Changing Heart Anatomy at Birth

Although the developing fetus shares with the adult the need to get oxygen and nutrients to its tissues, the physiology of the fetus differs dramatically from that of the adult. Chief among the differences is the fetus’s lack of functional lungs and intestines. All of its oxygen and nutrients must come from the placenta. This observation raises two questions. First, how does the fetus obtain oxygen and nutrients from maternal blood? And second, how is blood circulation redirected to the lungs once the umbilical cord is cut and breathing becomes necessary?

Human embryonic circulation

The human embryonic circulatory system is a modification of that used in birds and reptiles. (The circulatory system to and from the chick embryo and yolk sac is shown in Figure 12.1.) Blood pumped through the dorsal aorta passes over the aortic arches and down into the embryo. Some of this blood leaves the embryo through the vitelline arteries and enters the yolk sac. Nutrients and oxygen are absorbed from the yolk, and blood returns through the vitelline veins to re-enter the heart through the sinus venosus.

Mammalian embryos obtain food and oxygen from the placenta. Thus, although the embryo has vessels homologous to the vitelline veins, the main supply of food and oxygen comes from the umbilical vein, which unites the embryo with the placenta (Figure 1). This vein, which brings oxygenated, food-laden blood into the embryo, is derived from what would be the right vitelline vein in birds. The umbilical artery, carrying wastes to the placenta, is derived from what would have become the allantoic artery of the chick. It extends from the caudal portion of the aorta and proceeds along the allantois and then out to the placenta.

Figure 1

Figure 1  Circulatory system of a 4-week human embryo. Although at this stage all the major blood vessels are paired left and right, only the right vessels are shown here. Arteries are shown in red, veins in blue. (After Carlson 1981.)

Fetal hemoglobin

The solution to the fetus’s problem of getting oxygen from its mother’s blood involves the development of a specialized fetal hemoglobin. The hemoglobin in fetal red blood cells differs slightly from that in adult corpuscles. Two of the four peptides—the alpha (α) chains—that make up fetal and adult hemoglobin chains are identical, but adult hemoglobin has two beta (β) chains, whereas the fetus has two gamma (γ) chains (Figure 2). The β chains bind the natural regulator diphosphoglycerate, which assists in the unloading of oxygen. The γ chain proteins do not bind diphosphoglycerate as well, and therefore have a higher affinity for oxygen. In the low-oxygen environment of the placenta, oxygen is released from adult hemoglobin. In this same environment, fetal hemoglobin does not release oxygen, but binds it. This small difference in oxygen affinity mediates the transfer of oxygen from the mother to the fetus. In the fetus, the myoglobin of the fetal muscles has an even higher affinity for oxygen, so oxygen molecules pass from fetal hemoglobin to the fetal muscles.

Figure 2

Figure 2  Adult and fetal hemoglobin molecules differ in their globin subunits. The fetal g chain binds diphosphoglycerate less avidly than does the adult b chain. Consequently, fetal hemoglobin can bind oxygen more efficiently than can adult hemoglobin. In the placenta, there is a net flow (arrow) of oxygen from the mother’s blood (which gives up oxygen to the tissues at lower oxygen pressures) to the fetal blood (which at the same pressure is still taking up oxygen).

Fetal hemoglobin is not deleterious to the newborn, and in humans, the replacement of fetal hemoglobin-containing blood cells with adult hemoglobin-containing blood cells is not complete until about 6 months after birth (the molecular basis for this switch in globins was discussed on page 61).

From fetal to newborn circulation

Once the fetus is no longer obtaining its oxygen from its mother, how does it restructure its circulation to get oxygen from its own lungs? During fetal development, an opening—the ductus arteriosus—diverts blood from the pulmonary artery into the aorta (and thus to the placenta). Because blood does not return from the pulmonary vein in the fetus, the developing mammal has to have some other way of getting blood into the left ventricle to be pumped. This is accomplished by the foramen ovale, an opening in the septum separating the right and left atria. Blood can enter the right atrium, pass through the foramen into the left atrium, and then enter the left ventricle (Figure 3). When the first breath is drawn, blood pressure in the left side of the heart increases. This pressure closes the septa over the foramen ovale, thereby separating the pulmonary and systemic circulations. Moreover, the decrease in prostaglandins experienced by the newborn causes the muscles surrounding the ductus arteriosus to close that opening as well (Nguyen et al. 1997). Thus, when breathing begins, the respiratory circulation is shunted from the placenta to the lungs.

Figure 3

Figure 3  Redirection of human blood flow at birth. The expansion of air into the lungs causes pressure changes that redirect the flow of blood in the newborn infant. The ductus arteriosus squeezes shut, breaking off the connection between the aorta and the pulmonary artery, and the foramen ovale, a passageway between the left and right atria, also closes. In this way, pulmonary circulation is separated from systemic circulation.

In some infants, the septa fail to close and the foramen ovale is left open. Indeed, atrial and ventricular septum defects are among the most common congenital anomalies. Usually the atrial opening is so small that there are no physical symptoms, and the foramen eventually closes. If it does not close completely, however, and the secondary septum fails to form, the atrial septal opening may cause enlargement of the right side of the heart, which can lead to heart failure in early adulthood. This fine-tuning of septal growth is controlled by miRNA1-2, a microRNA that regulates translation of several proteins involved in cardiac muscle growth and electrical conduction (Zhao et al. 2007).