L1. Fetal circulation-1.pdf

01 Physiology Dr. Asad Zeidan Fetal Circulation 13th January 2020 Rizeq F Al-Hourani Mohamed M Tawengi 1 This document covers: 1. “Fetal Circulation” Lecture Slides by Dr. Asad Zeidan 2. Medical Physiology by Guyton & Hall 13th edition P.g, 1075 – 1076 Welcome back future doctors. We hope that you h...

01 Physiology Dr. Asad Zeidan Fetal Circulation 13th January 2020 Rizeq F Al-Hourani Mohamed M Tawengi 1 This document covers: 1. “Fetal Circulation” Lecture Slides by Dr. Asad Zeidan 2. Medical Physiology by Guyton & Hall 13th edition P.g, 1075 – 1076 Welcome back future doctors. We hope that you had a splendid vacation and are ready to get to work. Greatness awaits. The doctors thrusted us into the deep end right from the very beginning of this unit. So, prepare and study well and we wish you the best of luck in this new semester. Outline: Today, we will talk about the following in detail:  Outline the unique features of fetal circulation.  Describe the changes in fetal circulation after birth.  Explain the possible mechanisms responsible for circulatory changes after birth. Unique Features of the fetal circulation: For us to appreciate the differences of the fetal circulation, we must observe how the blood normally circulates in adults. Basically, the adult’s heart works through a double circulatory system; 2 loops which are the systemic and the pulmonary circulations.  The pulmonary circulation (loop) carries the oxygenpoor blood to the lungs, where it becomes oxygen-rich blood then carried back to the heart.  The systemic circulation carries the blood from the heart to the rest of the body as seen in (Fig.1). Keeping that in mind, you have to realize that for the fetus, the lungs and Figure 1 many other organs have not developed yet. Therefore, there must be some unique features that can circumvent these setbacks and provide the adequate amount of oxygen and nutrients for the fetus to grow. 2  The first feature is the placenta which acts as the fetal lung. The placenta is separated into the ① maternal and the ② fetal portion. The maternal portion is the endometrium, specifically the decidua basalis. After about 10 to 16 weeks of gestation, an intervillous space is formed between the fetal placental villi that is filled with maternal blood. Instead of micro vessels, there is a cavernous blood-filled space. The intervillous space is supplied by 100 to 200 spiral arteries of the maternal Figure 2 endometrium and is drained by the endometrial veins as shown in (Fig.2). The fetal potion of the placenta is also indicated. The fetal portion includes the chorion frondosum (bushy chorion) and the chorionic villus that contains the fetal capillaries. The fetal capillaries bring in the fetal blood from the umbilical arteries and then, blood leaves through sinusoidal capillaries to the umbilical venous system. Exchange occurs in the fetal capillaries and probably to some extent in the sinusoidal capillaries. The mother’s vascular system forms a reservoir around the treelike structure such that her blood envelops the placental villi.  In spite of this, the fetal and maternal circulations in the placenta with its combined structures create a significant diffusion barrier for oxygen. Special fetal adaptations are required for oxygen exchange, because of the limitations of passive exchange across the placenta.  The PO2 of maternal arterial blood is about 80 to 100 mmHg, whereas that of the incoming blood in the umbilical artery is about 20 to 25 mmHg.  This difference in oxygen concentration provides a large driving force for diffusion but results in an increase in the PO2 of fetal blood in the umbilical vein to only 30 to 35 mm Hg. Figure 3 3 Fortunately, the fetal hemoglobin carries more oxygen at a low PO2 than the adult hemoglobin carries at a PO2 two to three times higher. This can be clearly seen in (Fig.3) where at 35 mmHg, the fetal blood oxygen saturation is around 80%. This phenomenon can be explained by 3 special properties of fetal hemoglobin: 1. The fetal Hemoglobin (HbF) has a higher affinity to O2 than adult Hemoglobin (HbA). 2. Fetal blood has higher Hb content, which means that there is more RBCs in the fetus per cubic millimeters than adults. 3. 2,3-DPG increase can cause decrease in oxygen affinity as shown in the equation 2,3-DPG: 2,3-diphosphoglyceric acid below. The fetal hemoglobin has a lower affinity to 2,3-DPG, which means that its oxygen affinity is less affected. Blood Circulation in the fetus: The last few unique features of the fetus involve the blood vessels, and shunts or bypass channels. Starting from the fetal “lung”, the placenta, there are three connected blood vessels: A. Left umbilical vein, which carries oxygenated blood from the placenta to the heart. B. Left and right umbilical arteries, which carry deoxygenated blood from the heart to the placenta. The right Umbilical vein atrophies during the development, leaving only the left to carry the blood towards the liver.  The path of oxygenated blood starts from the placenta by the umbilical vein, where the blood moves towards the liver.  While the fetus is in utero, the function of the liver is still limited and underdeveloped. Therefore, majority of the blood gets shunted by the ductus venosus to the inferior vena cava.  Furthermore, blood from the intestines through the hepatic portal vein is connected to the ductus venosus through the portal shunt, which will also bypass the liver. Figure 4 4  Now, the blood oxygen saturation would drop from 80% to 65% since it mixed with deoxygenated blood that has an oxygen saturation of 25%, coming from the inferior vena cava.  