Fetal Gas Exchange and Circulation PDF

Fetal Gas Exchange and Circulation 2 Robert L. Joyner, Jr. Outline Embryological Overview Chamber Development Fertilization to Implantation...

Fetal Gas Exchange and Circulation 2 Robert L. Joyner, Jr. Outline Embryological Overview Chamber Development Fertilization to Implantation Maturation Maternal Fetal Gas Exchange Fetal Circulation and Fetal Shunts Cardiovascular Development Transition to Extrauterine Life Early Development Learning Objectives After reading this chapter the reader will be able to: 1. Discuss the identifiable stages of heart development and chambers, pulmonary artery, lungs, aorta, and umbilical explain the development of the heart chambers. arteries. 2. Name the three fetal shunts and discuss their role during 4. Describe the cardiac and pulmonary sequences of events fetal circulation. that occur when transitioning from fetal to extrauterine life, 3. Explain the direction of blood flow and relative vascular including the changes in fetal shunts. pressures in the placenta, umbilical vein, three fetal shunts, right-side heart chambers, left-side heart Key Terms angiogenic clusters chorionic villi mesoderm aorticopulmonary septum dextral looping placenta atrial bulge ectoderm septum primum blastocyst embryonic disk septum secundum bulboventricular loop endocardial cushions trophoblast bulbus cordis endoderm ventricular bulge chorion foramen ovale Wharton’s jelly chorionic membrane intimal mounds zygote What initially may seem like a remote concept for re- gas exchange. The fetus depends on the mother’s cir- spiratory care practitioners—a basic understanding of culation for nutrient and gas exchange; however, the embryology—is essential to understanding the care of maternal and fetal vascular networks are separate sys- the newborn. Whether care is being provided to a pre- tems, and no blood is shared between the two. By day mature newborn with respiratory distress syndrome 22 of gestation the primitive fetal heart begins to beat, as a result of insufficient or poorly functioning surfac- with myocardial pump function supporting circula- tant or to a newborn afflicted with persistent pulmo- tion by day 27 to day 29.1 nary hypertension resulting from severe meconium staining, all respiratory care practitioners working FERTILIZATION TO IMPLANTATION with infants must have a breadth of knowledge of em- As the fertilized egg, or zygote, travels to the uterus, it bryology and fetal development that provides them undergoes numerous iterations of cell division but has with an understanding of normal development and no nutrient source, as in a bird egg. The ball of develop- what to expect when something goes awry. ing cells, at this point termed the blastocyst, must attach itself and implant in the uterine lining for nour- ishment. The outer surrounding layer of the blastocyst EMBRYOLOGICAL OVERVIEW is the trophoblast, which combines with tissues from The rapidly growing embryo and fetus must develop the endometrium to form the chorionic membrane a vascular network to circulate nutrients and provide around the blastocyst.2 Inside the blastocyst, a group of 13 14 SECTION I Fetal Development, Assessment, and Delivery Box 2-1 Origin of the Various Tissue Systems From the Three Embryonic Germ Layers ECTODERM Central nervous system: brain and spinal cord Peripheral nervous system: cranial nerves and spinal nerves Chorion Sensory epithelia of the eyes, inner ears, and nose Chorionic villi Glandular tissues: posterior pituitary gland, adrenal medulla Skin: epidermal layer Specializations of the skin: sweat and sebaceous glands, hair follicles, nails, mammary glands Embryo Teeth: enamel Amniotic MESODERM sac Cardiovascular system: heart and blood vessels Lymphatic system vessels Amnion All connective tissue: general connective tissue and cartilage, bone, bone marrow, and blood cells Umbilical cord All muscle tissue: skeletal, cardiac, and smooth Skin: dermis and hypodermis Tail Kidneys and ureters, spleen Reproductive tissues (not including the germ cells) FIGURE 2-1 Implanted human embryo, approximately day 28, show- ing the relationship of the chorion, amnion, and chorionic villi. The The three major body cavities: pericardium, left and right umbilical cord and tail are difficult to differentiate in this view.  (From pleura, and peritoneum Blechschmidt E, editor: The stages of human development before Serous linings of organs within the body cavities birth. Philadelphia, 1961, WB Saunders.) Teeth: dentine, cementum, and pulp ENDODERM villi (Figure 2-1). Within the chorionic villi a capillary Digestive system: stomach, small and large intestines, network forms and connects to the umbilical stalk. The epithelial lining of the entire digestive system except parts of the mouth and pharynx, and anus (which are villi intertwine into the blood-filled lacunar cavities of supplied by the ectoderm) the endometrium of the maternal uterus.2 Oxygen, Respiratory system: pharynx, lungs, and epithelial lining carbon dioxide, and nutrients diffuse through the vast of the trachea and lungs capillary surface area of this indirect connection be- Urinary system: bladder and lining of the urethra tween mother and fetus. As fetal development contin- Liver and pancreas and epithelial lining of all glands that ues, the region of this interface becomes limited to the open into the digestive system discus-shaped placenta, because the amniotic sac Tonsils, thymus, thyroid, parathyroid completely fills the chorionic cavity. The umbilical Epithelial lining of auditory tube and tympanic cavity cord connects the placenta to the fetus with one large Adapted from Moore KL, Persaud TVN, editors: The developing human: clinically vein and two smaller arteries. As the cord grows, the oriented embryology, ed 6, Philadelphia: WB Saunders, 1998, pp 63-82. vessels tend to spiral.4 Wharton’s jelly, a gelatinous substance inside the umbilical cord, helps protect the vessels and may prevent the cord from kinking. cells arrange on one side in the shape of a figure eight. The central portion is the embryonic disk, which forms CARDIOVASCULAR DEVELOPMENT the three embryonic germ layers: the ectoderm and the endoderm, followed by the mesoderm.3 Box 2-1 lists the During the third week of gestation, the heart is fully tissue systems that arise from the three germ layers. formed. The heart is considered to be the first com- The outer or top loop of the figure eight envelops plete organ formed. By 8 weeks of gestation, the fetal the embryonic structure and forms the amniotic sac, heart is fully functional, complete with all chambers, whereas the inner or bottom loop forms the yolk sac. valves, and major vessels. In addition, the fetal heart The yolk sac soon degenerates and incorporates into must accommodate the circulatory configuration re- the embryo, giving way for the amniotic sac to grow. quired to support a fetus that is residing, growing, Suspended in the cavity of the blastocyst, the amniotic and maturing enclosed within a fluid-filled environ- sac then surrounds the entire embryo. The embryo at- ment. The anatomic solutions to circulate oxygenated taches to the outer layer through the umbilical stalk, blood cannot be the same in the placenta-respiring which later becomes the umbilical cord. fetus as it is in the air-breathing newborn. As the em- bryonic heart changes are described, note which of MATERNAL–FETAL GAS EXCHANGE them may result in the cardiac anomalies discussed in As the umbilical cord matures, finger-like projections Chapter 24. Table 2-1 lists the timing of the key cardiac extend into the outer lining of the chorion, or chorionic developments.  Fetal Gas Exchange and Circulation CHAPTER 2 15 Timetable of Significant Events into three identifiable structures called the bulbus cor- Table 2-1 dis, the ventricular bulge, and the atrial bulge. These During Fetal Heart Development structures empty into the sinus venosus, which also TIME OF GESTATION EVENT receives blood from three additional sources: the vitel- Early Development line veins (arising from the yolk sac), the common Week 3 cardinal veins (from the embryo), and the umbilical Day 16 Angiogenic clusters (blood islands) veins (from the primitive placenta) (Figure 2-2).7 appear These structures continue to bend, fold, and dilate by Day 18 Heart tubes form Day 21 Heart tubes fuse Chamber Development Arterial end of heart Week 4 First aortic arch Day 22 Fusion of heart tubes complete First branchial arch Heart begins to beat 21 mesoderm Bidirectional blood flow begins  1 day Splanchnic mesoderm Day 23 Folding, looping, ballooning begin Fusing heart tubes Day 25 Atrial septation begins with growth Unfused heart tubes of septum primum Septum transversum Day 28 Ventricular septation starts Endocardial cushions form Unidirectional blood flow begins Venous end of heart Week 5 Day 32 Septum secundum starts First aortic arch Week 6 Day 37 Foramen ovale complete 22 Bulbus cordis  1 day Maturation Day 46 Ventricle formation complete Ventricular bulge Day 49 Four chambers complete Atrial bulge Valve formation matures Week 8 Day 52 Aorta/pulmonary artery complete separation Truncus arteriosus 23 Day 56 Valve formation complete  1 day Bulbus cordis EARLY DEVELOPMENT Ventricular bulge During early embryonic development, small cellular Atrial bulge pools, referred to as angiogenic clusters or blood is- Sinus venosus lands, supply nutrition to the growing embryo. These clusters coalesce to form two heart tubes lined with Septum transversum specialized myocardial tissue.5 On approximately day First aortic arches 18 the heart tubes fold into what will become the tho- Second racic cavity. At this point they become close enough to 24  1 day Truncus arteriosus fuse, and they grow into a complete single-chamber Bulbus cordis tubular structure by day 21. The cardiovascular sys- Bu Ventricular bulge tem forms primarily from the mesoderm layer, but lbovent myocardial tissue has a diverse origin related to the Atrial bulge ric recruitment of myocytes from surrounding tissue u l a r l oo p Sinus venosus types during embryogenesis.6 By day 22 cardiac con- Common cardinal vein tractions are detectable and bidirectional tidal blood Umbilical vein flow begins.4 Vitelline vein CHAMBER DEVELOPMENT FIGURE 2-2 Formation of the primordial heart chambers after fusion of the heart tubes at a gestational age of 3 weeks.  (From Moore KL, Dramatic changes begin to occur during the fourth editor: The developing human: clinically oriented embryology, ed 3. week of gestation. The heart tubes continue to merge Philadelphia, 1982, WB Saunders.) 16 SECTION I Fetal Development, Assessment, and Delivery Primordial atrium Sinoatrial valve Septum primum guarding orifice of Bulbus sinus venosus cordis Foramen primum Right Ventral atrium Endocardial Left atrioventricular cushions canal Dorsal Fused endocardial cushions Primordial right ventricle Primordial interventricular A B septum FIGURE 2-3 A, Sagittal view of the developing heart during week 4, showing the position of the atrium, bulbus cordis, ventricles, and endocardial cushions merging from the ventral and dorsal sides. B, Traditional view of the developing heart during weeks 4 to 5, showing budding interventricular septum, fused endocardial cushions, septum primum, and the left and right atria. The ventricular septum continues to fold and grow upward between the ventricles. (Modified from Moore KL, editor: The developing human: clinically oriented embryology, ed 3. Philadelphia, 1982, WB Saunders.) incorporating components from surrounding tissue Superior Septum structures as the truncus arteriosus (which connects vena cava secundum Foramen the heart to the future arterial system) becomes recog- secundum nizable.8 Note that initially the atrial bulge is inferior Crista terminalis to the ventricular bulge. Between days 23 and 28 a process referred to as dextral looping occurs, whereby Septum the ventricular bulge balloons into a C-shaped loop primum that pushes the atrial bulge in a superior direction Septum (see Figure 2-2). Subsequently the embryonic heart secundum appears as a twisted S-shape, and the ventricular structure merges with the bulbus cordis to form a one- Mitral valve ventricle structure known as the bulboventricular loop, which continues to dilate.9 Simultaneous with the external changes, the septum Papillary primum begins the separation of the primitive atrium, muscle followed shortly by growth of the endocardial cush- ions, which will separate the atria from the ventricles. Left ventricle Tricuspid valve During this time the left atrium incorporates the pri- FIGURE 2-4 Frontal view of the fetal heart between weeks 5 and 6, mordial pulmonary veins as four pulmonary veins showing the development of the four chambers nearing completion. empty into the primordial left atrium. The right horn The arrow shows the one-way path through the foramen ovale. of the sinus venosus grows in dominance and merges (Modified from Moore KL, editor: The developing human: clinically into the future right atrium from the inferior and su- oriented embryology, ed 3. Philadelphia, 1982, WB Saunders.) perior vena cavae. By the end of the fourth week the dilating ventricular spaces fold into each other and force the ventricular septal bud upward at the base ventricular septum continues to grow into the ven- of the bulboventricular loop (Figure 2-3).4 By this tricular space as the two ventricles dilate. Ridges also time blood flow matures into a unidirectional path appear opposite each other in the bulbus cordis and as the myocardium continues to strengthen by recruit- truncus. They grow toward each other and fuse into a ing myocytes from the surrounding mesenchymal spiraling aorticopulmonary septum, which ultimately tissue.3,6 separates into the aorta and pulmonary arteries.3 A During weeks 5 and 6 the internal and external fetal heart rate of about 95 beats per minute becomes structures continue to mature rapidly. Between the discernible during this period and increases by ap- atria the septum secundum begins to appear. By week 6 proximately 4 beats per day until heart development is the septum secundum and a flap from the septum pri- complete.10 mum form the foramen ovale, one of the fetal shunts discussed later in this chapter (Figures 2-4 and 2-5). MATURATION The atrioventricular canal continues to mature, and Continuing maturation of the internal and external the endocardial cushions separate the ventricular structures characterizes weeks 7 and 8. The ventricles spaces from the atrium. The muscular portion of the finish forcing the ventricular septum up from its base.  