure eight grouping of cells begins to form and starts to divide into the three forms of embryonic germ layers.
Ectoderm
Mesoderm
Endoderm

4. Fetal Development
Until the formation of the umbilical chord, the embryo gets Oxygen, Carbon dioxide, and nutrients through a vast capillary network formed by the chorionic villi.
As the amniotic sac grows, it will limit the amount of surface area available to the chorionic villi. The chorionic villi are compressed and form into a discus shape formation the becomes the placenta.
As this happens, the umbilical chord starts to take over as the direct source of nutrition to the fetus.

6. Fetal Development
The umbilical chord is made up of two veins, one artery, and Wharton’s jelly.
Wharton's jelly is a transparent and rubbery substance in the umbilical chord that prevents the chard from getting kinked
It is important to note that Oxygenated blood flows to the fetus in the veins and the artery transports de-oxygenated blood and waste products back to the mothers circulation for disposal by her liver and kidneys.

7. Early Heart Development
In early development angiogenic clusters or “blood pools” supply nutrition to the embryo.
The angiogenic clusters will eventually coalesce into two heart tubes lined with myocardial tissue.
At approximately day 18 the heart tubes fold into each other and get close enough to fuse.

8. Chamber Development
At day 22, the heart tubes complete fusing together and the heart begins to beat. This will begin bidirectional blood flow.
The heart will begin to twist and balloon and loop into the shape we all know as the heart.
At day 28 unilateral blood flow begins.
By week 6 the heart is nearing completion of aligning itself into the proper shape and the heartbeat should be about 95 beats per min. The heart rate will increase by 4 beats per min a day until the heart formation is complete.

10. Fetal Circulation and Shunts
Fetal Circulation is dependent on shunts while inside the mother.
These shunts allow for the infants blood flow to bypass the lungs, liver, and kidneys while in utero.
These shunts have to close once born to allow for proper circulation and oxygenation to occur.
Starting from the mother, the blood is highly enriched with Oxygen and nutrients that cross over from the mothers circulatory system. It is taken into systemic circulation by the by the umbilical vein.
Why is it the umbilical vein that is carrying Oxygenated blood?
By definition veins carry blood towards the heart and arteries carry blood away from the heart.
What is the main differences between veins are arteries?
Arteries have thicker walls than veins to handle higher pressures because the blood is coming from the heart (high pressure), they also have more smooth muscle around them to help control blood pressure. Veins are much thinner than arteries and have sets of one way valves through them to prevent back flow.
The blood flow continues towards the fetal liver, but the first fetal shunt (ductus venosus) allows most of the blood to bypass the liver.
Why is it a good thing that the blood bypasses the liver?
First, the liver is still forming and is not completely functional. Second, and the main reason, this is fresh, already been filtered blood coming from the mother. There should not be a lot of waste products that need to be filtered out at this point.
The blood now enters the what we think of as the main circulation at the inferior vena cava. It will mix with some de-Oxygenated blood as it moves up towards the heart. This is Normal and does not present an issue to the fetus unless the mothers Oxygenation is compromise. If everything is as it should be the amount of Oxygen being carried in the blood is high enough that some admixture can occur and the Oxygen percentage in the blood will remain high enough to suit the needs of the developing fetus.
The blood then continues towards and eventually enters the right side of the heart. Now, lets look ahead where the blood is going to go. Normally, the blood would move into the right atrium, then into the right ventricle. The right ventricle would contract pushing the blood into the pulmonary trunk and eventually into the lungs.
What is different with the fetal lungs at this point?
Why would we not want to send the primary blood flow to the lungs?
What is the mechanism that prevents the main blood flow from going to the lungs?

11. Fetal Circulation
Oxygenated Blood travels through to umbilical vein through the ductus venosus, which allows % of the Oxygen rich blood to bypass the liver.
The oxygen rich blood then empties into the inferior vena cava and mixes with venous blood as it flows to the right atrium.
Once the blood is in the right atrium, most of it will pass through the foramen ovale into the left atrium. This effectively bypasses the infants lungs.
The remainder of the blood that does not pass through to foramen ovale travels through the right ventricle.

12. Fetal Circulation
The third fetal shunt is the Ductus arteriosus. Blood flowing from right ventricle is split by the ductus arteriosus allowing blood flow to bypass the lungs and move directly to the aorta.
The amount of blood flow diverted by the PDA is dependent on the pulmonary vascular resistance, which is kept high by lack of oxygen, and physical compression of the vessels by chemical mediators.
Due to the PFO and PDA only 13% - 25% of the infants blood flow reaches the lungs.