When it reaches the heart, most of the oxygenated blood will be diverted through the foramen ovale that connects the right atrium to the left atrium. From there, it will be pumped out from the aorta to the head.  The reason for this RL shunting is because of the resistance differential, as the lung have not completely developed yet and have not been inflated. The resistance in the pulmonary circulation would be much higher than the systemic circulation, and the blood then proceeds to the path of least resistance. The oxygen saturation remains at 65% during this time.  The deoxygenated blood coming from the superior vena cava is diverted to the right ventricle and pumped mostly through the pulmonary artery.  However, as said before, the lungs have high resistance which results in the blood being shunted towards the aorta through the ductus arteriosus from the pulmonary artery, where it proceeds to the feet and umbilical arteries. Some of the oxygenated blood coming from the inferior vena cava (65%) will mix with the deoxygenated coming from the superior vena cava (25%), resulting in about 50% oxygen Figure 5 saturation blood when leaving the right ventricle. However, after it shunts to the aorta, it mixes with the with blood coming Remember! from left ventricle and the oxygen saturation of this blood becomes 55%. The oxygen saturation is NOT cumulative. Therefore, it must be memorized individually. All the oxygen saturation is visually represented through the (Fig.5). 5 Finally, we will discuss how the blood flow is distributed in the fetal circulation (Fig.6): While the diagram in (Fig.5) explains it all, there are some differences from the adult circulation that should be highlighted.  First, only 55% of the blood goes through the placenta, leaving only 45% to pass through the tissues of the fetus (15% upper limbs, 18% lower limbs and 12% lungs).  Furthermore, in the fetal circulation, only 12% of the blood goes through the lungs. However, immediately after birth, virtually all the blood will flow through the lungs; 100%.  Lastly, in the diagram, it shows that the left ventricle pumps approximately 60% and right ventricle pumping approximately 40%. In the Figure 6 adult circulation, the right and left ventricles both pump 50% of the blood. Circulation After Birth: Right after birth, there are two major changes that occur: 1. The loss of the placenta, which results in almost doubling of the vascular In the fetus, before birth, hypoxia causes vasoconstriction of the lung blood vessels. systemic resistance at birth. This increases the aortic pressure as well as the pressures in the left ventricle and left atrium. 2. The expansion of the lungs, which greatly decreases pulmonary vascular resistance.  In the unexpanded fetal lungs, the blood vessels are compressed because of the small volume of the lungs. Immediately after expansion, these vessels are no longer compressed and the resistance to blood flow decreases several folds.  This reduces the ① pulmonary arterial pressure, ② right ventricular pressure, and ③ right atrial pressure. These changes are shown in (Fig.7). Figure 7 6 As a result of these changes, the effects will be seen on the unique features of the fetal circulation that are no longer needed. For example: a) Closure of the Foramen Ovale (Fig.8):  The low right atrial pressure resulting from the decreased resistance in pulmonary circulation and the high left atrial pressure resulting from the removal of the placenta that increased the resistance at birth will result in the blood attempting to flow backward through the foramen ovale. In other words, the blood will try to move from the left atrium into the right atrium, rather than the other direction, as it used to occur during fetal life. Figure 8  Add to that, the increase of blood flow to the lungs due to its expansion causes more blood to reach the left atrium, which results in a greater increase of pressure.  Immediately after birth, the valve of the foramen ovale (septum primum) fuses to the septum secundum, thereby preventing further flow through the foramen ovale and forming the fossa ovale.  Failure of this closure results in Atrial Septal Defect, or Patent foramen ovale, which may be asymptomatic if the defect is small. b) Closure of the ductus arteriosus (Fig.9):  First, the increased systemic resistance elevates the aortic pressure while the decreased pulmonary resistance reduces the pulmonary arterial pressure. As a consequence, after birth, the blood begins to flow backward from the aorta into the pulmonary artery through the ductus arteriosus, rather than in the other direction as in fetal life.  However, after only a few hours, the muscle wall of the ductus arteriosus constricts markedly, and within 1 to 8 days, the constriction is usually sufficient to stop all blood flow. This is called functional closure of the ductus arteriosus to prevent the backflow of blood from the aorta to the pulmonary trunk. Figure 9 7  The cause of ductus arteriosus closure relates to the increased oxygenation of the blood flowing through the ductus. In fetal life, the PO2 of the ductus blood is only 15 to 20 mm Hg. However, it increases to about 100 mm Hg within a few hours after birth. Furthermore, many experiments have shown that the degree of contraction of the smooth muscle in the ductus wall is highly related to this availability of oxygen.  Another reason is the release of bradykinin from the lungs, which also could result in the vasoconstriction of the smooth muscles. Interestingly, bradykinin is actually a vasodilator in adult blood vessels. This may indicate that fetal blood vessels may be different from their adult counterparts. This will result in the growth of fibrous tissue in the lumen causing the formation of the ligamentum arteriosum.  