Fetal Gas Exchange and Circulation CHAPTER 2 17 Superior vena cava Oval foramen open Valve of oval foramen Inferior vena cava (carrying well- oxygenated blood) FIGURE 2-5 Frontal view (right) and side view (left) schematics of the foramen ovale. The septum primum forms the flap, and the septum secundum remains open to form the foramen ovale. The arrows show the one-way path through the foramen ovale. (From Moore KL, editor: The developing human: clinically oriented embryology, ed 3. Philadelphia, 1982, WB Saunders.) A small intraventricular foramen remains, and blood effectively bypassing the fetal liver. The amount of flows between the two ventricles until the endocar- shunting through the ductus venosus appears to de- dial cushions fuse with the ventricular septum (see crease with gestational age.13 The oxygen-rich blood Figure 2-4). At the end of the seventh week, tissue within the umbilical vein empties into the inferior from remnants of the bulbus cordis and tissue from vena cava and mixes with oxygen-depleted systemic the endocardial cushions grow into the ventricular fo- venous blood as it flows to the right atrium. Even ramen, closing it as they merge with the muscular though some admixture occurs, the blood entering the ventricular septum. The tricuspid and mitral valves right atrium contains the highest oxygen saturations form from specialized tissue surrounding the two available to the fetus. atrioventricular openings. The aorticopulmonary sep- In the right atrium most of the blood flow from the tum divides the bulbus cordis and truncus into an inferior vena cava crosses through a hole within the aortic and pulmonary trunk. As these outflow tracts atrial septum, called the foramen ovale, into the left continue to mature, the semilunar valves form at the atrium. The foramen ovale, the second fetal shunt, is base of each structure.8 Early in the eighth week formed during septation of the atria, as described pre- the outflow tracts and valves are completely devel- viously. The septum primum acts as a one-way valve oped. At this stage, development of the cardiac struc- over the ostium secundum (see Figure 2-5). The re- tures is complete, and blood flows through the fetal mainder of the blood in the right atrium mixes with circulation pathway. The heart continues to develop, desaturated blood from the superior vena cava and increasing proportionately more in length than width, drains into the right ventricle. Blood in the right ven- paralleling embryonic growth.11,12 tricle contains slightly higher oxygen content than blood from the superior vena cava and is pumped into the pulmonary artery to the developing lungs. FETAL CIRCULATION AND FETAL SHUNTS The pulmonary vascular resistance (PVR) in utero is Fetal circulation necessarily differs from circulation high. Likely mechanisms include physical compres- after the infant is born, because external respiration by sion of the vessels resulting from relatively low lung the fetus does not occur within the lungs. Figure 2-6 volumes and hypoxic pulmonary vasoconstriction re- illustrates fetal circulation and the three shunts present sulting from the low partial pressure of oxygen within in the fetus that close soon after birth. The mother’s the alveolus of the fetus. Both mechanisms help induce lungs and liver perform most of the metabolic func- chemical mediators that maintain a high resistive tone tions required by the same organs of the fetus. The fe- in the pulmonary vascular bed.14 Up to 13% to 25% of tal circulation pathway allows blood flow to be shunted the fetal blood flow presented to the right atrium around the fetal liver and lungs. Shunting most of the reaches the lungs.11,15 blood volume through the fetal heart, bypassing the Blood from the pulmonary veins empties into the lungs, facilitates pumping the required large quanti- left atrium and then flows into the left ventricle, out ties of fetal blood to the placenta, which is the gas, the aortic valve, and into the ascending aorta, where it nutrient, and waste exchange interface between the supplies blood with the highest oxygen content to the maternal and fetal organ systems.11 head, right arm, and coronary circulation. The high Oxygenated blood travels from the placenta to the PVR causes most of the blood flowing through the fetus through the umbilical vein. The ductus venosus, pulmonary artery from the right ventricle to pass the first fetal shunt, appears continuous with the um- through the less resistant ductus arteriosus, the third bilical vein, shunting approximately 30% to 50% of the fetal shunt, directly into the aorta. This allows blood oxygen-rich blood directly to the inferior vena cava, within the pulmonary artery to bypass the lungs 18 SECTION I Fetal Development, Assessment, and Delivery Superior vena cava Arch of aorta 65% 40% Ductus arteriosus Lung 55% 60% Pulmonary artery Pulmonary veins Foramen ovale Left atrium Right atrium Valve of Right ventricle foramen ovale 70% 55% 65% Inferior vena cava Left hepatic vein Ductus venosus Descending aorta Sphincter Gut Oxygen