13. Fetal Circulation
Deoxygenated blood from the upper torso and head return to the right atrium which will eventually mix with oxygenated blood from the inferior vena cava.
Deoxygenated blood from the descending and abdominal aorta returns through the umbilical arteries to the placenta where it is oxygenated.
The placenta contains about ½ of the total fetal blood volume.

14. Fetal Lung Development
Reid’s Laws of Lung Fetal Lung Development
The bronchial tree develops by week 16 of intrauterine life.
After birth the alveoli develop in increasing numbers until the age of 8 years and increase in size until the growth of the chest wall is finished.
Pre-acinar arteries and veins develop after the airway has been established; intra acinar vessels develop after the alveoli are generated.

15. Stages of Lung Development
There are five stages of lung development
Embryonal
Pseudograndular
Canalicular
Saccular
Alveolar

17. Embryonal Stage
This stage generally encompasses the first 2 months of embryonic development.
The lung begins to bud from the trachea at day 26 and elongates and eventually splits to form two bronchial buds, which will eventually separate to form the esophagus and trachea.
Later in his stage, growth factors start to influence the tubular epithelium which starts the promotion of airway branching.
The mesenchyme, which is a network of embryonic connective tissues, will eventually differentiate to form smooth muscle, blood vessels, and cartilage.
The diaphragm also develops in this stage and completes development by approx. week 7.

18. Pseudoglandular Stage
This stage is named for the distinct glandular appearance of the developing lung tissue.
This stage extends to week 16 and id characterized by a continuation of the formation of the conducting airways.
There is extensive subdivision of the conducting airways in this stage.
The pattern of lung development is implemented in this stage and the framework for the terminal bronchioles and acini is completely laid down in this stage.

19. Pseudoglandular Stage
Various growth factors and chemical mediators begin to influence and transdifferentiate the primordial tracheal epithelium into respiratory type II epithelial cells. These cells are important because they are required for alveoli development.
Cillia, goblet cells, mucosal glands, smooth muscle, immature cartilage, lymphatic also start to appear in this stage.
By the end of this stage, airways, arteries, and veins are in the pattern that correspond to the adult lung.

20. Canalicular Stage
This stage named due to the appearance of vascular channels and capillary networks start to form around the air passages in the lungs however some may still be too far away from the air passages for adequate gas exchange to occur.
Survival of the fetus begins in this stage at weeks. This is due to the amount of capillaries present for gas exchange and the air- blood barrier thins enough around the saccules to support gas exchange.
Formation of pulmonary acinar units, alveolar ducts and alveolar saccules occur in this stage as well.
Type II cells further their development and can start producing surfactant.

21. Saccular Stage
This stage was thought to be the last stage of lung development but there is not currently a scientific consensus on when the actual separation of the saccular and alveolar stage occurs.
In this stage the smooth immature alveolar sacs, which are cylindrical and smooth start to develop ridges known as secondary crest. These crest protrude into each saccule and more capillaries start to grow around them forming a double capillary layer.
This results the eventual formation of alveoli and much more area for gas exchange. Mature alveoli can start to be seen around week 36 of gestation.

22. Alveolar Stage
This stage is the main stage where alveoli continue to develop and mature.
At birth it is thought that there is only 15%- 20% of the adult number of alveoli are present at birth.

23. Transition From Fetal Circulation
The umbilical chord is clamed and the baby takes the first breath.
The lungs expand and lungs clear fluid via lymphatics and active transport across type 2 cells.
Pulmonary pressures decrease which causes blood to flow into the pulmonary system instead most being diverted through the ductus arteriosus.
This decrease in pressure causes the PFO to close.
At birth, the umbilical cord is clamped and the baby no longer receives oxygen and nutrients from the mother. With the first breaths of life, the lungs begin to expand. As the lungs expand, the alveoli in the lungs are cleared of fluid. An increase in the baby's blood pressure and a significant reduction in the pulmonary pressures reduces the need for the ductus arteriosus to shunt blood. These changes promote the closure of the shunt. These changes increase the pressure in the left atrium of the heart, which decrease the pressure in the right atrium. The shift in pressure stimulates the foramen ovale to close.
The closure of the ductus arteriosus and foramen ovale completes the transition of fetal circulation to newborn circulation.