Finally, there is a decrease in the circulating prostaglandin E2. This results from the removal of the placenta that was the major source of it. Patent Ductus arteriosus results in excessive ductus dilation caused by the vasodilating prostaglandins in the ductus wall. In fact, administration of the drug indomethacin, which blocks the synthesis of prostaglandins, often leads to closure. c) Closure of the ductus venosus (Fig.10):  At birth, the liver would have been completely developed and functional. Therefore, there is no need for shunting of blood anymore.  As mentioned before, the portal blood from the fetus’s abdomen joins the blood from the umbilical vein, and these together pass by the ductus venosus directly into the inferior vena cava and above the liver, thus bypassing the liver.  However, immediately after birth, blood flow through the umbilical vein ceases, but most of the portal blood still flows through the ductus venosus with only a small amount passing through the channels of the liver. Within 1 to 3 hours, the sphincter near the umbilical vein of the ductus venosus contracts strongly and closes this avenue of flow. Figure 10  As a consequence, the portal venous pressure rises from near 0 to 6 to 10 mmHg, which is enough to force the portal venous blood flow through the liver sinuses. The ductus venosus also develops fibrous tissue, resulting in the formation of ligamentum venosum. 8 Although the ductus venosus rarely fails to close, we know almost nothing about what causes the failure of closure in a condition called Portosystematic shunt, where the blood will be continuously bypass the liver. d) Constriction of the umbilical vessels (Fig.11):  After birth, the lungs would have also developed and expanded, which means that there is no need for the placenta. So, the reason for the constriction is due to the umbilical cord cut to detach the neonate from the placenta.  Initially, the umbilical arteries constrict to reduce the amount of fetal blood loss to the placenta. Afterwards, the umbilical veins proceed to also constrict which allows enough time for any blood carrying nutrients and oxygen to move back into the fetal circulation.  After both constrictions, the umbilical vein is converted into fibrous ligament called the ligamentum teres. The distal part of the umbilical arteries is also converted into a ligament called medial umbilical ligament, while the proximal part of it persists and supplies the urinary bladder. Complications: Figure 11 Persistent Fetal Circulation (Fig.12):  Persistent Fetal Circulation is also known as persistent pulmonary hypertension of the newborn.  From the name, we can rationalize that the pulmonary circulation pressure still exceeds the left systemic circulation, which will likely result in RL shunting, reverting the newborn back to the fetal-type circulation. 9  The cause of the hypertension could be either hypoxia, hypercarbia, acidosis or cold; all of whom can result in pulmonary vasoconstriction which increases pulmonary resistance.  The consequence is that the right atrium, ventricle and pulmonary trunk pressure remain high. Moreover, the closure of the foramen ovale and ductus arteriosus relies on the reversal of the pressure differentials. So, as a Figure 12 result of this condition, they remain patent. Cyanosis:  Cyanosis is the bluish discoloration of the skin or the mucous membranes. The name cyanosis literally means the blue disease or the blue condition. The condition would only appear if the deoxygenated hemoglobin content is 3g% (3g per 100ml). The cyanosis can express into two different types: 1. Central cyanosis (Fig.13), where it is present throughout the body including the mucous membranes and tongue. It can be caused by: a. RL shunting, called congenital cyanotic heart disease, in which there is mixing of oxygenated and Figure 13 deoxygenated blood in the systemic circulation. b. Decreased PO2 of inspired air like high altitudes. c. Hypoventilation. d. Parenchymal Lung disease. 2. Peripheral cyanosis (Fig.14), where it is limited to the extremities. It is also known as acrocyanosis and is caused by: a. Congestive heart failure. b. Circulatory shock. c. Exposure to cold temperatures. Figure 14 d. Abnormalities of the peripheral circulation such as polycythemia. 10 LR shunting defects: There are three major locations for this defect: ① On the atrial septum which separates the two atriums and it is termed Atrial Septal defect (ASD). ② On the ventricular septum which separates the two ventricles and it is termed Ventricular Septal Defect (VSD). ③ Lastly, the ductus arteriosus if left patent. 1. ASD usually exists due to the failure of the foramen ovale to close, which results in LR shunting as the resistance is less in the pulmonary circulation. 2. VSD is the most common congenital heart disease accounting for almost 30% of all CHDs. It can either occur in the membranous portion (most common) or/and the muscular portion of the ventricular septum. The blood moves LR due to the pressure and resistance differentials of the left to the right ventricles. It can become RL if left untreated in what is termed as Eisenmenger's syndrome. 3. Patent Ductus Arteriosus is the persistence of normal fetal vessel connecting the aorta to the pulmonary trunk. It usually closes spontaneously in normal term infants at 3-5 days of age. It accounts for 10% of CHDs and has a higher incidence if the baby was born in high altitudes (> 10,000 feet) and it is also more common in females. After birth, the aortic pressure is obviously higher than the pulmonary pressure and therefore, the blood moves from the aorta to the pulmonary trunk resulting in a LR shunt. Don’t hesitate to contact Rizeq F Al-Hourani / Mohamed M Tawengi regarding any clarification, concern or suggestion! 11