content Portal vein Highest Umbilical vein Kidney Moderate Umbilicus Poorest Urinary bladder Umbilical arteries Placenta Legs Internal iliac artery FIGURE 2-6 A diagram of the fetal circulation showing blood containing oxygen and nourishment moving from the placenta to the fetal heart and through the three fetal shunts: the ductus venosus, the foramen ovale, and the ductus arteriosus. (Modified from Moore KL, editor: The developing human: clinically oriented embryology, ed 3. Philadelphia, 1982, WB Saunders.) and left heart. Because large quantities of blood are as much as half of the fetal blood volume. Because of required to flow to the placenta, this permits the the large vascular surface area of the placenta, imped- right ventricle and left ventricle to pump almost in ance to blood flow is extremely low, allowing blood parallel. The path of fetal circulation and percentage of flow through the placenta to remain consistent and oxygen saturation in various locations are illustrated stable.11 in Figure 2-6.16 The deoxygenated blood from the upper torso re- TRANSITION TO EXTRAUTERINE LIFE turns to the right atrium via the superior vena cava. Finally, blood in the descending and abdominal aorta Clamping the umbilical vessels removes the low- flows through common iliac arteries to two umbilical pressure system of the placenta from fetal circulation. arteries and back to the placenta for oxygenation.17 During the first breath, several factors drastically re- Initially 17% to 20% of the fetal cardiac output flows duce the PVR and increase pulmonary blood flow.19 through the umbilical arteries, but as the fetus matures, Inflation of the lungs initiates gas exchange, which in this rises to 33%.18 At any point, the placenta contains turn dilates the pulmonary arterioles. Rising systemic  Fetal Gas Exchange and Circulation CHAPTER 2 19 arterial oxygen pressure (Pao2) also stimulates the of the ductus arteriosus occurs as a result of being release of endogenous pulmonary vasodilating cyto- exposed to an increase in Pao2, a decrease in PVR kines that act locally to increase the diameter of the leading to the reduction in blood pressure within the pulmonary arterial vasculature.20 Stretching of the pul- ductal lumen, a decrease in the local production of monary parenchyma also physically expands the vas- prostaglandins, and a reduction in the number of culature. Besides vasodilation, lung inflation results in prostaglandin receptors within the tissue of the the inhibition of vasoconstricting agents produced by ductus arteriosus.21,22 Normally, constriction of the the lung to facilitate fetal circulation.19 ductus arteriosus starts to occur at birth, and 20% Once the cord is clamped and the PVR decreases, of the ductus closes within 24 hours, with 80% closed pressures in the right side of the heart decrease and in 48 hours and 100% by 96 hours after birth.23 Ana- pressures in the left side increase. Because the foramen tomic closure of the ductus arteriosus begins in the ovale flap allows blood to flow only from right to left, last trimester as endothelial tissue begins to prolifer- it closes when the pressures in the left atrium become ate into the lumen of the ductus, forming bulges greater than those in the right atrium. Closing the fora- known as intimal mounds. Initially assisted by vaso- men ovale further facilitates the increase of blood flow constriction, the ductal lumen closes completely as to the lungs during the transitional period and is nec- gestational and postgestational age advances.24 By essary to maintain normal extrauterine circulation. 2 to 4 weeks of age, the anatomic closure is complete Because the pressure in the aorta also increases and blood flow normalizes to the adult pattern of and becomes greater than the pressure in the pulmo- circulation.23 The structure that was once the ductus nary artery, the amount of shunting through the arteriosus is referred to as the ligamentum arteriosum ductus arteriosus decreases. The functional closure in adults. Case Study Dystocia-Associated Respiratory Distress A 32-year-old woman has just given birth to a 38-week new- pulse oximetry of the right hand and left foot, which revealed born after prolonged labor as a result of shoulder dystocia. saturations of 96% and 75%, respectively. The baby was born apneic, with minimal muscle tone and a 1. What two anatomic shunts normally present in the fetus heart rate of 80 beats per minute. The newborn was at- can result in persistent cyanosis in the newborn? tended to immediately by the neonatal resuscitation team, 2. Why would the newborn in this case be at risk for who provided positive pressure ventilation for approximately refractory hypoxemia? 30 seconds. The newborn began breathing spontaneously 3. Why are the two oximetry readings necessary, and why and was transferred to the intensive care nursery on supple- are the probes placed at the sites specified by the mental oxygen. Three hours later, despite the supplemental physician? oxygen, the baby was still cyanotic. The physician ordered See Evolve Resources for answers. Key Points Assessment Questions The heart is the first complete organ formed. Identifying Select the best answer. See Evolve Resources for answers. the stages of development of the heart is important in 1. Which of the following are true statements concerning understanding congenital problems that can occur the development of the circulatory system? when development does not proceed as expected. I. Heart development is completed by about 32 weeks The ductus venosus, foramen ovale, and ductus arterio- of gestation. sus are the anatomic shunts present in the fetus that II. Heart development, other than growth, is complete allow fetal circulation. These shunts are essential to when valve formation is complete. proper nutrient and gas exchange in the fetus. III. Angiogenic clusters supply nutrition in the earliest The three anatomic shunts and the pressure gradients stages of the growing embryo. induced by the circulatory systems (e.g., placental, IV. The right-side myocardial fibers begin contracting pulmonary, and systemic) are all necessary to ensure before the left side to provide blood flow to the lungs. proper directional blood flow through the fetus. This V. At about 3 weeks, two heart tubes fuse into what will provides for gas and nutrient exchange and appropriate become the basic structure of the four-chamber distribution of blood through the fetus. heart. Transition from fetal circulation to adult circulation A. I, III, and V during the birthing process is a complex event that takes B. II and III place flawlessly in nearly every birth. Recognizing the C. II, III, and IV signs and symptoms of inappropriate transition is impor- D. II, III, and V tant to ensure that the right care is quickly delivered. E. III and IV 20 SECTION I Fetal Development, Assessment, and Delivery 2. Which of the following are recognizable structures 7. Most of the fetal blood entering via the right atrium is during development of the heart after the heart tubes shunted to the left atrium through the ________. fuse? A. Foramen ovale I. Sinus venosus B. Ductus venosus II. Bulbus cordis C. Ductus arteriosus III. Atrial bulge D. Superior vena cava IV. Ventricular bulge E. Aortoiliac shunt V. Truncus arteriosus 8. When discussing fetal circulation, which of the following A. I and III is true? B. I, II, IV, and V A. Fetal shunts help shunt the best-oxygenated blood C. II, III, and IV to the head. D. II, III, IV, and V B. Pressure gradients related to blood flow are the E. III, IV, and V opposite of those in an adult. 3. The oxygenated blood leaves the placenta and travels C. Fetal shunts help bypass the lungs. to the fetus through the __________. D. The placenta has low vascular resistance. A. Aortic artery E. All of the above. B. Umbilical vein 9. What one set of actions causes the systemic circulation C. Umbilical artery to transition from a low-resistance system to a high- D. Spiral artery resistance system? E. Ductus arteriosus A. Clamping the umbilical cord and creating a short 4. Most of the fetal blood entering the main pulmonary period of hypoxia artery is shunted to the aorta through the _________. B. Getting a higher concentration of oxygen into the A. Foramen ovale lungs with the first breath B. Ductus venosus C. Clamping the umbilical cord, thus preventing blood C. Ductus arteriosus flow to the placenta D. Superior vena cava D. Pulmonary hypertension from a change in blood E. Iliac arteries flow direction 5. Most of the fetal blood entering via the umbilical E. Expulsion of the placenta at birth vein is shunted to the inferior vena cava through 10. Anatomic narrowing of the ductus arteriosus begins in the _________. the last trimester by which process? A. Foramen ovale A. The formation of bulges known as intimal mounds B. Ductus venosus B. The release of tolazoline compounds C. Ductus arteriosus C. Ductal termination D. Superior vena cava D. The formation of the aortic valve E. Iliac arteries E. Activating thrombokinins 6. Normal circulatory changes occurring within the transi- tional stage at birth include which of the following? I. A decrease in pulmonary vascular resistance II. A decrease in systemic vascular resistance III. A decrease in pulmonary artery pressure IV. An increase in left ventricular pressure V. An increase in pulmonary blood A. I and IV B. I, II, IV, and V C. I, III, IV, and V D. II, III, and V E. III, IV, and V 5. Gourdie RG, Kubalak S, Mikawa T. Conducting the embry- REFERENCES onic heart: orchestrating development of specialized cardiac 1. Pensky B. Review of medical embryology. New York: McMillan; tissues. Trends Cardiovasc Med. 1999;9(1–2):18. 1982:291-335. 6. Eisenberg LM, Markwald RR. Cellular recruitment and the 2. Kingdom JC, Kaufmann P. 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